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Evidence summaries

Pcsk9 Inhibitors for Prevention of Cardiovascular Disease

PCSK9 inhibitors (alirocumab and evolocumab) added to other LDL-chlesterol lowering medicines (e.g. statins or ezetimibe) slightly reduce the risk of cardiovascular diseases compared to placebo. Effects of PCSK9 inhibitors compared with active treatment are unclear. Level of evidence: "A"

Summary

A Cochrane review [Abstract] 1 included 24 studies with a total of 60 997 subjects to quantify the effects of PCSK9 inhibitors (alirocumab 18 studies, evolocumab 6 studies) compared to placebo or active treatment(s) for primary and secondary prevention of cardiovascular diseases (CVD). Most of the studies preferentially enrolled subjects with either established CVD or at a high risk already. All subjects received background lipid-lowering treatment or lifestyle counselling. Six alirocumab and 3 evolocumab studies used an active treatment comparison group and the remaining used placebo.

Alirocumab decreased the risk of CVD events (OR 0.87, 95% CI 0.80 to 0.94; 10 studies, n=23 868; absolute risk difference RD -2%), mortality (OR 0.83, 95% CI 0.72 to 0.96; 12 studies, n=24 797; absolute risk difference RD -1%), myocardial infarction (MI) (OR 0.86, 95% CI 0.79 to 0.94; 9 studies, n=23 352; absolute risk difference RD -2%) and any stroke (OR 0.73, 95% CI 0.58 to 0.91; 8 studies, n=22 835; absolute risk difference RD -0%) compared with placebo. There were no statistically significant differences when alirocumab was compared with active treatment group (ezetimibe and statins).

Evolocumab reduced the risk of CVD (OR 0.84, 95% CI 0.78 to 0.91; 3 studies, n=29 432; absolute risk difference RD -2%), MI (OR 0.72, 95% CI 0.64 to 0.82; 3 studies, n=29 432; absolute risk difference RD -1%), and any stroke (OR 0.79, 95% CI 0.65 to 0.94; 2 studies, n=28 531; absolute risk difference RD -1%), but there was no difference in mortality (OR 1.04, 95% CI 0.91 to 1.19; 3 studies, n=29 432). There were no statistically significant differences when evolocumab was compared with active treatment group (ezetimibe and statins).

Differences in risk between people treated with and without PCSK9 inhibitors suggested the absolute treatment benefit will likely be modest (e.g. absolute risk reduction often less than 1% over the follow-up period considered).

There was very limited evidence on any potential safety issues of both evolocumab and alirocumab.

Cochrane Summary of findings tableshttp://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011748.pub3/full#CD011748-sec-0008

Clinical comments

Note

Date of latest search:

    References

    • Schmidt AF, Carter JL, Pearce LS et al. PCSK9 monoclonal antibodies for the primary and secondary prevention of cardiovascular disease. Cochrane Database Syst Rev 2020;(10):CD011748. [PubMed]

Primary/Secondary Keywords