- Email: [email protected]
Outcome of Percutaneous Coronary Intervention Following Recent Surgery
Outcome of Percutaneous Coronary Intervention Following Recent Surgery John R. Hoyt, MDa, Milan Seth, MSa, Ivan Hanson, MDb, Simon Dixon, MDb, David Share, MD, MPHc, Thomas Lalonde, MDd, David Wohns, MDe, Mauro Moscucci, MD, MBAf, and Hitinder S. Gurm, MDa,* Outcome data regarding postoperative acute coronary syndrome treated with percutaneous coronary intervention (PCI) are limited. The objective of this study was to determine clinical outcomes of patients undergoing PCI within 7 days after a surgical procedure. We assessed outcomes of 517 patients who underwent PCI within 7 days after a surgery across 44 hospitals from January 2010 to December 2011 from the Blue Cross Blue Shield of Michigan Cardiovascular Consortium registry. Patients with postoperative PCI were compared with all other patients with PCI using propensity-matched analysis. Of the 65,175 patients who underwent PCI within the study period, 517 patients had undergone surgery within the previous 7 days. In unadjusted analysis, patients with postsurgical PCI had higher in-hospital mortality (6.96% vs 1.33%), stroke (0.96% vs 0.26%), bleeding events (6.96% vs 2.6%), heart failure (6.96% vs 2.36%), and cardiogenic shock (7.16% vs 1.95%). After propensity matching, mortality remained higher in postsurgical patients (6.5% vs 3.96%, odds ratio 1.7 [1.1 to 2.6], p [ 0.02). The odds of mortality were especially high among patients who would otherwise be considered low risk (<1% of predicted mortality in a nonsurgical setting) in whom a recent surgery was strongly associated with death (odds ratio 5.7, p [ 0.02). In conclusion, PCI performed within 7 days after a surgical procedure is associated with an increased risk of early mortality. Although some of this increased risk is related to an adverse clinical profile, higher mortality is also observed in patients otherwise considered low risk for PCI. Ó 2013 Elsevier Inc. All rights reserved. (Am J Cardiol 2013;112:1580e1585)
There is paucity of contemporary data on the outcome of percutaneous coronary intervention (PCI) performed among patients who have had a recent surgery. We accordingly used data from a large contemporary cohort of patients undergoing PCI in the state of Michigan to assess the prevalence and outcome of patients undergoing PCI after a recent surgery. Methods The study sample included 65,175 consecutive PCI procedures in a large multicenter PCI registry, the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2), from January 2010 to December 2011 in Michigan.1 This registry enrolls all consecutive patients undergoing PCI a Division of Cardiovascular Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; bWilliam Beaumont Health System, Royal Oak, Michigan; cBlue Cross Blue Shield of Michigan, Detroit, Michigan; dSt. John Providence Health System, Detroit, Michigan; e Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, Michigan; and fUniversity of Miami Health System, Miami, Florida. Manuscript received May 12, 2013; revised manuscript received and accepted July 12, 2013. The BMC2 registry is funded by the Blue Cross and Blue Shield of Michigan, the Blue Care Network, and the Blue Cross Blue Shield Foundation. The sponsors had no role in analysis, study design or decision to publish these results. See page 1584 for disclosure information. *Corresponding author: Tel: (734) 232-4276; fax: (734) 764-4142. E-mail address: [email protected] (H.S. Gurm).
0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.07.016
at nonfederal hospitals in Michigan. The registry has been approved by the institutional review board of each participating hospital. Data were prospectively collected using standardized definitions and a standardized data collection form. In addition to a random audit of 2% of all cases, medical records of all patients who underwent multiple procedures or coronary artery bypass grafting and of patients who died in the hospital were reviewed to ensure data accuracy. We divided the study population into those who underwent recent surgery and those undergoing PCI without having undergone recent surgery. Recent surgery was defined as a surgical procedure performed using general, spinal, or regional anesthesia in the 7 days before the PCI. The primary end point was in-hospital mortality. Secondary end points included in-hospital cerebral vascular accident (CVA), bleeding event within 72 hours, clinical heart failure, cardiogenic shock after procedure, and stent thrombosis. CVA was defined as a loss of neurologic function severe enough to leave a persistent deficit for >24 hours and included hemorrhagic and occlusive strokes. Bleeding events were defined as a hematocrit decrease of 10% and/or hemoglobin drop of 3 g/dl and/or transfusion. Cardiogenic shock was defined as a sustained episode of systolic blood pressure of <90 mm Hg, and/or cardiac index of <2.2 L/min/m2 secondary to cardiac dysfunction, and/or requirement for inotropic or vasopressor agents and/or mechanical support to maintain blood pressure and cardiac index above specified levels. Subacute stent thrombosis was defined by angiographic evidence of stent thrombosis in the original stent at repeat angiography. www.ajconline.org
Coronary Artery Disease/Outcome of PCI Following Recent Surgery
Figure 1. Type of surgery. Anatomical location of surgery in patients who received PCI within 7 days after a surgical procedure.
Categorical data are summarized as a group percentage with group comparisons tested using the Fisher’s exact test. Continuous data are summarized as the mean SD and comparisons were made using Student t tests. Patient-predicted risk of mortality was estimated from the updated BMC2 mortality risk adjustment model.2 Area under the receiver operating characteristic curve was used to assess the discrimination of the risk model, with confidence intervals obtained by the Delong method. Multivariate logistic regression models were fitted to the data with death as the outcome and postsurgical status, predicted mortality risk, and a risk by status interaction as predictors to evaluate the effect of a recent surgery on the risk of death adjusting for model-predicted risk and to determine whether that effect varied across the continuum of risk as estimated by other baseline clinical characteristics. Patients were grouped by predicted mortality risk into 3 categories: <1%, 1% to 3%, and >3% of predicted risk. Within each group, the ratio of observed to expected mortality (O/E ratio) was compared graphically between postsurgical and other patients. A generalized propensity score was developed using logistic regression models to estimate the likelihood that a given observation was postoperative based on other baseline clinical covariates.3 Postoperative and other patients were then matched on a 1:1 basis without replacement using the estimated propensity score to identify an analysis cohort balanced on baseline covariates. All analysis was performed in R version 2.14.4e7 Results Of a total of 65,175 PCIs performed during the study period, 517 patients had undergone a surgical procedure in the previous 7 days. The respective number and anatomic distribution of surgical procedures are depicted in Figure 1. The proportion of patients undergoing PCI after surgery was small at each of the participating institutions (median 0.7%, interquartile range 0.6% to 1.1%) and overall made up to only 0.8% of the total PCI volume. Baseline characteristics
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of patients who received PCI after a recent surgery and those receiving PCI without a recent surgery are listed in Table 1. In the postoperative PCI group, a greater prevalence of endstage renal disease requiring dialysis, peripheral arterial disease, cerebrovascular disease, diabetes, chronic lung disease, recent gastrointestinal bleed, and atrial fibrillation were observed. Patients who received PCI after a surgical procedure had higher rates of heart failure, left ventricular systolic dysfunction, cardiogenic shock within 24 hours, and cardiac arrest within 24 hours. Patients receiving PCI after a recent surgical procedure were more likely to be receiving immediate PCI for ST elevation myocardial infarction (STEMI) or non-STEMI. The preprocedural, intraprocedural, and postprocedural medications used are listed in Table 2. Patients undergoing PCI within 7 days after surgery were more likely to require vasopressors before, during, and after the procedure. There was no major difference in the periprocedural anticoagulation with glycoprotein IIb/IIIa inhibitor and bivalirudin use being similar in both groups. The unadjusted primary end point of death was significantly greater in the postsurgical PCI group (Table 3 and Figure 2). Unadjusted secondary end points of CVA, bleeding events within 72 hours, heart failure, and cardiogenic shock were also significantly greater in those patients receiving PCI in the postsurgical period (Table 3 and Figure 2). Rates of acute stent thrombosis were similar. In the propensity-matched analysis, 505 (97.7%) patients with postoperative PCI were successfully matched to an equal number of otherwise similar patients without postoperative PCI. After propensity matching, significant differences were present for only one of the baseline clinical characteristics listed in Table 1 and mortality remained significantly higher in patients receiving PCI within 7 days after a surgical procedure (6.54% vs 3.96%, p ¼ 0.02; Table 3). Most deaths were attributed to cardiovascular cause in each group (Table 4). The BMC2 mortality risk model predictions were available for 503 (97.3%) of postsurgical patients and 60,542 (93.6%) nonsurgical patients with nonmissing required baseline covariates. The risk model exhibited excellent patient-level discrimination, with area under the receiver operating characteristic curve of 0.92. Although mortality was higher in the postsurgical PCI population (odds ratio 3.4, p <0.001) across the continuum of risk, the effect of postsurgical status on mortality was inversely related to risk model predictions (p <0.001 for interaction), with the difference in mortality between postsurgical and other patients being greatest among those with the lowest predicted risk based on the existing risk model (Figure 3). In an exploratory analysis, we assessed the difference in outcome of patients treated with glycoprotein IIb/IIIa inhibitors versus bivalirudin and found no significant differences between postsurgical patients treated with either drug before or during PCI (data not shown). Discussion The main finding of this study was that patients who undergo PCI after a surgical procedure have a considerable risk of in-hospital mortality and morbidity. This risk is
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Table 1 Baseline characteristics of patients who underwent postsurgical percutaneous coronary intervention (PCI) within 7 days after a surgical procedure versus other patients receiving PCI outside that time frame Variable
Age (yrs) Men White Black Asian Hispanic Native American Current smoker Former smoker Hypertension* Dyslipidemia† Family history of premature CAD Previous MI History of heart failure Previous valve surgery Significant valve disease Previous PCI Previous CABG Previous ICD Patient height (cm) Patient weight (kg) BMI (kg/m2) Currently on dialysis Cerebrovascular disease PAD Chronic lung disease Diabetes mellitus Current or recent GI bleed Atrial fibrillation Cardiac transplant Heart failure within 24 h prior to PCI LV systolic dysfunction Cardiogenic shock within 24 h Cardiac arrest within 24 h STEMI (within 7 days) NSTEMI (within 7 days) Unstable angina Other CAD presentation
Unadjusted
Propensity Matched
Postsurgical PCI, n ¼ 517 (%)
Other PCI, n ¼ 64,658 (%)
p
Postsurgical PCI, n ¼ 505 (%)
Other PCI, n ¼ 505 (%)
p
68.5 11.3 59.2 84.7 13.0 1.4 1.0 0.2 25.5 38.5 89.8 80.3 13.5 38.3 23.0 3.3 10.4 40.4 20.3 4.6 170.1 10.4 87.5 20.2 30.2 6.3 7.2 23.8 29.2 25.7 45.3 5.6 19.3 0 26.9 14.3 7.5 5.0 26.1 40.2 23.0 10.6
65.3 12.1 66.1 86.9 10.6 1.0 1.3 0.2 29.4 31.8 85.0 83.3 20.82 35.0 15.4 1.6 5.4 44.9 18.7 2.7 171.1 10.6 89.5 21.3 30.6 7.8 2.2 15.2 16.5 18.4 37.1 1.1 10.5 0.1 9.9 10.3 1.6 1.8 14.9 18.5 36.7 29.9
<0.001 <0.001 0.15 0.09 0.34 0.46 0.83 0.06 0.001 0.003 0.07 <0.001 0.12 <0.001 0.002 <0.001 0.04 0.36 0.008 0.03 0.02 0.19 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.581 <0.001 0.002 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
68.5 11.3 59.2 84.6 13.1 1.4 1.0 0.2 25.5 38.4 89.9 80.4 13.3 38.0 23.6 3.4 10.7 40.4 20.2 4.8 170.0 10.5 87.7 20.3 30.3 6.4 7.1 24.2 29.1 25.9 45.4 5.7 19.8 0 27.5 14.3 7.1 4.6 25.5 40.6 23.0 10.9
67.9 11.3 59.2 81.2 15.0 1.2 2.0 1.2 25.7 33.3 89.9 76.4 16.8 37.6 21.6 1.8 10.7 37.8 21.2 3.6 169.6 11.4 87.4 22.7 30.5 8.6 6.7 26.1 25.5 24.6 46.1 5.7 19.6 0 21.8 16.4 6.3 7.1 26.3 42.4 20.8 10.5
0.44 1.00 0.16 0.37 0.78 0.19 0.06 0.94 0.09 1.00 0.13 0.11 0.90 0.45 0.11 1.00 0.40 0.70 0.34 0.56 0.81 0.73 0.80 0.47 0.20 0.61 0.80 1.00 0.94 NA 0.03 0.34 0.62 0.08 0.77 0.57 0.40 0.84
BMI ¼ body mass index; CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; ICD ¼ internal cardiac defibrillator; LV ¼ left ventricular; MI ¼ myocardial infarction; NSTEMI ¼ noneSTEMI; PAD ¼ peripheral arterial disease. * Hypertension is defined by any 1 of the following: a history of hypertension diagnosed and treated with medication, diet, and/or exercise, previous documentation of blood pressure of 140 mm Hg systolic and/or 90 mm Hg diastolic for patients without diabetes or chronic kidney disease, or previous documentation of blood pressure of 130 mm Hg systolic or 80 mm Hg diastolic on at least 2 occasions for patients with diabetes or chronic kidney disease. † Dyslipidemia is defined as a history of dyslipidemia that was diagnosed and/or treated by a physician, or levels of total cholesterol >200 mg/dl, low-density lipoprotein 130 mg/dl, and high-density lipoprotein <40 mg/dl in men and <50 mg/dl in women, or currently receiving antilipidemic treatment.
elevated both among those who would traditionally be considered to be at high risk of post-PCI complications and among those considered to be low risk in whom a 5.7-fold increase in mortality was demonstrated. Patients with postsurgical PCI also had higher rates of CVA and bleeding. The origin and pathophysiological basis of the observed excess mortality in patients receiving postsurgical PCI is not readily apparent. In general, rates of acute stent thrombosis were rare and there were no statistically significant differences in rates of acute stent thrombosis between groups.
Therefore, we presume that the excess in mortality in the postsurgical PCI group was not related to acute stent thrombosis, but given the very low event rate, this outcome must be viewed with caution as it lacks statistical power. It is also plausible that some patients who had an acute stent thrombosis had sudden cardiac death and did not survive to repeat angiography, thereby falsely lowering the observed stent thrombosis rate. Most deaths were attributed to cardiac origin in each group and statistically similar in each group. A higher rate of mortality attributed to pulmonary origin
Coronary Artery Disease/Outcome of PCI Following Recent Surgery
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Table 2 Medications used before, during, and after percutaneous coronary intervention (PCI) Medication
Before Procedure
During Procedure
Postsurgical PCI (%) Other PCI (%) Aspirin Clopidogrel Prasugrel Abciximab Eptifibatide GPI Bivalirudin Vasopressor Statin b Blocker
89.8 43.7 1.7 0.2 3.3 3.5 0.4 10.3 62.5 72.5
92.9 45.5 3.7 0.1 5.2 5.3 0.4 1.3 60.9 68.0
p
After Procedure
Postsurgical PCI (%) Other PCI (%)
0.005 0.42 0.02 0.42 0.06 0.06 0.89 <0.001 0.45 0.03
5.6 49.5 5.8 3.3 26.3 29.8 32.9 15.7 NA NA
p
4.3 47.9 11.8 1.9 31.7 33.5 36.5 4.5 NA NA
0.16 0.47 <0.001 0.02 0.01 0.07 0.09 <0.001 NA NA
Postsurgical PCI (%) Other PCI (%) 94.4 83.6 7.9 1.7 19.9 21.5 1.9 10.8 76.4 80.7
94.3 78.3 14.9 1.3 25.3 26.7 3.4 2.3 78.3 84.9
p 0.95 0.004 <0.001 0.37 0.005 0.008 0.06 <0.001 0.31 0.008
GPI ¼ platelet glycoprotein IIb/IIIa inhibitor.
Table 3 Primary and secondary outcomes of the cohort in unadjusted and propensity matched analysis End Point
In-hospital death CVA or stroke during or after procedure Bleeding event within 72 h* Heart failure during or after procedure Cardiogenic shock during or after procedure Acute stent thrombosis
Unadjusted
Propensity Matched
Postsurgical PCI, n ¼ 517 (%)
Other PCI, n ¼ 64,658 (%)
p
Postsurgical PCI, n ¼ 505 (%)
Other PCI, n ¼ 505 (%)
p
6.96 0.97 6.96 6.96 7.16 0.58
1.33 0.26 2.60 2.36 1.95 0.26
<0.001 0.002 <0.001 <0.001 <0.001 0.15
6.54 0.99 7.13 6.91 6.93 0.59
3.96 0.40 5.35 5.55 5.74 0.99
0.02 0.27 0.21 0.27 0.96 0.48
* Bleeding event is defined as a hematocrit decrease of 10% and/or hemoglobin decrease of 3 g/dl and/or transfusion.
was found in the postsurgical PCI group, which may have contributed to the mortality difference. We speculate that these pulmonary-related deaths may be secondary to postsurgical pneumonias and/or respiratory failure. The decision of whether to take a postoperative patient for PCI can be complex and is driven by many factors including type, timing and anatomical location of the recent surgical procedure, bleeding risk, type of acute coronary syndrome, and overall clinical condition. The risks of stent thrombosis and cardiovascular events are well known in the setting of PCI followed by a surgical procedure especially if dual antiplatelet therapy is interrupted.8e13 However, there is a paucity of published works regarding surgery followed by PCI in the postoperative period for acute coronary syndrome. There are no randomized trials or large observational studies published regarding postoperative PCI, and to our knowledge, our study is the largest to study PCI outcomes performed in the postoperative setting. Berger et al14 analyzed the outcomes of 48 patients who underwent coronary angiography for acute myocardial infarction within 7 days after a noncardiac surgery from 1990 to 1998. Most patients (33.7%) had STEMI and 21 (44%) had shock before catheterization. Most patients were treated with angioplasty only, and mortality was high with only 31 patients (65%) surviving to discharge. The strength of our study is that it provides contemporary PCI outcome data from both academic and nonacademic hospitals across a variety of patients and PCI risk. We recognize that there is likely considerable selection bias
regarding which patients are taken for PCI in the postoperative period. It is evident that patients who were taken for postoperative PCI had higher rates of STEMI, congestive heart failure, shock, vasopressor use, and greater percent of co-morbid conditions such as diabetes, end-stage renal disease on dialysis, significant valvular heart disease, and peripheral arterial disease that may have contributed to adverse events. In an effort to decrease some of this selection bias, propensity matching was performed and still showed greater mortality in patients with postoperative PCI. Although our study contributes to the current published works regarding PCI outcomes performed in the postoperative setting, it is not without limitation. Data were gathered from a registry and captured in-hospital events only. We were unable to determine whether bleeding was related to the surgical site, identify surgical complications that may have been exacerbated by the PCI procedure, or identify which types of surgical procedures were associated with the most risk for adverse events because of the small number of patients in each category. We did not have access to data regarding the exact timing and proximity of the PCI procedure in relation to the surgery, which may influence bleeding risk. Lastly, we did not have data regarding the overall burden of coronary disease at the time of angiography (i.e., SYNTAX score) or before the surgical procedure. Our study contributes significantly to our understanding of contemporary PCI outcomes but primarily provides observational data and cannot be used to make recommendations
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Figure 2. Unadjusted primary and secondary outcomes. Unadjusted outcomes of patients treated with PCI within 7 days after a surgical procedure versus those treated outside that time period. *Bleeding is defined as a hematocrit decrease of 10% and/or hemoglobin decrease of 3 g/dl and/or transfusion, CHF ¼ congestive heart failure. Table 4 Primary cause of death Primary Cause of Death Cardiac Neurologic Renal Vascular Infection Valvular Pulmonary Unknown Other
Postsurgical PCI, n ¼ 36 (%) 26 1 0 2
(72.2) (2.8) (0.0) (5.6) 0 0 5 (13.9) 1 (2.8) 1 (2.8)
Other PCI, n ¼ 858 (%) 699 27 7 14 9 15 25 31 31
(81.5) (3.1) (0.8) (1.6) (1.0) (1.7) (2.9) (3.6) (3.6)
regarding the optimal treatment of perioperative myocardial infarction. Directions for further study may include identifying the optimal timing and selection of patients for PCI after surgical procedures, preferred pharmacologic and anticoagulation strategies in the postoperative setting, and a longer term follow-up of clinical outcomes in patients who underwent medical therapy versus invasive therapy with PCI for perioperative myocardial infarction. Acknowledgment: The authors are indebted to all the study coordinators, investigators, and patients who participated in BMC2. Disclosures H.S.G. receives research funding from the National Institutes of Health and the Agency for Healthcare Research and Quality. D.S. is employed by the Blue Cross Blue Shield of Michigan. None of the authors have any conflicts directly relevant to this study.
Figure 3. Risk of mortality with postsurgical PCI. Risk of observed mortality with postsurgical PCI versus other PCI stratified by 3 different levels of predicted mortality (<1%, 1% to 3%, and >3% of predicted mortality). OR ¼ odds ratio; RR ¼ relative risk.
1. Moscucci M, Share D, Kline-Rogers E, O’Donnell M, Maxwell-Eward A, Meengs WL, Clark VL, Kraft P, De Franco AC, Chambers JL, Patel K, McGinnity JG, Eagle KA; Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2). The Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2) collaborative quality improvement initiative in percutaneous coronary interventions. J Interv Cardiol 2002;15:381e386. 2. Moscucci M, Kline-Rogers E, Share D, O’Donnell M, Maxwell-Eward A, Meengs WL, Kraft P, DeFranco AC, Chambers JL, Patel K, McGinnity JG, Eagle KA. Simple bedside additive tool for prediction of in-hospital mortality after percutaneous coronary interventions. Circulation 2001;104:263e268. 3. Rosenbaum PR, Rubin DB. Reducing bias in observational studies using subclassification on the propensity score. J Am Stat Assoc 1984;79:516e524. 4. R Development Core Team. A Language and Environment for Statistical Computing. R Foundation for Statistical Computing, Vienna, Austria. Available at: http://www.R-project.org/. Accessed January 24, 2013.
Coronary Artery Disease/Outcome of PCI Following Recent Surgery 5. Therneau T, Atkinson B, Ripley B. Recursive Partitioning. R Package Version 3.1-50. Available at: http://CRAN.R-project.org/package¼ rpart. Accessed January 24, 2013. 6. Robin X, Turck N, Hainard A, Tiberti N, Lisacek F, Sanchez JC, Muller M. pROC: an open-source package for R and Sþ to analyze and compare ROC curves. BMC Bioinformatics 2011;12:77. 7. Ho D, Imai K, King G, Stuart E. MatchIt: nonparametric preprocessing for parametric causal inference. J Stat Softw 2011;42:1e28. 8. Cruden NL, Harding SA, Flapan AD, Graham C, Wild SH, Slack R, Pell JP, Newby DE; Scottish Coronary Revascularisation Register Steering Committee. Previous coronary stent implantation and cardiac events in patients undergoing noncardiac surgery. Circ Cardiovasc Interv 2010;3:236e242. 9. Berger PB, Kleiman NS, Pencina MJ, Hsieh WH, Steinhubl SR, Jeremias A, Sonel A, Browne K, Barseness G, Cohen DJ; EVENT Investigators. Frequency of major noncardiac surgery and subsequent adverse events in the year after drug-eluting stent placement results from the EVENT (Evaluation of Drug-Eluting Stents and Ischemic Events) Registry. JACC Cardiovasc Interv 2010;3:920e927.
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10. Iakovou I, Schmidt T, Bonizzoni E, Ge L, Sangiorgi GM, Stankovic G, Airoldi F, Chieffo A, Montorfano M, Carlino M, Michev I, Corvaja N, Briguori C, Gerckens U, Grube E, Colombo A. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. JAMA 2005;293:2126e2130. 11. Gandhi NK, Abdel-Karim AR, Banerjee S, Brilakis ES. Frequency and risk of noncardiac surgery after drug-eluting stent implantation. Catheter Cardiovasc Interv 2011;77:972e976. 12. Matteau A, Mauri L. Optimal timing of noncardiac surgery after stents. Circulation 2012;126:1322e1324. 13. Wijeysundera DN, Wijeysundera HC, Yun L, Wasowicz M, Beattie WS, Velianou JL, Ko DT. Risk of elective major noncardiac surgery after coronary stent insertion: a population-based study. Circulation 2012;126:1355e1362. 14. Berger PB, Bellot V, Bell MR, Horlocker TT, Rihal CS, Hallett JW, Dalzell C, Melby SJ, Charnoff NE, Holmes DR. An immediate invasive strategy for the treatment of acute myocardial infarction early after noncardiac surgery. Am J Cardiol 2001;87: 1100e1102.
There is paucity of contemporary data on the outcome of percutaneous coronary intervention (PCI) performed among patients who have had a recent surgery. We accordingly used data from a large contemporary cohort of patients undergoing PCI in the state of Michigan to assess the prevalence and outcome of patients undergoing PCI after a recent surgery. Methods The study sample included 65,175 consecutive PCI procedures in a large multicenter PCI registry, the Blue Cross Blue Shield of Michigan Cardiovascular Consortium (BMC2), from January 2010 to December 2011 in Michigan.1 This registry enrolls all consecutive patients undergoing PCI a Division of Cardiovascular Disease, Department of Internal Medicine, University of Michigan, Ann Arbor, Michigan; bWilliam Beaumont Health System, Royal Oak, Michigan; cBlue Cross Blue Shield of Michigan, Detroit, Michigan; dSt. John Providence Health System, Detroit, Michigan; e Frederik Meijer Heart and Vascular Institute, Spectrum Health, Grand Rapids, Michigan; and fUniversity of Miami Health System, Miami, Florida. Manuscript received May 12, 2013; revised manuscript received and accepted July 12, 2013. The BMC2 registry is funded by the Blue Cross and Blue Shield of Michigan, the Blue Care Network, and the Blue Cross Blue Shield Foundation. The sponsors had no role in analysis, study design or decision to publish these results. See page 1584 for disclosure information. *Corresponding author: Tel: (734) 232-4276; fax: (734) 764-4142. E-mail address: [email protected] (H.S. Gurm).
0002-9149/13/$ - see front matter Ó 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.amjcard.2013.07.016
at nonfederal hospitals in Michigan. The registry has been approved by the institutional review board of each participating hospital. Data were prospectively collected using standardized definitions and a standardized data collection form. In addition to a random audit of 2% of all cases, medical records of all patients who underwent multiple procedures or coronary artery bypass grafting and of patients who died in the hospital were reviewed to ensure data accuracy. We divided the study population into those who underwent recent surgery and those undergoing PCI without having undergone recent surgery. Recent surgery was defined as a surgical procedure performed using general, spinal, or regional anesthesia in the 7 days before the PCI. The primary end point was in-hospital mortality. Secondary end points included in-hospital cerebral vascular accident (CVA), bleeding event within 72 hours, clinical heart failure, cardiogenic shock after procedure, and stent thrombosis. CVA was defined as a loss of neurologic function severe enough to leave a persistent deficit for >24 hours and included hemorrhagic and occlusive strokes. Bleeding events were defined as a hematocrit decrease of 10% and/or hemoglobin drop of 3 g/dl and/or transfusion. Cardiogenic shock was defined as a sustained episode of systolic blood pressure of <90 mm Hg, and/or cardiac index of <2.2 L/min/m2 secondary to cardiac dysfunction, and/or requirement for inotropic or vasopressor agents and/or mechanical support to maintain blood pressure and cardiac index above specified levels. Subacute stent thrombosis was defined by angiographic evidence of stent thrombosis in the original stent at repeat angiography. www.ajconline.org
Coronary Artery Disease/Outcome of PCI Following Recent Surgery
Figure 1. Type of surgery. Anatomical location of surgery in patients who received PCI within 7 days after a surgical procedure.
Categorical data are summarized as a group percentage with group comparisons tested using the Fisher’s exact test. Continuous data are summarized as the mean SD and comparisons were made using Student t tests. Patient-predicted risk of mortality was estimated from the updated BMC2 mortality risk adjustment model.2 Area under the receiver operating characteristic curve was used to assess the discrimination of the risk model, with confidence intervals obtained by the Delong method. Multivariate logistic regression models were fitted to the data with death as the outcome and postsurgical status, predicted mortality risk, and a risk by status interaction as predictors to evaluate the effect of a recent surgery on the risk of death adjusting for model-predicted risk and to determine whether that effect varied across the continuum of risk as estimated by other baseline clinical characteristics. Patients were grouped by predicted mortality risk into 3 categories: <1%, 1% to 3%, and >3% of predicted risk. Within each group, the ratio of observed to expected mortality (O/E ratio) was compared graphically between postsurgical and other patients. A generalized propensity score was developed using logistic regression models to estimate the likelihood that a given observation was postoperative based on other baseline clinical covariates.3 Postoperative and other patients were then matched on a 1:1 basis without replacement using the estimated propensity score to identify an analysis cohort balanced on baseline covariates. All analysis was performed in R version 2.14.4e7 Results Of a total of 65,175 PCIs performed during the study period, 517 patients had undergone a surgical procedure in the previous 7 days. The respective number and anatomic distribution of surgical procedures are depicted in Figure 1. The proportion of patients undergoing PCI after surgery was small at each of the participating institutions (median 0.7%, interquartile range 0.6% to 1.1%) and overall made up to only 0.8% of the total PCI volume. Baseline characteristics
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of patients who received PCI after a recent surgery and those receiving PCI without a recent surgery are listed in Table 1. In the postoperative PCI group, a greater prevalence of endstage renal disease requiring dialysis, peripheral arterial disease, cerebrovascular disease, diabetes, chronic lung disease, recent gastrointestinal bleed, and atrial fibrillation were observed. Patients who received PCI after a surgical procedure had higher rates of heart failure, left ventricular systolic dysfunction, cardiogenic shock within 24 hours, and cardiac arrest within 24 hours. Patients receiving PCI after a recent surgical procedure were more likely to be receiving immediate PCI for ST elevation myocardial infarction (STEMI) or non-STEMI. The preprocedural, intraprocedural, and postprocedural medications used are listed in Table 2. Patients undergoing PCI within 7 days after surgery were more likely to require vasopressors before, during, and after the procedure. There was no major difference in the periprocedural anticoagulation with glycoprotein IIb/IIIa inhibitor and bivalirudin use being similar in both groups. The unadjusted primary end point of death was significantly greater in the postsurgical PCI group (Table 3 and Figure 2). Unadjusted secondary end points of CVA, bleeding events within 72 hours, heart failure, and cardiogenic shock were also significantly greater in those patients receiving PCI in the postsurgical period (Table 3 and Figure 2). Rates of acute stent thrombosis were similar. In the propensity-matched analysis, 505 (97.7%) patients with postoperative PCI were successfully matched to an equal number of otherwise similar patients without postoperative PCI. After propensity matching, significant differences were present for only one of the baseline clinical characteristics listed in Table 1 and mortality remained significantly higher in patients receiving PCI within 7 days after a surgical procedure (6.54% vs 3.96%, p ¼ 0.02; Table 3). Most deaths were attributed to cardiovascular cause in each group (Table 4). The BMC2 mortality risk model predictions were available for 503 (97.3%) of postsurgical patients and 60,542 (93.6%) nonsurgical patients with nonmissing required baseline covariates. The risk model exhibited excellent patient-level discrimination, with area under the receiver operating characteristic curve of 0.92. Although mortality was higher in the postsurgical PCI population (odds ratio 3.4, p <0.001) across the continuum of risk, the effect of postsurgical status on mortality was inversely related to risk model predictions (p <0.001 for interaction), with the difference in mortality between postsurgical and other patients being greatest among those with the lowest predicted risk based on the existing risk model (Figure 3). In an exploratory analysis, we assessed the difference in outcome of patients treated with glycoprotein IIb/IIIa inhibitors versus bivalirudin and found no significant differences between postsurgical patients treated with either drug before or during PCI (data not shown). Discussion The main finding of this study was that patients who undergo PCI after a surgical procedure have a considerable risk of in-hospital mortality and morbidity. This risk is
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Table 1 Baseline characteristics of patients who underwent postsurgical percutaneous coronary intervention (PCI) within 7 days after a surgical procedure versus other patients receiving PCI outside that time frame Variable
Age (yrs) Men White Black Asian Hispanic Native American Current smoker Former smoker Hypertension* Dyslipidemia† Family history of premature CAD Previous MI History of heart failure Previous valve surgery Significant valve disease Previous PCI Previous CABG Previous ICD Patient height (cm) Patient weight (kg) BMI (kg/m2) Currently on dialysis Cerebrovascular disease PAD Chronic lung disease Diabetes mellitus Current or recent GI bleed Atrial fibrillation Cardiac transplant Heart failure within 24 h prior to PCI LV systolic dysfunction Cardiogenic shock within 24 h Cardiac arrest within 24 h STEMI (within 7 days) NSTEMI (within 7 days) Unstable angina Other CAD presentation
Unadjusted
Propensity Matched
Postsurgical PCI, n ¼ 517 (%)
Other PCI, n ¼ 64,658 (%)
p
Postsurgical PCI, n ¼ 505 (%)
Other PCI, n ¼ 505 (%)
p
68.5 11.3 59.2 84.7 13.0 1.4 1.0 0.2 25.5 38.5 89.8 80.3 13.5 38.3 23.0 3.3 10.4 40.4 20.3 4.6 170.1 10.4 87.5 20.2 30.2 6.3 7.2 23.8 29.2 25.7 45.3 5.6 19.3 0 26.9 14.3 7.5 5.0 26.1 40.2 23.0 10.6
65.3 12.1 66.1 86.9 10.6 1.0 1.3 0.2 29.4 31.8 85.0 83.3 20.82 35.0 15.4 1.6 5.4 44.9 18.7 2.7 171.1 10.6 89.5 21.3 30.6 7.8 2.2 15.2 16.5 18.4 37.1 1.1 10.5 0.1 9.9 10.3 1.6 1.8 14.9 18.5 36.7 29.9
<0.001 <0.001 0.15 0.09 0.34 0.46 0.83 0.06 0.001 0.003 0.07 <0.001 0.12 <0.001 0.002 <0.001 0.04 0.36 0.008 0.03 0.02 0.19 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 0.581 <0.001 0.002 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
68.5 11.3 59.2 84.6 13.1 1.4 1.0 0.2 25.5 38.4 89.9 80.4 13.3 38.0 23.6 3.4 10.7 40.4 20.2 4.8 170.0 10.5 87.7 20.3 30.3 6.4 7.1 24.2 29.1 25.9 45.4 5.7 19.8 0 27.5 14.3 7.1 4.6 25.5 40.6 23.0 10.9
67.9 11.3 59.2 81.2 15.0 1.2 2.0 1.2 25.7 33.3 89.9 76.4 16.8 37.6 21.6 1.8 10.7 37.8 21.2 3.6 169.6 11.4 87.4 22.7 30.5 8.6 6.7 26.1 25.5 24.6 46.1 5.7 19.6 0 21.8 16.4 6.3 7.1 26.3 42.4 20.8 10.5
0.44 1.00 0.16 0.37 0.78 0.19 0.06 0.94 0.09 1.00 0.13 0.11 0.90 0.45 0.11 1.00 0.40 0.70 0.34 0.56 0.81 0.73 0.80 0.47 0.20 0.61 0.80 1.00 0.94 NA 0.03 0.34 0.62 0.08 0.77 0.57 0.40 0.84
BMI ¼ body mass index; CABG ¼ coronary artery bypass grafting; CAD ¼ coronary artery disease; ICD ¼ internal cardiac defibrillator; LV ¼ left ventricular; MI ¼ myocardial infarction; NSTEMI ¼ noneSTEMI; PAD ¼ peripheral arterial disease. * Hypertension is defined by any 1 of the following: a history of hypertension diagnosed and treated with medication, diet, and/or exercise, previous documentation of blood pressure of 140 mm Hg systolic and/or 90 mm Hg diastolic for patients without diabetes or chronic kidney disease, or previous documentation of blood pressure of 130 mm Hg systolic or 80 mm Hg diastolic on at least 2 occasions for patients with diabetes or chronic kidney disease. † Dyslipidemia is defined as a history of dyslipidemia that was diagnosed and/or treated by a physician, or levels of total cholesterol >200 mg/dl, low-density lipoprotein 130 mg/dl, and high-density lipoprotein <40 mg/dl in men and <50 mg/dl in women, or currently receiving antilipidemic treatment.
elevated both among those who would traditionally be considered to be at high risk of post-PCI complications and among those considered to be low risk in whom a 5.7-fold increase in mortality was demonstrated. Patients with postsurgical PCI also had higher rates of CVA and bleeding. The origin and pathophysiological basis of the observed excess mortality in patients receiving postsurgical PCI is not readily apparent. In general, rates of acute stent thrombosis were rare and there were no statistically significant differences in rates of acute stent thrombosis between groups.
Therefore, we presume that the excess in mortality in the postsurgical PCI group was not related to acute stent thrombosis, but given the very low event rate, this outcome must be viewed with caution as it lacks statistical power. It is also plausible that some patients who had an acute stent thrombosis had sudden cardiac death and did not survive to repeat angiography, thereby falsely lowering the observed stent thrombosis rate. Most deaths were attributed to cardiac origin in each group and statistically similar in each group. A higher rate of mortality attributed to pulmonary origin
Coronary Artery Disease/Outcome of PCI Following Recent Surgery
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Table 2 Medications used before, during, and after percutaneous coronary intervention (PCI) Medication
Before Procedure
During Procedure
Postsurgical PCI (%) Other PCI (%) Aspirin Clopidogrel Prasugrel Abciximab Eptifibatide GPI Bivalirudin Vasopressor Statin b Blocker
89.8 43.7 1.7 0.2 3.3 3.5 0.4 10.3 62.5 72.5
92.9 45.5 3.7 0.1 5.2 5.3 0.4 1.3 60.9 68.0
p
After Procedure
Postsurgical PCI (%) Other PCI (%)
0.005 0.42 0.02 0.42 0.06 0.06 0.89 <0.001 0.45 0.03
5.6 49.5 5.8 3.3 26.3 29.8 32.9 15.7 NA NA
p
4.3 47.9 11.8 1.9 31.7 33.5 36.5 4.5 NA NA
0.16 0.47 <0.001 0.02 0.01 0.07 0.09 <0.001 NA NA
Postsurgical PCI (%) Other PCI (%) 94.4 83.6 7.9 1.7 19.9 21.5 1.9 10.8 76.4 80.7
94.3 78.3 14.9 1.3 25.3 26.7 3.4 2.3 78.3 84.9
p 0.95 0.004 <0.001 0.37 0.005 0.008 0.06 <0.001 0.31 0.008
GPI ¼ platelet glycoprotein IIb/IIIa inhibitor.
Table 3 Primary and secondary outcomes of the cohort in unadjusted and propensity matched analysis End Point
In-hospital death CVA or stroke during or after procedure Bleeding event within 72 h* Heart failure during or after procedure Cardiogenic shock during or after procedure Acute stent thrombosis
Unadjusted
Propensity Matched
Postsurgical PCI, n ¼ 517 (%)
Other PCI, n ¼ 64,658 (%)
p
Postsurgical PCI, n ¼ 505 (%)
Other PCI, n ¼ 505 (%)
p
6.96 0.97 6.96 6.96 7.16 0.58
1.33 0.26 2.60 2.36 1.95 0.26
<0.001 0.002 <0.001 <0.001 <0.001 0.15
6.54 0.99 7.13 6.91 6.93 0.59
3.96 0.40 5.35 5.55 5.74 0.99
0.02 0.27 0.21 0.27 0.96 0.48
* Bleeding event is defined as a hematocrit decrease of 10% and/or hemoglobin decrease of 3 g/dl and/or transfusion.
was found in the postsurgical PCI group, which may have contributed to the mortality difference. We speculate that these pulmonary-related deaths may be secondary to postsurgical pneumonias and/or respiratory failure. The decision of whether to take a postoperative patient for PCI can be complex and is driven by many factors including type, timing and anatomical location of the recent surgical procedure, bleeding risk, type of acute coronary syndrome, and overall clinical condition. The risks of stent thrombosis and cardiovascular events are well known in the setting of PCI followed by a surgical procedure especially if dual antiplatelet therapy is interrupted.8e13 However, there is a paucity of published works regarding surgery followed by PCI in the postoperative period for acute coronary syndrome. There are no randomized trials or large observational studies published regarding postoperative PCI, and to our knowledge, our study is the largest to study PCI outcomes performed in the postoperative setting. Berger et al14 analyzed the outcomes of 48 patients who underwent coronary angiography for acute myocardial infarction within 7 days after a noncardiac surgery from 1990 to 1998. Most patients (33.7%) had STEMI and 21 (44%) had shock before catheterization. Most patients were treated with angioplasty only, and mortality was high with only 31 patients (65%) surviving to discharge. The strength of our study is that it provides contemporary PCI outcome data from both academic and nonacademic hospitals across a variety of patients and PCI risk. We recognize that there is likely considerable selection bias
regarding which patients are taken for PCI in the postoperative period. It is evident that patients who were taken for postoperative PCI had higher rates of STEMI, congestive heart failure, shock, vasopressor use, and greater percent of co-morbid conditions such as diabetes, end-stage renal disease on dialysis, significant valvular heart disease, and peripheral arterial disease that may have contributed to adverse events. In an effort to decrease some of this selection bias, propensity matching was performed and still showed greater mortality in patients with postoperative PCI. Although our study contributes to the current published works regarding PCI outcomes performed in the postoperative setting, it is not without limitation. Data were gathered from a registry and captured in-hospital events only. We were unable to determine whether bleeding was related to the surgical site, identify surgical complications that may have been exacerbated by the PCI procedure, or identify which types of surgical procedures were associated with the most risk for adverse events because of the small number of patients in each category. We did not have access to data regarding the exact timing and proximity of the PCI procedure in relation to the surgery, which may influence bleeding risk. Lastly, we did not have data regarding the overall burden of coronary disease at the time of angiography (i.e., SYNTAX score) or before the surgical procedure. Our study contributes significantly to our understanding of contemporary PCI outcomes but primarily provides observational data and cannot be used to make recommendations
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Figure 2. Unadjusted primary and secondary outcomes. Unadjusted outcomes of patients treated with PCI within 7 days after a surgical procedure versus those treated outside that time period. *Bleeding is defined as a hematocrit decrease of 10% and/or hemoglobin decrease of 3 g/dl and/or transfusion, CHF ¼ congestive heart failure. Table 4 Primary cause of death Primary Cause of Death Cardiac Neurologic Renal Vascular Infection Valvular Pulmonary Unknown Other
Postsurgical PCI, n ¼ 36 (%) 26 1 0 2
(72.2) (2.8) (0.0) (5.6) 0 0 5 (13.9) 1 (2.8) 1 (2.8)
Other PCI, n ¼ 858 (%) 699 27 7 14 9 15 25 31 31
(81.5) (3.1) (0.8) (1.6) (1.0) (1.7) (2.9) (3.6) (3.6)
regarding the optimal treatment of perioperative myocardial infarction. Directions for further study may include identifying the optimal timing and selection of patients for PCI after surgical procedures, preferred pharmacologic and anticoagulation strategies in the postoperative setting, and a longer term follow-up of clinical outcomes in patients who underwent medical therapy versus invasive therapy with PCI for perioperative myocardial infarction. Acknowledgment: The authors are indebted to all the study coordinators, investigators, and patients who participated in BMC2. Disclosures H.S.G. receives research funding from the National Institutes of Health and the Agency for Healthcare Research and Quality. D.S. is employed by the Blue Cross Blue Shield of Michigan. None of the authors have any conflicts directly relevant to this study.
Figure 3. Risk of mortality with postsurgical PCI. Risk of observed mortality with postsurgical PCI versus other PCI stratified by 3 different levels of predicted mortality (<1%, 1% to 3%, and >3% of predicted mortality). OR ¼ odds ratio; RR ¼ relative risk.
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