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The prevalence of intolerance varies widely. Stopping statin therapy is associated with worse outcomes in patients with cardiovascular disease. Despite extensive studies, the benefits and risks of statins continue to be debated by clinicians and the lay public. We searched the PubMed, Medline, and Cochrane Central Register of Controlled Trials (CENTRAL) databases for all randomized controlled trials of statins compared with placebo. Studies were included if they had ≥1,000 participants, had patients who were followed up for ≥1 year, and reported rates of drug discontinuation. Studies were pooled as per the random effects model. A total of 22 studies (statins = 66,024, placebo = 63,656) met the inclusion criteria. The pooled analysis showed that, over a mean follow-up of 4.1 years, the rates of discontinuation were 13.3% (8,872 patients) for statin-treated patients and 13.9% (8,898 patients) for placebo-treated patients. The random effects model showed no significant difference between the placebo and statin arms (odds ratio Statin intolerance is a common phenomenon and is reported in 5% to 20% of patients, often resulting in drug discontinuation.[1 Stopping statin therapy has been associated with worsened outcomes in patients with cardiovascular diseases (CVDs).2 With acceptance of the latest American College of Cardiology guidelines, the number of patients who require treatment with statins has increased even further.3 A number of mechanisms have been proposed to explain the phenomenon of statin intolerance. However, despite extensive studies, statin intolerance remains an elusive phenomenon.Most of our knowledge of the incidence of statin intolerance stems from observational studies and post hoc analyses. Assessing statin intolerance is important, as it can have widespread implications on public health. A number of patients on statins report muscle-related symptoms. There is little consensus among clinicians on whether to attribute muscle symptoms to statins; and in the absence of confirming laboratory parameters, judgment frequently remains subjective. Given this backdrop, we conducted a rigorous meta-analysis of historical randomized controlled trials (RCTs) to compare the rates of drug discontinuation for patients treated with statins and for patients treated with placebo. MethodsA PubMed and Medline literature search was conducted using the keywords "statin" and "clinical trials" (phase 1, phase 2, phase 3, and phase 4) as a filter. We also searched for "metaanalysis" as the article type and hand searched the reference lists of the selected systematic reviews to identify further studies. We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) database to expand the literature search using the keywords "statin AND placebo." No language restrictions were applied and the databases were searched from the inception of these databases until October 2016.

Background The American College of Cardiology guidelines recommend 3 months of anticoagulation after replacement of the aortic valve with a bioprosthesis. However, there remains great variability in the current clinical practice and conflicting results from clinical studies. To assist clinical decision making, we pooled the existing evidence to assess whether anticoagulation in the setting of a new bioprosthesis was associated with improved outcomes or greater risk of bleeding. Methods and Results We searched the PubMed database from the inception of these databases until April 2015 to identify original studies (observational studies or clinical trials) that assessed anticoagulation with warfarin in comparison with either aspirin or no antiplatelet or anticoagulant therapy. We included the studies if their outcomes included thromboembolism or stroke/transient ischemic attacks and bleeding events. Quality assessment was performed in accordance with the Newland Ottawa Scale, and random effects analysis was used to pool the data from the available studies. I2 testing was done to assess the heterogeneity of the included studies. After screening through 170 articles, a total of 13 studies (cases=6431; controls=18210) were included in the final analyses. The use of warfarin was associated with a significantly increased risk of overall bleeding (odds ratio, 1.96; 95% confidence interval, 1.25–3.08; P<0.0001) or bleeding risk at 3 months (odds ratio, 1.92; 95% confidence interval, 1.10–3.34; P<0.0001) compared with aspirin or placebo. With regard to composite primary outcome variables (risk of venous thromboembolism, stroke, or transient ischemic attack) at 3 months, no significant difference was seen with warfarin (odds ratio, 1.13; 95% confidence interval, 0.82–1.56; P=0.67). Moreover, anticoagulation was also not shown to improve outcomes at time interval >3 months (odds ratio, 1.12; 95% confidence interval, 0.80–1.58; P=0.79). Conclusions Contrary to the current guidelines, a meta-analysis of previous studies suggests that anticoagulation in the setting of an aortic bioprosthesis significantly increases bleeding risk without a favorable effect on thromboembolic events. Larger, randomized controlled studies should be performed to further guide this clinical practice.