Oral ximelagatran for secondary prophylaxis after myocardial infarction: the ESTEEM randomised controlled trial
Topic: Anticoagulation in acute coronary syndrome (direct thrombin inhibitors)
- Assess the effectiveness of ximelagatran and acetylsalicylic acid for prevention of death, non-fatal myocardial infarction, and severe recurrent ischaemia after a recent myocardial infarction.
- Prospective, multi-centered, randomized, placebo controlled
- Oral ximelagatran (24 mg, 36 mg, 48 mg, or 60 mg) twice daily, with aspirin (160 mg) daily.
- Placebo with aspirin (160 mg) daily.
- 1,883 patients
- Ischemic chest pain within 14 days (positive cardiac biomarkers and ischemic ECG changes)
- At least one of the following risk factors: >65 years of age, diabetes mellitus, prior MI, known CAD, CHF, LVEF <40%, or prior stroke
- PCI done in last 4 months
- Platelet count <100,000
- Need for treatment with other antiplatelet or oral anticoagulation
- Recent stroke
- Systolic blood pressure >180 mm Hg; diastolic blood pressure >100 mm Hg
- Renal dysfunction (CrCl <30 mL/min)
- Liver disease
- 6 months
- Composite clinical endpoint of death (all-cause mortality), non-fatal myocardial infarction, and severe recurrent ischemia.
- Composite clinical endpoints of cardiovascular death, myocardial infarction, ischaemic stroke, severe recurrent ischaemia, and death or myocardial infarction, and the safety and tolerability of the four doses of ximelagatran, compared with placebo, with special regard to bleeding and biochemical changes.
- Mean age 69 years, 68% men.
- Ximelagatran was started 6 to 12 hours after the end of unfractionated heparin or enoxaparin.
- Distribution of STEMI, NSTEMI and UA were roughly equal between groups (approximately 66%, 20%, 10%, respectively).
- Oral ximelagatran in combination with acetylsalicylic acid was more effective than acetylsalicylic acid alone (placebo) in reducing the risk for the composite endpoint of death, non-fatal myocardial infarction, and severe recurrent ischemia (p=0·0357).
- The efficacy did not differ between the individual ximelagatran doses.
- Effect was maintained at first month and 6 months of therapy (3.6% absolute and 24% relative reduction in risk over the 6-month treatment period).
- The frequency of major bleeding did not differ between the treatment groups, however cumulative risk of total bleeding was higher in those on ximelagatran than on those on placebo (hematuria and epistaxis were most common types of bleeding).
TAKE AWAY: Long-term treatment with oral direct thrombin inhibitor (ximelagatran), in combination with aspirin, reduces arterial thrombotic events.