Increased Mortality Associated With Low Use of Clopidogrel in HF
Objectives We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI).
Background Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel is associated with absolute mortality reduction in AMI patients.
Methods All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan-Meier method and Cox regression analyses.
Results We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n = 5,050) and a mean follow-up of 1.50 years (SD = 1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively (p = 0.002). The corresponding numbers for patients without HF (n = 6,092), with a mean follow-up of 2.05 years (SD = 1.3), were 285 (9.4%) and 294 (9.7%), respectively (p = 0.83). Patients with HF receiving clopidogrel demonstrated reduced mortality (hazard ratio: 0.86; 95% confidence interval: 0.78 to 0.95) compared with patients with HF not receiving clopidogrel. No difference was observed among patients without HF (hazard ratio: 0.98; 95% confidence interval: 0.83 to 1.16).
Conclusions Clopidogrel was associated with reduced mortality in patients with HF who do not undergo PCI after their first-time AMI, whereas this association was not apparent in patients without HF. Further studies of the benefit of clopidogrel in patients with HF and AMI are warranted.
Heart failure (HF) complicating acute myocardial infarction (AMI) is associated with a poor prognosis. Current European and American guidelines recommend dual antiplatelet treatment with aspirin and clopidogrel in all patients with AMI in the absence of an increased risk of bleeding. Three major randomized controlled studies have provided important knowledge regarding the benefit of clopidogrel in patients hospitalized with acute coronary syndrome. One trial investigated the effect of clopidogrel versus aspirin, another investigated the effect of clopidogrel versus placebo, and another showed an effect of clopidogrel versus placebo in addition to aspirin. A favorable effect of clopidogrel with respect to the composite end point of death, reinfarction, or stroke was found in all studies, and in the latter study, also a decreased risk of all-cause mortality was found. Patients with HF comprised a modest part of the study population in all 3 studies, and no subgroup analyses of patients with HF were performed. The clinical benefit of clopidogrel in AMI patients with HF is not clarified, which may cause uncertainty and may lead to differences in clinical practice among physicians treating this high-risk patient population. This notion is supported by studies evaluating the implementation of non–ST-segment elevation myocardial infarction (NSTEMI) guidelines, which have demonstrated low initiation rates of clopidogrel in patients not undergoing percutaneous coronary intervention (PCI) and even lower initiation rates of clopidogrel in patients with HF.
Patients with HF have an approximately 3% annual risk of atherothrombotic events, which may be because of the significantly increased platelet activity. Indeed, it has been demonstrated that the addition of clopidogrel to aspirin in patients with HF significantly inhibits the increased platelet activity. Whether clopidogrel provides additional survival benefit for AMI patients with concomitant HF compared with patients without HF is unknown. This uncertainty prompted us to conduct a nationwide study examining the effect of clopidogrel on mortality in a population of patients with and without HF discharged after their first-time AMI and not undergoing PCI.
Abstract and Introduction
Abstract
Objectives We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI).
Background Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel is associated with absolute mortality reduction in AMI patients.
Methods All patients hospitalized with first-time AMI (2000 through 2005) and not undergoing PCI within 30 days from discharge were identified in national registers. Patients with HF treated with clopidogrel were matched by propensity score with patients not treated with clopidogrel. Similarly, 2 groups without HF were identified. Risks of all-cause death were obtained by the Kaplan-Meier method and Cox regression analyses.
Results We identified 56,944 patients with first-time AMI. In the matched cohort with HF (n = 5,050) and a mean follow-up of 1.50 years (SD = 1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively (p = 0.002). The corresponding numbers for patients without HF (n = 6,092), with a mean follow-up of 2.05 years (SD = 1.3), were 285 (9.4%) and 294 (9.7%), respectively (p = 0.83). Patients with HF receiving clopidogrel demonstrated reduced mortality (hazard ratio: 0.86; 95% confidence interval: 0.78 to 0.95) compared with patients with HF not receiving clopidogrel. No difference was observed among patients without HF (hazard ratio: 0.98; 95% confidence interval: 0.83 to 1.16).
Conclusions Clopidogrel was associated with reduced mortality in patients with HF who do not undergo PCI after their first-time AMI, whereas this association was not apparent in patients without HF. Further studies of the benefit of clopidogrel in patients with HF and AMI are warranted.
Introduction
Heart failure (HF) complicating acute myocardial infarction (AMI) is associated with a poor prognosis. Current European and American guidelines recommend dual antiplatelet treatment with aspirin and clopidogrel in all patients with AMI in the absence of an increased risk of bleeding. Three major randomized controlled studies have provided important knowledge regarding the benefit of clopidogrel in patients hospitalized with acute coronary syndrome. One trial investigated the effect of clopidogrel versus aspirin, another investigated the effect of clopidogrel versus placebo, and another showed an effect of clopidogrel versus placebo in addition to aspirin. A favorable effect of clopidogrel with respect to the composite end point of death, reinfarction, or stroke was found in all studies, and in the latter study, also a decreased risk of all-cause mortality was found. Patients with HF comprised a modest part of the study population in all 3 studies, and no subgroup analyses of patients with HF were performed. The clinical benefit of clopidogrel in AMI patients with HF is not clarified, which may cause uncertainty and may lead to differences in clinical practice among physicians treating this high-risk patient population. This notion is supported by studies evaluating the implementation of non–ST-segment elevation myocardial infarction (NSTEMI) guidelines, which have demonstrated low initiation rates of clopidogrel in patients not undergoing percutaneous coronary intervention (PCI) and even lower initiation rates of clopidogrel in patients with HF.
Patients with HF have an approximately 3% annual risk of atherothrombotic events, which may be because of the significantly increased platelet activity. Indeed, it has been demonstrated that the addition of clopidogrel to aspirin in patients with HF significantly inhibits the increased platelet activity. Whether clopidogrel provides additional survival benefit for AMI patients with concomitant HF compared with patients without HF is unknown. This uncertainty prompted us to conduct a nationwide study examining the effect of clopidogrel on mortality in a population of patients with and without HF discharged after their first-time AMI and not undergoing PCI.
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