primary outcome:
Primary prophylaxis for venous thromboembolism in patients undergoing cardiac or thoracic surgery
The main effectiveness outcome was symptomatic VTE (that is symptomatic DVT, symptomatic PE, or both), which is typically objectively verified by means of Doppler (compression) ultrasonography or ascending bilateral venography for (proximal and distal) DVT, and spiral computed tomography, ventilation/perfusion lung scan, pulmonary angiography, or autopsy for PE.The main safety outcome was major bleeding, typically defined as overt bleeding associated with a fall in haemoglobin of 2 g/dL or more, or leading to a transfusion of two or more units of packed red blood cells or whole blood, or bleeding that occurs in a critical site (intracranial, intraspinal, intraocular, pericardial, intra‐articular, intramuscular with compartment syndrome, retroperitoneal), or contributing to death.The effect of UFH versus LMWH on symptomatic VTE was evaluated in the small study of Beghi and colleagues (Beghi 1993), who reported no cases of VTE in either trial arm (Analysis 1.1). The effect of mechanical interventions on symptomatic VTE was evaluated in two studies, which reported a total number of 71 events in 2881 participants (Goldhaber 1995; Ramos 1996; Analysis 1.2; Analysis 1.3). Goldhaber 1995 observed one case of symptomatic VTE both in participants with IPC plus graded elastic compression stockings and in those with graded elastic compression stockings. In Ramos 1996, the combination of UFH with IPC was associated with a significant 61% reduction of symptomatic VTE compared to UFH alone (1.5% versus 4.0%; RR 0.39; 95% CI 0.23 to 0.64, P value = 0.0002, NNTB 40; 95% CI 26 to 83). In Mirhosseini 2013, there were no PEs in the UFH group nor in the UFH plus aspirin group (Analysis 1.4).Major bleeding events were only reported in the study Pfisterer 1989, where VKAs were associated with a significantly higher incidence of major bleeds relative to platelet inhibitors (11.3% versus 1.6%, RR 7.06; 95% CI 1.64 to 30.40, P value = 0.009, NNTH 11; 95% CI 6 to 27; Analysis 3.1).None of the studies showed any statistically significant difference between pharmacological thromboprophylaxis on any of the primary outcomes.Across the six studies reporting on symptomatic VTEs in 2890 participants undergoing thoracic surgery, 15 symptomatic VTEs occurred in total (Azorin 1997; Dahan 1990; Gallus 1973; Le Brigand 1981; Marchetti 1983; Rizzi 1987).Three studies evaluated the impact of heparin versus inactive control on symptomatic VTE (Gallus 1973; Le Brigand 1981; Marchetti 1983), but the risk ratio could not be estimated in two of these, because of zero event rates in both trial arms (Gallus 1973; Marchetti 1983; Analysis 2.1). The third study by Le Brigand 1981 could not detect a statistically significant difference in symptomatic VTE between UFH and inactive control treatment (0.7% versus 0%; RR 6.71; 95% CI 0.40 to 112.65). Three additional studies studied the effect of heparin versus active control on symptomatic VTE (Azorin 1997; Dahan 1990; Rizzi 1987; Analysis 2.2; Analysis 2.3; Analysis 2.4). In the small study by Rizzi 1987, there were two symptomatic VTEs in the UFH group and none with defibrotide, while no VTE was observed in either trial arm in the studies of Azorin 1997 and Dahan 1990.Major bleeding was reported in two studies (Azorin 1997; Dahan 1990), which found no difference between the experimental and control groups. In the study Azorin 1997, major bleeds occurred in 2.7% of participants receiving fixed‐dose LMWH compared to 8.1% in those on weight‐adjusted LMWH (RR 0.33; 95% CI 0.07 to 1.60). In Dahan 1990, these occurred in 6% in the UFH and in 4% in the LMWH groups (RR 1.50; 95% CI 0.26 to 8.60).