Safety of warfarin in "high-risk" populations: A meta-analysis of randomized and controlled trials.

INTRODUCTION: Few data are available about safety of vitamin K antagonists (VKAs) in patients with clinical/demographic characteristics predisposing to an increased risk of bleeding. We performed a meta-analysis to evaluate the safety of VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE) in the following subgroups of "high-risk" patients: elderly patients, patients with low body weight and patients with impaired renal function.

MATERIALS AND METHODS: Major electronic databases were systematically searched to identify randomized controlled trials (RCTs) addressing this issue. Pooled Risk Ratios (RR) and 95% Confidence Intervals (CI) were calculated for each outcome using a random effects model.

RESULTS: Eleven RCTs for a total of 41,015 patients treated with VKAs (25,901 with AF and 15,114 with VTE) were included. We found a significant association between age>75years and bleeding in patients receiving VKAs (RR: 1.62, 95%CI: 1.28-2.05; P<0.0001). Moreover, the prevalence of bleeding events under VKAs was significantly higher in patients with low body weight (RR: 1.20, 95%CI: 1.03-1.40; P=0.02) and in those with impaired renal function (RR: 1.59, 95%CI: 1.30-1.94; P<0.00001). Results were confirmed when separately analyzing data on AF and VTE. Regression models showed that treatment duration did not impact on the differences found in the safety profile of VKAs in different settings analyzed.

CONCLUSIONS: Results of our meta-analysis suggest an increased risk of bleeding complications in "high-risk" patients. Although all results are significant, other studies focused on this issue are warranted to further validate these results.