Current issues of ACP Journal Club are published in Annals of Internal Medicine


Therapeutics

Long-term anticoagulation reduced cerebrovascular events and recurrent myocardial infarction

ACP J Club. 1994 July-Aug;121:7. doi:10.7326/ACPJC-1994-121-1-007


Source Citation

Anticoagulants in the Secondary Prevention of Events in Coronary Thrombosis (ASPECT)Research Group. Effect of long-term oral anticoagulant treatment on mortality and cardiovascular morbidity after myocardial infarction. Lancet. 1994 Feb 26;343:499-503.


Abstract

Objective

To evaluate the effectiveness of long-term oral anticoagulant treatment in reducing mortality, recurrent myocardial infarction (MI), and cerebrovascular events among patients discharged from the hospital after an acute MI.

Design

Randomized, double-blind, placebo-controlled trial with a mean follow-up of 37 months.

Setting

60 hospitals in the Netherlands.

Patients

3404 patients (mean age 61 y, 80% men) discharged from the hospital after an acute MI. Exclusion criteria were an indication for oral anticoagulant treatment, anticoagulant therapy within the past 6 months, increased bleeding tendency, anticipated coronary revascularization procedure, malignant disease with poor prognosis, mental disorder, pregnancy, or oral anticoagulant treatment of other household members. No patient was lost to follow-up.

Intervention

1700 patients were allocated to receive nicoumalone or phenprocoumon within 6 weeks of hospital discharge. The target prothrombin time was 2.8 to 4.8 (international normalized ratio [INR]). 1704 patients were allocated to receive placebo. Patients were not treated with antiplatelet agents.

Main outcome measures

Death, recurrent MI, cerebrovascular events, and major bleeding.

Main results

The groups did not differ for mortality: 170 patients (10%) in the anticoagulation group died compared with 189 patients (11%) in the placebo group (Table). When compared with placebo, anticoagulant treatment led to reductions in recurrent MI and cerebrovascular events (Table). Event-free survival was higher in the anticoagulation group (85% vs 76%, P < 0.001). Major bleeding complications occurred in 73 patients (4%) receiving anticoagulants and in 19 patients (1%) receiving placebo (Table).

Conclusion

Long-term oral anticoagulant treatment after acute myocardial infarction reduced the risk for recurrent myocardial infarction and cerebrovascular events in patients not receiving antiplatelet therapy.

Sources of funding: Praeventiefonds, Netherlands and the Netherlands Thrombosis Foundation.

For article reprint: Dr. J.J. Jonker, Rotterdam Medical Research Foundation (ROMERES), Mathenesseriaan 247, 3021 HC Rotterdam, the Netherlands. FAX 31-10-42-54852.


Table. Long-term anticoagulation vs placebo after myocardial infarction (MI) for patients who were not receiving antiplatelet therapy

Outcomes at mean follow-up of 37 mo Anticoagulation Placebo RRR (95% CI) NNT (CI)
Death 10.0% 11.1% 10.5% (-9 to 26) Not significant
Recurrent MI 6.7% 14.2% 53% (42 to 62) 13 (10 to 18)
Cerebrovascular events 2.0% 3.6% 45% (18 to 64) 61 (36 to 182)
RRI NNH
Major bleeding 4.5% 1.1% 283% (134 to 509) 32 (23 to 47)

*Abbreviations defined in Glossary; RRR, RRI, NNT, NNH, and CI calculated from data in article.


Commentary

The study by the ASPECT Research Group confirms evidence from an earlier trial that long-term oral anticoagulation after an acute MI reduces the risk for reinfarction or stroke (1). In both studies, all-cause mortality was lower among patients receiving anticoagulants, but this did not reach statistical significance in the ASPECT trial, perhaps because patients at lower risk were randomized and some patients may have started anticoagulants late. The protection conferred by oral anticoagulation is similar to that provided by aspirin treatment (2), which is now widely used for secondary prevention. Because no published study has directly compared aspirin and warfarin after MI, their relative effectiveness, risks, and utilities are not clear. It is difficult, however, to improve on the convenience, safety, and low cost of 325 mg/d of aspirin.

ASPECT confirmed the expected excess of major hemorrhage among patients receiving anticoagulants with high-target INRs. This occurred despite well-organized monitoring of therapy by specialized regional centers. It is also clear from ASPECT that anticoagulation placed a heavy burden on patients and their physicians because 46% of surviving patients discontinued treatment within 3 years.

Aspirin should retain its primary role in post-MI prevention, although oral anticoagulation is preferable in selected situations, such as mural thrombus or very poor left ventricular function (3).

Kent L. Woods, MD
University of LeicesterLeicester, England, United Kingdom


References

1. Smith P, Arnesen H, Holme I. The effect of warfarin on mortality and reinfarction after myocardial infarction. N Engl J Med. 1990;323:147-52.

2. Antiplatelet Trialists' Collaboration. Collaborative overview of randomised trials of antiplatelet therapy--I: Prevention of death, myocardial infarction, and stroke by prolonged antiplatelet therapy in various categories of patients. Antiplatelet Trialists' Collaboration. BMJ. 1994;308:81-106.

3. Cairns JA. Oral anticoagulants or aspirin after myocardial infarction? Lancet. 1994;343:497-8.


Author's Response

The effects of oral anticoagulant treatment on nonfatal MI, nonfatal stroke, and vascular events are of a magnitude that seems to be better than was reported in the Antiplatelet Trialists' Collaboration meta-analysis (2). The ASPECT-II trial is designed to directly compare coumarin with aspirin and with a third arm in which low doses of coumarin and aspirin are combined.