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Long-term anticoagulant treatment after acute myocardial infarction. The Warfarin Re-Infarction Study
1Department of Cardiology, Ullevaal Hospital, Oslo, Norway.
Insights
Long-term warfarin treatment significantly reduced death, reinfarction, and stroke in heart attack survivors. This anticoagulant therapy is recommended after acute myocardial infarction, with a low incidence of serious bleeding.
Area of Science:
- Cardiology
- Thrombosis Research
- Pharmacology
Background:
- Elevated fibrinogen and clotting factor VII correlate with increased cardiovascular disease risk.
- Coronary thrombus formation is linked to acute Q-wave myocardial infarction.
- Antithrombotic agents can mitigate thrombosis and related events.
Purpose of the Study:
- To evaluate the efficacy of long-term warfarin therapy in reducing mortality, reinfarction, and thromboembolic events in survivors of acute myocardial infarction.
- To assess the safety profile of warfarin, specifically the incidence of serious bleeding.
Main Methods:
- The Warfarin Re-Infarction Study (WARIS) was a double-blind, placebo-controlled trial.
- 1214 patients (aged ≤75 years) surviving acute myocardial infarction were randomized.
- Patients were followed for a mean of 37 months, with intention-to-treat analysis.
Main Results:
- Warfarin therapy reduced all-cause mortality by 24% (P=0.026) and by 35% (P=0.005) when considering patients on treatment or within 28 days of discontinuation.
- Fatal and nonfatal reinfarctions decreased by 43% (P=0.0001).
- Cerebrovascular attacks were reduced by 61% (P=0.0003) in the warfarin group. Serious bleeding occurred in 0.6% per year of warfarin treatment.
Conclusions:
- Long-term anticoagulant therapy with warfarin is effective in reducing major adverse cardiovascular events after acute myocardial infarction.
- Warfarin demonstrates a favorable risk-benefit profile in this patient population.
- The findings support the recommendation of anticoagulant therapy post-myocardial infarction.
Abstract:
High levels of fibrinogen and clotting factor VII are associated with an increased risk for subsequent death and cardiovascular disease in apparently healthy individuals. Furthermore, pathoanatomic studies and coronary angiography have confirmed a relationship between coronary thrombus formation and acute Q-wave infarction. Effective antithrombotic agents may prevent or limit thrombus formation and events related to thrombosis. The Warfarin Re-Infarction Study (WARIS) studied the effect of warfarin in survivors of acute myocardial infarction. Patients aged 75 years or less were randomized in a double-blind, placebo-controlled study to test whether long-term treatment with warfarin reduces the risk of death, reinfarction, and thromboembolic morbidity. A total of 1918 patients were screened for participation; 1214 were recruited. The mean follow-up was 37 months. Analyzed on an intention-to-treat basis, 123 (20%) in the placebo group died, versus 94 (15%) in the warfarin group, a risk reduction of 24% (P = 0.026). Considering patients on treatment or within 28 days after discontinuing the test medication, 92 in the placebo group died, as compared with 60 of the warfarin-treated patients, a risk reduction of 35% (P = 0.005). Relapsing myocardial infarction (fatal and nonfatal) was reduced by 43% (P = 0.0001). The incidence of cerebrovascular attacks was lower in the warfarin group (16 patients) than the placebo group (41 patients), a highly significant reduction of 61% (P = 0.0003). Serious bleeding occurred in 11 patients taking warfarin, an incidence of 0.6% per year. In conclusion, long-term anticoagulant therapy may be recommended after acute myocardial infarction.