JACC in a Flash | Is Clopidogrel Effective for Conservatively-Managed NSTEMI and UA Patients?
For patients with unstable angina (UA) or non-ST-segment elevation myocardial infarction (NSTEMI) who do not undergo revascularization, medical management typically consists of dual antiplatelet therapy with clopidogrel to prevent future ischemic events. However, these recommendations are based on findings from the CURE trial, which was conducted more than a decade ago in a largely non-US population. Though clopidogrel led to reductions in MI and mortality in this highly-selective clinical trial population, the effectiveness of clopidogrel in a real-world, community-based cohort of patients managed medically after discharge for UA or NSTEMI remains unclear.
To answer some of these questions, Matthew D. Solomon, MD, PhD, and colleagues conducted a retrospective cohort study of patients in the Kaiser Permanente system who presented with UA/NSTEMI; over 2 years of follow-up, the investigators measured the association between clopidogrel use and a composite endpoint of death or MI requiring hospitalization, as well as those outcomes individually. Of the 16,365 patients with UA (35%) or NSTEMI (65%), 36% were prescribed clopidogrel within 7 days of discharge, and those who did not fill their prescription within 7 days had a low rate of subsequent initiation of clopidogrel. More than one-third of patients who did initiate clopidogrel more than 7 days after discharge did so after a subsequent percutaneous coronary intervention (PCI; 38% or 332 of 859), most of which occurred well after discharge. Patients who used clopidogrel were younger and more likely to be male and to smoke, but were otherwise healthier with fewer comorbidities.
Ultimately, the reductions in composite endpoint at 2 years replicated the results from the landmark CURE trial in a real-world cohort—both in the overall population and in the propensity score-matched cohort (n = 8,562). In the latter group, however, while the mortality rate was significantly lower for clopidogrel users (8.3% vs. 13.0%; p < 0.01), the rate of acute MI was not (6.7% vs. 7.2%; p = 0.30).
Interestingly, there was evidence of treatment effect modification by clinical presentation (NSTEMI vs. UA) and a history of smoking but not by a history of diabetes. Patients who presented with NSTEMI had a stronger association of clopidogrel use with the various endpoints (TABLE). The investigators suggest that this relationship was due to differing factors between NSTEMI and UA that may influence the risk of MI or death; for instance, long-term antiplatelet therapy may be more effective in patients with more severe ischemia that ultimately leads to infarction, as occurs in NSTEMI but not UA.
According to an accompanying editorial by E. Magnus Ohman, MD, and Ralf E. Harskamp, MD, one of the most intriguing findings of the study by Dr. Solomon and colleagues was the strong association of clopidogrel use with outcomes among older patients (HR = 0.70 vs. 0.88; pint = 0.04)—a result that was not seen in the CURE trial or recent trials with either prasugrel or ticagelor—which suggests that "there may be substantial benefit of treating the elderly with DAPT." Solomon et al. also noted the importance of these findings, especially given the concern of risk of bleeding from dual antiplatelet therapy that can often tilt the perceived risk-benefit ratio against aggressive treatment in older populations. "In a 'real-world' setting the continued use of clopidogrel for several months after hospital discharge is of clear benefit to patients with NSTEACS, particularly in those with NSTEMI and the elderly," Drs. Ohman and Harskamp added. "We hope that this new body of evidence will sway those who continue to withhold clopidogrel to consider further implementation of clopidogrel use into their practice to help improve outcomes in these high risk patients with ACS who do not undergo revascularization procedures."
Ohman EM, Harskamp RE. J Am Coll Cardiol. 2014;63:2249-57.
Solomon MD, Go AS, Shilane D, et al. J Am Coll Cardiol. 2014;63:2258-60.
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