Key result
PCSK9 inhibitors reduce cardiovascular events by ~13% in statin-treated patients at risk.
Why the study?
It was unknown whether PCSK9 inhibitor use is associated with cardiovascular and safety events in statin-treated patients with cardiovascular risk.
Does the addition of PCSK9 inhibitors reduce cardiovascular events in statin-treated patients with cardiovascular risk?
Meta-Analysis (n=50,053)
Does the addition of PCSK9 inhibitors reduce cardiovascular events in statin-treated patients with cardiovascular risk?
Effect estimate: RR 0.87 (95% CI 0.83-0.91)
p-value: p=<0.00001
In statin-treated patients with cardiovascular risk, adding a PCSK9 inhibitor marginally reduces cardiovascular events, nonfatal MI, and ischemic stroke, but increases injection-site reactions without affecting mortality.
Supports adding PCSK9 inhibitors to statins for further CVE reduction; confirms efficacy across prior RCTs.
OBJECTIVES: To evaluate whether proprotein convertase subtilisin/kexin type 9 inhibitor (PCSK9i) is associated with cardiovascular and safety events in statin-treated patients with cardiovascular risk. METHODS: Electronic databases (Pubmed, Cochrane, MEDLINE, EMBASE, ClinicalTrials.gov) were searched through March 31, 2020. Included randomized clinical trials (RCTs) compared PCSK9i use with no PCSK9i in statin treated patients. Two investigators abstracted data and appraised risks of bias. A meta-analysis was performed to calculate risk ratios (RRs) and 95% CIs using fix-effects models. Adjudicated cardiovascular events (CVE) and adverse drug events (ADE) were defined as the primary outcome. Secondary outcomes were cardiovascular (CV) death, all-cause death, nonfatal myocardial infarction, ischemic stroke, serious ADE and injection-site reaction. RESULTS: A total of 10 RCTs 50 053 participants were included. PCSK9i use was associated with signigicant reductions in the CVE (RR, 0.87 [95%CI, 0.83-0.91]; NNT, 54; P<0.00001; I2=0%, heterogeneity P=0.86), nonfatal myocardial infarction (RR, 0.86 [95% CI, 0.78-0.96]; NNT, 95; P=0.005; I2=0%, heterogeneity P=0.88), and ischemic stroke (RR, 0.75 [95%CI 0.64-0.87]; NNT, 244; P=0.00; I2=0%, heterogeneity P=0.82) compared with no PCSK9i in statin-treated patients with CV risk. No significant associations were found between PCSK9i use and no PCSK9i in ADE and serious ADE. PCSK9i use was associated with signigicant increasing in injection-site reaction (RR, 1.55 [95%CI 1.38-1.75]; NNT, 101; P<0.00001; I2=0%, heterogeneity P=0.44). CONCLUSIONS: Among statin-treated patients with CV risk, the use of PCSK9i was associated with improving CV outcomes. The use of PCSK9i was well tolerated, but had significantly injection-site reactions.
No takes yet. Share an insight, caveat, or question.
Zhao et al. (2020) conducted a meta-analysis in Hyperlipidemia with cardiovascular risk on statin therapy (n=50,053). PCSK9 inhibitors vs. Placebo or ezetimibe was evaluated on Adjudicated cardiovascular events (CVE) (RR 0.87, 95% CI 0.83-0.91, p=<0.00001). Among statin-treated patients with cardiovascular risk, the use of PCSK9 inhibitors significantly reduced adjudicated cardiovascular events (RR 0.87) compared to no PCSK9 inhibitor.
Synapse has enriched 5 closely related papers on similar clinical questions. Consider them for comparative context: