Scientific article
Open access

Lipid-lowering trials are not representative of patients managed in clinical practice : a systematic review and meta-analysis of exclusion criteria

Publication date2023-01-03
First online date2022-12-24

Background Randomized clinical trials (RCTs) might not be representative of the real-world population because of unreasonable exclusion criteria. We sought to determine which groups of patients are excluded from RCTs that included lipid-lowering therapy. Methods and Results We retrieved all trials from the Cholesterol Treatment Trialists Collaboration and systematically searched for large (≥1000 participants) lipid-lowering therapy RCTs, defined as statins, ezetimibe, and PCSK9 inhibitors. We predefined groups: older adults (>70 or >75 years), women, non-Whites, chronic kidney failure, heart failure, immunosuppression, cancer, dementia, treated thyroid disease, chronic obstructive pulmonary disease, mental illness, atrial fibrillation, multimorbidity (≥2 chronic diseases), and polypharmacy. We counted the number of RCTs excluding patients of the predefined groups and meta-analyzed the prevalence of included patients to obtain pooled estimates with a random-effects model. We included 42 RCTs (298 605 patients). Eighty-one percent of trials excluded patients with severe and 76% those with moderate kidney failure. Seventy-one percent of trials excluded groups of women, 64% excluded patients with moderate to severe heart failure, 64% those with immunosuppressant conditions, 48% those with cancer, 29% those with dementia, and 29% of trials excluded older adults. The pooled prevalence for patients >70 years of age was 25% (95% CI, 0%-49%), 11% (3%-18%) for >75 years of age, and 51% (38%-63%) for multimorbidity. Conclusions The majority of lipid-lowering therapy trials excluded patients with common diseases, such as moderate-to-severe kidney disease or heart failure or with immunosuppression. Underrepresenting certain populations, including women and older adults, might lead to limited transportability of study results and uncertainty on possible side-effects and efficacy in these groups. Future trials should promote diversity in the recruitment strategies and improve equity in cardiovascular research. Registration URL: ClinicalTrials.gov; Unique Identifier: CRD42021253909.

  • Exclusion criteria
  • External validity
  • Generalizability
  • Lipid trials
  • Multimorbidity
  • Statins
  • Female
  • Humans
  • Aged
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Ezetimibe / therapeutic use
  • Cholesterol
  • Heart Failure / drug therapy
  • Heart Failure / epidemiology
  • Dementia
  • Proprotein Convertase 9
Citation (ISO format)
AESCHBACHER-GERMANN, Martina et al. Lipid-lowering trials are not representative of patients managed in clinical practice : a systematic review and meta-analysis of exclusion criteria. In: Journal of the American Heart Association. Cardiovascular and cerebrovascular disease, 2023, vol. 12, n° 1, p. e026551. doi: 10.1161/JAHA.122.026551
Main files (1)
Article (Published version)
ISSN of the journal2047-9980

Technical informations

Creation10/19/2023 1:48:00 PM
First validation02/27/2024 4:57:54 PM
Update time02/27/2024 4:57:54 PM
Status update02/27/2024 4:57:54 PM
Last indexation05/06/2024 6:02:21 PM
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