Aspirin + clopidogrel therapy: How does your care compare to the evidence?
Did you know that patients with drug-eluting stents should receive dual therapy for at least a year, and that dual therapy for stroke prevention may put patients at risk?
Dual therapy reduces future MI risk in ACS
The Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) trial in 2001 was one of the first combination trials published; it looked at combination antiplatelet therapy in ACS.4 CURE enrolled patients with NSTEMI and randomized them to receive aspirin plus clopidogrel or aspirin plus placebo for 3 to 12 months. Out of the total number of patients, 9.3% of the dual therapy group reached the endpoint of cardiovascular death, MI, or stroke, compared with 11.4% of the aspirin-only group (relative risk [RR]=0.80 for dual therapy). Further, the rate of each component of the composite outcome tended to be lower in the combination-therapy group.
Colored scanning electron micrograph of a blood clot.In particular, there was an RR of 0.77 for MI and, more specifically, an RR of 0.60 for Q-wave MI in the dual therapy group. There was, however, a 1.38 RR for major bleeding (defined as bleeding resulting in disability, vision loss, or transfusion of at least 2 units of blood) in the combination-therapy group vs the aspirin-only group (3.7% to 2.7%). However, neither rates of life-threatening bleeding nor hemorrhagic stroke were significantly different between the 2 groups.
Overall, the CURE trial showed that combining clopidogrel and aspirin was superior to aspirin alone in preventing repeat ischemic events in patients with NSTEMI for up to 12 months, and this conclusion was supported by a 2007 Cochrane review.5
The Clopidogrel as Adjunctive Reperfusion Therapy (CLARITY)-Thrombolysis in Myocardial Infarction (TIMI) trial studied the short-term (30 days) effect of clopidogrel combined with aspirin and fibrinolytic therapy in patients with ST elevation MI (STEMI).6 The study showed that the addition of clopidogrel improved the patency rate of infarctrelated arteries and reduced short-term ischemic complications.
There are, however, no trials looking at combination antiplatelet therapy for STEMI patients beyond 30 days.
Unstable angina/non-ST elevation MI/acute coronary syndrome
The American Heart Association/American College of Cardiology Guidelines recommend that patients with unstable angina (UA)/NSTEMI or ACS receive both clopidogrel 75 mg and aspirin (75 to 162 mg/day) for at least a month, and preferably, up to 12 months (TABLE).1,7
Prolonged therapy needed with drug-eluting stents
The Clopidogrel for the Reduction of Events During Observation (CREDO) trial, published in 2002, enrolled patients referred for percutaneous coronary intervention (PCI), about 89% of whom received at least 1 cardiac stent, and followed them for 12 months.8 All patients received aspirin and clopidogrel up to day 28. From day 29 to 1 year, half the patients continued dual antiplatelet therapy and the other half received aspirin plus placebo.
The primary outcome measure was death, MI, or stroke. The combination therapy group showed a relative risk reduction of 37.4% (RR=0.73) in the combined endpoint, compared with the aspirin/placebo group. CREDO did not show a significant difference in risk for major bleeding between the 2 groups.
Further data from the CURE trial was released in 2004. Researchers conducted a subgroup analysis to see if there was a benefit to combination antiplatelet therapy for patients with NSTEMI who underwent PCI or coronary artery bypass grafting (CABG). This further analysis revealed an RR of 0.72 for the outcome of CV death, MI, or stroke with the addition of long-term (3 to 12 months) clopidogrel to aspirin in the PCI group and an RR of 0.89 for the CABG group with combination therapy. These findings led researchers to conclude that combination antiplatelet therapy is beneficial for high-risk patients undergoing revascularization for NSTEMI regardless of the type of revascularization.9
A 2007 observational study conducted at the Duke Heart Center investigated the addition of long-term clopidogrel to aspirin for both drug-eluting stents (DES) and bare-metal stents (BMS).2 The study population was split into 4 groups:
- combination antiplatelet therapy in patients with DES,
- aspirin alone with DES,
- combination therapy with BMS, and
- aspirin alone with BMS.
Follow-up was conducted at 6, 12, and 24 months. For patients with DES, continuing clopidogrel with aspirin therapy was associated with a significant decrease in death or MI at 24 months (3.1% vs 7.2%, RR=0.43). For patients with BMS, researchers found no significant benefit for those who continued dual antiplatelet therapy longer than 6 months compared with aspirin alone.
The data from this study led the authors to speculate that drug-eluting stents may require protracted—and possibly indefinite—dual antiplatelet therapy with clopidogrel and aspirin. Additional research with a large clinical trial is necessary to assess the appropriate length of treatment with combination antiplatelet therapy after DES, as it may extend even longer than current recommendations suggest.
