Effects of Long-Term, Moderate-Intensity Oral Anticoagulation in Addition to Aspirin in Unstable Angina - OASIS-2

Description:

In this trial, investigators sought to evaluate whether oral anticoagulant (AC) therapy given for five months was superior to standard (control) therapy in patients with unstable angina receiving aspirin

Hypothesis:

Is oral AC therapy given for five months superior to standard therapy in patients with unstable angina receiving aspirin?

Study Design

Study Design:

Patients Enrolled: 10,141

Drug/Procedures Used:

The Organization to Assess Strategies for Ischemic Syndromes-2 (OASIS-2) trial compared a three-day regimen of heparin versus hirudin in patients with unstable angina or non-ST-elevation myocardial infarction (MI). Of the 10,141 patients enrolled in this study, 3,712 already on aspirin were randomized 12 to 48 hours later to receive oral AC therapy (n=1,848) or standard therapy (n=1,864).

Principal Findings:

The primary endpoint (cardiovascular death, MI, or stroke) occurred in 140 patients (7.6%) receiving oral ACs compared with 155 patients (8.3%) on standard therapy (relative risk [RR] 0.90, 95% confidence interval [CI] 0.72-1.14; p=0.40). Secondary outcome rates (cardiovascular death, MI, or stroke) were 16.7% (n=308) versus 17.5% (n=327) (RR 0.95, 95% CI 0.81-1.11; p=0.53).

There were significant reductions in the risks of both the primary and secondary outcomes with oral AC in the "good-complier" countries (those with oral AC used ≥70% at 35 days), with little difference in the "poor-complier" countries for both endpoints. Overall, there was an excess of major bleeding (2.7% vs. 1.3%; p=0.004), which was larger in the good-complier countries (RR 2.71) compared with the poor-complier countries (RR 1.58). There were reductions in cardiac catheterization (RR 0.80; p=0.004) and coronary revascularization procedures (RR 0.82; p=0.06) in the good-complier countries, but not in the poor-complier countries.

Oral anticoagulation in addition to aspirin, resulted in a small, nonsignificant reduction in the risk of the primary and secondary endpoints that was more pronounced in the "good-complier" countries.

Interpretation:

This study demonstrated the modest potential benefit of adding anticoagulation to aspirin to improve outcomes in patients with unstable angina/non-ST elevation MI (albeit with increased risk of bleeding). The study highlights another important well-known issue with such therapy: patients' noncompliance and physicians' reluctance to expose their patients to long-term monitoring and risks of oral anticoagulation. Further studies are needed to help claify the risk-benefit ratio of combined antiplatelet and AC therapy.

References:

Effects of long-term, moderate-intensity oral anticoagulation in addition to aspirin in unstable angina. The Organization to Assess Strategies for Ischemic Syndromes (OASIS) Investigators. J Am Coll Cardiol 2001;37:475-84.

Clinical Topics: Anticoagulation Management

Keywords: Risk, Myocardial Infarction, Stroke, Platelet Aggregation Inhibitors, Research Personnel, Cardiac Catheterization, Heparin, Confidence Intervals, Hirudins


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