Platelet-Active Drugs: Effectiveness and Side Effects
The Pulmonary Embolism Prevention trial has established that aspirin is effective in preventing venous thromboembolism after surgery for hip fracture. This was a double-blind multicenter study of 13,356 patients undergoing surgery for hip fracture and of an additional 4,088 patients undergoing elective hip or knee arthroplasty. Patients were assigned to receive aspirin, 160 mg, or placebo, once daily for 5 weeks, with the first dose starting before surgery. Other forms of prophylaxis were allowed, and either heparin or low-molecular-weight heparin was used in about 40% of the patients. Among the 13,356 patients with hip fracture, aspirin produced a 36% reduction in symptomatic deep venous thrombosis or pulmonary embolism (PE) [absolute risk reduction, 0.9%; p = 0.0003]. A similar RR reduction in patients who were assigned to received aspirin was observed in patients who also received heparin. 
This important study, therefore, clearly shows that therapy with aspirin reduces the incidence of fatal PE and symptomatic nonfatal deep venous thrombosis or PE in patients with hip fracture. The results of the Pulmonary Embolism Prevention trial are consistent with the metaanalysis performed by the Antiplatelet Trialists’ Collabo-ration and supercede the findings in most of the previous trials. However, smaller studies using mandatory venography at or close to hospital discharge indicate that aspirin therapy is not as effective as other forms of prophylaxis. Thus, the overall event rate was high with aspirin in the studies that used mandatory venography, and in indirect comparisons of studies in elective hip surgery Mohr and associates reported that aspirin use was associated with a pooled incidence of 47% for venous thrombosis. Similar conclusions were reached in the analysis by Gallus and associates. The weakness of these two analyses is that they included only a relatively small number of patients who were treated with aspirin, and the comparisons with other forms of prophylaxis were indirect. However, the indirect comparisons are supported by the results of three randomized studies in patients undergoing major orthopedic surgery comparing therapy with aspirin with either warfarin or a low-molecular-weight hepa-rin. In all three studies, the incidence of venous thrombosis was significantly higher in the aspirin group.
Рlacental insufficiency
The pathogenesis of preeclampsia and fetal growth retardation is related to reduced placental blood flow, which is believed to be caused by constriction and/or thrombosis of small placental arteries. The initial reports that low-dose aspirin therapy reduces the risk of severe low birth weight among newborns and the risk of cesarean section in mothers with pregnancy-induced hy-pertension led to the widespread use of prophylactic aspirin therapy to prevent preeclampsia. Subsequently, several larger trials reported no beneficial effects of aspirin.
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