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Statins Provide Less Benefit in Populations with High Noncardiovascular Mortality Risk: Meta-Regression of Randomized Controlled Trials.

ABSTRACT: To examine whether the benefit of statins varied according to cardiovascular (CV) and non-CV mortality of the treated population.Meta-analysis and meta-regression of 16 randomized placebo-controlled trials.Community and hospital.Statin- (n = 59,671) and placebo-treated (n = 59,707) individuals with and without CV disease (mean age 55 to 75).Meta-regression was used to model relative risks (RRs) of major CV events (myocardial infarction and stroke) and total mortality for statins versus placebo as a function of CV and non-CV mortality risks of the study population.Every 1% increase in 5-year non-CV mortality risk of the study population was associated with a 3.7% (95% confidence interval (CI) = 1.2 to 6.3%) greater RR of major CV events and a 4.4% (95% CI = 2.1 to 6.9%) greater RR of total mortality. (Higher RRs indicate smaller benefits.) CV mortality was not associated with statin effects (P > .05). In stratified analysis according to CV (?5.3% vs <5.3%) and non-CV mortality (?3.8% vs <3.8%) of the study population, statins had little mortality benefit in populations with high non-CV mortality, regardless of CV mortality (random-effects pooled RR = 0.81, 95% CI = 0.72 to 0.91, for low CV and low non-CV mortality; random-effects pooled RR = 0.90, 95% CI = 0.76 to 1.06 for low CV and high non-CV mortality; random-effects pooled RR = 0.79, 95% CI = 0.72 to 0.87 for high CV and low non-CV mortality; random-effects pooled RR = 0.94, 95% CI = 0.87 to 1.02 for high CV and high non-CV mortality). The CV event reduction was also attenuated in populations with high non-CV mortality (random-effects pooled RR = 0.67, 95% CI = 0.60 to 0.75, for low CV and low non-CV mortality; random-effects pooled RR = 0.73, 95% CI = 0.66 to 0.81 for low CV and high non-CV mortality; random-effects pooled RR = 0.77, 95% CI = 0.69 to 0.87 for high CV and low non-CV mortality; random-effects pooled RR = 0.83, 95% CI = 0.74 to 0.92 for high CV and high non-CV mortality).Benefits of statins may depend on the non-CV mortality risk of the treated population. This should be confirmed using individual-level data.

SUBMITTER: Kim CA

PROVIDER: S-EPMC4509928 | biostudies-literature | 2015 Jul

REPOSITORIES: biostudies-literature

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Statins Provide Less Benefit in Populations with High Noncardiovascular Mortality Risk: Meta-Regression of Randomized Controlled Trials.

Kim Caroline A CA Kim Dae Hyun DH

Journal of the American Geriatrics Society 20150714 7

<h4>Objectives</h4>To examine whether the benefit of statins varied according to cardiovascular (CV) and non-CV mortality of the treated population.<h4>Design</h4>Meta-analysis and meta-regression of 16 randomized placebo-controlled trials.<h4>Setting</h4>Community and hospital.<h4>Participants</h4>Statin- (n = 59,671) and placebo-treated (n = 59,707) individuals with and without CV disease (mean age 55 to 75).<h4>Measurements</h4>Meta-regression was used to model relative risks (RRs) of major C ...[more]

PMID: 26173475

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Project description:ObjectiveTo analyse the benefits and harms of statins in patients with chronic kidney disease (pre-dialysis, dialysis, and transplant populations).DesignMeta-analysis.Data sourcesCochrane Central Register of Controlled Trials, Medline, Embase, and Renal Health Library (July 2006).Study selectionRandomised and quasi-randomised controlled trials of statins compared with placebo or other statins in chronic kidney disease.Data extraction and analysisTwo reviewers independently assessed trials for inclusion, extracted data, and assessed trial quality. Differences were resolved by consensus. Treatment effects were summarised as relative risks or weighted mean differences with 95% confidence intervals by using a random effects model.ResultsFifty trials (30 144 patients) were included. Compared with placebo, statins significantly reduced total cholesterol (42 studies, 6390 patients; weighted mean difference -42.28 mg/dl (1.10 mmol/l), 95% confidence interval -47.25 to -37.32), low density lipoprotein cholesterol (39 studies, 6216 patients; -43.12 mg/dl (1.12 mmol/l), -47.85 to -38.40), and proteinuria (g/24 hours) (6 trials, 311 patients; -0.73 g/24 hour, -0.95 to -0.52) but did not improve glomerular filtration rate (11 studies, 548 patients; 1.48 ml/min (0.02 ml/s), -2.32 to 5.28). Fatal cardiovascular events (43 studies, 23 266 patients; relative risk 0.81, 0.73 to 0.90) and non-fatal cardiovascular events (8 studies, 22 863 patients; 0.78, 0.73 to 0.84) were reduced with statins, but statins had no significant effect on all cause mortality (44 studies, 23 665 patients; 0.92, 0.82 to 1.03). Meta-regression analysis showed that treatment effects did not vary significantly with stage of chronic kidney disease. The side effect profile of statins was similar to that of placebo. Most of the available studies were small and of suboptimal quality; mortality data were provided by a few large trials only.ConclusionStatins significantly reduce lipid concentrations and cardiovascular end points in patients with chronic kidney disease, irrespective of stage of disease, but no benefit on all cause mortality or the role of statins in primary prevention has been established. Reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.

Project description:BackgroundThe sequential organ failure assessment score (SOFA) is increasingly used as an endpoint in intensive care randomized controlled trials (RCTs). Although serially measured SOFA is independently associated with mortality in observational cohorts, the association between treatment effects on SOFA vs. effects on mortality has not yet been quantified in RCTs. The aim of this study was to quantify the relationship between SOFA and mortality in RCTs and to identify which SOFA derivative best reflects between-group mortality differences.MethodsThe review protocol was prospectively registered (Prospero CRD42016034014). We performed a literature search (up to May 1, 2016) for RCTs reporting both SOFA and mortality, and analyzed between-group differences in these outcomes. Treatment effects on SOFA and mortality were calculated as the between-group SOFA standardized difference and log odds ratio (OR), respectively. We used random-effects meta-regression to (1) quantify the linear relationship between RCT treatment effects on mortality (logOR) and SOFA (i.e. responsiveness) and (2) quantify residual heterogeneity (i.e. consistency, expressed as I 2).ResultsOf 110 eligible RCTs, 87 qualified for analysis. Using all RCTs, SOFA was significantly associated with mortality (slope = 0.49 (95% CI 0.17; 0.82), p = 0.006, I 2 = 5%); the overall mortality effect explained by SOFA score (R 2) was 9%. Fifty-eight RCTs used Fixed-day SOFA as an endpoint (i.e. the score on a fixed day after randomization), 25 studies used Delta SOFA as an endpoint (i.e. the trajectory from baseline score) and 15 studies used other SOFA derivatives as an endpoint. Fixed-day SOFA was not significantly associated with mortality (slope = 0.35 (95% CI -0.04; 0.75), p = 0.08, I 2 = 12%) and explained 3% of the overall mortality effect (R 2). Delta SOFA was significantly associated with mortality (slope = 0.70 (95% CI 0.26; 1.14), p = 0.004, I 2 = 0%) and explained 32% of the overall mortality effect (R 2).ConclusionsTreatment effects on Delta SOFA appear to be reliably and consistently associated with mortality in RCTs. Fixed-day SOFA was the most frequently reported outcome among the reviewed RCTs, but was not significantly associated with mortality. Based on this study, we recommend using Delta SOFA rather than Fixed-day SOFA as an endpoint in future RCTs.

Project description:In 2012, the United States Food and Drug Administration (FDA) issued a warning regarding potential adverse effects of HMG-CoA reductase inhibitors (statins) on cognition, based on the Adverse Events Reporting System and a review of the medical literature. We aimed to synthesize randomized clinical trial (RCTs) evidence on the association between statin therapy and cognitive outcomes.We searched MEDLINE, EMBASE, and Cochrane CENTRAL through December 2012, and reviewed published systematic reviews of statin treatment. We sought RCTs that compared statin treatment versus placebo or standard care, and reported at least one cognitive outcome (frequency of adverse cognitive events or measurements using standard neuropsychological cognitive test scores). Studies reporting sufficient information to calculate effect sizes were included in meta-analyses. Standardized and unstandardized mean differences were calculated for continuous outcomes for global cognition and for pre-specified cognitive domains. The main outcome was change in cognition measured by neuropsychological tests; an outcome of secondary interest was the frequency of adverse cognitive events observed during follow-up.We identified 25 RCTs (all placebo-controlled) reporting cognitive outcomes in 46,836 subjects, of which 23 RCTs reported cognitive test results in 29,012 participants. Adverse cognitive outcomes attributable to statins were rarely reported in trials involving cognitively normal or impaired subjects. Furthermore, meta-analysis of cognitive test data (14 studies; 27,643 participants) failed to show significant adverse effects of statins on all tests of cognition in either cognitively normal subjects (standardized mean difference 0.01, 95% confidence interval, CI, -0.01 to 0.03, p?=?0.42) or Alzheimer's disease subjects (standardized mean difference -0.05, 95% CI -0.19 to 0.10, p?=?0.38).Statin therapy was not associated with cognitive impairment in RCTs. These results raise questions regarding the continued merit of the FDA warning about potential adverse effects of statins on cognition.

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Statins Provide Less Benefit in Populations with High Noncardiovascular Mortality Risk: Meta-Regression of Randomized Controlled Trials.

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Statins Provide Less Benefit in Populations with High Noncardiovascular Mortality Risk: Meta-Regression of Randomized Controlled Trials.

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