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Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants.
Am Heart J. 2019 04; 210:18-28.AH

Abstract

The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations.

METHODS

We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes.

RESULTS

In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile.

CONCLUSIONS

All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit.

Links

Publisher Full Text (DOI)

Authors+Show Affiliations

Yebyo HG
Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Zurich, Switzerland; School of Public Health, Mekelle University, Ayder, Mekelle, Ethiopia.
Aschmann HE
Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Zurich, Switzerland.
Kaufmann M
Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Zurich, Switzerland.
Puhan MA
Department of Epidemiology, Epidemiology, Biostatistics and Prevention Institute, University of Zurich, Hirschengraben 84, Zurich, Switzerland. Electronic address: miloalan.puhan@uzh.ch.

MeSH

AtorvastatinCardiovascular DiseasesCause of DeathChemical and Drug Induced Liver InjuryDouble-Blind MethodFluvastatinHeadacheHumansHydroxymethylglutaryl-CoA Reductase InhibitorsKidney DiseasesLovastatinMiddle AgedMuscular DiseasesNauseaNeoplasmsNetwork Meta-AnalysisPlacebosPravastatinRandomized Controlled Trials as TopicRisk AssessmentRosuvastatin CalciumSimvastatinWithholding Treatment

Pub Type(s)

Comparative Study
Journal Article
Meta-Analysis
Research Support, Non-U.S. Gov't
Systematic Review

Language

eng

PubMed ID

30716508

Citation

Yebyo, Henock G., et al. "Comparative Effectiveness and Safety of Statins as a Class and of Specific Statins for Primary Prevention of Cardiovascular Disease: a Systematic Review, Meta-analysis, and Network Meta-analysis of Randomized Trials With 94,283 Participants." American Heart Journal, vol. 210, 2019, pp. 18-28.
Yebyo HG, Aschmann HE, Kaufmann M, et al. Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. Am Heart J. 2019;210:18-28.
Yebyo, H. G., Aschmann, H. E., Kaufmann, M., & Puhan, M. A. (2019). Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. American Heart Journal, 210, 18-28. https://doi.org/10.1016/j.ahj.2018.12.007
Yebyo HG, et al. Comparative Effectiveness and Safety of Statins as a Class and of Specific Statins for Primary Prevention of Cardiovascular Disease: a Systematic Review, Meta-analysis, and Network Meta-analysis of Randomized Trials With 94,283 Participants. Am Heart J. 2019;210:18-28. PubMed PMID: 30716508.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Comparative effectiveness and safety of statins as a class and of specific statins for primary prevention of cardiovascular disease: A systematic review, meta-analysis, and network meta-analysis of randomized trials with 94,283 participants. AU - Yebyo,Henock G, AU - Aschmann,Hélène E, AU - Kaufmann,Marco, AU - Puhan,Milo A, Y1 - 2019/01/10/ PY - 2018/04/18/received PY - 2018/12/05/accepted PY - 2019/2/5/pubmed PY - 2019/12/20/medline PY - 2019/2/5/entrez SP - 18 EP - 28 JF - American heart journal JO - Am Heart J VL - 210 N2 - : The current guidelines of statins for primary cardiovascular disease (CVD) prevention were based on results from systematic reviews and meta-analyses that suffer from limitations. METHODS: We searched in PubMed for existing systematic reviews and individual open-label or double-blinded randomized controlled trials that compared a statin with a placebo or another, which were published in English until January 01, 2018. We performed a random-effect pairwise meta-analysis of all statins as a class and network meta-analysis for the specific statins on different benefit and harm outcomes. RESULTS: In the pairwise meta-analyses, statins as a class showed statistically significant risk reductions on non-fatal MI (risk ratio [RR] 0.62, 95% CI 0.53-0.72), CVD mortality (RR 0.80, 0.71-0.91), all-cause mortality (RR 0.89, 0.85-0.93), non-fatal stroke (RR 0.83, 0.75-0.92), unstable angina (RR 0.75, 0.63-0.91), and composite major cardiovascular events (RR 0.74, 0.67-0.81). Statins increased statistically significantly relative and absolute risks of myopathy (RR 1.08, 1.01-1.15; Risk difference [RD] 13, 2-24 per 10,000 person-years); renal dysfunction (RR 1.12, 1.00-1.26; RD 16, 0-36 per 10,000 person-years); and hepatic dysfunction (RR 1.16, 1.02-1.31; RD 8, 1-16 per 10,000 person-years). The drug-level network meta-analyses showed that atorvastatin and rosuvastatin were most effective in reducing CVD events while atorvastatin appeared to have the best safety profile. CONCLUSIONS: All statins showed statistically significant risk reduction of CVD and all-cause mortality in primary prevention populations while increasing the risk for some harm risks. However, the benefit-harm profile differed by statin type. A quantitative assessment of the benefit-harm balance is thus needed since meta-analyses alone are insufficient to inform whether statins provide net benefit. SN - 1097-6744 UR - https://www.unboundmedicine.com/medline/citation/30716508/Comparative_effectiveness_and_safety_of_statins_as_a_class_and_of_specific_statins_for_primary_prevention_of_cardiovascular_disease:_A_systematic_review_meta_analysis_and_network_meta_analysis_of_randomized_trials_with_94283_participants_ DB - PRIME DP - Unbound Medicine ER -