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Primary percutaneous coronary intervention in octogenarians
IJCA-23171; No of Pages 7 International Journal of Cardiology xxx (2016) xxx–xxx
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International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Primary percutaneous coronary intervention in octogenarians Beatrice Ricci MD a, Olivia Manfrini MD a,⁎, Edina Cenko MD, PhD a, Zorana Vasiljevic MD, PhD b, Maria Dorobantu MD, PhD c,d, Sasko Kedev MD, PhD e, Goran Davidovic MD f, Marija Zdravkovic MD g, Olivija Gustiene MD h, Božidarka Knežević MD i, Davor Miličić MD, PhD j, Lina Badimon MD, PhD k, Raffaele Bugiardini MD a a
Department of Experimental, Diagnostic and Specialty Medicine, Section of Cardiology, University of Bologna, Bologna, Italy Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia c University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania d Department of Cardiology and Internal Medicine, Floreasca Emergency Hospital, Bucharest, Romania e University Clinic of Cardiology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Macedonia f Clinic for Cardiology, Clinical Center Kragujevac, Kragujevac Faculty of Medical Sciences, University in Kragujevac, Kragujevac, Serbia g University Clinical Hospital Center Bezanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia h Department of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania i Clinical Center of Montenegro, Center of Cardiology, Podgorica, Montenegro j Department for Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia k Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain b
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Article history: Received 25 July 2016 Accepted 28 July 2016 Available online xxxx Keywords: Elderly patients Octogenarians ST segment elevation myocardial infarction Primary percutaneous intervention Reperfusion
a b s t r a c t Background: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. Methods: 2225 STEMI patients ≥70 years old (mean age 76.8 ± 5.1 years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79 years old (elderly) and 27.2% were ≥80 years old (very-elderly). The primary end-point was 30-day mortality. Results: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24–0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30–0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the veryelderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease. Conclusions: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients. © 2016 Published by Elsevier Ireland Ltd.
1. Introduction Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in elderly patients with acute ST segment elevation myocardial infarction (STEMI), as elderly patients are underrepresented in randomized trials [1–12]. Uncertainty about benefits of ⁎ Corresponding author at: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 9 (Padiglione 11), 40138 Bologna, Italy. E-mail address: [email protected] (O. Manfrini).
invasive treatments is more pronounced in the setting of a very advanced age [13–15]. Given these knowledge gaps in evidence from clinical trials and the importance of this information to help clinical decision making, we sought to investigate clinical characteristics, treatment and outcome of octogenarian patients admitted to the hospital for STEMI. The current study investigated, to the best of our knowledge, the largest cohort of octogenarians treated with primary PCI and assessed their outcomes and risk factors influencing outcomes as compared with those patients older than 70 but younger than 80 years of age.
http://dx.doi.org/10.1016/j.ijcard.2016.07.204 0167-5273/© 2016 Published by Elsevier Ireland Ltd.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
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B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
2. Methods 2.1. Setting and design The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) is an observational registry initiated in year 2010. The details of the ISACS-TC registry protocol (ClinicalTrials.gov: NCT01218776) have been previously published [16–20]. ISACS-TC is a large, ongoing, multicenter cohort study designed to obtain data of patients with acute coronary syndromes (ACS), and herewith control and optimize international guideline recommended therapies in countries whose economies are in transition [21–28]. The data coordinating center has been established at the University of Bologna. Patients were enrolled from 41 geographically different sites in 12 countries (Bosnia and Herzegovina, Croatia, Italy, Kosovo, Lithuania, Macedonia, Hungary, Moldova, Montenegro, Romania, Russian Federation, and Serbia). The study aims to assess the prognostic role of primary PCI, in those patients with STEMI older than 70 years. The study was approved by the local research ethics committee from each hospital. 2.2. Study population The study population consisted of 8997 eligible patients with STEMI enrolled between October 2010 and April 2016. Appropriateness of inclusion was judged by a specialist cardiologist taking into account clinical history, physical exam, ECG, cardiac biomarkers, angiography, and/or postmortem findings [29]. The diagnosis of STEMI was made by the detection of positive myocardial markers of necrosis (troponins or creatinkinase MB) with typical temporal evolution associated with at least one of the following evidence of ischemia: 1) acute onset of prolonged [≥20 min] typical ischemic chest pain; 2) STsegment elevation (measured of J-point) of at least 1 mm in 2 or more contiguous leads, or new left bundle branch block, or development of pathological Q waves. Only STEMI patients ≥70 years were included in the present study. Of these, patients who received fibrinolysis, facilitated and rescue PCI or coronary artery bypass grafting (CABG) were excluded from the analysis (Fig. 1). Patients were stratified in two groups: elderly (70 to 79 years old) and very-elderly patients (≥80 years old).
We had complete data on age, gender and 30-day mortality. Some patients had missing data on other variables. We charged the missing values of the variables whose missing rate was less than 10% using STATA software. For the features whose missing rate exceeded 10%, we carried out a Pearson Chi-square statistical test for independence between those features and mortality. Only the variables “hypercholesterolemia” and “atypical chest pain” had missing rates that exceed 10%, and were found to be statistically dependent on the endpoint mortality. We therefore did not dismiss these variables from the predictive model of mortality and we kept it as missing [30]. 2.4. Statistical analysis The results were displayed by the two groups of patients: elderly (70 to 79 years old) and very-elderly patients (≥80 years old). Baseline characteristics were reported as numbers and percentages for categorical variables and means (±standard deviation [SD]) for continuous variables. Pearson's X2 test and the two sample t-test or Kruskal–Wallis rank test were used as appropriate to compare the two groups for categorical variables and continuous variables respectively. Estimates of the odd ratios (OR) and associated 95% confidence intervals (CI) were obtained with the use of univariate and multivariable logistic regression analyses to evaluate factors associated with the use of primary PCI and with 30-day mortality. For all analyses, statistical significance was defined as a value of p b 0.05. Statistical evaluation was performed using STATA 11 (StataCorp. College Station, TX, USA).
3. Results Of the 8997 STEMI patients enrolled in the ISACS-TC registry from October 2010 to April 2016, only 2225 patients were eligible for the study (Fig. 1). The mean age of our cohort was 76.8 ± 5.1 years and 1197 (53.8%) subjects were men. There were 1620 (72.8%) patients between 70 and 79 years old and 605 (27.2%) patients aged ≥80 years.
2.3. Endpoints and measurements
3.1. Patient characteristics
The primary outcome was the incidence of 30-day all-cause mortality. The analysis evaluated also factors associated with the absence of primary PCI in this elderly population. We analyzed demographic and clinical factors: age, gender, cardiovascular risk factors (history of hypercholesterolemia, history of diabetes, history of hypertension, and smoking status); clinical history of ischemic heart disease (prior angina, prior myocardial infarction, prior PCI and prior CABG), comorbidities (prior heart failure, prior stroke and history of chronic kidney disease) and clinical presentation (Killip class, systolic blood pressure, heart rate, and atypical chest pain), in-hospital medications and invasive procedures.
Comparisons of demographic and clinical variables between veryelderly (≥ 80 years old, mean 83.6 years) and elderly patients (70 to 79 years old, mean 74.3 years) are shown in Table 1. In the veryelderly group, the proportion of women was significantly higher than in the elderly group. Among conventional cardiovascular risk factors, the prevalence of diabetes, hypertension and hypercholesterolemia was similar between the two age groups, but very-elderly patients were significantly less likely to be smokers than the elderly ones.
Fig. 1. Flow diagram of patients entered into the study. STEMI = ST segment elevation myocardial infarction; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
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Table 1 Baseline characteristics of the participants. Variables
Elderly 70–79 year (N = 1620)
Very-elderly ≥80 year (N = 605)
P value
Women Age — year Cardiovascular risk factors Hypercholesterolemia — no./total no. (%) Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior angina pectoris Prior myocardial infarction Prior PCI Prior CABG Comorbidities Prior heart failure Prior stroke Chronic kidney disease Clinical presentation Atypical chest pain — no./total no. (%) Systolic blood pressure at baseline — mm Hg Heart rate at baseline — beats per minute Killip class ≥ 2 — no./total no. (%)
698 (43.1) 74.29 ± 2.7
330 (54.5) 83.57 ± 3.43
b0.001 b0.001
496/1385 (35.8) 499 (30.8) 1179 (72.8) 279 (17.2)
153/489 (31.3) 170 (28.1) 439 (72.6) 44 (7.3)
0.071 0.46 0.56 b0.001
292 (18.0) 264 (16.3) 206 (12.7) 36 (2.2)
136 (22.5) 79 (13.1) 48 (7.9) 10 (1.6)
0.018 0.06 0.002 0.40
96 (5.9) 119 (7.3) 169 (10.4)
60 (9.9) 51 (8.4) 106 (17.5)
0.001 0.39 b0.001
111/1347 (8.2) 138.51 ± 25.3 80.85 ± 24.7 392/1091 (35.9)
71/551 (12.9) 136.20 ± 28.1 81.99 ± 19.1 219/431 (50.8)
0.002 0.06 0.30 b0.001
Values are n (%) or mean ± SD unless stated otherwise. PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft.
Regarding clinical history of ischemic heart disease, very-elderly patients were more likely to have a history of angina pectoris, but less likely to have a history of prior PCI. A history of heart failure and/or chronic kidney disease was significantly higher in the very-elderly group. In addition, the very-elderly patients were admitted more frequently than the elderly patients with atypical chest pain and Killip class ≥2.
3.2. In-hospital treatment The proportion of patients with hospital admission within 12 h from symptom onset was lower (p b 0.001) in the very-elderly group than in the elderly group (61.9% vs 67.1%, p = 0.023). Similarly, the rate of invasive reperfusion was significantly (p b 0.001) lower in the very-elderly group (42.9%) compared with the elderly group (58.9%). The proportion of patients receiving adjuvant evidence-base therapies (aspirin, clopidogrel, heparins, beta-blockers, and ACE-inhibitors) is reported in Table 2. There were no significant differences in the use of medications between the two age groups apart from clopidogrel (which was given less frequently in the very-elderly group).
3.3. Outcomes Of the 2225 patients, 362 (16.3%) died at 30-day follow-up. The rate of death was significantly superior (p b 0.001) for those patients who did not undergo primary PCI (24.2%) compared with those undergoing primary PCI (9.7%), either in the elderly (21.2% vs 7.9%) or veryelderly (29.9% vs 16.1%) group. Primary PCI decreased the unadjusted risk of death both in elderly (OR: 0.32, 95% CI 0.24–0.43) and veryelderly patients (OR: 0.45, 95% CI 0.30–0.68), without a significant difference (p = 0.19) between groups. The incidence of 30-day mortality was significantly higher (p b 0.001) in the very-elderly versus the elderly patients (23.9% vs 13.4%). Accordingly, age ≥ 80 years old was a predictor of 30-day mortality in the unadjusted logistic regression analysis (OR: 2.04, 95% CI 1.61–2.58).
3.4. Factors associated with poor outcome After adjusting for demographic and clinical variables (Table 3), regression multivariable analysis showed that primary PCI had a
Table 2 In-hospital medications, procedures and outcomes.
Time from symptom onset to admission ≤12 h In-hospital acute medications Aspirin Clopidogrel Unfractioned heparin LMWH β blockers ACE inhibitors In-hospital reperfusion therapy Primary PCI Outcomes 30-day mortality
Elderly 70–79 yr. (N = 1620)
Very-elderly ≥80 yr. (N = 605)
P value
1087 (67.1)
375 (61.9)
0.023
1539 (95.0) 1392 (85.9) 809 (49.9) 632 (39.0) 417 (25.7) 464 (28.6)
565 (93.4) 479 (79.2) 274 (45.3) 264 (43.4) 153 (25.3) 190 (31.4)
0.29 b0.001 0.14 0.13 0.95 0.44
955 (58.9)
260 (42.9)
b0.001
217 (13.4)
145 (23.9)
b0.001
Values are n (%) or mean ± SD unless stated otherwise. LMWH = low molecular weight heparins; ACE = angiotensin-converting-enzyme; PCI = percutaneous coronary intervention.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
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Table 3 Factors associated with 30-day mortality (multivariate analysis). Overall study population
Age ≥ 80 year Women Hypercholesterolemia Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior heart failure Prior stroke Atypical chest pain Killip class ≥ 2 Time from symptom onset to admission ≤12 h Chronic kidney disease Primary PCI
Elderly
Very-elderly
OR (95%CI)
P value
OR (95%CI)
P value
OR (95%CI)
P value
1.62 (1.19–2.19) 1.31 (0.98–1.76) 0.99 (0.95–1.04) 0.98 (0.91–1.04) 1.12 (1.02–1.23) 1.05 (0.97–1.14) 0.72 (0.53–0.99) 0.76 (0.45–1.29) 2.14 (1.41–3.26) 1.04 (0.96–1.14) 4.57 (3.34–6.25) 0.98 (0.94–1.08) 1.36 (1.12–1.66) 0.54 (0.39–0.74)
0.002 0.067 0.79 0.52 0.019 0.20 0.042 0.31 b0.001 0.34 b0.001 0.86 0.002 b0.001
– 1.61 (1.11–2.35) 1.01 (0.95–1.07) 0.98 (0.91–1.07) 1.08 (0.96–1.22) 1.03 (0.93–1.14) 0.89 (0.60–1.32) 0.66 (0.32–1.37) 2.19 (1.28–3.74) 0.99(0.87–1.12) 6.23 (4.16–9.42) 0.98 (0.95–1.13) 1.40 (1.08–1.83) 0.53 (0.35–0.79)
– 0.012 0.73 0.71 0.19 0.55 0.57 0.26 0.004 0.83 b0.001 0.41 0.011 0.002
– 0.93 (0.57–1.49) 0.97 (0.91–1.05) 0.95 (0.83–1.09) 1.25 (1.02–1.53) 1.10 (0.96–1.26) 0.55 (0.33–0.92) 0.92 (0.42–1.99) 1.87 (0.91–3.84) 1.11 (0.98–1.27) 2.85 (1.74–4.70) 0.97 (0.87–1.09) 1.32 (0.96–1.82) 0.53 (0.31–0.91)
– 0.76 0.53 0.48 0.031 0.15 0.024 0.83 0.087 0.094 b0.001 0.66 0.090 0.021
Clinical history of ischemic heart disease = prior angina, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft. PCI = percutaneous coronary intervention.
significant protective effect in both very-elderly (OR: 0.53; 95% CI 0.31– 0.91) and elderly groups (OR 0.53; 95% CI 0.35–0.79), although age ≥ 80 years was a significant independent factor associated with 30-day mortality (OR: 1.62; 95% CI 1.19–2.19). In addition, in the very-elderly patients, hypertension and Killip class ≥2 were independent factors associated with mortality; whereas in the elderly patients, female gender, prior stroke, chronic kidney disease and Killip class ≥2 were independent factors associated with mortality. Multivariate analysis was also performed to identify factors associated with 30-day mortality in patients undergoing primary PCI. Female gender (OR: 1.78; 95% CI 1.05–3.04), prior stroke (OR: 3.55; 95% CI 1.59–7.94), Killip class ≥ 2 (OR: 6.75, 95% CI 3.80–11.96), and chronic kidney disease (OR: 1.57; 95% CI 1.07–2.32) were associated with poor outcome. The same analysis was repeated in patients who did not undergo reperfusion therapy. In this subgroup, prior stroke (OR: 1.77; 95% CI 1.08–2.88), Killip class ≥ 2 (OR: 3.86: 95% CI 2.65–5.64), and chronic kidney disease (OR; 1.32; 95% CI 1.06–1.64) were still associated with 30-day mortality, but not female gender. Moreover, in patients not undergoing reperfusion therapy, age ≥ 80 years old (OR: 1.61; 95% CI 1.12–2.31) and hypertension (OR: 1.14; 95% CI 1.02–1.27) were also associated with poor outcome. 3.5. Factors associated with no reperfusion therapy Finally, we sought to analyze which factors were associated with lack of invasive coronary reperfusion. Age ≥ 80 years was an independent predictor of lack of primary PCI (OR: 1.49; 95% CI 1.17–1.89). When demographic and clinical variables were assessed simultaneously
by multivariable analysis in the two age subgroups, the major determinants of no reperfusion therapy were different (Table 4). In the elderly factors associated with no reperfusion were female gender, history of diabetes, current smoking, prior stroke, atypical chest pain, Killip class ≥2 and history of chronic kidney disease. In the very-elderly patients only female gender and atypical chest pain were independent predictive factors of no primary PCI. 4. Discussion In the present population-based cohort study, we sought to investigate the effect of primary PCI in octogenarian patients admitted to the hospital for STEMI. The study shows that primary PCI had a protective role on 30-day mortality in patients older than 80 years and that its beneficial effect was similar to that obtained for patients of 70 to 79 years old. 4.1. Size of the problem Octogenarians are a growing segment of the population with acute coronary syndrome. For them, STEMI is one of the leading cause of death, both in the male and female gender [31–35]. Its diagnosis and treatment is challenging because many elderly patients have atypical symptoms and comorbidities [36–42]. Intracranial hemorrhage is a serious complication of reperfusion therapy; actually, in patients ≥75 years old, thrombolytic therapy has a rate of intracranial hemorrhage over 1.4% [43]. Some studies have indicated improved survival and lower risk of stroke in elderly STEMI patients treated with primary
Table 4 Factors associated with the use of no primary PCI (multivariate analysis). Elderly
Women Hypercholesterolemia Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior heart failure Prior stroke Atypical chest pain Killip class ≥ 2 Chronic kidney disease
Very-elderly
OR (95%CI)
P value
OR (95%CI)
P value
1.36 (1.05–1.75) 0.98 (0.94–1.03) 1.15 (1.07–1.24) 0.98 (0.88–1.09) 1.17 (1.05–1.29) 0.79 (0.61–1.02) 1.42 (0.82–2.46) 2.31 (1.45–3.69) 1.21 (1.06–1.38) 1.71 (1.30–2.24) 1.59 (1.11–2.26)
0.018 0.47 b0.001 0.75 0.005 0.075 0.21 b0.001 0.005 b0.001 0.011
1.49 (1.01–2.24) 0.97 (0.91–1.03) 1.15 (0.98–1.33) 0.87 (0.73–1.03) 1.03 (0.89–1.18) 0.62 (0.41–0.95) 1.14 (0.56–2.32) 1.19 (0.58–2.43) 2.12 (1.13–4.00) 1.22 (0.79–1.87) 1.30 (0.86–1.97)
0.049 0.33 0.078 0.12 0.70 0.027 0.72 0.64 0.020 0.36 0.20
Clinical history of ischemic heart disease = prior angina, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft. PCI = percutaneous coronary intervention.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
PCI compared with those treated with thrombolysis [44–49]. However, limited data are available on the best treatment options from randomized clinical trials [1–12]. Indeed, most randomized clinical trials frequently have excluded the enrollment of older patients [1–12]. 4.2. Characteristics of elderly patients Our cohort consisted of more than 2200 patients older than 70 years enrolled in the ISACS-TC registry. This study is a reflection of a real life cohort and actual practice of clinicians in Eastern Europe. Patients who underwent primary PCI were 54.6%. As generally reported previously, the rate of some clinical characteristics of STEMI patients increases with age [50,51]. These positive trends of some clinical characteristics have been recognized even in our population that is characterized by the presence of only aged patients. Female gender, comorbidities (history of heart failure and chronic kidney disease), atypical presentation and late hospital arrival were more frequently found in patients aged ≥ 80 years compared with those aged 70 to 79 years. Moreover, severe clinical presentation (Killip class ≥2) increased with the age of the study population. 4.3. Primary PCI and mortality In our cohort, the rate of death was significantly greater (two times more) for those patients who did not undergo primary PCI compared with those undergoing primary PCI. The crude differences (p b 0.001) in the rate of death was confirmed both in elderly and very-elderly groups. Also multivariate analysis documented that primary PCI was an independent factor associated with survival both in patients ≥70 to 79 years and ≥80 years old, although age ≥ 80 years old gave a higher risk of death at 30-day follow-up. These findings suggested that reperfusion therapy by PCI in old STEMI patients is beneficial, leading to a reduced risk of 30-day mortality. Our data are discordant from early published registry data [52] which found that 30-day mortality rate in the elderly who received reperfusion therapy was larger than the mortality rate of patients not receiving reperfusion therapy. Our data are concordant with recent observations from a small study population [53], which showed a favorable effect of primary PCI. Differences may depend from the characteristics of the study population. Advancements in PCI techniques may be a reason. 4.4. Prognostic factors associated with 30-day mortality The present study also provides evidence of additional independent factors influencing outcome other than older age and reperfusion. Killip class ≥ 2 at admission was a significant negative prognostic factor of death in both age groups; whereas female gender, prior stroke and chronic kidney disease were associated with poor outcomes in the elderly group; and history of hypertension was associated with poor outcome in the very-elderly group. These findings suggest that the practice of grouping all ancient patients together in a single group may provide a perspective that is not representative of all patients in this group, because the strength of a prognostic factor may be greater during one age than another age. It may underline the prevalence of different pathophysiological mechanisms of the disease or different responses to medical treatments [54–57]. Our data emphasize the prognostic role of some clinical characteristics and comorbidities in elderly and very elderly patients [58–63]. A consistent message that emerges is that revascularization by PCI is better than medical therapy in both elderly and very elderly patients. 4.5. Factors associated with lack of reperfusion The present study shows that factors influencing clinicians' decision making on the management of old STEMI patients are different in the elderly and very elderly. Factors influencing the lack of reperfusion
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treatment of our younger sub-group (≥70–79 years old) were female gender, atypical chest pain, history of diabetes, current smoking, prior stroke, Killip class ≥ 2 and history of chronic kidney disease, which is in keeping with prior work [64–69]. On the opposite, only female sex and atypical chest pain induced a low rate of primary PCI in our older sub-group (≥80 years old). Although a distinction between old age and really old age is arbitrary and determined more by socioeconomic considerations than by either prevalence and treatment of coronary disease, we expect a continuous increase in patients N80 years old as a substantial percentage of the population with STEMI. These patients clearly deserve special consideration for health care delivery and correct application of international guidelines [21,22]. 4.6. Limitations The complexity of the decision making process in the treatment of elderly with STEMI may have multiple confounders unaccounted for. 5. Conclusions Old subjects are commonly considered as a single group. The present study addresses the need to take a more critical look at the very elderly (≥80 years) on whom very few data are published compared with the 70 to 79 year old group for whom more data are available. There are differences in the clinical characteristics, management and outcome of the old population admitted for STEMI. Primary PCI causes a remarkable reduction in 30-day mortality in old patients even older than 80 years. Funding None. Conflict of interest The authors report no relationships that could be construed as a conflict of interest [70–72]. References [1] E.C. Keeley, J.A. Boura, C.L. Grines, Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials, Lancet 361 (2003) 13–20. [2] M.W. Rich, M.S. Bosner, M.K. Chung, J. Shen, J.P. McKenzie, Is age an independent predictor of early and late mortality in patients with acute myocardial infarction? Am. J. Med. 92 (1992) 7–13. [3] S.C. Smith Jr., E. Gilpin, S. Ahnve, et al., Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years, J. Am. Coll. Cardiol. 16 (1990) 784–792. [4] P.Y. Lee, K.P. Alexander, B.G. Hammill, S.K. Pasquali, E.D. Peterson, Representation of elderly persons and women in published randomized trials of acute coronary syndromes, JAMA 286 (2001) 708–713. [5] J.H. Gurwitz, N.F. Col, J. Avorn, The exclusion of the elderly and women from clinical trials in acute myocardial infarction, JAMA 268 (1992) 1417–1422. [6] K.P. Alexander, L.K. Newby, P.W. Armstrong, et al., American Heart Association Council on Clinical Cardiology, Society of Geriatric Cardiology, Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology, Circulation 115 (2007) 2570–2589. [7] R.H. Mehta, C.B. Granger, K.P. Alexander, E. Bossone, H.D. White, M.H. Sketch Jr., Reperfusion strategies for acute myocardial infarction in the elderly: benefits and risks, J. Am. Coll. Cardiol. 45 (2005) 471–478. [8] T.I.M.E. Investigators, Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial, Lancet 358 (2001) 951–957. [9] The GUSTO investigators, An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction, N. Engl. J. Med. 329 (1993) 673–682. [10] GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico, Lancet 336 (1990) 65–71.
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Contents lists available at ScienceDirect
International Journal of Cardiology journal homepage: www.elsevier.com/locate/ijcard
Primary percutaneous coronary intervention in octogenarians Beatrice Ricci MD a, Olivia Manfrini MD a,⁎, Edina Cenko MD, PhD a, Zorana Vasiljevic MD, PhD b, Maria Dorobantu MD, PhD c,d, Sasko Kedev MD, PhD e, Goran Davidovic MD f, Marija Zdravkovic MD g, Olivija Gustiene MD h, Božidarka Knežević MD i, Davor Miličić MD, PhD j, Lina Badimon MD, PhD k, Raffaele Bugiardini MD a a
Department of Experimental, Diagnostic and Specialty Medicine, Section of Cardiology, University of Bologna, Bologna, Italy Clinical Center of Serbia, Medical Faculty, University of Belgrade, Belgrade, Serbia c University of Medicine and Pharmacy “Carol Davila”, Bucharest, Romania d Department of Cardiology and Internal Medicine, Floreasca Emergency Hospital, Bucharest, Romania e University Clinic of Cardiology, Medical Faculty, University “Ss. Cyril and Methodius”, Skopje, Macedonia f Clinic for Cardiology, Clinical Center Kragujevac, Kragujevac Faculty of Medical Sciences, University in Kragujevac, Kragujevac, Serbia g University Clinical Hospital Center Bezanijska Kosa, Faculty of Medicine, University of Belgrade, Belgrade, Serbia h Department of Cardiology, Lithuanian University of Health Sciences, Kaunas, Lithuania i Clinical Center of Montenegro, Center of Cardiology, Podgorica, Montenegro j Department for Cardiovascular Diseases, University Hospital Center Zagreb, University of Zagreb, Zagreb, Croatia k Cardiovascular Research Center, CSIC-ICCC, Hospital de la Santa Creu i Sant Pau, Autonomous University of Barcelona, Barcelona, Spain b
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Article history: Received 25 July 2016 Accepted 28 July 2016 Available online xxxx Keywords: Elderly patients Octogenarians ST segment elevation myocardial infarction Primary percutaneous intervention Reperfusion
a b s t r a c t Background: Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in octogenarian patients, as the elderly are under-represented in randomized trials. This study aims to provide insights on clinical characteristics, management and outcome of the elderly and very elderly presenting with STEMI. Methods: 2225 STEMI patients ≥70 years old (mean age 76.8 ± 5.1 years and 53.8% men) were admitted into the network of the ISACS-TC registry. Of these patients, 72.8% were ≥70 to 79 years old (elderly) and 27.2% were ≥80 years old (very-elderly). The primary end-point was 30-day mortality. Results: Thirty-day mortality rates were 13.4% in the elderly and 23.9% in the very-elderly. Primary PCI decreased the unadjusted risk of death both in the elderly (OR: 0.32, 95% CI: 0.24–0.43) and very-elderly patients (OR: 0.45, 95% CI 0.30–0.68), without significant difference between groups. In the very-elderly hypertension and Killip class ≥2 were the only independent factors associated with mortality; whereas in the elderly female gender, prior stroke, chronic kidney disease and Killip class ≥2 were all factors independently associated with mortality. Factors associated with the lack of use of reperfusion were female gender and atypical chest pain in the veryelderly and in the elderly; in the elderly, however, there were some more factors, namely: history of diabetes, current smoking, prior stroke, Killip class ≥2 and history chronic kidney disease. Conclusions: Age is relevant in the prognosis of STEMI, but its importance should not be considered secondary to other major clinical factors. Primary PCI appears to have beneficial effects in the octogenarian STEMI patients. © 2016 Published by Elsevier Ireland Ltd.
1. Introduction Limited data are available on the outcome of primary percutaneous coronary intervention (PCI) in elderly patients with acute ST segment elevation myocardial infarction (STEMI), as elderly patients are underrepresented in randomized trials [1–12]. Uncertainty about benefits of ⁎ Corresponding author at: Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 9 (Padiglione 11), 40138 Bologna, Italy. E-mail address: [email protected] (O. Manfrini).
invasive treatments is more pronounced in the setting of a very advanced age [13–15]. Given these knowledge gaps in evidence from clinical trials and the importance of this information to help clinical decision making, we sought to investigate clinical characteristics, treatment and outcome of octogenarian patients admitted to the hospital for STEMI. The current study investigated, to the best of our knowledge, the largest cohort of octogenarians treated with primary PCI and assessed their outcomes and risk factors influencing outcomes as compared with those patients older than 70 but younger than 80 years of age.
http://dx.doi.org/10.1016/j.ijcard.2016.07.204 0167-5273/© 2016 Published by Elsevier Ireland Ltd.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
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B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
2. Methods 2.1. Setting and design The International Survey of Acute Coronary Syndromes in Transitional Countries (ISACS-TC) is an observational registry initiated in year 2010. The details of the ISACS-TC registry protocol (ClinicalTrials.gov: NCT01218776) have been previously published [16–20]. ISACS-TC is a large, ongoing, multicenter cohort study designed to obtain data of patients with acute coronary syndromes (ACS), and herewith control and optimize international guideline recommended therapies in countries whose economies are in transition [21–28]. The data coordinating center has been established at the University of Bologna. Patients were enrolled from 41 geographically different sites in 12 countries (Bosnia and Herzegovina, Croatia, Italy, Kosovo, Lithuania, Macedonia, Hungary, Moldova, Montenegro, Romania, Russian Federation, and Serbia). The study aims to assess the prognostic role of primary PCI, in those patients with STEMI older than 70 years. The study was approved by the local research ethics committee from each hospital. 2.2. Study population The study population consisted of 8997 eligible patients with STEMI enrolled between October 2010 and April 2016. Appropriateness of inclusion was judged by a specialist cardiologist taking into account clinical history, physical exam, ECG, cardiac biomarkers, angiography, and/or postmortem findings [29]. The diagnosis of STEMI was made by the detection of positive myocardial markers of necrosis (troponins or creatinkinase MB) with typical temporal evolution associated with at least one of the following evidence of ischemia: 1) acute onset of prolonged [≥20 min] typical ischemic chest pain; 2) STsegment elevation (measured of J-point) of at least 1 mm in 2 or more contiguous leads, or new left bundle branch block, or development of pathological Q waves. Only STEMI patients ≥70 years were included in the present study. Of these, patients who received fibrinolysis, facilitated and rescue PCI or coronary artery bypass grafting (CABG) were excluded from the analysis (Fig. 1). Patients were stratified in two groups: elderly (70 to 79 years old) and very-elderly patients (≥80 years old).
We had complete data on age, gender and 30-day mortality. Some patients had missing data on other variables. We charged the missing values of the variables whose missing rate was less than 10% using STATA software. For the features whose missing rate exceeded 10%, we carried out a Pearson Chi-square statistical test for independence between those features and mortality. Only the variables “hypercholesterolemia” and “atypical chest pain” had missing rates that exceed 10%, and were found to be statistically dependent on the endpoint mortality. We therefore did not dismiss these variables from the predictive model of mortality and we kept it as missing [30]. 2.4. Statistical analysis The results were displayed by the two groups of patients: elderly (70 to 79 years old) and very-elderly patients (≥80 years old). Baseline characteristics were reported as numbers and percentages for categorical variables and means (±standard deviation [SD]) for continuous variables. Pearson's X2 test and the two sample t-test or Kruskal–Wallis rank test were used as appropriate to compare the two groups for categorical variables and continuous variables respectively. Estimates of the odd ratios (OR) and associated 95% confidence intervals (CI) were obtained with the use of univariate and multivariable logistic regression analyses to evaluate factors associated with the use of primary PCI and with 30-day mortality. For all analyses, statistical significance was defined as a value of p b 0.05. Statistical evaluation was performed using STATA 11 (StataCorp. College Station, TX, USA).
3. Results Of the 8997 STEMI patients enrolled in the ISACS-TC registry from October 2010 to April 2016, only 2225 patients were eligible for the study (Fig. 1). The mean age of our cohort was 76.8 ± 5.1 years and 1197 (53.8%) subjects were men. There were 1620 (72.8%) patients between 70 and 79 years old and 605 (27.2%) patients aged ≥80 years.
2.3. Endpoints and measurements
3.1. Patient characteristics
The primary outcome was the incidence of 30-day all-cause mortality. The analysis evaluated also factors associated with the absence of primary PCI in this elderly population. We analyzed demographic and clinical factors: age, gender, cardiovascular risk factors (history of hypercholesterolemia, history of diabetes, history of hypertension, and smoking status); clinical history of ischemic heart disease (prior angina, prior myocardial infarction, prior PCI and prior CABG), comorbidities (prior heart failure, prior stroke and history of chronic kidney disease) and clinical presentation (Killip class, systolic blood pressure, heart rate, and atypical chest pain), in-hospital medications and invasive procedures.
Comparisons of demographic and clinical variables between veryelderly (≥ 80 years old, mean 83.6 years) and elderly patients (70 to 79 years old, mean 74.3 years) are shown in Table 1. In the veryelderly group, the proportion of women was significantly higher than in the elderly group. Among conventional cardiovascular risk factors, the prevalence of diabetes, hypertension and hypercholesterolemia was similar between the two age groups, but very-elderly patients were significantly less likely to be smokers than the elderly ones.
Fig. 1. Flow diagram of patients entered into the study. STEMI = ST segment elevation myocardial infarction; PCI = percutaneous coronary intervention; CABG = coronary artery bypass grafting.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
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Table 1 Baseline characteristics of the participants. Variables
Elderly 70–79 year (N = 1620)
Very-elderly ≥80 year (N = 605)
P value
Women Age — year Cardiovascular risk factors Hypercholesterolemia — no./total no. (%) Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior angina pectoris Prior myocardial infarction Prior PCI Prior CABG Comorbidities Prior heart failure Prior stroke Chronic kidney disease Clinical presentation Atypical chest pain — no./total no. (%) Systolic blood pressure at baseline — mm Hg Heart rate at baseline — beats per minute Killip class ≥ 2 — no./total no. (%)
698 (43.1) 74.29 ± 2.7
330 (54.5) 83.57 ± 3.43
b0.001 b0.001
496/1385 (35.8) 499 (30.8) 1179 (72.8) 279 (17.2)
153/489 (31.3) 170 (28.1) 439 (72.6) 44 (7.3)
0.071 0.46 0.56 b0.001
292 (18.0) 264 (16.3) 206 (12.7) 36 (2.2)
136 (22.5) 79 (13.1) 48 (7.9) 10 (1.6)
0.018 0.06 0.002 0.40
96 (5.9) 119 (7.3) 169 (10.4)
60 (9.9) 51 (8.4) 106 (17.5)
0.001 0.39 b0.001
111/1347 (8.2) 138.51 ± 25.3 80.85 ± 24.7 392/1091 (35.9)
71/551 (12.9) 136.20 ± 28.1 81.99 ± 19.1 219/431 (50.8)
0.002 0.06 0.30 b0.001
Values are n (%) or mean ± SD unless stated otherwise. PCI = percutaneous coronary intervention; CABG = coronary artery bypass graft.
Regarding clinical history of ischemic heart disease, very-elderly patients were more likely to have a history of angina pectoris, but less likely to have a history of prior PCI. A history of heart failure and/or chronic kidney disease was significantly higher in the very-elderly group. In addition, the very-elderly patients were admitted more frequently than the elderly patients with atypical chest pain and Killip class ≥2.
3.2. In-hospital treatment The proportion of patients with hospital admission within 12 h from symptom onset was lower (p b 0.001) in the very-elderly group than in the elderly group (61.9% vs 67.1%, p = 0.023). Similarly, the rate of invasive reperfusion was significantly (p b 0.001) lower in the very-elderly group (42.9%) compared with the elderly group (58.9%). The proportion of patients receiving adjuvant evidence-base therapies (aspirin, clopidogrel, heparins, beta-blockers, and ACE-inhibitors) is reported in Table 2. There were no significant differences in the use of medications between the two age groups apart from clopidogrel (which was given less frequently in the very-elderly group).
3.3. Outcomes Of the 2225 patients, 362 (16.3%) died at 30-day follow-up. The rate of death was significantly superior (p b 0.001) for those patients who did not undergo primary PCI (24.2%) compared with those undergoing primary PCI (9.7%), either in the elderly (21.2% vs 7.9%) or veryelderly (29.9% vs 16.1%) group. Primary PCI decreased the unadjusted risk of death both in elderly (OR: 0.32, 95% CI 0.24–0.43) and veryelderly patients (OR: 0.45, 95% CI 0.30–0.68), without a significant difference (p = 0.19) between groups. The incidence of 30-day mortality was significantly higher (p b 0.001) in the very-elderly versus the elderly patients (23.9% vs 13.4%). Accordingly, age ≥ 80 years old was a predictor of 30-day mortality in the unadjusted logistic regression analysis (OR: 2.04, 95% CI 1.61–2.58).
3.4. Factors associated with poor outcome After adjusting for demographic and clinical variables (Table 3), regression multivariable analysis showed that primary PCI had a
Table 2 In-hospital medications, procedures and outcomes.
Time from symptom onset to admission ≤12 h In-hospital acute medications Aspirin Clopidogrel Unfractioned heparin LMWH β blockers ACE inhibitors In-hospital reperfusion therapy Primary PCI Outcomes 30-day mortality
Elderly 70–79 yr. (N = 1620)
Very-elderly ≥80 yr. (N = 605)
P value
1087 (67.1)
375 (61.9)
0.023
1539 (95.0) 1392 (85.9) 809 (49.9) 632 (39.0) 417 (25.7) 464 (28.6)
565 (93.4) 479 (79.2) 274 (45.3) 264 (43.4) 153 (25.3) 190 (31.4)
0.29 b0.001 0.14 0.13 0.95 0.44
955 (58.9)
260 (42.9)
b0.001
217 (13.4)
145 (23.9)
b0.001
Values are n (%) or mean ± SD unless stated otherwise. LMWH = low molecular weight heparins; ACE = angiotensin-converting-enzyme; PCI = percutaneous coronary intervention.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
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Table 3 Factors associated with 30-day mortality (multivariate analysis). Overall study population
Age ≥ 80 year Women Hypercholesterolemia Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior heart failure Prior stroke Atypical chest pain Killip class ≥ 2 Time from symptom onset to admission ≤12 h Chronic kidney disease Primary PCI
Elderly
Very-elderly
OR (95%CI)
P value
OR (95%CI)
P value
OR (95%CI)
P value
1.62 (1.19–2.19) 1.31 (0.98–1.76) 0.99 (0.95–1.04) 0.98 (0.91–1.04) 1.12 (1.02–1.23) 1.05 (0.97–1.14) 0.72 (0.53–0.99) 0.76 (0.45–1.29) 2.14 (1.41–3.26) 1.04 (0.96–1.14) 4.57 (3.34–6.25) 0.98 (0.94–1.08) 1.36 (1.12–1.66) 0.54 (0.39–0.74)
0.002 0.067 0.79 0.52 0.019 0.20 0.042 0.31 b0.001 0.34 b0.001 0.86 0.002 b0.001
– 1.61 (1.11–2.35) 1.01 (0.95–1.07) 0.98 (0.91–1.07) 1.08 (0.96–1.22) 1.03 (0.93–1.14) 0.89 (0.60–1.32) 0.66 (0.32–1.37) 2.19 (1.28–3.74) 0.99(0.87–1.12) 6.23 (4.16–9.42) 0.98 (0.95–1.13) 1.40 (1.08–1.83) 0.53 (0.35–0.79)
– 0.012 0.73 0.71 0.19 0.55 0.57 0.26 0.004 0.83 b0.001 0.41 0.011 0.002
– 0.93 (0.57–1.49) 0.97 (0.91–1.05) 0.95 (0.83–1.09) 1.25 (1.02–1.53) 1.10 (0.96–1.26) 0.55 (0.33–0.92) 0.92 (0.42–1.99) 1.87 (0.91–3.84) 1.11 (0.98–1.27) 2.85 (1.74–4.70) 0.97 (0.87–1.09) 1.32 (0.96–1.82) 0.53 (0.31–0.91)
– 0.76 0.53 0.48 0.031 0.15 0.024 0.83 0.087 0.094 b0.001 0.66 0.090 0.021
Clinical history of ischemic heart disease = prior angina, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft. PCI = percutaneous coronary intervention.
significant protective effect in both very-elderly (OR: 0.53; 95% CI 0.31– 0.91) and elderly groups (OR 0.53; 95% CI 0.35–0.79), although age ≥ 80 years was a significant independent factor associated with 30-day mortality (OR: 1.62; 95% CI 1.19–2.19). In addition, in the very-elderly patients, hypertension and Killip class ≥2 were independent factors associated with mortality; whereas in the elderly patients, female gender, prior stroke, chronic kidney disease and Killip class ≥2 were independent factors associated with mortality. Multivariate analysis was also performed to identify factors associated with 30-day mortality in patients undergoing primary PCI. Female gender (OR: 1.78; 95% CI 1.05–3.04), prior stroke (OR: 3.55; 95% CI 1.59–7.94), Killip class ≥ 2 (OR: 6.75, 95% CI 3.80–11.96), and chronic kidney disease (OR: 1.57; 95% CI 1.07–2.32) were associated with poor outcome. The same analysis was repeated in patients who did not undergo reperfusion therapy. In this subgroup, prior stroke (OR: 1.77; 95% CI 1.08–2.88), Killip class ≥ 2 (OR: 3.86: 95% CI 2.65–5.64), and chronic kidney disease (OR; 1.32; 95% CI 1.06–1.64) were still associated with 30-day mortality, but not female gender. Moreover, in patients not undergoing reperfusion therapy, age ≥ 80 years old (OR: 1.61; 95% CI 1.12–2.31) and hypertension (OR: 1.14; 95% CI 1.02–1.27) were also associated with poor outcome. 3.5. Factors associated with no reperfusion therapy Finally, we sought to analyze which factors were associated with lack of invasive coronary reperfusion. Age ≥ 80 years was an independent predictor of lack of primary PCI (OR: 1.49; 95% CI 1.17–1.89). When demographic and clinical variables were assessed simultaneously
by multivariable analysis in the two age subgroups, the major determinants of no reperfusion therapy were different (Table 4). In the elderly factors associated with no reperfusion were female gender, history of diabetes, current smoking, prior stroke, atypical chest pain, Killip class ≥2 and history of chronic kidney disease. In the very-elderly patients only female gender and atypical chest pain were independent predictive factors of no primary PCI. 4. Discussion In the present population-based cohort study, we sought to investigate the effect of primary PCI in octogenarian patients admitted to the hospital for STEMI. The study shows that primary PCI had a protective role on 30-day mortality in patients older than 80 years and that its beneficial effect was similar to that obtained for patients of 70 to 79 years old. 4.1. Size of the problem Octogenarians are a growing segment of the population with acute coronary syndrome. For them, STEMI is one of the leading cause of death, both in the male and female gender [31–35]. Its diagnosis and treatment is challenging because many elderly patients have atypical symptoms and comorbidities [36–42]. Intracranial hemorrhage is a serious complication of reperfusion therapy; actually, in patients ≥75 years old, thrombolytic therapy has a rate of intracranial hemorrhage over 1.4% [43]. Some studies have indicated improved survival and lower risk of stroke in elderly STEMI patients treated with primary
Table 4 Factors associated with the use of no primary PCI (multivariate analysis). Elderly
Women Hypercholesterolemia Diabetes Hypertension Current smoker Clinical history of ischemic heart disease Prior heart failure Prior stroke Atypical chest pain Killip class ≥ 2 Chronic kidney disease
Very-elderly
OR (95%CI)
P value
OR (95%CI)
P value
1.36 (1.05–1.75) 0.98 (0.94–1.03) 1.15 (1.07–1.24) 0.98 (0.88–1.09) 1.17 (1.05–1.29) 0.79 (0.61–1.02) 1.42 (0.82–2.46) 2.31 (1.45–3.69) 1.21 (1.06–1.38) 1.71 (1.30–2.24) 1.59 (1.11–2.26)
0.018 0.47 b0.001 0.75 0.005 0.075 0.21 b0.001 0.005 b0.001 0.011
1.49 (1.01–2.24) 0.97 (0.91–1.03) 1.15 (0.98–1.33) 0.87 (0.73–1.03) 1.03 (0.89–1.18) 0.62 (0.41–0.95) 1.14 (0.56–2.32) 1.19 (0.58–2.43) 2.12 (1.13–4.00) 1.22 (0.79–1.87) 1.30 (0.86–1.97)
0.049 0.33 0.078 0.12 0.70 0.027 0.72 0.64 0.020 0.36 0.20
Clinical history of ischemic heart disease = prior angina, prior myocardial infarction, prior percutaneous coronary intervention, prior coronary artery bypass graft. PCI = percutaneous coronary intervention.
Please cite this article as: B. Ricci, et al., Primary percutaneous coronary intervention in octogenarians, Int J Cardiol (2016), http://dx.doi.org/ 10.1016/j.ijcard.2016.07.204
B. Ricci et al. / International Journal of Cardiology xxx (2016) xxx–xxx
PCI compared with those treated with thrombolysis [44–49]. However, limited data are available on the best treatment options from randomized clinical trials [1–12]. Indeed, most randomized clinical trials frequently have excluded the enrollment of older patients [1–12]. 4.2. Characteristics of elderly patients Our cohort consisted of more than 2200 patients older than 70 years enrolled in the ISACS-TC registry. This study is a reflection of a real life cohort and actual practice of clinicians in Eastern Europe. Patients who underwent primary PCI were 54.6%. As generally reported previously, the rate of some clinical characteristics of STEMI patients increases with age [50,51]. These positive trends of some clinical characteristics have been recognized even in our population that is characterized by the presence of only aged patients. Female gender, comorbidities (history of heart failure and chronic kidney disease), atypical presentation and late hospital arrival were more frequently found in patients aged ≥ 80 years compared with those aged 70 to 79 years. Moreover, severe clinical presentation (Killip class ≥2) increased with the age of the study population. 4.3. Primary PCI and mortality In our cohort, the rate of death was significantly greater (two times more) for those patients who did not undergo primary PCI compared with those undergoing primary PCI. The crude differences (p b 0.001) in the rate of death was confirmed both in elderly and very-elderly groups. Also multivariate analysis documented that primary PCI was an independent factor associated with survival both in patients ≥70 to 79 years and ≥80 years old, although age ≥ 80 years old gave a higher risk of death at 30-day follow-up. These findings suggested that reperfusion therapy by PCI in old STEMI patients is beneficial, leading to a reduced risk of 30-day mortality. Our data are discordant from early published registry data [52] which found that 30-day mortality rate in the elderly who received reperfusion therapy was larger than the mortality rate of patients not receiving reperfusion therapy. Our data are concordant with recent observations from a small study population [53], which showed a favorable effect of primary PCI. Differences may depend from the characteristics of the study population. Advancements in PCI techniques may be a reason. 4.4. Prognostic factors associated with 30-day mortality The present study also provides evidence of additional independent factors influencing outcome other than older age and reperfusion. Killip class ≥ 2 at admission was a significant negative prognostic factor of death in both age groups; whereas female gender, prior stroke and chronic kidney disease were associated with poor outcomes in the elderly group; and history of hypertension was associated with poor outcome in the very-elderly group. These findings suggest that the practice of grouping all ancient patients together in a single group may provide a perspective that is not representative of all patients in this group, because the strength of a prognostic factor may be greater during one age than another age. It may underline the prevalence of different pathophysiological mechanisms of the disease or different responses to medical treatments [54–57]. Our data emphasize the prognostic role of some clinical characteristics and comorbidities in elderly and very elderly patients [58–63]. A consistent message that emerges is that revascularization by PCI is better than medical therapy in both elderly and very elderly patients. 4.5. Factors associated with lack of reperfusion The present study shows that factors influencing clinicians' decision making on the management of old STEMI patients are different in the elderly and very elderly. Factors influencing the lack of reperfusion
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treatment of our younger sub-group (≥70–79 years old) were female gender, atypical chest pain, history of diabetes, current smoking, prior stroke, Killip class ≥ 2 and history of chronic kidney disease, which is in keeping with prior work [64–69]. On the opposite, only female sex and atypical chest pain induced a low rate of primary PCI in our older sub-group (≥80 years old). Although a distinction between old age and really old age is arbitrary and determined more by socioeconomic considerations than by either prevalence and treatment of coronary disease, we expect a continuous increase in patients N80 years old as a substantial percentage of the population with STEMI. These patients clearly deserve special consideration for health care delivery and correct application of international guidelines [21,22]. 4.6. Limitations The complexity of the decision making process in the treatment of elderly with STEMI may have multiple confounders unaccounted for. 5. Conclusions Old subjects are commonly considered as a single group. The present study addresses the need to take a more critical look at the very elderly (≥80 years) on whom very few data are published compared with the 70 to 79 year old group for whom more data are available. There are differences in the clinical characteristics, management and outcome of the old population admitted for STEMI. Primary PCI causes a remarkable reduction in 30-day mortality in old patients even older than 80 years. Funding None. Conflict of interest The authors report no relationships that could be construed as a conflict of interest [70–72]. References [1] E.C. Keeley, J.A. Boura, C.L. Grines, Primary angioplasty versus intravenous thrombolytic therapy for acute myocardial infarction: a quantitative review of 23 randomised trials, Lancet 361 (2003) 13–20. [2] M.W. Rich, M.S. Bosner, M.K. Chung, J. Shen, J.P. McKenzie, Is age an independent predictor of early and late mortality in patients with acute myocardial infarction? Am. J. Med. 92 (1992) 7–13. [3] S.C. Smith Jr., E. Gilpin, S. Ahnve, et al., Outlook after acute myocardial infarction in the very elderly compared with that in patients aged 65 to 75 years, J. Am. Coll. Cardiol. 16 (1990) 784–792. [4] P.Y. Lee, K.P. Alexander, B.G. Hammill, S.K. Pasquali, E.D. Peterson, Representation of elderly persons and women in published randomized trials of acute coronary syndromes, JAMA 286 (2001) 708–713. [5] J.H. Gurwitz, N.F. Col, J. Avorn, The exclusion of the elderly and women from clinical trials in acute myocardial infarction, JAMA 268 (1992) 1417–1422. [6] K.P. Alexander, L.K. Newby, P.W. Armstrong, et al., American Heart Association Council on Clinical Cardiology, Society of Geriatric Cardiology, Acute coronary care in the elderly, part II: ST-segment-elevation myocardial infarction: a scientific statement for healthcare professionals from the American Heart Association Council on Clinical Cardiology: in collaboration with the Society of Geriatric Cardiology, Circulation 115 (2007) 2570–2589. [7] R.H. Mehta, C.B. Granger, K.P. Alexander, E. Bossone, H.D. White, M.H. Sketch Jr., Reperfusion strategies for acute myocardial infarction in the elderly: benefits and risks, J. Am. Coll. Cardiol. 45 (2005) 471–478. [8] T.I.M.E. Investigators, Trial of invasive versus medical therapy in elderly patients with chronic symptomatic coronary-artery disease (TIME): a randomised trial, Lancet 358 (2001) 951–957. [9] The GUSTO investigators, An international randomized trial comparing four thrombolytic strategies for acute myocardial infarction, N. Engl. J. Med. 329 (1993) 673–682. [10] GISSI-2: a factorial randomised trial of alteplase versus streptokinase and heparin versus no heparin among 12,490 patients with acute myocardial infarction. Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico, Lancet 336 (1990) 65–71.
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