Clinical Pearls & Morning Reports
Despite the use of effective secondary prevention strategies, 5 to 10% of patients with cardiovascular disease have recurrent events each year. Eikelboom et al. designed the Cardiovascular Outcomes for People Using Anticoagulation Strategies (COMPASS) trial to test the hypothesis that rivaroxaban in combination with aspirin or given alone is more effective than aspirin alone in preventing recurrent cardiovascular events, with acceptable safety, in patients with stable atherosclerotic vascular disease. Read the latest NEJM Original Article.
Q: How useful is aspirin for secondary prevention in patients with cardiovascular disease?
A: When used for secondary prevention, aspirin results in a 19% lower risk of major adverse cardiovascular events and a 9% lower risk of cardiovascular death than placebo.
Q: What are some of the alternatives to aspirin that have been tested for long-term cardiovascular prevention?
A: Various antithrombotic regimens have been tested as alternatives to aspirin for long-term cardiovascular prevention. Trials of vitamin K antagonists involving patients with stable cardiovascular disease showed a reduction in the risk of subsequent cardiovascular events, but there was no benefit in patients with peripheral arterial disease, and there was a significant increase in bleeding, including intracranial bleeding. Among patients with stable cardiovascular disease, those who received clopidogrel had a lower risk of major adverse cardiovascular events than those who received aspirin, but there was no significant difference in the risk of cardiovascular death or death from any cause. Among patients with symptomatic stable cardiovascular disease or multiple risk factors, the combination of clopidogrel and aspirin did not result in a significantly lower rate of major adverse cardiovascular events or death from any cause than aspirin alone.
A: In the trial by Eikelboom et al., among patients with stable atherosclerotic vascular disease, a high proportion of whom were receiving proven secondary prevention therapies, the rate of the primary outcome (a composite of cardiovascular death, stroke, or myocardial infarction) was lower by 24% with rivaroxaban (2.5 mg twice daily) plus aspirin (100 mg once daily) than with aspirin (100 mg once daily) alone (4.1% vs. 5.4%). The secondary composite outcome of ischemic stroke, myocardial infarction, acute limb ischemia, or death from coronary heart disease occurred in fewer patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (329 patients [3.6%] vs. 450 patients [4.9%]; hazard ratio, 0.72; 95% CI, 0.63 to 0.83; P<0.001). The comparison of rivaroxaban (5 mg twice daily) alone with aspirin alone did not show a significant difference in the primary outcome.
A: In the trial by Eikelboom et al., major bleeding events occurred in more patients in the rivaroxaban-plus-aspirin group than in the aspirin-alone group (288 patients [3.1%] vs. 170 patients [1.9%]; hazard ratio, 1.70; 95% CI, 1.40 to 2.05; P<0.001), mainly owing to a difference in bleeding that led to presentation to an acute care facility or hospitalization. Most of the excess major bleeding was into the gastrointestinal tract, with no significant between-group difference in the rate of fatal bleeding, intracranial bleeding, or symptomatic bleeding into a critical organ. The effects of rivaroxaban plus aspirin as compared with aspirin alone on the primary outcome and on major bleeding were consistent among subgroups that were defined according to age, sex, geographic region, race or ethnic group, body weight, renal function, and history of cardiovascular risk factors (tobacco use, hypertension, diabetes, or dyslipidemia).