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Reference: JAMA 2013;310(23):2510-2522, (level 2 [mid-level] evidence)
As the use of drug-eluting stents in percutaneous coronary intervention (PCI) has become more common, physicians have grown more accustomed to seeing antiplatelet regimens on their patients medication lists. Despite recommendations for limits on the duration of antiplatelet therapy, patients may continue to be on these potentially harmful medications long after they are indicated. Multiple, high-quality studies have looked at various antiplatelet regimens and durations but none so far have looked specifically at 3 versus 12 month courses of dual antiplatelet therapy in second generation stents, specifically zotarolimus-eluting. As drug-eluting stents become the standard over bare metal stents (due to their reduction in intra-stent thrombosis), physicians will have to be aware of what the optimal anti-platelet regimen is in order to balance the risks of intra-stent thrombosis with the harms of serious bleeding.
The OPTIMIZE trial is a randomized, open label, non-inferiority study from Brazil that looked at 3,119 patients. Criteria for participation in the study included having low-risk acute coronary syndrome (ACS) or symptoms of stable angina and proceeding with PCI with zotarolimus-eluting stents. All patients were prescribed aspirin (100-200mg daily) with the addition of clopidogrel (75mg daily) for either 3 months or 12 months. The primary end point was net adverse clinical and cerebral events (NACCE), which consisted of all-cause death, myocardial infarction (MI), stroke, or major bleeding. A non-inferiority margin of 2.7% was selected at a presumed 12-month NACCE rate of 9% based on previous data. Secondary outcomes were major adverse cardiac events (MACE), which consisted of all-cause death, MI, emergent coronary artery bypass graft surgery, or target lesion revascularization. Bleeding events and stent thrombosis were also evaluated. Regarding attrition, 2.4% of the patients either refused or were lost to follow-up. At the 1-year clinical follow-up, the rates of aspirin and clopidogrel use were 98.9% and 6.2% respectively for the 3-month group, and 98.8% and 97.9% in the 12-month group.
The primary outcome, NACCE, was found to have a risk difference of 0.17 between the 3-month group and 12-month group with the upper bound of the confidence interval (CI) being less than 2.7, thus indicating non-inferiority. Individual outcomes consisting of all-cause death, MI, and stroke also showed non-inferiority. Major bleeding event rates from day 90 to 360 were 0.2% for the 3-month group and 0.4% for the 12-month group (hazard ratio [HR], 0.43 [95% CI, 0.16-1.11]). The rates of stent thrombosis were 0.3% and 0.1%, respectively (HR, 3.97 [95% CI, 0.44-35.49]). Finally, there was no statistically significant difference between groups with regards to all bleeding events. Possible shortcomings of the study included a lower than expected event rate compared to previous studies, a low-risk ACS population as ST-segment elevation MI was excluded, and relatively large confidence intervals.
This randomized trial adds to the growing body of evidence helping to guide the safe and effective use of anti-platelet medications in patients with drug-eluting stents. Specifically, by showing that 3 months of dual anti-platelet therapy was noninferior to 12 months of therapy, physicians can now consider discontinuing clopidogrel after 3 months of treatment in patients with Zotarolimus-eluting stents.
For more information, see Antiplatelet and anticoagulant drugs for coronary artery disease in DynaMed.