Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria
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 f...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2023-01-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| Subjects: | |
| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.122.026551 |
| _version_ | 1797905074673942528 |
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| author | Martina Aeschbacher‐Germann Nathalie Kaiser Alexandre Speierer Manuel R. Blum Douglas C. Bauer Cinzia Del Giovane Drahomir Aujesky Baris Gencer Nicolas Rodondi Elisavet Moutzouri |
| author_facet | Martina Aeschbacher‐Germann Nathalie Kaiser Alexandre Speierer Manuel R. Blum Douglas C. Bauer Cinzia Del Giovane Drahomir Aujesky Baris Gencer Nicolas Rodondi Elisavet Moutzouri |
| author_sort | Martina Aeschbacher‐Germann |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-04-10T09:59:15Z |
| format | Article |
| id | doaj.art-c965d218180148ee96de59a0b3aff9db |
| institution | Directory Open Access Journal |
| issn | 2047-9980 |
| language | English |
| last_indexed | 2024-04-10T09:59:15Z |
| publishDate | 2023-01-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj.art-c965d218180148ee96de59a0b3aff9db2023-02-16T10:55:33ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802023-01-0112110.1161/JAHA.122.026551Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion CriteriaMartina Aeschbacher‐Germann0Nathalie Kaiser1Alexandre Speierer2Manuel R. Blum3Douglas C. Bauer4Cinzia Del Giovane5Drahomir Aujesky6Baris Gencer7Nicolas Rodondi8Elisavet Moutzouri9Department of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandDepartments of Medicine and Epidemiology and Biostatistics University of California San Francisco CAInstitute of Primary Health Care (BIHAM) University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandInstitute of Primary Health Care (BIHAM) University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandDepartment of General Internal Medicine, Inselspital Bern University Hospital, University of Bern SwitzerlandBackground 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.https://www.ahajournals.org/doi/10.1161/JAHA.122.026551exclusion criteriaexternal validitygeneralizabilitylipid trialsmultimorbiditystatins |
| spellingShingle | Martina Aeschbacher‐Germann Nathalie Kaiser Alexandre Speierer Manuel R. Blum Douglas C. Bauer Cinzia Del Giovane Drahomir Aujesky Baris Gencer Nicolas Rodondi Elisavet Moutzouri Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease exclusion criteria external validity generalizability lipid trials multimorbidity statins |
| title | Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria |
| title_full | Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria |
| title_fullStr | Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria |
| title_full_unstemmed | Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria |
| title_short | Lipid‐Lowering Trials Are Not Representative of Patients Managed in Clinical Practice: A Systematic Review and Meta‐Analysis of Exclusion Criteria |
| title_sort | lipid lowering trials are not representative of patients managed in clinical practice a systematic review and meta analysis of exclusion criteria |
| topic | exclusion criteria external validity generalizability lipid trials multimorbidity statins |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.122.026551 |
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