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Research Article | Open Access

Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study)

Yu-Qi LIU1, Dan-Dan LI1, Meng CHAI2, Hong-Liang CONG3, Xiao-Qiang CONG4, Jun DAI5, Rong-Pin DU6, Ming GAO7, Jin-Cheng GUO8, Yan-Qing GUO9, Xiao-Jian HONG10, Rong-Chong HUANG11, Feng-Shun JIA12, Jia-Yu LI13, Qing LI14, Jia-Mei LIU15, Xin-Ping LIU14, Yu-Guo LIU16, Hong-Gang NIE17, Bing SHAO18, Xiao-Yu SHEN19, Hai-Qing SONG20, Yi-Jun SONG21, Li-Jun WANG22, Shuo WANG23, Dong-Mei WU24, Jing XIA25, Zhi-Yong YANG26, Hong-Ying YU27, Hui ZHANG28, Tie-Mei ZHANG29, Ji-Yi ZHAO30, Liang-Chen ZHAO31, Ming-Qi ZHENG32, Yun-Dai CHEN1()
Department of Cardiology, Chinese PLA General Hospital, Beijing, China
Department of Cardiology, Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart Lung and Blood Vessel Disease, Beijing Key Laboratory of Precision Medicine of Coronary Atherosclerotic Disease, Clinical Center for Coronary Heart Disease, Capital Medical University, Beijing, China
Department of Cardiology, Tianjin Chest Hospital, Tianjin, China
Department of Cardiology, the First Hospital of Jilin University, Changchun, China
Department of Cardiology, Fuwai Hospital, National Center for Cardiovascular Disease, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China
Department of Cardiology, Hebei People’s Hospital, Shijiazhuang, China
Department of Cardiology, Kailuan General Hospital, Hebei Union University, Tangshan, China
Department of Cardiology, Beijing Luhe Hospital, Capital Medical University, Beijing, China
Department of Cardiology, Shanxi Cardiovascular Hospital, Taiyuan, China
Department of Cardiology, the Fourth Affiliated Hospital of Harbin Medical University, Harbin, China
Department of Cardiology, Beijing Friendship Hospital, Capital Medical University, Beijing, China
Department of Cardiology, Tangshan Worker’s Hospital, Tangshan, China
Department of Cardiology, China-Japan Friendship Hospital Affiliated Jilin University, Changchun, China
Department of Cardiology, Handan Central Hospital, Hebei, China
Heart Center, Beijing Key Laboratory of Hypertension, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, China
Department of Cardiology, the First Affiliated Hospital of Dalian Medical University, Liaoning, China
Department of Cardiology, the Second Affiliated Hospital of Harbin Medical University, Harbin, China
Department of Cardiology, the Second Affiliated Hospital of Shenyang Medical College, Shenyang, China
Department of Cardiology, the Second Hospital of Shanxi Medical University, Taiyuan, China
Department of Neurology, Xuanwu Hospital Capital Medical University, Beijing, China
Department of Neurology, Tianjin Medical University General Hospital, Tianjin, China
Department of Cardiology, the Third Hospital of Shijiazhuang City, Shijiazhuang, China
Department of Cardiology, the First Hospital of Shijiazhuang City, Shijiazhuang, China
Department of Cardiology, Taigang General Hospital, Shanxi Medical University, Taiyuan, China
Department of Cardiology, the Sixth Medical Center of Chinese PLA General Hospital, Beijing, China
Department of Cardiology, Shengjing Hospital of China Medical University, Shengyang, China
Department of Cardiology, Daqing Oilfield General Hospital, Heilongjiang, China
Department of Cardiology, the Second Hospital of Baoding, Hebei, China
Department of Cardiology and Macrovascular Disease, Beijing Tiantan Hospital, Capital Medical University, Beijing, China
Department of Cardiology, the First Affiliated Hospital of Harbin Medical University, Harbin, China
Department of Cardiology, Jilin Central Hospital, Changchun, China
Heart Center, the First Hospital of Hebei Medical University, Shijiazhuang, China
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Abstract

BACKGROUND

The efficacy and safety of proprotein convertase subtilisin/kexin type 9 (PCSK-9) inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China has not been evaluated. This study aims to describe the real world effectiveness of PCSK-9 inhibitors combined with statins compared with statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease (ASCVD).

METHODS

This is a multi-center observational study, enrolled patients from 32 hospitals who underwent percutaneous coronary intervention (PCI) from January to June in 2019. There are 453 patients treated with PCSK-9 inhibitors combined with statins in PCSK-9 inhibitor group and 2,610 patients treated with statins-based lipid lowering therapies in statins-based group. The lipid control rate and incidence of major adverse cardiovascular events (MACE) over six months were compared between two groups. A propensity score-matched (PSM) analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for MACE.

RESULTS

In a total of 3,063 patients, 89.91% of patients had received moderate or high-intensity statins-based therapy before PCI, but only 9.47% of patients had low-density lipoprotein cholesterol (LDL-C) levels below 1.4 mmol/L at baseline. In the PSM selected patients, LDL-C level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P < 0.001) in statins-based group after six months. The proportion of LDL-C ≤ 1.0 mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins-based group, and the proportion of LDL-C ≤ 1.4 mmol/L increased from 10.36% to 47.69% in PCSK-9 inhibitor group and 2.99% to 18.43% in statins-based group (P < 0.001 for both). There was no significant difference between PCSK-9 inhibitor and statins-based treatment in reducing the risk of MACE (hazard ratio = 2.52, 95% CI: 0.49−12.97, P = 0.250).

CONCLUSIONS

In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL-C levels among patients with very high risk of ASCVD in China. The long-term clinical benefits for patients received PCSK-9 inhibitor to reduce the risk of MACE is still unclear and requires further study.

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Journal of Geriatric Cardiology
Volume 18 Issue 4,
April 2021
Pages 261-270
DOI: 10.11909/j.issn.1671-5411.2021.04.005
Cite this article:
LIU Y-Q, LI D-D, CHAI M, et al. Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins-based therapy among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study). Journal of Geriatric Cardiology, 2021, 18(4): 261-270. https://doi.org/10.11909/j.issn.1671-5411.2021.04.005
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Demographic and diseases characteristics of patients in PCSK-9 inhibitor and statins-based treatment groups after matched.

VariablesStatins-based group (n = 434)PCSK-9 inhibitor group (n = 434)P-value
Data are presented as n (%). *Presented as median (interquartile range). PCSK-9: proprotein convertase subtilisin/kexin type 9.
Age, yrs 60 (54–66)* 60 (52–68)* 0.350
Male gender 287 (66.1%) 294 (67.7%) 0.614
Body mass index 24.68 (23.28−27.09)* 24.77 (23.36−26.50)* 0.059
Hypertension 288 (66.4%) 293 (67.5%) 0.718
Diabetes mellitus 98 (22.6%) 117 (27.0%) 0.135
Stroke 60 (13.8%) 58 (13.4%) 0.843
Chronic kidney disease 3 (0.7%) 7 (1.6%) 0.341
Smoker 206 (47.5%) 207 (47.7%) 0.945
Medical history
　Myocardial infarction 24 (5.5%) 121 (27.9%) < 0.001
　Percutaneous coronary intervention 28 (6.5%) 88 (20.3%) < 0.001
　Coronary artery bypass graft 3 (0.7%) 43 (9.9%) < 0.001
Inpatient diagnose
　Stable angina 44 (10.1%) 23 (5.3%) 0.008
　Unstable angina 273 (62.9%) 263 (60.6%) 0.485
　Non-ST-elevation myocardial infarction 73 (16.8%) 61 (14.1%) 0.260
　ST-elevation myocardial infarction 44 (10.1%) 79 (18.2%) < 0.001
　Ischemic cardiomyopathy 0 8 (1.8%) −
Medication
　Other lipid lowering therapy 10 (2.3%) − −
　Aspirin 390 (89.9%) 392 (90.3%) 0.820
　β-blocker 170 (39.2%) 186 (42.9%) 0.270
　Calcium channel blockers 149 (34.3%) 155 (35.7%) 0.669
　Renin angiotensin-aldosterone 71 (16.4%) 63 (14.5%) 0.452

Demographic and diseases characteristics of patients in PCSK-9 inhibitor and statins groups before matched.

VariablesStatins group(n = 2,610)PCSK-9 inhibitor group (n = 453)P-valueMatched (n = 434)Unmatched (n = 2,176)P-value
Data are presented as n (%). *Presented as median (interquartile range). PCSK-9: proprotein convertase subtilisin/kexin type 9.
Age, yrs 59 (52−65)* 60 (51−68)* 0.510 60 (54−66)* 59 (51−65)* 0.002
Male gender 620 (23.8%) 311 (68.7%) < 0.001 287 (66.1%) 332 (15.3%) < 0.001
Body mass index 25.71 (23.72−27.78)* 24.78 (23.29−26.53)* < 0.001 24.58 (23.70−26.34)* 25.95 (23.95−28.08)* < 0.001
Hypertension 1,521 (58.3%) 302 (66.7%) 0.001 288 (66.4%) 1,233 (56.7%) < 0.001
Diabetes mellitus 730 (28.0%) 125 (27.6%) 0.869 98 (22.6%) 632 (29.0%) < 0.001
Stroke 172 (6.6%) 61 (13.5%) < 0.001 60 (13.8%) 112 (5.1%) < 0.001
Chronic kidney disease 19 (0.7%) 7 (1.5%) 0.80 3 (0.7%) 16 (0.7%) 1.000
Smoker 1,315 (50.4%) 216 (47.7%) 0.289 106 (24.4%) 1,209 (55.6%) < 0.001
Medical history
　Myocardial infarction 225 (8.6%) 123 (27.2%) < 0.001 24 (5.5%) 201 (9.2%) 0.012
　Percutaneous coronary intervention 316 (12.1%) 90 (19.9%) < 0.001 28 (6.5%) 288 (13.2%) < 0.001
　Coronary artery bypass graft 26 (1.0%) 44 (9.7%) < 0.001 3 (0.7%) 23 (1.1%) 0.605
Inpatient diagnose
　Stable angina 231 (8.9%) 25 (5.5%) 0.018 44 (10.1%) 187 (8.6%) 0.301
　Unstable angina 1,589 (60.9%) 274 (60.5%) 0.844 273 (62.9%) 1,316 (60.4%) 0.422
　Non-ST-elevation myocardial infarction 494 (18.9%) 66 (14.6%) 0.026 73 (16.8%) 421 (18.9%) 0.220
　ST-elevation myocardial infarction 292 (11.2%) 80 (17.7%) < 0.001 44 (10.1%) 248 (11.4%) 0.432
　Ischemic cardiomyopathy 4 (0.2%) 8 (1.8%) < 0.001 0 4 (0.2%) −
Laboratory test
　Low-density lipoprotein cholesterol, mmol/L 2.31 (1.78−2.97)* 3.04 (2.16−4.00)* < 0.001 2.89 (2.19−3.58)* 2.22 (1.74−2.82)* < 0.001
　High-density lipoprotein cholesterol, mmol/L 0.97 (0.82−1.14)* 1.08 (0.92−1.28)* < 0.001 1.08 (0.90−1.24)* 0.95 (0.81−1.12) * < 0.001
　Total cholesterol, mmol/L 3.90 (3.30−4.70)* 4.97 (3.95−6.04)* < 0.001 4.81 (3.98−5.63)* 3.77 (3.22−4.52)* < 0.001
　Triglycerides, mmol/L 1.45 (1.04−2.01)* 1.97 (1.24−3.09)* < 0.001 1.70 (1.15−2.71)* 1.42 (1.02−1.92)* < 0.001