Efficacy and safety of alirocumab and evolocumab: a systematic review and meta-analysis of randomized controlled trials
Open accessAbstract
Aims: The effect of low-density lipoprotein cholesterol-lowering therapy with alirocumab or evolocumab on individual clinical efficacy and safety endpoints remains unclear. We aimed to evaluate the efficacy and safety of alirocumab and evolocumab in patients with dyslipidaemia or atherosclerotic cardiovascular disease. Methods and results: We performed a review of randomized controlled trials (RCTs) comparing treatment with alirocumab or evolocumab vs. placebo or other lipid-lowering therapies up to March 2018. Primary efficacy endpoints were all-cause death, cardiovascular death, myocardial infarction (MI), and stroke. We estimated risk ratios (RR) and 95% confidence intervals (CI) using random effect models. We included 39 RCTs comprising 66 478 patients of whom 35 896 were treated with proprotein convertase subtilisin–kexin type 9 (PCSK9) inhibitors (14 639 with alirocumab and 21 257 with evolocumab) and 30 582 with controls. Mean weighted follow-up time across trials was 2.3 years with an exposure time of 150 617 patient-years. Overall, the effects of PCSK9 inhibition on all-cause death and cardiovascular death were not statistically significant (P = 0.15 and P = 0.34, respectively). Proprotein convertase subtilisin–kexin type 9 inhibitors were associated with lower risk of MI (1.49 vs. 1.93 per 100 patient-year; RR 0.80, 95% CI 0.74–0.86; I 2 = 0%; P < 0.0001), ischaemic stroke (0.44 vs. 0.58 per 100 patient-year; RR 0.78, 95% CI 0.67–0.89; I 2 = 0%; P = 0.0005), and coronary revascularization (2.16 vs. 2.64 per 100 patient-year; RR 0.83, 95% CI 0.78–0.89; I 2 = 0%; P < 0.0001), compared with the control group. Use of these PCSK9 inhibitors was not associated with increased risk of neurocognitive adverse events (P = 0.91), liver enzymes elevations (P = 0.34), rhabdomyolysis (P = 0.58), or new-onset diabetes mellitus (P = 0.97). Conclusion: Proprotein convertase subtilisin–kexin type 9 inhibition with alirocumab or evolocumab was associated with lower risk of MI, stroke, and coronary revascularization, with favourable safety profile.
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PCSK9 inhibitors profoundly reduce LDL cholesterol levels and lower cardiovascular risk.
“Proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitors profoundly reduce low-density lipoprotein (LDL) cholesterol levels and lower cardiovascular risk.1”
From Adherence to PCSK9 Inhibitors in Clinical Practice (2026) · cites this paper as [1]
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- Authors
- Guedeney, P., Giustino, G., Sorrentino, S., Claessen, B. E., Camaj, A., Kalkman, D. N., Vogel, B., Sartori, S., De Rosa, S., Baber, U., Indolfi, C., Montalescot, G., Dangas, G. D., Rosenson, R. S., Pocock, S. J., & Mehran, R.
- Affiliations
- Inserm (FR)
- Icahn School of Medicine at Mount Sinai (US)
- Magna Graecia University (IT)
- Amsterdam UMC Location University of Amsterdam (NL)
- Magna Graecia University Division of Cardiology, Department of Medical and Surgical Sciences, , Catanzaro, Italy
- London School of Hygiene & Tropical Medicine (GB)
- Corresponding author
- Mehran, Roxana
- ORCID
- Venue
- European Heart Journal
- Publisher
- Oxford University Press (OUP)
- Published
- 2019-07-03
- Volume
- 43
- Issue
- 7
- Pages
- e17-e25
- ISSN
- 0195-668X (ISSN-L)
- 1522-9645
- OpenAlex
- W2955200437
- Cited by
- 208
- References
- 12
- Citations by year
- 2026: 22 · 2025: 27 · 2024: 33 · 2023: 36 · 2022: 26 · 2021: 23 · 2020: 36 · 2019: 5
- FWCI
- 4.64
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Licence
- Locations
- European Heart Journal (publishedVersion)
- PubMed (publishedVersion)
- Amsterdam UMC (VU Amsterdam) - Institutional Repository (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- HAL (submittedVersion)
- Archive of Doctoral Theses and Digital Collections (University of Calabria) (submittedVersion)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Acute Myocardial Infarction Research
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Keywords
- alirocumab, evolocumab, PCSK9 inhibitors, LDL cholesterol lowering, dyslipidemia, atherosclerotic cardiovascular disease, myocardial infarction, ischemic stroke, coronary revascularization, all-cause mortality, cardiovascular mortality, drug safety, adverse events, lipid-lowering therapy, PCSK9 inhibition
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