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General medicine
Upholding trust in therapeutic trials and evidence-based medicine: need for full disclosure of data, crowdsourcing data analysis and independent review?
  1. Pierre Vladimir Ennezat1,
  2. Raphaëlle Ashley Guerbaai2,
  3. Thierry H Le Jemtel3
  1. 1Cardiology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France
  2. 2Department of Public Health, Medizinische Fakultät, Universität Basel, Basel, Switzerland
  3. 3Department of Cardiology, Tulane University School of Medicine; Tulane University Heart and Vascular Institute, New Orleans, Louisiana, USA
  1. Correspondence to Dr Pierre Vladimir Ennezat, Cardiology, Centre Hospitalier Universitaire Grenoble Alpes, Grenoble 38043, France; ennezat{at}yahoo.com

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An active 74-year-old woman with hypertension and a family history of hypercholesterolaemia was referred for evaluation of chest pain and underwent coronary angiography. Low-density lipoprotein (LDL) cholesterol was 270 mg/dL. Coronary and carotid arteries were patent, and the echocardiogram was normal. The patient could not tolerate statins due to incapacitating muscle weakness and pain. Age combined with a history of familial hypercholesterolaemia are high cardiovascular risk factors, and the 2019 European Society of Cardiology guidelines recommend LDL cholesterol reduction by at least 50% from baseline and targeting LDL cholesterol <55 mg/dL (class IIa, level of evidence C).1 She declined the recently marketed treatment with proprotein convertase subtilisin/kexin type-9 serine protease (PCSK9) inhibitor due to the lack of long-term outcome data.

In early 2019, the editors-in-chief of leading cardiovascular journals wrote a joint editorial (published in 15 journals) that held media responsible for the distrust in vaccination and statin therapy.2 In 1996, the editor-in-chief of the American Journal of Cardiology wrote that statins are to atherosclerosis what penicillin is to infectious disease3; Fausto Pinto, immediate ESC past-president, stated ‘After antibiotics, statins may have contributed more to prolonging life expectancy than any other type of medications’. We discuss in the following sections, the overestimation of the effect of statins, as well as the small size effect present in most trials and methodological bias.

Overestimation of the effects of drugs

The results of positive statin trials are commonly viewed as impressive with a relative risk reduction of events of 20%–40%, when the absolute risk reduction is a modest 1%–5% (see online supplementary table 1). Danish investigators did evaluate the beneficial effects of statins on outcome as a postponement of death by a median of 10.2 and 17.4 days over the duration of relevant primary and secondary prevention trials, respectively.4 Similarly, ezetimibe, which has no effect on …

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Footnotes

  • Contributors The three authors substantially contributed to the conception or design of the work, the acquisition, analysis and interpretation of data for the work; PVE drafted the work; THLJ and RAG revised it critically for important intellectual content; and finally approved the version to be published; and agreed to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Patient consent for publication Obtained.

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

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