CLINICAL EFFECTS OF ANTICOAGULANT-THERAPY IN SUSPECTED ACUTE MYOCARDIAL-INFARCTION - SYSTEMATIC OVERVIEW OF RANDOMIZED TRIALS

Objectives-Most randomised trials of anticoagulant therapy for suspect ed acute myocardial infarction have been small and, in some, aspirin a nd fibrinolytic therapy were not used routinely. A systematic overview (meta-analysis) of their results is needed, in particular to assess t he clinical effects of adding heparin to aspirin. Design-Computer aide d searches, scrutiny of reference lists, and inquiry of investigators and companies were used to identify potentially eligible studies. On c entral review, 26 studies were found to involve unconfounded randomise d comparisons of anticoagulant therapy versus control in suspected acu te myocardial infarction. Additional information on study design and o utcome was sought by correspondence with study investigators. Subjects -Patients with suspected acute myocardial infarction. Interventions-No routine aspirin was used among about 5000 patients in 21 trials (incl uding half of one small trial) that assessed heparin alone or heparin plus oral anticoagulants, and aspirin was used routinely among 68 000 patients in six trials (including the other half of one small trial) t hat assessed the addition of intravenous or high dose subcutaneous hep arin. Main outcome measurements-Death, reinfarction, stroke, pulmonary embolism, and major bleeds (average follow up of about 10 days). Resu lts-In the absence of aspirin, anticoagulant therapy reduced mortality by 25% (SD 8%; 95% confidence interval 10% to 38%; 2P = 0.002), repre senting 35 (11) fewer deaths per 1000. There were also 10 (4) fewer st rokes per 1000 (2P = 0.01), 19 (5) fewer pulmonary emboli per 1000 (2P <0.001), and non-significantly fewer reinfarctions, with about 13 (5) extra major bleeds per 1000 (2P = 0.01). Similar sized effects were se en with the different anticoagulant regimens studied. in the presence of aspirin, however, heparin reduced mortality by only 6% (SD 3%; 0% t o 10%; 2P = 0.03), representing just 5 (2) fewer deaths per 1000. Ther e were 3 (1.3) fewer reinfarctions per 1000 (2P = 0.04) and 1 (0.5) fe wer pulmonary emboli per 1000 (2P = 0.01), but there was a small non-s ignificant excess of stroke and a definite excess of 3 (1) major bleed s per 1000 (2P<0.0001). Conclusions-The clinical evidence from randomi sed trials does not justify the routine addition of either intravenous or subcutaneous heparin to aspirin in the treatment of acute myocardi al infarction (irrespective of whether any type of fibrinolytic therap y is used).