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Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.

ABSTRACT: Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementation compared with controls. Overall, the statin group showed significant risk reductions in total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke; however, omega-3 supplementation significantly decreased the risks of coronary heart disease and myocardial infarction only, in the comparison with the control group. In comparison with omega-3 supplementation, pravastatin significantly reduced the risks of total cardiovascular disease (RR = 0.81, 95% CI = 0.72-0.91), coronary heart disease (RR = 0.75, 95% CI = 0.60-0.94), and myocardial infarction (RR = 0.71, 95% CI = 0.55-0.94). Risks of total cardiovascular disease, coronary heart disease, myocardial infarction, and stroke in the atorvastatin group were statistically lower than those in the omega-3 group, with RRs (95% CIs) of 0.80 (0.73-0.88), 0.64 (0.50-0.82), 0.75 (0.60-0.93), and 0.81 (0.66-0.99), respectively. The findings of this study suggest that pravastatin and atorvastatin may be more beneficial than omega-3 supplementation in reducing the risk of total cardiovascular disease, coronary heart disease, and myocardial infarction.

SUBMITTER: Hoang T

PROVIDER: S-EPMC7468776 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.

Hoang Tung T Kim Jeongseon J

Nutrients 20200725 8

Statins and omega-3 supplementation have been recommended for cardiovascular disease prevention, but comparative effects have not been investigated. This study aimed to summarize current evidence of the effect of statins and omega-3 supplementation on cardiovascular events. A meta-analysis and a network meta-analysis of 63 randomized controlled trials were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs) for the effects of specific statins and omega-3 supplementat ...[more]

PMID: 32722395

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Project description:BackgroundThe clinical benefits of omega-3 fatty acids (FAs) supplementation in preventing and treating coronary heart disease (CHD) remain controversial. Therefore, this study aimed to investigate the clinical benefits of omega-3 FA supplementation, with special attention given to specific subgroups.MethodsRandomized controlled trials (RCTs) that compared the effects of omega-3 FA supplementation for CHD vs. a control group and including at least 1,000 patients were eligible for the inclusion in this meta-analysis. The relative risk (RR) of all-cause death, major adverse cardiovascular events (MACEs), cardiovascular death, myocardial infarction (MI), stroke, and revascularization were estimated. We analyzed the association between cardiovascular risk and omega-3 FA supplementation in the total subjects. We focused on the cardiovascular risk compared to omega-3 FA in subgroups with different development stages of CHD, omega-3 FA supplementation application dose, diabetes, and sex. PROSPERO Registration Number: CRD42021282459.ResultsThis meta-analysis included 14 clinical RCTs, including 1,35,291 subjects. Omega-3 FA supplementation reduced the risk of MACE (RR; 0.95; CI: 0.91-0.99; p for heterogeneity 0.27; I 2 = 20%; p = 0.03), cardiovascular death (RR; 0.94; CI: 0.89-0.99; p for heterogeneity 0.21; I 2 = 25%; p = 0.02), and MI (RR; 0.86; CI: 0.79-0.93; p for heterogeneity 0.28; I 2 = 19%; p < 0.01), but had no significant effect on all-cause death, stroke, and revascularization. In the subgroup analysis, omega-3 FA supplementation decreased the incidence of MACE and cardiovascular death in acute patients with MI, the risk of MI and stroke in patients with CHD, and the risk of MI in patients with high-risk CHD. 0.8-1.2 g omega-3 FA supplementation reduced the risk of MACE, cardiovascular death, and MI. It was revealed that gender and diabetes have no significant association between omega-3 FA supplementation and MACE risk.ConclusionsOmega-3 FA supplementation had a positive effect in reducing the incidence of MACE, cardiovascular death, MI. Regardless of the stage of CHD, omega-3 FA supplementation can prevent the occurrence of MI. The 0.8-1.2 g omega-3 FA supplementation alleviated CHD risk more effectively than lower or higher doses.Systematic review registrationhttps://www.crd.york.ac.uk/prospero/, identifier CRD42021282459.

Project description:BackgroundIt has been suggested that statins substantially reduce the risk of venous thromboembolic events. We sought to test this hypothesis by performing a meta-analysis of both published and unpublished results from randomised trials of statins.Methods and findingsWe searched MEDLINE, EMBASE, and Cochrane CENTRAL up to March 2012 for randomised controlled trials comparing statin with no statin, or comparing high dose versus standard dose statin, with 100 or more randomised participants and at least 6 months' follow-up. Investigators were contacted for unpublished information about venous thromboembolic events during follow-up. Twenty-two trials of statin versus control (105,759 participants) and seven trials of an intensive versus a standard dose statin regimen (40,594 participants) were included. In trials of statin versus control, allocation to statin therapy did not significantly reduce the risk of venous thromboembolic events (465 [0.9%] statin versus 521 [1.0%] control, odds ratio [OR] = 0.89, 95% CI 0.78-1.01, p = 0.08) with no evidence of heterogeneity between effects on deep vein thrombosis (266 versus 311, OR 0.85, 95% CI 0.72-1.01) and effects on pulmonary embolism (205 versus 222, OR 0.92, 95% CI 0.76-1.12). Exclusion of the trial result that provided the motivation for our meta-analysis (JUPITER) had little impact on the findings for venous thromboembolic events (431 [0.9%] versus 461 [1.0%], OR = 0.93 [95% CI 0.82-1.07], p = 0.32 among the other 21 trials). There was no evidence that higher dose statin therapy reduced the risk of venous thromboembolic events compared with standard dose statin therapy (198 [1.0%] versus 202 [1.0%], OR = 0.98, 95% CI 0.80-1.20, p = 0.87). Risk of bias overall was small but a certain degree of effect underestimation due to random error cannot be ruled out. Please see later in the article for the Editors' Summary.ConclusionsThe findings from this meta-analysis do not support the previous suggestion of a large protective effect of statins (or higher dose statins) on venous thromboembolic events. However, a more moderate reduction in risk up to about one-fifth cannot be ruled out.

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.

Project description:Omega-3 polyunsaturated fatty acid (PUFA) supplementation has been proposed as (adjuvant) treatment for major depressive disorder (MDD). In the present meta-analysis, we pooled randomized placebo-controlled trials assessing the effects of omega-3 PUFA supplementation on depressive symptoms in MDD. Moreover, we performed meta-regression to test whether supplementation effects depended on eicosapentaenoic acid (EPA) or docosahexaenoic acid dose, their ratio, study duration, participants' age, percentage antidepressant users, baseline MDD symptom severity, publication year and study quality. To limit heterogeneity, we only included studies in adult patients with MDD assessed using standardized clinical interviews, and excluded studies that specifically studied perinatal/perimenopausal or comorbid MDD. Our PubMED/EMBASE search resulted in 1955 articles, from which we included 13 studies providing 1233 participants. After taking potential publication bias into account, meta-analysis showed an overall beneficial effect of omega-3 PUFAs on depressive symptoms in MDD (standardized mean difference=0.398 (0.114-0.682), P=0.006, random-effects model). As an explanation for significant heterogeneity (I(2)=73.36, P<0.001), meta-regression showed that higher EPA dose (β=0.00037 (0.00009-0.00065), P=0.009), higher percentage antidepressant users (β=0.0058 (0.00017-0.01144), P=0.044) and earlier publication year (β=-0.0735 (-0.143 to 0.004), P=0.04) were significantly associated with better outcome for PUFA supplementation. Additional sensitivity analyses were performed. In conclusion, present meta-analysis suggested a beneficial overall effect of omega-3 PUFA supplementation in MDD patients, especially for higher doses of EPA and in participants taking antidepressants. Future precision medicine trials should establish whether possible interactions between EPA and antidepressants could provide targets to improve antidepressant response and its prediction. Furthermore, potential long-term biochemical side effects of high-dosed add-on EPA supplementation should be carefully monitored.

Dataset Information

Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.

Publications

Comparative Effect of Statins and Omega-3 Supplementation on Cardiovascular Events: Meta-Analysis and Network Meta-Analysis of 63 Randomized Controlled Trials Including 264,516 Participants.

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