Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia: A meta-analysis of 35 randomized controlled trials

Aris Karatasakis, Barbara A. Danek, Judit Karacsonyi, Bavana V. Rangan, Michele K. Roesle, Thomas Knickelbine, Michael D. Miedema, Houman Khalili, Zahid Ahmad, Shuaib Abdullah, Subhash Banerjee, Emmanouil S. Brilakis

Research output: Contribution to journalReview article

47 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article numbere006910
JournalJournal of the American Heart Association
Volume6
Issue number12
DOIs
StatePublished - Dec 1 2017

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Hypercholesterolemia
Meta-Analysis
Randomized Controlled Trials
Odds Ratio
Confidence Intervals
Mortality
LDL Cholesterol
Proprotein Convertase 9
Myalgia
Therapeutics
Creatine Kinase
Aspartate Aminotransferases
Alanine Transaminase
Diabetes Mellitus
Stroke
Myocardial Infarction
Safety

Keywords

  • Alirocumab
  • Evolocumab
  • Hyperlipidemia
  • Outcome
  • PCSK9

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

Cite this

Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia : A meta-analysis of 35 randomized controlled trials. / Karatasakis, Aris; Danek, Barbara A.; Karacsonyi, Judit; Rangan, Bavana V.; Roesle, Michele K.; Knickelbine, Thomas; Miedema, Michael D.; Khalili, Houman; Ahmad, Zahid; Abdullah, Shuaib; Banerjee, Subhash; Brilakis, Emmanouil S.

In: Journal of the American Heart Association, Vol. 6, No. 12, e006910, 01.12.2017.

Research output: Contribution to journalReview article

Karatasakis, Aris ; Danek, Barbara A. ; Karacsonyi, Judit ; Rangan, Bavana V. ; Roesle, Michele K. ; Knickelbine, Thomas ; Miedema, Michael D. ; Khalili, Houman ; Ahmad, Zahid ; Abdullah, Shuaib ; Banerjee, Subhash ; Brilakis, Emmanouil S. / Effect of PCSK9 inhibitors on clinical outcomes in patients with hypercholesterolemia : A meta-analysis of 35 randomized controlled trials. In: Journal of the American Heart Association. 2017 ; Vol. 6, No. 12.
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abstract = "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.",
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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.

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

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DO - 10.1161/JAHA.117.006910

M3 - Review article

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JO - Journal of the American Heart Association

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