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Research ArticleResearch

Lipid-lowering therapies for cardiovascular disease prevention and management in primary care

PEER umbrella systematic review of systematic reviews

Nicolas Dugré, Adrienne J. Lindblad, Danielle Perry, G. Michael Allan, Émélie Braschi, Jamie Falk, Liesbeth Froentjes, Scott R. Garrison, Jessica E.M. Kirkwood, Christina S. Korownyk, James P. McCormack, Samantha S. Moe, Allison Paige, Jen Potter, Betsy S. Thomas, Joey Ton, Jennifer Young, Justin Weresch and Michael R. Kolber
Canadian Family Physician October 2023; 69 (10) 701-711; DOI: https://doi.org/10.46747/cfp.6910701
Nicolas Dugré
Pharmacist at the CIUSSS du Nord-de-l’Île-de-Montréal and Clinical Associate Professor in the Faculty of Pharmacy at the University of Montréal in Quebec.
PharmD MSc BCACP
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  • For correspondence: nicolas.dugre@umontreal.ca
Adrienne J. Lindblad
Clinical Evidence Expert Lead for the College of Family Physicians of Canada (CFPC) and Associate Clinical Professor in the Department of Family Medicine at the University of Alberta in Edmonton.
PharmD ACPR
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Danielle Perry
Clinical Evidence Expert for the CFPC and Assistant Adjunct Professor in the Department of Family Medicine at the University of Alberta.
RN MSc
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G. Michael Allan
Director of Programs and Practice Support at the CFPC.
MD CCFP FCFP
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Émélie Braschi
Hospitalist at the Élisabeth Bruyère Hospital in Ottawa, Ont, and a physician adviser at the CFPC.
MD PhD CCFP
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Jamie Falk
Pharmacist and Associate Professor in the College of Pharmacy at the University of Manitoba in Winnipeg.
PharmD
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Liesbeth Froentjes
Research assistant, Department of Family Medicine at the University of Alberta.
MSc
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Scott R. Garrison
Professor, Department of Family Medicine at the University of Alberta.
MD CCFP PhD
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Jessica E.M. Kirkwood
Family physician and Assistant Professor, Department of Family Medicine at the University of Alberta.
MD CCFP(AM)
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Christina S. Korownyk
Professor, Department of Family Medicine at the University of Alberta.
MD CCFP
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James P. McCormack
Professor in the Faculty of Pharmaceutical Sciences at the University of British Columbia in Vancouver.
PharmD
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Samantha S. Moe
Clinical Evidence Expert at the CFPC.
PharmD ACPR
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Allison Paige
Assistant Professor in the Department of Family Medicine at the University of Manitoba.
MD CCFP
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Jen Potter
Assistant Professor in the Department of Family Medicine at the University of Manitoba.
MD CCFP
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Betsy S. Thomas
Clinical Evidence Expert at the CFPC and Assistant Adjunct Professor in the Department of Family Medicine at the University of Alberta.
BScPharm
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Joey Ton
Program Manager of Programs and Practice Support at the CFPC.
PharmD
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Jennifer Young
Family physician practising in Collingwood, Ont.
MD CCFP(EM) FCFP
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Justin Weresch
Assistant Professor in the Department of Family Medicine at McMaster University in Hamilton, Ont.
MD CCFP
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Michael R. Kolber
Professor in the Department of Family Medicine at the University of Alberta.
MD MSc CCFP
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Abstract

Objective To assess the benefits and harms of lipid-lowering therapies used to prevent or manage cardiovascular disease including bile acid sequestrants (BAS), ezetimibe, fibrates, niacin, omega-3 supplements, proprotein convertase subtilisin-kexin type 9 (PCSK9) inhibitors, and statins.

Data sources MEDLINE, the Cochrane Database of Systematic Reviews, and a grey literature search.

Study selection Systematic reviews of randomized controlled trials published between January 2017 and March 2022 looking at statins, ezetimibe, PCSK9 inhibitors, fibrates, BAS, niacin, and omega-3 supplements for preventing cardiovascular outcomes were selected. Outcomes of interest included major adverse cardiovascular events (MACE), cardiovascular mortality, all-cause mortality, and adverse events.

Synthesis A total of 76 systematic reviews were included. Four randomized controlled trials were also included for BAS because no efficacy systematic review was identified. Statins significantly reduced MACE (6 systematic reviews; median risk ratio [RR]=0.74; interquartile range [IQR]=0.71 to 0.76), cardiovascular mortality (7 systematic reviews; median RR=0.85, IQR=0.83 to 0.86), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.88 to 0.92). Major adverse cardiovascular events were also significantly reduced by ezetimibe (3 systematic reviews; median RR=0.93, IQR=0.93 to 0.94), PCSK9 inhibitors (14 systematic reviews; median RR=0.84, IQR=0.83 to 0.87), and fibrates (2 systematic reviews; mean RR=0.86), but these interventions had no effect on cardiovascular or all-cause mortality. Fibrates had no effect on any cardiovascular outcomes when added to a statin. Omega-3 combination supplements had no effect on MACE or all-cause mortality but significantly reduced cardiovascular mortality (5 systematic reviews; median RR=0.93, IQR=0.93 to 0.94). Eicosapentaenoic acid ethyl ester alone significantly reduced MACE (1 systematic review, RR=0.78) and cardiovascular mortality (2 systematic reviews; RRs of 0.82 and 0.82). In primary cardiovascular prevention, only statins showed consistent benefits on MACE (6 systematic reviews; median RR=0.75, IQR=0.73 to 0.78), cardiovascularall-cause mortality (7 systematic reviews, median RR=0.83, IQR=0.81 to 0.90), and all-cause mortality (8 systematic reviews; median RR=0.91, IQR=0.87 to 0.91).

Conclusion Statins have the most consistent evidence for the prevention of cardiovascular complications with a relative risk reduction of about 25% for MACE and 10% to 15% for mortality. The addition of ezetimibe, a PCSK9 inhibitor, or eicosapentaenoic acid ethyl ester to a statin provides additional MACE risk reduction but has no effect on all-cause mortality.

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Canadian Family Physician: 69 (10)
Canadian Family Physician
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Lipid-lowering therapies for cardiovascular disease prevention and management in primary care
Nicolas Dugré, Adrienne J. Lindblad, Danielle Perry, G. Michael Allan, Émélie Braschi, Jamie Falk, Liesbeth Froentjes, Scott R. Garrison, Jessica E.M. Kirkwood, Christina S. Korownyk, James P. McCormack, Samantha S. Moe, Allison Paige, Jen Potter, Betsy S. Thomas, Joey Ton, Jennifer Young, Justin Weresch, Michael R. Kolber
Canadian Family Physician Oct 2023, 69 (10) 701-711; DOI: 10.46747/cfp.6910701

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Lipid-lowering therapies for cardiovascular disease prevention and management in primary care
Nicolas Dugré, Adrienne J. Lindblad, Danielle Perry, G. Michael Allan, Émélie Braschi, Jamie Falk, Liesbeth Froentjes, Scott R. Garrison, Jessica E.M. Kirkwood, Christina S. Korownyk, James P. McCormack, Samantha S. Moe, Allison Paige, Jen Potter, Betsy S. Thomas, Joey Ton, Jennifer Young, Justin Weresch, Michael R. Kolber
Canadian Family Physician Oct 2023, 69 (10) 701-711; DOI: 10.46747/cfp.6910701
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