Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials

Abstract

Purpose

Proprotein convertase subtilisin/kexin 9 (PCSK9) inhibitors treatment induce large reductions in low-density lipoprotein cholesterol (LDLc) and major cardiovascular events. Clinical trials might have been underpowered to test the effect of PSCK9 inhibitors treatment on myocardial infarction and stroke, two of the most relevant cardiovascular events, since all analyzed a combined endpoint.

Methods

we performed a meta-analysis, with currently available studies involving PCSK9 inhibitors and event rate adjudication, with the aim of assessing treatment effects on myocardial infarction and stroke.

Results

We included 81,700 patients, 41,979 treated with a PSCK9 inhibitors: 17,244 with evolocumab; 13,720 with bococizumab and 11,015 with alirocumab. A total of 1,319 cases of myocardial infarctions were registered in the treatment group vs. 1,608 in controls, resulting in 19.0% reduction associated with PCSK9 treatment (RR: 0.81, 95% CI 0.76–0.87). Similarly, PCSK9 inhibitors treatment resulted in a 25% reduction of stroke (RR: 0.75, 95% CI 0.65–0.85) when all studies were analyzed together and the statistically significant heterogeneity was not observed in the analysis restricted to end-point based clinical trials. PCSK9 inhibitors treatment had no effect on mortality (RR: 0.95, 95% CI 0.86–1.04).

Conclusions

PCSK9 inhibitors reduce the incidence of myocardial infarction by 19% and stroke by 25%.

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Acknowledgements

Investigators received the support of the Centro de Investigación Biomédica en Red de Enfermedades Cardiovasculares (CIBERCV) Spain, the National Network for Biomedical Research in Cardiovascular Disease.

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Correspondence to Alberto Cordero.

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Cordero, A., Rodríguez-Mañero, M., Fácila, L. et al. Prevention of myocardial infarction and stroke with PCSK9 inhibitors treatment: a metanalysis of recent randomized clinical trials. J Diabetes Metab Disord (2020). https://doi.org/10.1007/s40200-020-00557-6

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Keywords

  • PCSK9
  • LDLc
  • Acute coronary syndrome
  • Stroke
  • Meta-analysis