Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: A systematic review and meta-analysis

Heyue Du, Xiaodan Li, Na Su, Ling Li, Xiaoting Hao, Haihui Gao, Joey SW. Kwong, Per Olav Vandvik, Xueli Yang, Imola Nemeth, Ify Mordi, Qianrui Li, Longhao Zhang, Li Rao, Chim Lang, Jianshu Li, Haoming Tian, Sheyu Li (Lead / Corresponding author)

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Abstract

Background: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). Methods: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. Results: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. Conclusions: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. Trial registration: PROSPERO; CRD42017073904.

Original languageEnglish
JournalHeart
Early online date6 Mar 2019
DOIs
Publication statusE-pub ahead of print - 6 Mar 2019

Fingerprint

Proprotein Convertases
Subtilisin
Meta-Analysis
Stroke
Myocardial Infarction
Control Groups
Unstable Angina
Primary Prevention
Secondary Prevention
Hypercholesterolemia
Hyperlipidemias

Keywords

  • cardiovascular disease
  • lipid-lowering drugs
  • low-density lipoprotein cholesterol
  • proprotein convertase subtilisin/kexin type 9 inhibitors
  • systematic review

Cite this

Du, Heyue ; Li, Xiaodan ; Su, Na ; Li, Ling ; Hao, Xiaoting ; Gao, Haihui ; Kwong, Joey SW. ; Vandvik, Per Olav ; Yang, Xueli ; Nemeth, Imola ; Mordi, Ify ; Li, Qianrui ; Zhang, Longhao ; Rao, Li ; Lang, Chim ; Li, Jianshu ; Tian, Haoming ; Li, Sheyu . / Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes : A systematic review and meta-analysis. In: Heart. 2019.
@article{9805a290032740d899268e2b904c2096,
title = "Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: A systematic review and meta-analysis",
abstract = "Background: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). Methods: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95{\%} CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. Results: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16{\%} (RR, 0.84; 95{\%} CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95{\%} CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17{\%} (RR, 0.83; 95{\%} CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95{\%} CI 13 to 53 fewer) and any stroke by 25{\%} (RR, 0.75; 95{\%} CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95{\%} CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. Conclusions: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. Trial registration: PROSPERO; CRD42017073904.",
keywords = "cardiovascular disease, lipid-lowering drugs, low-density lipoprotein cholesterol, proprotein convertase subtilisin/kexin type 9 inhibitors, systematic review",
author = "Heyue Du and Xiaodan Li and Na Su and Ling Li and Xiaoting Hao and Haihui Gao and Kwong, {Joey SW.} and Vandvik, {Per Olav} and Xueli Yang and Imola Nemeth and Ify Mordi and Qianrui Li and Longhao Zhang and Li Rao and Chim Lang and Jianshu Li and Haoming Tian and Sheyu Li",
year = "2019",
month = "3",
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Du, H, Li, X, Su, N, Li, L, Hao, X, Gao, H, Kwong, JSW, Vandvik, PO, Yang, X, Nemeth, I, Mordi, I, Li, Q, Zhang, L, Rao, L, Lang, C, Li, J, Tian, H & Li, S 2019, 'Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes: A systematic review and meta-analysis' Heart. https://doi.org/10.1136/heartjnl-2019-314763

Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes : A systematic review and meta-analysis. / Du, Heyue ; Li, Xiaodan ; Su, Na ; Li, Ling ; Hao, Xiaoting ; Gao, Haihui ; Kwong, Joey SW. ; Vandvik, Per Olav ; Yang, Xueli ; Nemeth, Imola; Mordi, Ify; Li, Qianrui ; Zhang, Longhao ; Rao, Li ; Lang, Chim; Li, Jianshu ; Tian, Haoming ; Li, Sheyu (Lead / Corresponding author).

In: Heart, 06.03.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Proprotein convertase subtilisin/kexin 9 inhibitors in reducing cardiovascular outcomes

T2 - A systematic review and meta-analysis

AU - Du, Heyue

AU - Li, Xiaodan

AU - Su, Na

AU - Li, Ling

AU - Hao, Xiaoting

AU - Gao, Haihui

AU - Kwong, Joey SW.

AU - Vandvik, Per Olav

AU - Yang, Xueli

AU - Nemeth, Imola

AU - Mordi, Ify

AU - Li, Qianrui

AU - Zhang, Longhao

AU - Rao, Li

AU - Lang, Chim

AU - Li, Jianshu

AU - Tian, Haoming

AU - Li, Sheyu

PY - 2019/3/6

Y1 - 2019/3/6

N2 - Background: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). Methods: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. Results: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. Conclusions: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. Trial registration: PROSPERO; CRD42017073904.

AB - Background: To evaluate the effects of proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors on major adverse cardiovascular events (MACE). Methods: Our systematic review included randomised controlled trials if they studied PCSK9 inhibitors in patients for primary and/or secondary prevention of cardiovascular diseases or with hypercholesterolaemia/hyperlipidaemia. Dichotomous variables from individual studies were pooled by relative risks (RR) and their 95% CIs using the random-effect model. Risk difference (RD) in the 10-year frame was also estimated using the pooled RR and the estimated baseline risk using the control group. Grading of Recommendation Assessment, Development and Evaluation was used to assess the quality of evidence. Results: We included 54 trials with 97 910 patients in the analysis. Compared with controls, PCSK9 inhibitors significantly reduced the risk of MACE by 16% (RR, 0.84; 95% CI 0.79 to 0.89; RD: 47 fewer per 1000 vs 286 as the baseline risk; 95% CI 32 to 59 fewer), non-fatal myocardial infarction (MI) by 17% (RR, 0.83; 95% CI 0.74 to 0.93; RD, 35 fewer per 1000 vs 207 as the baseline; 95% CI 13 to 53 fewer) and any stroke by 25% (RR, 0.75; 95% CI 0.65 to 0.85; RD, 16 fewer per 1000 vs 61 as the baseline; 95% CI 9 to 21 fewer) with moderate quality evidence. No significant differences were found between PCSK9 inhibitors and control groups in all-cause mortality, cardiovascular death, heart failure or unstable angina with low-quality evidence. Conclusions: This study demonstrated that PCSK9 inhibitors could significantly reduce the risk of MACE, non-fatal MI and stroke. Trial registration: PROSPERO; CRD42017073904.

KW - cardiovascular disease

KW - lipid-lowering drugs

KW - low-density lipoprotein cholesterol

KW - proprotein convertase subtilisin/kexin type 9 inhibitors

KW - systematic review

UR - http://www.scopus.com/inward/record.url?scp=85062665968&partnerID=8YFLogxK

U2 - 10.1136/heartjnl-2019-314763

DO - 10.1136/heartjnl-2019-314763

M3 - Article

JO - Heart

JF - Heart

SN - 1355-6037

ER -