Are the risk factors listed in warfarin prescribing information associated with anticoagulation-related bleeding? A systematic literature review.

Warfarin significantly reduces thromboembolic risk, but perceptions of associated bleeding risk limit its use. The evidence supporting the association between bleeding and individual patient risks factors is unclear. This systematic review aims to determine the strength of evidence supporting an accentuated bleeding risk when patients with risk factors listed in the warfarin prescribing information are prescribed the drug. A systematic literature search of MEDLINE and Cochrane CENTRAL was conducted to identify studies reporting multivariate relationships between prespecified covariates and the risk of bleeding in patients receiving warfarin. The prespecified covariates were identified based on patient characteristics for bleeding listed in the warfarin package insert. Each covariate was evaluated for its association with specific types of bleeding. The quality of individual evaluations was rated as 'good', 'fair' or 'poor' using methods consistent with those recommended by the Agency for Healthcare Research and Quality (AHRQ). Overall strength of evidence was determined using the Grading of Recommendations Assessment, Development (GRADE) criteria and categorised as 'insufficient', 'very low', 'low', 'moderate' or 'high'. Thirty-four studies, reporting 134 multivariate evaluations of the association between a covariate and bleeding risk were identified. The majority of evaluations had a low strength of evidence for the association between covariates and bleeding and none had a high strength of evidence. Malignancy and renal insufficiency were the only two covariates that had a moderate strength of evidence for their association with major and minor bleeding respectively. The associations between covariates listed in the warfarin prescribing information and increased bleeding risk are not well supported by the medical literature.

Statin use and the prevention of venous thromboembolism: a meta-analysis.

AIMS: Statins are thought to have antithrombotic properties and may attenuate patients' odds of developing venous thromboembolism (VTE), but clinical studies have yielded variable estimates of this effect. The aim was to conduct a meta-analysis to evaluate the effect of statin use on development of VTE. METHODS: Randomised controlled trials (RCTs) and observational studies evaluating the effects of statins on the incidence of VTE were selected from MEDLINE (1996 to August 2009), Cochrane CENTRAL (second quarter, 2009), Cochrane Database of Systematic Reviews (second quarter, 2009) and a manual review of references. While no further restrictions were placed on RCTs, observational studies were only included if they reported adjusted effect sizes using appropriate methods. Development of deep vein thrombosis (DVT), pulmonary embolism (PE) and any VTE from RCTs and observational studies were pooled using traditional meta analytic techniques with a random-effects model. RESULTS: Ten studies were identified and eligible for meta-analysis. Upon meta-analysis, statin use was associated with a statistically significant reduction in the odds of developing VTE (AOR 0.68, 95% CI 0.54-0.86), DVT (AOR 0.59, 95% CI 0.43-0.82) and PE (AOR 0.70, 95% CI 0.53-0.94). DISCUSSION: Statin use is associated with significantly reduced odds of developing VTE, DVT or PE by 32%, 41% and 30% respectively. Our meta-analysis included one RCT, JUPITER, which alone provided statistically significant reduction in the odds of developing VTE and DVT (43% and 55% respectively), and a nonsignificant reduction on PE. CONCLUSION: Currently available evidence suggests that statins can reduce patients' odds of developing VTE.