TY - JOUR
T1 - Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia
T2 - A meta-analysis of 35 randomized controlled trials
AU - Karatasakis, Aris
AU - Danek, Barbara A.
AU - Karacsonyi, Judit
AU - Rangan, Bavana V.
AU - Roesle, Michele K.
AU - Knickelbine, Thomas
AU - Miedema, Michael D.
AU - Khalili, Houman
AU - Ahmad, Zahid
AU - Abdullah, Shuaib
AU - Banerjee, Subhash
AU - Brilakis, Emmanouil S.
N1 - Funding Information:
Dr Ahmad has received research grants from NIH and Regeneron (modest); honoraria from Genzyme and Sanofi (modest); and serves as consultant/advisory board for Genzyme (modest). Dr Banerjee has received research grants from Boston Scientific and Merck (significant); honoraria from Medtronic, Cardiovascular Systems, Inc., and GORE (significant); and has ownership in HygeiaTel and MDCARE Global (spouse, significant). Dr Brilakis has received research grants
Publisher Copyright:
© 2017 The Authors.
PY - 2017/12/1
Y1 - 2017/12/1
N2 - Background--We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab. Methods and Results--We performed a systematic review and meta-analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow-up: 85.5 weeks) were included. Mean age was 61.0±2.8 years, and mean baseline low-density lipoprotein cholesterol was 106±22 mg/dL. Compared with no PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64-0.81]; P < 0.001), stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67-0.96]; P=0.02), and coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71-0.86]; P < 0.001). Overall, no significant change was observed in all-cause mortality (OR: 0.71 [95% CI, 0.47- 1.09]; P=0.12) or cardiovascular mortality (OR: 1.01 [95% CI, 0.85-1.19]; P=0.95). A significant association was observed between higher baseline low-density lipoprotein cholesterol and benefit in all-cause mortality (P=0.038). No significant change was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88-1.42]; P=0.37), myalgia (OR: 0.95 [95% CI, 0.75-1.20]; P=0.65), new onset or worsening of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95-1.17]; P=0.32), and increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70-1.01]; P=0.06) or alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82- 1.12]; P=0.61). Conclusions--Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes. Although no overall benefit was noted in all-cause or cardiovascular mortality, such benefit may be achievable in patients with higher baseline lowdensity lipoprotein cholesterol.
AB - Background--We sought to examine the efficacy and safety of 2 PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitors: alirocumab and evolocumab. Methods and Results--We performed a systematic review and meta-analysis of randomized controlled trials comparing treatment with and without PCSK9 inhibitors; 35 randomized controlled trials comprising 45 539 patients (mean follow-up: 85.5 weeks) were included. Mean age was 61.0±2.8 years, and mean baseline low-density lipoprotein cholesterol was 106±22 mg/dL. Compared with no PCSK9 inhibitor therapy, treatment with a PCSK9 inhibitor was associated with a lower rate of myocardial infarction (2.3% versus 3.6%; odds ratio [OR]: 0.72 [95% confidence interval (CI), 0.64-0.81]; P < 0.001), stroke (1.0% versus 1.4%; OR: 0.80 [95% CI, 0.67-0.96]; P=0.02), and coronary revascularization (4.2% versus 5.8%; OR: 0.78 [95% CI, 0.71-0.86]; P < 0.001). Overall, no significant change was observed in all-cause mortality (OR: 0.71 [95% CI, 0.47- 1.09]; P=0.12) or cardiovascular mortality (OR: 1.01 [95% CI, 0.85-1.19]; P=0.95). A significant association was observed between higher baseline low-density lipoprotein cholesterol and benefit in all-cause mortality (P=0.038). No significant change was observed in neurocognitive adverse events (OR: 1.12 [95% CI, 0.88-1.42]; P=0.37), myalgia (OR: 0.95 [95% CI, 0.75-1.20]; P=0.65), new onset or worsening of preexisting diabetes mellitus (OR: 1.05 [95% CI, 0.95-1.17]; P=0.32), and increase in levels of creatine kinase (OR: 0.84 [95% CI, 0.70-1.01]; P=0.06) or alanine or aspartate aminotransferase (OR: 0.96 [95% CI, 0.82- 1.12]; P=0.61). Conclusions--Treatment with a PCSK9 inhibitor is well tolerated and improves cardiovascular outcomes. Although no overall benefit was noted in all-cause or cardiovascular mortality, such benefit may be achievable in patients with higher baseline lowdensity lipoprotein cholesterol.
KW - Alirocumab
KW - Evolocumab
KW - Hyperlipidemia
KW - Outcome
KW - PCSK9
UR - http://www.scopus.com/inward/record.url?scp=85038866681&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85038866681&partnerID=8YFLogxK
U2 - 10.1161/JAHA.117.006910
DO - 10.1161/JAHA.117.006910
M3 - Review article
C2 - 29223954
AN - SCOPUS:85038866681
SN - 2047-9980
VL - 6
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 12
M1 - e006910
ER -