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Original research article
Estimated individual lifetime benefit from PCSK9 inhibition in statin-treated patients with coronary artery disease
  1. Lotte Kaasenbrood1,
  2. Kausik K Ray2,
  3. S Matthijs Boekholdt3,
  4. Yvo M Smulders4,
  5. John C LaRosa5,
  6. John J P Kastelein6,
  7. Yolanda van der Graaf7,
  8. Johannes A N Dorresteijn1,
  9. Frank L J Visseren1
  1. 1 Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht, The Netherlands
  2. 2 Department of Primary Care and Public Health, School of Public Health, Imperial College London, London, UK
  3. 3 Department of Cardiology, Academic Medical Centre, Amsterdam, The Netherlands
  4. 4 Department of Internal Medicine, VU University Medical Center, Amsterdam, The Netherlands
  5. 5 SUNY Health Science Center, Brooklyn, New York, USA
  6. 6 Department of Vascular Medicine, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
  7. 7 Julius Centre for Health Sciences and Primary Care, University Medical Centre Utrecht, Utrecht, The Netherlands
  1. Correspondence to Dr Frank L J Visseren, Department of Vascular Medicine, University Medical Centre Utrecht, Utrecht 3584 CX, The Netherlands; F.L.J.Visseren{at}


Objective In statin-treated patients with stable coronary artery disease (CAD), residual risk of cardiovascular events is partly explained by plasma levels of low-density lipoprotein cholesterol (LDL-C). This study aimed to estimate individual benefit of proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibition in CAD patients already treated with high-dose statin.

Methods Individual lifetime benefit was estimated in months gain free of stroke or myocardial infarction (MI) until age 80 years. Predictions were based on two competing risk models developed in data from 4853 patients with CAD originating from the atorvastatin 80 mg arm of the Treating to New Targets (TNT) trial. The relative effect of PCSK9 inhibition was added to the models and was assumed based on average estimates from large clinical trials. We accounted for individual LDL-C levels, assuming 50% LDL-C reduction by PCSK9 inhibition and 21% cardiovascular risk reduction per mmol/L (39 mg/dL) LDL-C lowering.

Results Estimated individual gain was <6 months in 61% of the patients, 6–12 months in 28% of the patients and ≥12 months in 10% of the patients (median 5, quartiles 2–8 months). Highest estimated benefit was observed in younger patients (aged 40–60 years) with high risk factor burden, particularly if LDL-C levels were >1.8 mmol/L (>70 mg/dL). Estimated benefit was lowest (≤5 months) in older patients (≥70 years), in particular if LDL-C and other risk factors levels were low.

Conclusion The individual estimated lifetime benefit from PCSK9 inhibition in patients with stable CAD on high-dose statin varied from <6 to ≥12 months free of stroke or MI. Highest benefit is expected in younger patients (age 40–60 years) with high risk factor burden and relatively high LDL-C levels.

Trial registration number NCT00327691; Post-results

  • cardiac risk factors and prevention
  • coronary artery disease

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  • Contributors LK designed and carried out the data analyses, interpreted the results and drafted the manuscript. KKR, SMB, YvdG, YMS, JAND and FLJV designed the data analyses, interpreted the results and revised the manuscript for important intellectual content. JJPK and JCL collected the data, interpreted the results and revised the manuscript for important intellectual content.

  • Funding This work was supported by ZonMw, the Netherlands Organization for Health Research and Development (grant number 836011027). The TNT trial was sponsored by Pfizer. For the present study, the supporting sources had no involvement in study design, analysis, interpretation and writing of the results and decision to submit the report for publication.

  • Competing interests LK, YvdG, JAND and FLJV: declares no conflict of interest. KKR reports in the past year research grants to Institution: Pfizer, Amgen, MSD, Sanofi and Regeneron, and consulting for Aegerion, Amgen, Astra Zeneca, Boehringer Ingelheim, Cerenis, Eli Lilly, Kowa, Merck, Pfizer, Regeneron, Resverlogix, Sanofi and Takeda. SMB declares receiving consultancy fees from Pfizer. YMS declares no conflict of interest. JCL declares consulting fees from Pfizer, Merck, Bristol-Myers Squibb and AstraZeneca and lecture fees from Pfizer. JJPK declares that he has acted as a consultant to and received honoraria from the following companies: Amgen, AstraZeneca, Boehringer Ingelheim, Catabasis, Cerenis, CSL Behring, Dezima Pharmaceuticals, Eli Lilly, Esperion, Isis, Merck, Novartis, Pronova, Regeneron, Sanofi, The Medicines Company, Kowa, Gemfire, Cymabay and Roche.

  • Patient consent Not required.

  • Ethics approval Approval was obtained from institutional review boards.

  • Provenance and peer review Not commissioned; externally peer reviewed.