A systematic review of Cochrane anticoagulation reviews.

CONTEXT: I coauthored a published review of anticoagulation for venous thromboembolism in the Cochrane Database of Systematic Reviews and published a review on the same topic in MedGenMed (now the Medscape Journal of Medicine). In contrast to the article in Medscape, the discussion and conclusions in the Cochrane review were altered appreciably during the review process. Consequently, I decided to critique all anticoagulation drug-related reviews and protocols in the Cochrane database with feedback letters concerning any issues of potential controversy. EVIDENCE ACQUISITION: Using key words in the search engine of the Cochrane Reviews, I located reviews and protocols involving anticoagulant drugs. I critiqued each anticoagulation review and protocol and sent a total of 57 feedback letters to Cochrane concerning each publication to elicit a response/rebuttal from the authors. EVIDENCE SYNTHESIS: Cochrane anticoagulation review editors acknowledged receipt of all letters. As of 12 months after receipt of my last letter, the Cochrane authors have replied to 13 of the 57 and agreed with many of my points. Two protocols were withdrawn after my feedback letters were acknowledged. The 58 Cochrane anticoagulation drug reviews, including mine, contained 9 categories of methodological errors (207 total instances) and 4 types of biases (18 total instances). This review of those Cochrane reviews suggests that the effectiveness of anticoagulants for 30 medical indications is questionable. CONCLUSIONS: The efficacy of anticoagulants for treatment and prophylaxis for 30 current medical indications should be reconsidered by the scientific community and medical regulatory agencies. At least 50,000 people per year worldwide have fatal bleeding due to anticoagulant treatment or prophylaxis for these indications.

Clinical evidence for rebound hypercoagulability after discontinuing oral anticoagulants for venous thromboembolism.

CONTEXT: In vitro studies and anecdotal clinical reports have suggested that clinically significant rebound hypercoagulability may occur after discontinuation of oral anticoagulants (OACs), such as vitamin K antagonists and ximelagatran, for venous thromboembolism (VTE). OBJECTIVE: Assess the extent to which rebound hypercoagulability-related VTE recurrences occur in the 2 months following discontinuation of OACs. DATA SOURCES: Published, randomized controlled trials (RCTs) of OAC treatment of VTE. STUDY SELECTION: RCTs of varying durations of OAC treatment of VTE that include VTE recurrence (or extension) data for more than 2 months after discontinuation of anticoagulants. DATA EXTRACTION: Rates of VTE recurrences (1) while taking OACs, (2) within 2 months of discontinuing OACs, and (3) from > 2 months until the end of the study were extracted along with major bleeding episodes while on OACs. The rate of VTE recurrences possibly attributable to rebound hypercoagulability was estimated by subtracting the VTE recurrence rate after the 2-month rebound period from the rate during the rebound period. DATA SYNTHESIS: In 20 trials (n = 5822), VTE recurrences were 2.62 times as frequent in the 2 months following discontinuation of OACs as subsequently (1.57% VTE recurrences per month falling to 0.56% per month, odds ratio = 2.62, 95% confidence interval: 2.19-3.14), corresponding to 2.02% of patients with rebound hypercoagulability-related VTE recurrences (1.57% per month - 0.56% per month x 2 months = 2.02%). In the 11 trials with evaluable data from the shorter- and longer-duration OAC arms, total adverse events (VTE recurrences plus major bleeding) over the entire durations of the trials were not significantly different. CONCLUSIONS: Rebound hypercoagulability accounts for about 2% of patients having recurrent VTE in the first 2 months after discontinuing OACs. RCTs evaluating the efficacy of OACs should include data for at least 2 months following OAC treatment. Increasing the duration of OAC treatment does not reduce the overall adverse events.

Relation of omega-3 Fatty Acid intake to other dietary factors known to reduce coronary heart disease risk.

Data supporting the inverse correlation of fish or long-chain omega-3 fatty acid (FA) (eicosapentaenoic acid plus docosahexaenoic acid) supplement consumption and coronary heart disease are inconclusive and may be confounded by other dietary and lifestyle factors. Using the Diabetic Control and Complications Trial (DCCT) database (n = 1,441), correlations between consumption of omega-3 FAs and saturated FAs to dietary variables (kilocalories, macronutrients, sodium, and cholesterol) and to age, gender, exercise level, and tobacco use were tested using Pearson correlation coefficients. Long-chain omega-3 FA intake inversely correlated with consumption of calories (r = -0.16, p <0.0001), percent calories from total fat (r = -0.14, p <0.0001), and percent calories from saturated FAs (r = -0.21, p <0.0001) and directly with dietary fiber intake (grams per 1,000 kcal, r = 0.20, p <0.0001). In the DCCT database, long-chain omega-3 FAs (i.e., fish consumption) inversely correlated with an overall low risk nutritional profile for coronary heart disease. In conclusion, these findings provide evidence that associations observed in studies suggesting a benefit of fish or long-chain omega-3 FAs may be due to a convergence of greater fish intakes with an overall healthier dietary pattern rather than with a specific effect of long-chain omega-3 FAs.