BMJ 1994;308:235-246 (22 January)

Papers

Collaborative overview of randomised trials of antiplatelet therapy - III: Reduction in venous thrombosis and pulmonary embolism by antiplatelet prophylaxis among surgical and medical patients

APT Statistical Secretariat, ICRF/BHF/MRC Clinical Trial Service Unit, Nuffield Department of Clinical Medicine, Radcliffe Infirmary, Oxford OX2 6HE, or APT Clinical Secretariat, Department of Clinical Neurosciences, Western General Hospital, Edinburgh EH4 2XU.

Abstract

Objective : To determine the efficacy of antiplatelet therapy as prophylaxis against deep venous thrombosis or pulmonary embolism in surgical and high risk medical patients.
Design : Overviews of all randomised trials of antiplatelet therapy that could have been available by March 1990 and in which deep venous thrombosis was assessed systematically.
Setting : 53 trials (total 8400 patients) of an average of two weeks of antiplatelet therapy versus control in general or orthopaedic surgery; nine trials (600 patients) of antiplatelet therapy versus control in other types of immobility; 18 trials (1000 patients) of one antiplatelet regimen versus another.
Results : Overall, a few weeks of antiplatelet therapy produced a highly significant (2P < 0.00001) reduction in deep venous thrombosis. 25% of patients allocated antiplatelet therapy versus 34% of appropriately adjusted controls had deep venous thrombosis detected by systematic fibrinogen scanning or venography, representing prevention in about 90 patients per 1000 allocated antiplatelet therapy. There was an even greater proportional reduction in pulmonary embolism: such emboli were detected among 47 (1.0%) antiplatelet allocated patients versus an adjusted control total of 129 (2.7%), representing prevention among about 17 patients per 1000 treated (2P < 0.00001). In analyses confined to surgical trials, the proportional reductions were similar and separately significant for nonfatal pulmonary embolism (0.7% antiplatelet therapy upsilion 1.8% control; 2P < 0.00001) and for deaths attributed to pulmonary embolism (0.2% upsilion 0.9%; 2P = 0.0001). There was a slight but non - significant excess of deaths from other causes (1.0% upsilion 0.7%), which made the difference in total mortality non-significant, though still favourable (1.2% upsilion 1.5%). Information on adding antiplatelet therapy to heparin was limited but, at least for pulmonary embolism, suggested more protection from the combination than from heparin alone.
Conclusion : It had previously been supposed that antiplatelet therapy did not influence venous thromboembolism, and many surgeons and physicians do not use it routinely for thromboprophylaxis, even for patients who are at substantial risk of deep venous thrombosis or pulmonary embolism. These results indicate that antiplatelet therapy - either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis (such as subcutaneous heparin) - should be considered.

Clinical implications

  • Clinical implications

  • Prolonged general and orthopaedic surgery (as well as other periods of limited mobility) are associated with increased risks of venous thromboembolism

  • A few weeks of antiplatelet therapy roughly halved the risk both of deep venous thrombosis and of pulmonary embolism in a wide range of surgical patients (and the limited evidence in immobilised medical patients was also encouraging)

  • The absolute benefits appeared to be greater for those at higher risk (for example, those undergoing orthopaedic surgery)

  • Antiplatelet therapy can be conveniently continued after discharge from hospital (in contrast with many other forms of prophylaxis) for as long as the risk of thromboembolism is still substantial

  • Antiplatelet therapy - either alone or, for greater effect, in addition to other proved forms of thromboprophylaxis - should be considered for patients at high risk of thromboembolism


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Relevant Article

Antiplatelet prophylaxis Combination treatment may cause bleeding
V Seagroatt, C Bulstrode, D W Murray, P H Wittmann, F W Wittmann, R Collins, C Baigent, R Peto, B Farrell, and J L Sullivan
BMJ 1994 308: 651-652. [Extract] [Full Text]

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