Eleven RCTs (n=3,556) met the predefined inclusion criteria. A further 4 RCTs (n=2,026) were identified that did not have a period of follow-up after cessation of treatment. These were not eligible for the primary analysis, although they were included in the secondary analysis comparing the risk recurrence with lifelong and fixed duration therapy.
Both quality scales rated the quality of the included studies as generally good.
Recurrent VTE.
The primary analysis of interest in the review (11 studies) found that longer durations of anticoagulation therapy were associated with a decrease in the risk of recurrent VTE events in comparison with short-term therapy; the IRR was 0.69 (95% CI: 0.53, 0.91, P=0.009) and the rate difference -0.20 (95% CI: -0.039, -0.001, P=0.04). No evidence of significant statistical heterogeneity was identified (P=0.33 and P=0.13, respectively).
The secondary analysis (12 studies) found that lifelong therapy was associated with a decrease in the risk of recurrent VTE in comparison with fixed duration therapy; the IRR was 0.21 (95% CI: 0.14, 0.31, P<0.001) and the rate difference -0.106 (95% CI: -0.145, -0.067, P<0.001). There was evidence of significant statistical heterogeneity in the pooled rate difference (P<0.001), but not in the pooled IRR (P=0.13).
The meta-regression found no relationship between outcome and level of anticoagulation, percentage of patients with risk factors or percentage of those with idiopathic VTE, or study quality. There was no evidence of publication bias using the Begg rank correlation method or meta-regression. However, the Egger weighted regression method showed evidence of some publication bias.
Death from recurrence of pulmonary embolism (10 studies).
There was a slight reduction in the risk of death from recurrence of pulmonary embolism in those receiving long-term therapy compared with short-term therapy, but this was not statistically significant (IRR 0.92, 95% CI: 0.43, 1.94, P=0.82). No evidence of significant statistical heterogeneity was identified.
Major bleeding while receiving treatment (7 studies). There was an increased risk of major bleeding in those receiving long-term therapy compared with short-term therapy, but this was not statistically significant (IRR 1.8, 95% CI: 0.72, 4.51, P=0.21). No evidence of significant statistical heterogeneity was identified.