- Email: [email protected]
Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease - from the ACSIS registry
IJCA-28296; No of Pages 6 International Journal of Cardiology xxx (xxxx) xxx
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Temporal trends of patients with acute coronary syndrome and multivessel coronary artery disease - from the ACSIS registry Arthur Shiyovich a,b,⁎, Nir Shlomo c, Tal Cohen c, Zaza Iakobishvili b,d, Ran Kornowski a,b, Alon Eisen a,b a
Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Israeli Center of Cardiovascular Research, Tel Hashomer, Israel d Department of Community Cardiology, Tel Aviv Jaffa District, Clalit Health Services, Tel Aviv, Israel b c
a r t i c l e
i n f o
Article history: Received 27 September 2019 Received in revised form 13 January 2020 Accepted 20 January 2020 Available online xxxx
a b s t r a c t Introduction: Multi-vessel coronary artery disease (MV-CAD) is common among patients with acute coronary syndrome (ACS) and is associated with worse outcomes. Objectives: To examine temporal trends of patients presenting with ACS and MV-CAD. Methods: Time-dependent analysis of patients enrolled in the ACS Israeli Surveys (ACSIS) between 2004–2016 by 3 time periods: early (2004–2006; n = 2111), mid (2008–2010; n = 2049), and late (2013–2016; n = 2010). MV-CAD was defined as N50% stenosis in ≥2 separate coronary territories at the index coronary catheterization. Outcomes were 30-day MACE and 1-year all-cause mortality. Results: Overall 6170/9321 patients (66%) had MV-CAD (age 64.5 ± 12.1, males 80%). Patients from later periods were older with a higher prevalence of cardiovascular risk-factors and comorbidity. Among patients with MVCAD, STEMI decreased significantly (early-46% vs. late-37%, p b 0.001). The rates of PCI were similar, however rates of MV-PCI have increased (early-16.8% vs. late −37.1%, p b 0.001) while the rates of CABG decreased over-time (early-12.7% vs. late −9.2%, p b 0.001). Thirty-day outcomes improved significantly; MACE (early18.2%, mid-12.6%, late-11.2%, p b 0.001), mortality (early-4.7%, mid-4.2%, late-3.1%, p = 0.03) and re-infarction (early = 3.0%, mid = 2.4% and late 1.1%, p b 0.001). No significant change in 1-year mortality was observed (early = 9.3%, mid = 7.8%, late = 7.7%, p = 0.13). A multivariate adjusted analysis demonstrated that the mid and late periods (vs. the early period) were associated with significantly reduced risk for 30-day MACE (OR = 0.65 [0.54–0.77] and 0.54 [0.45–0.65], respectively). Conclusions: During the last decade, the burden of cardiovascular risk factors among ACS patients with MV- CAD has increased, more invasive treatment was provided and a significant improvement in 30-day outcomes was observed. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Patients presenting with acute coronary syndrome (ACS) have multi-vessel coronary artery disease (MV-CAD) in 40–70% of cases [1–3]. MV-CAD in this setting [both in ST-segment elevation (STEACS) and in non-ST segment elevation (NSTE-ACS)] is associated with worse clinical outcomes compared with single vessel coronary artery disease despite coronary revascularization [4–7]. Furthermore, patients with MV-CAD have a more advanced atherosclerotic disease in other vascular beds, worse endothelial dysfunction, increased platelet reactivity, higher fibrinogen levels, and increased thrombin activation [8,9]. Over the past decades, significant improvements in the medical and ⁎ Corresponding author at: Department of Cardiology, Rabin Medical Center, 39 Jabotinsky St., 49100 Petah Tikva, Israel. E-mail address: [email protected] (A. Shiyovich).
interventional treatments of ACS were introduced into clinical practice [10–12]. Multiple high quality studies [9,13–15] focused particularly on patients presenting with MV-CAD in the setting of ACS, incorporating their results into international care guidelines [16–19]. However, data regarding period-dependent changes in these patients' care are scarce. The objective of the present study was to evaluate the temporal trends in clinical characteristics, management and outcomes of patients presenting with ACS and MV-CAD using a large periodic registry. 2. Methods 2.1. Study design and population The current study included consecutive patients from the ACS Israeli Surveys (ACSIS) between 2004 and 2016, who had MV-CAD, defined as N50% stenosis in ≥2 separate major coronary territories at the index ACS.
https://doi.org/10.1016/j.ijcard.2020.01.040 0167-5273/© 2020 Elsevier B.V. All rights reserved.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
2
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
The ACSIS is a prospective survey, conducted every 2–3 years that enrolls consecutive patients from all 26 coronary care units operating in Israel over a 2-month period. Dedicated and specifically trained research personnel using a central questionnaire entered the data electronically. The institutional review board (IRB) of all the participating hospitals approved the survey, which was performed in accordance with the Helsinki declaration. Despite reflecting the standard of care, all patients since 2010 signed informed consent for participating in the ACSIS registry trials. The pre-specified demographic, cardio-vascular risk factors, comorbidities, medications and clinical data were recorded along with admission and discharge diagnoses as defined by the attending physicians based on clinical, electrocardiographic, and biochemical criteria. Patient management was at the discretion of the attending physicians. Patients were classified into three groups according to the following time periods of admission: early (2004–2006), mid (2008–2010), and late (2013–2016). Each of the time-periods included a total of 2 surveys. MV-PCI was defined, per coronary angiography, as PCI performed in more than one coronary artery throughout the index admission or up to 30d of follow-up (i.e. staged PCI). MV-PPCI was defined when nonculprit artery PCI was performed in STEMI patients (in addition to the culprit-artery PCI) throughout the PPCI index procedure. 2.2. Outcomes The outcomes included 30-day major adverse cardiovascular events (MACE), comprised of: all-cause mortality, myocardial infarction (MI), stroke, unstable angina, stent thrombosis and urgent revascularization. Additional outcome was 1-year all-cause mortality. Data regarding the outcomes were determined by hospital chart review, telephone contact, clinical follow-up and by matching identification numbers of patients with the Israeli National Population Registry (for 30-day and 1-year mortality). 2.3. Statistical analysis Comparison between the three period groups were perfomed with chi-square for categorical variables and with ANOVA or Kruskal-Wallis test as appropriate for normal/non-normal distributed continuous variables. Logistic regression was calculated to assess the relationship between periods and MACE, adjusted for potential confounders. Survival analysis between the groups was performed using the Kaplan-Meier curves followed by the Log-Rank test. Cox proportional hazards analysis was used to assess the effects of period, adjusted for different covariates on 1-year mortality outcome. P-value b0.05 was considered statistically significant for all tests.
P<0.001
P=0.03 P<0.001
MACE: major adverse cardiac event
Fig. 1. 30-days outcomes according to admission period. MACE: major adverse cardiac event.
(ARBs) and anti-diabetic therapy has increased while that of ACE inhibitors, diuretics and calcium channel blockers has significantly decreased. Interestingly, the LDL cholesterol levels upon admission have decreased with time (mean: early- 112 mg/dL, mid- 100 mg/dL. Late 99 mg/dL, p b 0.001). The rates of interventional treatments by period are presented in fig. 2 (appendix). No statistically significant trend was found in the overall rates of PCI. However, the rates of MV-PCI have increased (early-16.8% vs. late-37.1%, p b 0.001) while the rates of CABG decreased significantly over time (early-12.7%, late - 9.2%, p b 0.001). Furthermore, overall PCI in the subgroup of patients with NSTE-ACS did not change while the rate of MV-PCI has increased significantly (early 25%, late = 41.3% p b 0.001). In patients with STEMI the overall PCI (early-84.1%, late-89.6%, p = 0.003) and the rate of MV- PPCI (early 17%, late 35.5%) have both increased. Nevertheless the rates of CABG decreased significantly in both NSTE-ACS and STEMI. The trends of the discharge medical therapy are presented in fig. 3 (appendix). A significant increase in the rate of aspirin, P2Y12 inhibitors and statins was observed while no changes were found in the rates of discharge with angiotensin converting enzyme inhibitors/angiotensinogen receptor blockers and beta-blockers. A statistically significant improvement in 30-day outcomes were observed: MACE (early = 18.2%, mid = 12.6%, late 11.2%, p b 0.001), Table 1 Baseline characteristics according to the admission period.
3. Results Out of 9321 patients who were admitted with an ACS between 2004–2016, 6170 patients had MV-CAD (66%, age 64.5 ± 12.1, males 80%) and were analyzed in the current study. The proportion of patients with MV-CAD (out of all patients with ACS) has decreased over time (early-67.3%, late-64.1%, p b 0.008). The latter decrease was observed both in STEMI (early-60.4%, late-56.1%, p = 0.003) and NSTE-ACS (early-74.6%, late-69.8%, p = 0.008) as presented in fig. 1 (appendix). Baseline characteristics of the patients with MV-CAD according to the study period are presented in Table 1. Patients admitted in the later periods were somewhat older with a higher prevalence of cardiovascular risk factors and prior CAD. Among patients with MV-CAD presenting with ACS, presentation as STEMI has decreased throughout the years (early- 46%, mid- 43%, late- 37%, P b 0.001). The medical treatment prior to the index hospitalization is presented in Table 1 in the Supplementary appendix. The rate of statins, angiotensin receptor blockers
n Age, years (mean ± SD) Gender (male) Dyslipidemia Hypertension Current smokers Diabetes mellitus Family history of CAD BMI (kg/m2), (mean ± SD) Prior MI Prior CABG Prior PCI Chronic renal failure PVD History of CHF
Early
Mid
Late
p
2111 64.3 (12.3) 78.5 63.2 60.9 36.0 35.1 23.6 27.5 (4.3) 32.3 13.7 28 10.4 9.3 6.9
2049 64.1 (12.1) 81.5 77.3 65.3 38.1 40.5 30.0 27.8 (4.9) 36.1 12.7 38.8 12.1 9.7 8.7
2010 65.3 (12) 80.2 77.2 70.0 37.4 44.3 30.9 29.7 (20.8) 36.9 11.2 37.7 12.8 7.4 7.0
0.005 0.061 b0.001 b0.001 0.370 b0.001 b0.001 b0.001 0.004 0.057 b0.001 0.040 0.025 0.057
CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, CABG: coronary artery bypass graft surgery, PVD: peripheral vascular disease, CHF: congestive heart failure
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
3
Fig. 2. One year survival curves according to the admission period.
mortality (early 4.7%, mid = 4.2%, late 3.1%, p = 0.03) and re-infarction (early = 3%, mid = 2.4% and late 1.1%, p b 0.001) (fig. 1). A trend of reduction in 1-year mortality (fig. 2) was observed with time, yet it did not reach statistical significance. Multivariate adjusted analysis (fig. 3) demonstrated that the mid and late periods were associated with a significantly reduced risk for 30-day MACE compared to the earlier period (OR = 0.65 [0.54–0.77] and 0.54 [0.45–0.65], respectively). 4. Discussion The present study evaluated the temporal trends of patients presenting with ACS and MV-CAD throughout 2004–2016 based on a national multi-center registry. The main findings include: 1) decrease in the rate of MV-CAD among patients with ACS throughout the years for both STEMI and NSTE-ACS, 2) decrease in the rate of presentation as STEMI among these patients, 3) an increase in the burden of cardiovascular risk factors and non-cardiovascular co-morbidity among ACS
patients with MV-CAD, 3) an increase in the rate of guidelinerecommended pharmacotherapy and PCI (mostly in STEMI), yet decrease in the rate of CABG were over time, and 4) significant improvement in the short-term outcomes yet not in 1-year mortality. The finding of decline in the relative proportion of STEMI among ACS patients with MV-CAD is consistent with the trends of decline in STEMI hospitalizations, but not of NSTE-ACS in several contemporary registries [20–22]. This trend was previously attributed to improved primary and secondary preventive measures and adherence to guidelines-recommended treatments over time [23–28]. The latter suggested explanations could also be responsible, at least in part, to the decline in the proportion of MV-CAD observed in our report. The trend of increase in the prevalence of most cardiovascular risk factors is consistent with previous reports [29–32]. This could possibly be explained by improved survival of these patients, more advanced age and/or in the prevalence of obesity and diabetes mellitus among patients with cardiovascular disease and the general population [33–36].
CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, PVD: peripheral vascular disease Fig. 3. Multivariate model for prediction of 30-day MACE. CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, PVD: peripheral vascular disease.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
4
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
However, better detection and recording of risk factors could also explain the increased prevalence. The increasing rate of PCI and the decrease in CABG over time are consistent with a growing body of literature on ACS patients with MVCAD during the last two decades [37–39]. Furthermore, a previous study from the NCDR registry demonstrated an increasing trend in use of PCI in patients with MV-CAD even among those with Class I indication for CABG [38]. These trends could possibly be explained by improved PCI techniques and results over time, growing operators' experience with complex MV-PCI and augmented prevalence of prohibitive surgical risks with the increase in mean age and more comorbidities [40–44]. The worse outcomes of MV-CAD versus single-vessel disease in the context of ACS [4–6], in addition to the concept that plaque instability is a widespread coronary process [45], explains the rationale behind performing more MV-PCI. Based mostly on observational studies [46,47], the 2013 American College of Cardiology Foundation/ American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines (ACCF/AHA) [16] recommended against MV-PCI strategy (Class III B) during PCI of STEMI. However, recently published randomized controlled trials (RCTs),[13–15] have shown significant advantages for MV-PCI compared with infarct-related artery only (IRA)-PCI in composite MACE endpoints, primarily due to preventing additional coronary revascularization. Thus, although the “do not do the non-culprit vessel” paradigm was changed by the professional organizations [17,19] MV-PCI in STEMI patients is still not a highly recommended practice (i.e. class I). However, the recently published well-powered randomized control (Complete vs Culprit-Only Revascularization to Treat MV-CAD after Primary PCI for STEMI) COMPLETE [48] trial, which enrolled 4041 patients in 31 countries found that among patients with STEMI and MV-CAD, complete revascularization was superior to culprit-lesion-only PCI in the reduction of cardiovascular death or MI and the composite of cardiovascular death, MI and ischemia-driven revascularization at three years of median follow-up. It should be mentioned that the MV-PCI in this trial was a staged procedure (separate from the index PCI procedure for STEMI). Evidence supporting MV-PCI in NSTE-ACS exist as well yet these are less substantiated [49]. In consistence with previously reported trends [23–28,50] we found that discharge with guideline recommended antithrombotic and lipid lowering pharmacotherapy has increased throughout the investigation period while the proportion of patients discharged on beta-blockers (BB) and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) remained constant. With partial agreement with our findings, Makam et al. [50] found an increase in all groups of medications in 11 Massachusetts hospitals, United States, between the years 2001–2011. The most important finding of the current study is probably the significant improvement in the short-term outcomes of patients with MVCAD, yet not 1-year mortality. The short term improvement is consistent with findings reported by others for ACS patients [10,20,21]. The improvement in short-term prognosis observed in the present study could be attributable to upgrades in the acute phase management of AMI patients [23], improvements in timelines which are of utmost importance for STEMI patients, increased use of PCI and technological progress [10,23]. However, it is interesting that significant differences in 1-year mortality rates were not found throughout the follow-up period, which is inconsistent with most contemporary studies reporting a trend of improvement in 1-year prognosis in patients with ACS [20,23]. It is possible that 1-year trends are different in patients with MV-CAD which are usually higher risk patients. In such a case postdischarge management and secondary prevention as well as long term patient adherence with therapeutic recommendations could be pivotal for explaining differences or lack of, in 1-year mortality. Alternatively, it is possible that evaluating mortality rather than MACE with relatively few events precluded reaching statistical significance.
5. Limitations The current study was retrospective and observational and thus shares the limitations of such a registry design. In particular, causality between various trends in patient management and outcomes cannot be firmly substantiated based on our findings. Coronary angiograms were analyzed by operators in every center rather than by an external core lab, which could introduce bias in angiographic interpretation. Moreover, the treatment decision was left to the operator discretion, thus the mode of practice has been heterogenous. Changes in data recording in the participating center and by the ACSIS investigator could introduce bias. Data of patients' post-discharge, lifestyle practices, management, and adherence with treatment recommendations were not collected and could be unaccounted confounders. 6. Conclusions Throughout 2004–2016, the relative rate of MV-CAD among ACS patients has decreased. The burden of cardiovascular risk factors and noncardiovascular co-morbidity has increased among ACS patients with MV-CAD. Furthermore, an increase in the rate of pharmacological therapy and PCI (mostly among STEMI), yet decrease in the rate of CABG were observed throughout the follow-up period. 30-day outcomes of these patients have improved significantly yet not 1 year mortality. Prospective and randomized trials focusing on the management of ACS patients with MV-CAD are warranted to improve the outcomes of these patients. Declarations of competing interest The authors report no relationships that could be construed as a conflict of interest CRediT authorship contribution statement Arthur Shiyovich:Conceptualization, Data curation, Investigation, Methodology, Project administration, Validation, Writing - original draft.Nir Shlomo:Data curation, Investigation, Methodology, Project administration, Validation, Writing - review & editing.Tal Cohen:Data curation, Investigation.Zaza Iakobishvili:Methodology, Supervision, Writing - review & editing.Ran Kornowski:Methodology, Supervision, Writing - review & editing.Alon Eisen:Conceptualization, Methodology, Project administration, Supervision, Validation, Writing - review & editing. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijcard.2020.01.040. References [1] S. Rasoul, J.P. Ottervanger, M.J. de Boer, J.H. Dambrink, J.C. Hoorntje, A.T. Marcel Gosselink, et al., Predictors of 30-day and 1-year mortality after primary percutaneous coronary intervention for ST-elevation myocardial infarction, Coron. Artery Dis. 20 (6) (2009) 415–421(Epub 2009/07/31). [2] D. Zhang, X. Song, S. Lv, F. Yuan, F. Xu, M. Zhang, et al., Culprit vessel only versus multivessel percutaneous coronary intervention in patients presenting with STsegment elevation myocardial infarction and multivessel disease, PLoS One 9 (3) (2014), e92316(Epub 2014/03/22). [3] M. Toma, C.E. Buller, C.M. Westerhout, Y. Fu, W.W. O'Neill, D.R. Holmes Jr., et al., Non-culprit coronary artery percutaneous coronary intervention during acute STsegment elevation myocardial infarction: insights from the APEX-AMI trial, Eur. Heart J. 31 (14) (2010) 1701–1707(Epub 2010/06/10). [4] P. Sorajja, B.J. Gersh, D.A. Cox, M.G. McLaughlin, P. Zimetbaum, C. Costantini, et al., Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction, Eur. Heart J. 28 (14) (2007) 1709–1716(Epub 2007/06/09). [5] F. Cardarelli, A. Bellasi, F.S. Ou, L.J. Shaw, E. Veledar, M.T. Roe, et al., Combined impact of age and estimated glomerular filtration rate on in-hospital mortality after
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
percutaneous coronary intervention for acute myocardial infarction (from the American College of Cardiology National Cardiovascular Data Registry), Am. J. Cardiol. 103 (6) (2009) 766–771(Epub 2009/03/10). D.W. Park, R.M. Clare, P.J. Schulte, K.S. Pieper, L.K. Shaw, R.M. Califf, et al., Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction, Jama 312 (19) (2014) 2019–2027(Epub 2014/11/17). L. Feldman, P.G. Steg, M. Amsallem, E. Puymirat, E. Sorbets, M. Elbaz, et al., (Eds.), Editor's choice-medically managed patients with non-ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease, Eur. Heart J. Acute Cardiovasc. Care 6 (3) (2017) 262–271(Epub 2016/01/14). E. Mahmud, O. Behnamfar, F. Lin, R. Reeves, M. Patel, L. Ang, Elevated serum fibrinogen is associated with 12-month major adverse cardiovascular events following percutaneous coronary intervention, J. Am. Coll. Cardiol. 67 (21) (2016) 2556–2557Epub 2016/05/28. S. Bansilal, M.P. Bonaca, J.H. Cornel, R.F. Storey, D.L. Bhatt, P.G. Steg, et al., Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease, J. Am. Coll. Cardiol. 71 (5) (2018) 489–496(Epub 2018/02/07). E.D. Peterson, B.R. Shah, L. Parsons, C.V. Pollack Jr., W.J. French, J.G. Canto, et al., Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006, Am. Heart J. 156 (6) (2008) 1045–1055(Epub 2008/11/27). E. Braunwald, E.M. Antman, J.W. Beasley, R.M. Califf, M.D. Cheitlin, J.S. Hochman, et al., ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina), J. Am. Coll. Cardiol. 40 (7) (2002) 1366–1374(Epub 2002/10/18). Kushner FG, Hand M, Smith SC, Jr., King SB, 3rd, Anderson JL, Antman EM, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with STelevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol.. 2009;54(23):2205–7. (Epub 2009/11/28). D.S. Wald, J.K. Morris, N.J. Wald, A.J. Chase, R.J. Edwards, L.O. Hughes, et al., Randomized trial of preventive angioplasty in myocardial infarction, N. Engl. J. Med. 369 (12) (2013) 1115–1123(Epub 2013/09/03). Gershlick AH, Khan JN, Kelly DJ, Greenwood JP, Sasikaran T, Curzen N, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. Journal of the American College of Cardiology. 2015;65(10): 963–72. Epub 2015/03/15. Engstrom T, Kelbaek H, Helqvist S, Hofsten DE, Klovgaard L, Holmvang L, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3PRIMULTI): an open-label, randomised controlled trial. Lancet (London, England). 2015;386(9994):665–71. Epub 2015/09/09. O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr., Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2013;61(4):e78–140. Epub 2012/12/22. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2015 ACC/ AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/ SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of st-elevation myocardial infarction. Journal of the American College of Cardiology. 2016;67(10):1235–50. Epub 2015/10/27. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European heart journal. 2012;33(20):2569–619. Epub 2012/08/28. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European heart journal. 2018;39(2): 119–77. Epub 2017/09/10. H.M. Krumholz, S.L. Normand, Y. Wang, Trends in hospitalizations and outcomes for acute cardiovascular disease and stroke, 1999–2011, Circulation. 130 (12) (2014) 966–975Epub 2014/08/20. R.W. Yeh, S. Sidney, M. Chandra, M. Sorel, J.V. Selby, A.S. Go, Population trends in the incidence and outcomes of acute myocardial infarction, N. Engl. J. Med. 362 (23) (2010) 2155–2165Epub 2010/06/19. Y. Plakht, H. Gilutz, A. Shiyovich, Temporal trends in acute myocardial infarction: What about survival of hospital survivors? Disparities between STEMI & NSTEMI remain. Soroka acute myocardial infarction II (SAMI-II) project, Int. J. Cardiol. 203 (2016) 1073–1081Epub 2015/12/08. Arbel Y, Matetzky S, Gavrielov-Yusim N, Shlezinger M, Keren G, Roth A, et al. Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized with ST-segment elevation myocardial infarction. International journal of cardiology. 2014;176(1):171–6. Epub 2014/07/30. B.R. Shah, E.C. O'Brien, M.T. Roe, A.Y. Chen, E.D. Peterson, The association of inhospital guideline adherence and longitudinal postdischarge mortality in older
[25]
[26]
[27]
[28] [29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
5
patients with non-ST-segment elevation myocardial infarction, Am. Heart J. 170 (2) (2015) 273–280e1. Epub 2015/08/25. Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008;52(5):818–27. Epub 2008/10/15. T.J. Hoerger, P. Zhang, J.E. Segel, E.W. Gregg, K.M. Narayan, K.A. Hicks, Improvements in risk factor control among persons with diabetes in the United States: evidence and implications for remaining life expectancy, Diabetes Res. Clin. Pract. 86 (3) (2009) 225–232Epub 2009/10/17. Steinberg BA, Bhatt DL, Mehta S, Poole-Wilson PA, O'Hagan P, Montalescot G, et al. Nine-year trends in achievement of risk factor goals in the US and European outpatients with cardiovascular disease. American Heart Journal. 2008;156(4):719–27. Epub 2008/10/18. D.E. Newby, K.A. Fox, Unstable angina: the first 48 hours and later in-hospital management, Br. Med. Bull. 59 (2001) 69–87Epub 2002/01/05. S. Agarwal, K. Sud, B. Thakkar, V. Menon, W.A. Jaber, S.R. Kapadia, Changing trends of atherosclerotic risk factors among patients with acute myocardial infarction and acute ischemic stroke, Am. J. Cardiol. 119 (10) (2017) 1532–1541Epub 2017/04/05. Shah B, Bangalore S, Gianos E, Liang L, Peacock WF, Fonarow GC, et al. Temporal trends in clinical characteristics of patients without known cardiovascular disease with a first episode of myocardial infarction. American Heart Journal. 2014;167 (4):480–8 e1. Epub 2014/03/25. Lee MS, Flammer AJ, Kim HS, Hong JY, Li J, Lennon RJ, et al. The prevalence of cardiovascular disease risk factors and the Framingham Risk Score in patients undergoing percutaneous intervention over the last 17 years by gender: time-trend analysis from the Mayo Clinic PCI Registry. Journal of preventive medicine and public health = Yebang Uihakhoe chi. 2014;47(4):216–29. Epub 2014/08/21. Y. Plakht, A. Abu Eid, H. Gilutz, A. Shiyovich, Trends of cardiovascular risk factors in patients with acute myocardial infarction: Soroka acute myocardial infarction II (SAMI II) project, Angiology. 70 (6) (2019) 530–538Epub 2018/12/07. C. Bergerot, F. Farhat, N. Mewton, Letter by Bergerot et al. regarding article, “Efficacy of long-term beta-blocker therapy for secondary prevention of long-term outcomes after coronary artery bypass grafting surgery”, Circulation. 133 (6) (2016), e392Epub 2016/02/10. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet (London, England). 2016;387(10026):1377–96. Epub 2016/04/27. Rabani S, Sardarinia M, Akbarpour S, Azizi F, Khalili D, Hadaegh F. 12-year trends in cardiovascular risk factors (2002–2005 through 2011–2014) in patients with cardiovascular diseases: Tehran lipid and glucose study. PloS one. 2018;13(5): e0195543. Epub 2018/05/17. P. Muntner, K.B. DeSalvo, R.P. Wildman, P. Raggi, J. He, P.K. Whelton, Trends in the prevalence, awareness, treatment, and control of cardiovascular disease risk factors among noninstitutionalized patients with a history of myocardial infarction and stroke, Am. J. Epidemiol. 163 (10) (2006) 913–920Epub 2006/04/07. Pandey A, McGuire DK, de Lemos JA, Das SR, Berry JD, Brilakis ES, et al. Revascularization trends in patients with diabetes mellitus and multivessel coronary artery disease presenting with non-ST elevation myocardial infarction: insights from the national cardiovascular data registry acute coronary treatment and intervention outcomes network registry-get with the guidelines (NCDR ACTION RegistryGWTG). Circulation Cardiovascular Quality And Outcomes. 2016;9(3):197–205. Epub 2016/05/12. Frutkin AD, Lindsey JB, Mehta SK, House JA, Spertus JA, Cohen DJ, et al. Drug-eluting stents and the use of percutaneous coronary intervention among patients with class I indications for coronary artery bypass surgery undergoing index revascularization: analysis from the NCDR (National Cardiovascular Data Registry). JACC Cardiovascular interventions. 2009;2(7):614–21. Epub 2009/07/25. Kumbhani DJ, Fonarow GC, Cannon CP, Hernandez AF, Peterson ED, Peacock WF, et al. Temporal trends for secondary prevention measures among patients hospitalized with coronary artery disease. The American Journal of Medicine. 2015;128(4): 426 e1–9. Epub 2014/11/30. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. European Heart Journal. 2019;40(2):87–165. Epub 2018/08/31. Morice MC, Serruys PW, Kappetein AP, Feldman TE, Stahle E, Colombo A, et al. Fiveyear outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial. Circulation. 2014;129(23):2388–94. Epub 2014/04/05. Valle JA, Tamez H, Abbott JD, Moussa ID, Messenger JC, Waldo SW, et al. Contemporary use and trends in unprotected left main coronary artery percutaneous coronary intervention in the United States: an analysis of the national cardiovascular data registry research to practice initiative. JAMA Cardiology. 2019;4(2):100–9. Epub 2019/01/03. Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Yoon SH, et al. Temporal trends in revascularization strategy and outcomes in left main coronary artery stenosis: data from the ASAN Medical Center-left MAIN Revascularization registry. Circulation Cardiovascular Interventions. 2015;8(3):e001846. Epub 2015/03/07. Lee PH, Ahn JM, Chang M, Baek S, Yoon SH, Kang SJ, et al. Left main coronary artery disease: secular trends in patient characteristics, treatments, and outcomes. Journal of the American College of Cardiology. 2016;68(11):1233–46. Epub 2016/09/10. J.A. Goldstein, D. Demetriou, C.L. Grines, M. Pica, M. Shoukfeh, W.W. O'Neill, Multiple complex coronary plaques in patients with acute myocardial infarction, N. Engl. J. Med. 343 (13) (2000) 915–922Epub 2000/09/28. M.A. Cavender, S. Milford-Beland, M.T. Roe, E.D. Peterson, W.S. Weintraub, S.V. Rao, Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
6
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry), Am. J. Cardiol. 104 (4) (2009) 507–513Epub 2009/08/08. [47] A. Bagai, P. Thavendiranathan, W. Sharieff, H.A. Al Lawati, A.N. Cheema, Non-infarctrelated artery revascularization during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review and metaanalysis, Am. Heart J. 166 (4) (2013) 684–693e1. Epub 2013/10/08. [48] S.R. Mehta, D.A. Wood, R.F. Storey, R. Mehran, K.R. Bainey, H. Nguyen, et al., Complete revascularization with multivessel PCI for myocardial infarction, N. Engl. J. Med. 381 (15) (2019) 1411–1421Epub 2019/09/03.
[49] Sardella G, Lucisano L, Garbo R, Pennacchi M, Cavallo E, Stio RE, et al. Single-staged compared with multi-staged PCI in multivessel NSTEMI patients: the SMILE trial. Journal of the American College of Cardiology. 2016;67(3):264–72. Epub 2016/01/ 23. [50] Makam RC, Erskine N, McManus DD, Lessard D, Gore JM, Yarzebski J, et al. Decadelong trends (2001 to 2011) in the use of evidence-based medical therapies at the time of hospital discharge for patients surviving acute myocardial infarction. The American Journal of Cardiology. 2016;118(12):1792–7. Epub 2016/10/17.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Temporal trends of patients with acute coronary syndrome and multivessel coronary artery disease - from the ACSIS registry Arthur Shiyovich a,b,⁎, Nir Shlomo c, Tal Cohen c, Zaza Iakobishvili b,d, Ran Kornowski a,b, Alon Eisen a,b a
Department of Cardiology, Rabin Medical Center, Petah Tikva, Israel Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel Israeli Center of Cardiovascular Research, Tel Hashomer, Israel d Department of Community Cardiology, Tel Aviv Jaffa District, Clalit Health Services, Tel Aviv, Israel b c
a r t i c l e
i n f o
Article history: Received 27 September 2019 Received in revised form 13 January 2020 Accepted 20 January 2020 Available online xxxx
a b s t r a c t Introduction: Multi-vessel coronary artery disease (MV-CAD) is common among patients with acute coronary syndrome (ACS) and is associated with worse outcomes. Objectives: To examine temporal trends of patients presenting with ACS and MV-CAD. Methods: Time-dependent analysis of patients enrolled in the ACS Israeli Surveys (ACSIS) between 2004–2016 by 3 time periods: early (2004–2006; n = 2111), mid (2008–2010; n = 2049), and late (2013–2016; n = 2010). MV-CAD was defined as N50% stenosis in ≥2 separate coronary territories at the index coronary catheterization. Outcomes were 30-day MACE and 1-year all-cause mortality. Results: Overall 6170/9321 patients (66%) had MV-CAD (age 64.5 ± 12.1, males 80%). Patients from later periods were older with a higher prevalence of cardiovascular risk-factors and comorbidity. Among patients with MVCAD, STEMI decreased significantly (early-46% vs. late-37%, p b 0.001). The rates of PCI were similar, however rates of MV-PCI have increased (early-16.8% vs. late −37.1%, p b 0.001) while the rates of CABG decreased over-time (early-12.7% vs. late −9.2%, p b 0.001). Thirty-day outcomes improved significantly; MACE (early18.2%, mid-12.6%, late-11.2%, p b 0.001), mortality (early-4.7%, mid-4.2%, late-3.1%, p = 0.03) and re-infarction (early = 3.0%, mid = 2.4% and late 1.1%, p b 0.001). No significant change in 1-year mortality was observed (early = 9.3%, mid = 7.8%, late = 7.7%, p = 0.13). A multivariate adjusted analysis demonstrated that the mid and late periods (vs. the early period) were associated with significantly reduced risk for 30-day MACE (OR = 0.65 [0.54–0.77] and 0.54 [0.45–0.65], respectively). Conclusions: During the last decade, the burden of cardiovascular risk factors among ACS patients with MV- CAD has increased, more invasive treatment was provided and a significant improvement in 30-day outcomes was observed. © 2020 Elsevier B.V. All rights reserved.
1. Introduction Patients presenting with acute coronary syndrome (ACS) have multi-vessel coronary artery disease (MV-CAD) in 40–70% of cases [1–3]. MV-CAD in this setting [both in ST-segment elevation (STEACS) and in non-ST segment elevation (NSTE-ACS)] is associated with worse clinical outcomes compared with single vessel coronary artery disease despite coronary revascularization [4–7]. Furthermore, patients with MV-CAD have a more advanced atherosclerotic disease in other vascular beds, worse endothelial dysfunction, increased platelet reactivity, higher fibrinogen levels, and increased thrombin activation [8,9]. Over the past decades, significant improvements in the medical and ⁎ Corresponding author at: Department of Cardiology, Rabin Medical Center, 39 Jabotinsky St., 49100 Petah Tikva, Israel. E-mail address: [email protected] (A. Shiyovich).
interventional treatments of ACS were introduced into clinical practice [10–12]. Multiple high quality studies [9,13–15] focused particularly on patients presenting with MV-CAD in the setting of ACS, incorporating their results into international care guidelines [16–19]. However, data regarding period-dependent changes in these patients' care are scarce. The objective of the present study was to evaluate the temporal trends in clinical characteristics, management and outcomes of patients presenting with ACS and MV-CAD using a large periodic registry. 2. Methods 2.1. Study design and population The current study included consecutive patients from the ACS Israeli Surveys (ACSIS) between 2004 and 2016, who had MV-CAD, defined as N50% stenosis in ≥2 separate major coronary territories at the index ACS.
https://doi.org/10.1016/j.ijcard.2020.01.040 0167-5273/© 2020 Elsevier B.V. All rights reserved.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
2
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
The ACSIS is a prospective survey, conducted every 2–3 years that enrolls consecutive patients from all 26 coronary care units operating in Israel over a 2-month period. Dedicated and specifically trained research personnel using a central questionnaire entered the data electronically. The institutional review board (IRB) of all the participating hospitals approved the survey, which was performed in accordance with the Helsinki declaration. Despite reflecting the standard of care, all patients since 2010 signed informed consent for participating in the ACSIS registry trials. The pre-specified demographic, cardio-vascular risk factors, comorbidities, medications and clinical data were recorded along with admission and discharge diagnoses as defined by the attending physicians based on clinical, electrocardiographic, and biochemical criteria. Patient management was at the discretion of the attending physicians. Patients were classified into three groups according to the following time periods of admission: early (2004–2006), mid (2008–2010), and late (2013–2016). Each of the time-periods included a total of 2 surveys. MV-PCI was defined, per coronary angiography, as PCI performed in more than one coronary artery throughout the index admission or up to 30d of follow-up (i.e. staged PCI). MV-PPCI was defined when nonculprit artery PCI was performed in STEMI patients (in addition to the culprit-artery PCI) throughout the PPCI index procedure. 2.2. Outcomes The outcomes included 30-day major adverse cardiovascular events (MACE), comprised of: all-cause mortality, myocardial infarction (MI), stroke, unstable angina, stent thrombosis and urgent revascularization. Additional outcome was 1-year all-cause mortality. Data regarding the outcomes were determined by hospital chart review, telephone contact, clinical follow-up and by matching identification numbers of patients with the Israeli National Population Registry (for 30-day and 1-year mortality). 2.3. Statistical analysis Comparison between the three period groups were perfomed with chi-square for categorical variables and with ANOVA or Kruskal-Wallis test as appropriate for normal/non-normal distributed continuous variables. Logistic regression was calculated to assess the relationship between periods and MACE, adjusted for potential confounders. Survival analysis between the groups was performed using the Kaplan-Meier curves followed by the Log-Rank test. Cox proportional hazards analysis was used to assess the effects of period, adjusted for different covariates on 1-year mortality outcome. P-value b0.05 was considered statistically significant for all tests.
P<0.001
P=0.03 P<0.001
MACE: major adverse cardiac event
Fig. 1. 30-days outcomes according to admission period. MACE: major adverse cardiac event.
(ARBs) and anti-diabetic therapy has increased while that of ACE inhibitors, diuretics and calcium channel blockers has significantly decreased. Interestingly, the LDL cholesterol levels upon admission have decreased with time (mean: early- 112 mg/dL, mid- 100 mg/dL. Late 99 mg/dL, p b 0.001). The rates of interventional treatments by period are presented in fig. 2 (appendix). No statistically significant trend was found in the overall rates of PCI. However, the rates of MV-PCI have increased (early-16.8% vs. late-37.1%, p b 0.001) while the rates of CABG decreased significantly over time (early-12.7%, late - 9.2%, p b 0.001). Furthermore, overall PCI in the subgroup of patients with NSTE-ACS did not change while the rate of MV-PCI has increased significantly (early 25%, late = 41.3% p b 0.001). In patients with STEMI the overall PCI (early-84.1%, late-89.6%, p = 0.003) and the rate of MV- PPCI (early 17%, late 35.5%) have both increased. Nevertheless the rates of CABG decreased significantly in both NSTE-ACS and STEMI. The trends of the discharge medical therapy are presented in fig. 3 (appendix). A significant increase in the rate of aspirin, P2Y12 inhibitors and statins was observed while no changes were found in the rates of discharge with angiotensin converting enzyme inhibitors/angiotensinogen receptor blockers and beta-blockers. A statistically significant improvement in 30-day outcomes were observed: MACE (early = 18.2%, mid = 12.6%, late 11.2%, p b 0.001), Table 1 Baseline characteristics according to the admission period.
3. Results Out of 9321 patients who were admitted with an ACS between 2004–2016, 6170 patients had MV-CAD (66%, age 64.5 ± 12.1, males 80%) and were analyzed in the current study. The proportion of patients with MV-CAD (out of all patients with ACS) has decreased over time (early-67.3%, late-64.1%, p b 0.008). The latter decrease was observed both in STEMI (early-60.4%, late-56.1%, p = 0.003) and NSTE-ACS (early-74.6%, late-69.8%, p = 0.008) as presented in fig. 1 (appendix). Baseline characteristics of the patients with MV-CAD according to the study period are presented in Table 1. Patients admitted in the later periods were somewhat older with a higher prevalence of cardiovascular risk factors and prior CAD. Among patients with MV-CAD presenting with ACS, presentation as STEMI has decreased throughout the years (early- 46%, mid- 43%, late- 37%, P b 0.001). The medical treatment prior to the index hospitalization is presented in Table 1 in the Supplementary appendix. The rate of statins, angiotensin receptor blockers
n Age, years (mean ± SD) Gender (male) Dyslipidemia Hypertension Current smokers Diabetes mellitus Family history of CAD BMI (kg/m2), (mean ± SD) Prior MI Prior CABG Prior PCI Chronic renal failure PVD History of CHF
Early
Mid
Late
p
2111 64.3 (12.3) 78.5 63.2 60.9 36.0 35.1 23.6 27.5 (4.3) 32.3 13.7 28 10.4 9.3 6.9
2049 64.1 (12.1) 81.5 77.3 65.3 38.1 40.5 30.0 27.8 (4.9) 36.1 12.7 38.8 12.1 9.7 8.7
2010 65.3 (12) 80.2 77.2 70.0 37.4 44.3 30.9 29.7 (20.8) 36.9 11.2 37.7 12.8 7.4 7.0
0.005 0.061 b0.001 b0.001 0.370 b0.001 b0.001 b0.001 0.004 0.057 b0.001 0.040 0.025 0.057
CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, CABG: coronary artery bypass graft surgery, PVD: peripheral vascular disease, CHF: congestive heart failure
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
3
Fig. 2. One year survival curves according to the admission period.
mortality (early 4.7%, mid = 4.2%, late 3.1%, p = 0.03) and re-infarction (early = 3%, mid = 2.4% and late 1.1%, p b 0.001) (fig. 1). A trend of reduction in 1-year mortality (fig. 2) was observed with time, yet it did not reach statistical significance. Multivariate adjusted analysis (fig. 3) demonstrated that the mid and late periods were associated with a significantly reduced risk for 30-day MACE compared to the earlier period (OR = 0.65 [0.54–0.77] and 0.54 [0.45–0.65], respectively). 4. Discussion The present study evaluated the temporal trends of patients presenting with ACS and MV-CAD throughout 2004–2016 based on a national multi-center registry. The main findings include: 1) decrease in the rate of MV-CAD among patients with ACS throughout the years for both STEMI and NSTE-ACS, 2) decrease in the rate of presentation as STEMI among these patients, 3) an increase in the burden of cardiovascular risk factors and non-cardiovascular co-morbidity among ACS
patients with MV-CAD, 3) an increase in the rate of guidelinerecommended pharmacotherapy and PCI (mostly in STEMI), yet decrease in the rate of CABG were over time, and 4) significant improvement in the short-term outcomes yet not in 1-year mortality. The finding of decline in the relative proportion of STEMI among ACS patients with MV-CAD is consistent with the trends of decline in STEMI hospitalizations, but not of NSTE-ACS in several contemporary registries [20–22]. This trend was previously attributed to improved primary and secondary preventive measures and adherence to guidelines-recommended treatments over time [23–28]. The latter suggested explanations could also be responsible, at least in part, to the decline in the proportion of MV-CAD observed in our report. The trend of increase in the prevalence of most cardiovascular risk factors is consistent with previous reports [29–32]. This could possibly be explained by improved survival of these patients, more advanced age and/or in the prevalence of obesity and diabetes mellitus among patients with cardiovascular disease and the general population [33–36].
CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, PVD: peripheral vascular disease Fig. 3. Multivariate model for prediction of 30-day MACE. CAD: coronary artery disease, BMI: body mass index, MI: myocardial infarction, PVD: peripheral vascular disease.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
4
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
However, better detection and recording of risk factors could also explain the increased prevalence. The increasing rate of PCI and the decrease in CABG over time are consistent with a growing body of literature on ACS patients with MVCAD during the last two decades [37–39]. Furthermore, a previous study from the NCDR registry demonstrated an increasing trend in use of PCI in patients with MV-CAD even among those with Class I indication for CABG [38]. These trends could possibly be explained by improved PCI techniques and results over time, growing operators' experience with complex MV-PCI and augmented prevalence of prohibitive surgical risks with the increase in mean age and more comorbidities [40–44]. The worse outcomes of MV-CAD versus single-vessel disease in the context of ACS [4–6], in addition to the concept that plaque instability is a widespread coronary process [45], explains the rationale behind performing more MV-PCI. Based mostly on observational studies [46,47], the 2013 American College of Cardiology Foundation/ American Heart Association/Society for Cardiovascular Angiography and Interventions guidelines (ACCF/AHA) [16] recommended against MV-PCI strategy (Class III B) during PCI of STEMI. However, recently published randomized controlled trials (RCTs),[13–15] have shown significant advantages for MV-PCI compared with infarct-related artery only (IRA)-PCI in composite MACE endpoints, primarily due to preventing additional coronary revascularization. Thus, although the “do not do the non-culprit vessel” paradigm was changed by the professional organizations [17,19] MV-PCI in STEMI patients is still not a highly recommended practice (i.e. class I). However, the recently published well-powered randomized control (Complete vs Culprit-Only Revascularization to Treat MV-CAD after Primary PCI for STEMI) COMPLETE [48] trial, which enrolled 4041 patients in 31 countries found that among patients with STEMI and MV-CAD, complete revascularization was superior to culprit-lesion-only PCI in the reduction of cardiovascular death or MI and the composite of cardiovascular death, MI and ischemia-driven revascularization at three years of median follow-up. It should be mentioned that the MV-PCI in this trial was a staged procedure (separate from the index PCI procedure for STEMI). Evidence supporting MV-PCI in NSTE-ACS exist as well yet these are less substantiated [49]. In consistence with previously reported trends [23–28,50] we found that discharge with guideline recommended antithrombotic and lipid lowering pharmacotherapy has increased throughout the investigation period while the proportion of patients discharged on beta-blockers (BB) and angiotensin converting enzyme inhibitors (ACEi)/angiotensin receptor blockers (ARB) remained constant. With partial agreement with our findings, Makam et al. [50] found an increase in all groups of medications in 11 Massachusetts hospitals, United States, between the years 2001–2011. The most important finding of the current study is probably the significant improvement in the short-term outcomes of patients with MVCAD, yet not 1-year mortality. The short term improvement is consistent with findings reported by others for ACS patients [10,20,21]. The improvement in short-term prognosis observed in the present study could be attributable to upgrades in the acute phase management of AMI patients [23], improvements in timelines which are of utmost importance for STEMI patients, increased use of PCI and technological progress [10,23]. However, it is interesting that significant differences in 1-year mortality rates were not found throughout the follow-up period, which is inconsistent with most contemporary studies reporting a trend of improvement in 1-year prognosis in patients with ACS [20,23]. It is possible that 1-year trends are different in patients with MV-CAD which are usually higher risk patients. In such a case postdischarge management and secondary prevention as well as long term patient adherence with therapeutic recommendations could be pivotal for explaining differences or lack of, in 1-year mortality. Alternatively, it is possible that evaluating mortality rather than MACE with relatively few events precluded reaching statistical significance.
5. Limitations The current study was retrospective and observational and thus shares the limitations of such a registry design. In particular, causality between various trends in patient management and outcomes cannot be firmly substantiated based on our findings. Coronary angiograms were analyzed by operators in every center rather than by an external core lab, which could introduce bias in angiographic interpretation. Moreover, the treatment decision was left to the operator discretion, thus the mode of practice has been heterogenous. Changes in data recording in the participating center and by the ACSIS investigator could introduce bias. Data of patients' post-discharge, lifestyle practices, management, and adherence with treatment recommendations were not collected and could be unaccounted confounders. 6. Conclusions Throughout 2004–2016, the relative rate of MV-CAD among ACS patients has decreased. The burden of cardiovascular risk factors and noncardiovascular co-morbidity has increased among ACS patients with MV-CAD. Furthermore, an increase in the rate of pharmacological therapy and PCI (mostly among STEMI), yet decrease in the rate of CABG were observed throughout the follow-up period. 30-day outcomes of these patients have improved significantly yet not 1 year mortality. Prospective and randomized trials focusing on the management of ACS patients with MV-CAD are warranted to improve the outcomes of these patients. Declarations of competing interest The authors report no relationships that could be construed as a conflict of interest CRediT authorship contribution statement Arthur Shiyovich:Conceptualization, Data curation, Investigation, Methodology, Project administration, Validation, Writing - original draft.Nir Shlomo:Data curation, Investigation, Methodology, Project administration, Validation, Writing - review & editing.Tal Cohen:Data curation, Investigation.Zaza Iakobishvili:Methodology, Supervision, Writing - review & editing.Ran Kornowski:Methodology, Supervision, Writing - review & editing.Alon Eisen:Conceptualization, Methodology, Project administration, Supervision, Validation, Writing - review & editing. Appendix A. Supplementary data Supplementary data to this article can be found online at https://doi. org/10.1016/j.ijcard.2020.01.040. References [1] S. Rasoul, J.P. Ottervanger, M.J. de Boer, J.H. Dambrink, J.C. Hoorntje, A.T. Marcel Gosselink, et al., Predictors of 30-day and 1-year mortality after primary percutaneous coronary intervention for ST-elevation myocardial infarction, Coron. Artery Dis. 20 (6) (2009) 415–421(Epub 2009/07/31). [2] D. Zhang, X. Song, S. Lv, F. Yuan, F. Xu, M. Zhang, et al., Culprit vessel only versus multivessel percutaneous coronary intervention in patients presenting with STsegment elevation myocardial infarction and multivessel disease, PLoS One 9 (3) (2014), e92316(Epub 2014/03/22). [3] M. Toma, C.E. Buller, C.M. Westerhout, Y. Fu, W.W. O'Neill, D.R. Holmes Jr., et al., Non-culprit coronary artery percutaneous coronary intervention during acute STsegment elevation myocardial infarction: insights from the APEX-AMI trial, Eur. Heart J. 31 (14) (2010) 1701–1707(Epub 2010/06/10). [4] P. Sorajja, B.J. Gersh, D.A. Cox, M.G. McLaughlin, P. Zimetbaum, C. Costantini, et al., Impact of multivessel disease on reperfusion success and clinical outcomes in patients undergoing primary percutaneous coronary intervention for acute myocardial infarction, Eur. Heart J. 28 (14) (2007) 1709–1716(Epub 2007/06/09). [5] F. Cardarelli, A. Bellasi, F.S. Ou, L.J. Shaw, E. Veledar, M.T. Roe, et al., Combined impact of age and estimated glomerular filtration rate on in-hospital mortality after
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
[6]
[7]
[8]
[9]
[10]
[11]
[12]
[13]
[14]
[15]
[16]
[17]
[18]
[19]
[20]
[21]
[22]
[23]
[24]
percutaneous coronary intervention for acute myocardial infarction (from the American College of Cardiology National Cardiovascular Data Registry), Am. J. Cardiol. 103 (6) (2009) 766–771(Epub 2009/03/10). D.W. Park, R.M. Clare, P.J. Schulte, K.S. Pieper, L.K. Shaw, R.M. Califf, et al., Extent, location, and clinical significance of non-infarct-related coronary artery disease among patients with ST-elevation myocardial infarction, Jama 312 (19) (2014) 2019–2027(Epub 2014/11/17). L. Feldman, P.G. Steg, M. Amsallem, E. Puymirat, E. Sorbets, M. Elbaz, et al., (Eds.), Editor's choice-medically managed patients with non-ST-elevation acute myocardial infarction have heterogeneous outcomes, based on performance of angiography and extent of coronary artery disease, Eur. Heart J. Acute Cardiovasc. Care 6 (3) (2017) 262–271(Epub 2016/01/14). E. Mahmud, O. Behnamfar, F. Lin, R. Reeves, M. Patel, L. Ang, Elevated serum fibrinogen is associated with 12-month major adverse cardiovascular events following percutaneous coronary intervention, J. Am. Coll. Cardiol. 67 (21) (2016) 2556–2557Epub 2016/05/28. S. Bansilal, M.P. Bonaca, J.H. Cornel, R.F. Storey, D.L. Bhatt, P.G. Steg, et al., Ticagrelor for secondary prevention of atherothrombotic events in patients with multivessel coronary disease, J. Am. Coll. Cardiol. 71 (5) (2018) 489–496(Epub 2018/02/07). E.D. Peterson, B.R. Shah, L. Parsons, C.V. Pollack Jr., W.J. French, J.G. Canto, et al., Trends in quality of care for patients with acute myocardial infarction in the National Registry of Myocardial Infarction from 1990 to 2006, Am. Heart J. 156 (6) (2008) 1045–1055(Epub 2008/11/27). E. Braunwald, E.M. Antman, J.W. Beasley, R.M. Califf, M.D. Cheitlin, J.S. Hochman, et al., ACC/AHA 2002 guideline update for the management of patients with unstable angina and non-ST-segment elevation myocardial infarction—summary article: a report of the American College of Cardiology/American Heart Association task force on practice guidelines (Committee on the Management of Patients With Unstable Angina), J. Am. Coll. Cardiol. 40 (7) (2002) 1366–1374(Epub 2002/10/18). Kushner FG, Hand M, Smith SC, Jr., King SB, 3rd, Anderson JL, Antman EM, et al. 2009 focused updates: ACC/AHA guidelines for the management of patients with STelevation myocardial infarction (updating the 2004 guideline and 2007 focused update) and ACC/AHA/SCAI guidelines on percutaneous coronary intervention (updating the 2005 guideline and 2007 focused update) a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. J. Am. Coll. Cardiol.. 2009;54(23):2205–7. (Epub 2009/11/28). D.S. Wald, J.K. Morris, N.J. Wald, A.J. Chase, R.J. Edwards, L.O. Hughes, et al., Randomized trial of preventive angioplasty in myocardial infarction, N. Engl. J. Med. 369 (12) (2013) 1115–1123(Epub 2013/09/03). Gershlick AH, Khan JN, Kelly DJ, Greenwood JP, Sasikaran T, Curzen N, et al. Randomized trial of complete versus lesion-only revascularization in patients undergoing primary percutaneous coronary intervention for STEMI and multivessel disease: the CvLPRIT trial. Journal of the American College of Cardiology. 2015;65(10): 963–72. Epub 2015/03/15. Engstrom T, Kelbaek H, Helqvist S, Hofsten DE, Klovgaard L, Holmvang L, et al. Complete revascularisation versus treatment of the culprit lesion only in patients with ST-segment elevation myocardial infarction and multivessel disease (DANAMI-3PRIMULTI): an open-label, randomised controlled trial. Lancet (London, England). 2015;386(9994):665–71. Epub 2015/09/09. O'Gara PT, Kushner FG, Ascheim DD, Casey DE, Jr., Chung MK, de Lemos JA, et al. 2013 ACCF/AHA guideline for the management of ST-elevation myocardial infarction: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Journal of the American College of Cardiology. 2013;61(4):e78–140. Epub 2012/12/22. Levine GN, Bates ER, Blankenship JC, Bailey SR, Bittl JA, Cercek B, et al. 2015 ACC/ AHA/SCAI focused update on primary percutaneous coronary intervention for patients with ST-elevation myocardial infarction: an update of the 2011 ACCF/AHA/ SCAI guideline for percutaneous coronary intervention and the 2013 ACCF/AHA guideline for the management of st-elevation myocardial infarction. Journal of the American College of Cardiology. 2016;67(10):1235–50. Epub 2015/10/27. Steg PG, James SK, Atar D, Badano LP, Blomstrom-Lundqvist C, Borger MA, et al. ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation. European heart journal. 2012;33(20):2569–619. Epub 2012/08/28. Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, et al. 2017 ESC guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: the task force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). European heart journal. 2018;39(2): 119–77. Epub 2017/09/10. H.M. Krumholz, S.L. Normand, Y. Wang, Trends in hospitalizations and outcomes for acute cardiovascular disease and stroke, 1999–2011, Circulation. 130 (12) (2014) 966–975Epub 2014/08/20. R.W. Yeh, S. Sidney, M. Chandra, M. Sorel, J.V. Selby, A.S. Go, Population trends in the incidence and outcomes of acute myocardial infarction, N. Engl. J. Med. 362 (23) (2010) 2155–2165Epub 2010/06/19. Y. Plakht, H. Gilutz, A. Shiyovich, Temporal trends in acute myocardial infarction: What about survival of hospital survivors? Disparities between STEMI & NSTEMI remain. Soroka acute myocardial infarction II (SAMI-II) project, Int. J. Cardiol. 203 (2016) 1073–1081Epub 2015/12/08. Arbel Y, Matetzky S, Gavrielov-Yusim N, Shlezinger M, Keren G, Roth A, et al. Temporal trends in all-cause mortality of smokers versus non-smokers hospitalized with ST-segment elevation myocardial infarction. International journal of cardiology. 2014;176(1):171–6. Epub 2014/07/30. B.R. Shah, E.C. O'Brien, M.T. Roe, A.Y. Chen, E.D. Peterson, The association of inhospital guideline adherence and longitudinal postdischarge mortality in older
[25]
[26]
[27]
[28] [29]
[30]
[31]
[32]
[33]
[34]
[35]
[36]
[37]
[38]
[39]
[40]
[41]
[42]
[43]
[44]
[45]
[46]
5
patients with non-ST-segment elevation myocardial infarction, Am. Heart J. 170 (2) (2015) 273–280e1. Epub 2015/08/25. Cutler JA, Sorlie PD, Wolz M, Thom T, Fields LE, Roccella EJ. Trends in hypertension prevalence, awareness, treatment, and control rates in United States adults between 1988–1994 and 1999–2004. Hypertension. 2008;52(5):818–27. Epub 2008/10/15. T.J. Hoerger, P. Zhang, J.E. Segel, E.W. Gregg, K.M. Narayan, K.A. Hicks, Improvements in risk factor control among persons with diabetes in the United States: evidence and implications for remaining life expectancy, Diabetes Res. Clin. Pract. 86 (3) (2009) 225–232Epub 2009/10/17. Steinberg BA, Bhatt DL, Mehta S, Poole-Wilson PA, O'Hagan P, Montalescot G, et al. Nine-year trends in achievement of risk factor goals in the US and European outpatients with cardiovascular disease. American Heart Journal. 2008;156(4):719–27. Epub 2008/10/18. D.E. Newby, K.A. Fox, Unstable angina: the first 48 hours and later in-hospital management, Br. Med. Bull. 59 (2001) 69–87Epub 2002/01/05. S. Agarwal, K. Sud, B. Thakkar, V. Menon, W.A. Jaber, S.R. Kapadia, Changing trends of atherosclerotic risk factors among patients with acute myocardial infarction and acute ischemic stroke, Am. J. Cardiol. 119 (10) (2017) 1532–1541Epub 2017/04/05. Shah B, Bangalore S, Gianos E, Liang L, Peacock WF, Fonarow GC, et al. Temporal trends in clinical characteristics of patients without known cardiovascular disease with a first episode of myocardial infarction. American Heart Journal. 2014;167 (4):480–8 e1. Epub 2014/03/25. Lee MS, Flammer AJ, Kim HS, Hong JY, Li J, Lennon RJ, et al. The prevalence of cardiovascular disease risk factors and the Framingham Risk Score in patients undergoing percutaneous intervention over the last 17 years by gender: time-trend analysis from the Mayo Clinic PCI Registry. Journal of preventive medicine and public health = Yebang Uihakhoe chi. 2014;47(4):216–29. Epub 2014/08/21. Y. Plakht, A. Abu Eid, H. Gilutz, A. Shiyovich, Trends of cardiovascular risk factors in patients with acute myocardial infarction: Soroka acute myocardial infarction II (SAMI II) project, Angiology. 70 (6) (2019) 530–538Epub 2018/12/07. C. Bergerot, F. Farhat, N. Mewton, Letter by Bergerot et al. regarding article, “Efficacy of long-term beta-blocker therapy for secondary prevention of long-term outcomes after coronary artery bypass grafting surgery”, Circulation. 133 (6) (2016), e392Epub 2016/02/10. Trends in adult body-mass index in 200 countries from 1975 to 2014: a pooled analysis of 1698 population-based measurement studies with 19.2 million participants. Lancet (London, England). 2016;387(10026):1377–96. Epub 2016/04/27. Rabani S, Sardarinia M, Akbarpour S, Azizi F, Khalili D, Hadaegh F. 12-year trends in cardiovascular risk factors (2002–2005 through 2011–2014) in patients with cardiovascular diseases: Tehran lipid and glucose study. PloS one. 2018;13(5): e0195543. Epub 2018/05/17. P. Muntner, K.B. DeSalvo, R.P. Wildman, P. Raggi, J. He, P.K. Whelton, Trends in the prevalence, awareness, treatment, and control of cardiovascular disease risk factors among noninstitutionalized patients with a history of myocardial infarction and stroke, Am. J. Epidemiol. 163 (10) (2006) 913–920Epub 2006/04/07. Pandey A, McGuire DK, de Lemos JA, Das SR, Berry JD, Brilakis ES, et al. Revascularization trends in patients with diabetes mellitus and multivessel coronary artery disease presenting with non-ST elevation myocardial infarction: insights from the national cardiovascular data registry acute coronary treatment and intervention outcomes network registry-get with the guidelines (NCDR ACTION RegistryGWTG). Circulation Cardiovascular Quality And Outcomes. 2016;9(3):197–205. Epub 2016/05/12. Frutkin AD, Lindsey JB, Mehta SK, House JA, Spertus JA, Cohen DJ, et al. Drug-eluting stents and the use of percutaneous coronary intervention among patients with class I indications for coronary artery bypass surgery undergoing index revascularization: analysis from the NCDR (National Cardiovascular Data Registry). JACC Cardiovascular interventions. 2009;2(7):614–21. Epub 2009/07/25. Kumbhani DJ, Fonarow GC, Cannon CP, Hernandez AF, Peterson ED, Peacock WF, et al. Temporal trends for secondary prevention measures among patients hospitalized with coronary artery disease. The American Journal of Medicine. 2015;128(4): 426 e1–9. Epub 2014/11/30. Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, et al. 2018 ESC/EACTS guidelines on myocardial revascularization. European Heart Journal. 2019;40(2):87–165. Epub 2018/08/31. Morice MC, Serruys PW, Kappetein AP, Feldman TE, Stahle E, Colombo A, et al. Fiveyear outcomes in patients with left main disease treated with either percutaneous coronary intervention or coronary artery bypass grafting in the synergy between percutaneous coronary intervention with taxus and cardiac surgery trial. Circulation. 2014;129(23):2388–94. Epub 2014/04/05. Valle JA, Tamez H, Abbott JD, Moussa ID, Messenger JC, Waldo SW, et al. Contemporary use and trends in unprotected left main coronary artery percutaneous coronary intervention in the United States: an analysis of the national cardiovascular data registry research to practice initiative. JAMA Cardiology. 2019;4(2):100–9. Epub 2019/01/03. Park SJ, Ahn JM, Kim YH, Park DW, Yun SC, Yoon SH, et al. Temporal trends in revascularization strategy and outcomes in left main coronary artery stenosis: data from the ASAN Medical Center-left MAIN Revascularization registry. Circulation Cardiovascular Interventions. 2015;8(3):e001846. Epub 2015/03/07. Lee PH, Ahn JM, Chang M, Baek S, Yoon SH, Kang SJ, et al. Left main coronary artery disease: secular trends in patient characteristics, treatments, and outcomes. Journal of the American College of Cardiology. 2016;68(11):1233–46. Epub 2016/09/10. J.A. Goldstein, D. Demetriou, C.L. Grines, M. Pica, M. Shoukfeh, W.W. O'Neill, Multiple complex coronary plaques in patients with acute myocardial infarction, N. Engl. J. Med. 343 (13) (2000) 915–922Epub 2000/09/28. M.A. Cavender, S. Milford-Beland, M.T. Roe, E.D. Peterson, W.S. Weintraub, S.V. Rao, Prevalence, predictors, and in-hospital outcomes of non-infarct artery intervention
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040
6
A. Shiyovich et al. / International Journal of Cardiology xxx (xxxx) xxx
during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction (from the National Cardiovascular Data Registry), Am. J. Cardiol. 104 (4) (2009) 507–513Epub 2009/08/08. [47] A. Bagai, P. Thavendiranathan, W. Sharieff, H.A. Al Lawati, A.N. Cheema, Non-infarctrelated artery revascularization during primary percutaneous coronary intervention for ST-segment elevation myocardial infarction: a systematic review and metaanalysis, Am. Heart J. 166 (4) (2013) 684–693e1. Epub 2013/10/08. [48] S.R. Mehta, D.A. Wood, R.F. Storey, R. Mehran, K.R. Bainey, H. Nguyen, et al., Complete revascularization with multivessel PCI for myocardial infarction, N. Engl. J. Med. 381 (15) (2019) 1411–1421Epub 2019/09/03.
[49] Sardella G, Lucisano L, Garbo R, Pennacchi M, Cavallo E, Stio RE, et al. Single-staged compared with multi-staged PCI in multivessel NSTEMI patients: the SMILE trial. Journal of the American College of Cardiology. 2016;67(3):264–72. Epub 2016/01/ 23. [50] Makam RC, Erskine N, McManus DD, Lessard D, Gore JM, Yarzebski J, et al. Decadelong trends (2001 to 2011) in the use of evidence-based medical therapies at the time of hospital discharge for patients surviving acute myocardial infarction. The American Journal of Cardiology. 2016;118(12):1792–7. Epub 2016/10/17.
Please cite this article as: A. Shiyovich, N. Shlomo, T. Cohen, et al., Temporal trends of patients with acute coronary syndrome and multi-vessel coronary artery disease -..., International Journal of Cardiology, https://doi.org/10.1016/j.ijcard.2020.01.040