Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial
Introduction Statins are among the most widely used drugs. While they are effective for primary and secondary prevention of cardiovascular (CV) disease in middle-aged subjects, their benefits for prevention in older adults (aged ≥70 years) without CV disease are uncertain, particularly for those wit...
Saved in:
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
BMJ Publishing Group
2025-05-01
|
| Series: | BMJ Open |
| Online Access: | https://bmjopen.bmj.com/content/15/5/e093833.full |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1849730313570222080 |
|---|---|
| author | Mirjam Christ-Crain Manuel R Blum Philipp Schuetz Luise Adam Elisavet Moutzouri Martin Feller Drahomir Aujesky Sven Trelle Nicolas Rodondi Marie Méan Rosalinde K E Poortvliet Jürg-Hans Beer Stefano Bassetti Fabrice Bonnet Sebastian Carballo Baris Gencer Robert Escher Dina Zekry Maria M Wertli Luca Gabutti Philipp Stefan Aebi Moa Haller Julia Bianca Bardoczi Alan G Haynes Patricia Orializ Chocano-Bedoya Martin Egger Douglas Bauer |
| author_facet | Mirjam Christ-Crain Manuel R Blum Philipp Schuetz Luise Adam Elisavet Moutzouri Martin Feller Drahomir Aujesky Sven Trelle Nicolas Rodondi Marie Méan Rosalinde K E Poortvliet Jürg-Hans Beer Stefano Bassetti Fabrice Bonnet Sebastian Carballo Baris Gencer Robert Escher Dina Zekry Maria M Wertli Luca Gabutti Philipp Stefan Aebi Moa Haller Julia Bianca Bardoczi Alan G Haynes Patricia Orializ Chocano-Bedoya Martin Egger Douglas Bauer |
| author_sort | Mirjam Christ-Crain |
| collection | DOAJ |
| description | Introduction Statins are among the most widely used drugs. While they are effective for primary and secondary prevention of cardiovascular (CV) disease in middle-aged subjects, their benefits for prevention in older adults (aged ≥70 years) without CV disease are uncertain, particularly for those with multimorbidity. Statin side effects and drug interactions are common in older patients and may negatively impact quality of life. To date, the only randomised controlled trial (RCT) investigating statin discontinuation in older adults has demonstrated no difference in survival but did note a small improvement in quality of life for those who discontinued statins. However, this trial exclusively enrolled patients with a life expectancy <1 year. Therefore, the present RCT aims to assess the safety and potential benefits of statin discontinuation in primary prevention for the ever-growing population of multimorbid older adults.Methods and analysis This study is a multicentre, randomised, non-inferiority trial conducted in both inpatient and outpatient settings in Switzerland, France and the Netherlands, targeting patients using statins for primary prevention. 1800 participants are randomly assigned 1:1 to either discontinue (intervention arm) or continue (control arm) statin therapy. The primary objective is to compare the primary composite endpoint of major CV events (non-fatal myocardial infarction or non-fatal ischaemic stroke) and all-cause death between the control and intervention groups over a follow-up duration of up to 48 months. We hypothesise that discontinuing statins does not result in shorter event-free survival, with a non-inferiority margin set at 5.2 weeks over a 2-year observation period. Secondary objectives are to compare patient-centred outcomes (health-related quality of life, muscle pain symptoms, falls and sarcopenia) and all-cause death, non-CV death, major CV events and coronary and peripheral artery revascularisation. The study is open-labelled, with blinded outcome adjudication of the primary endpoints.Ethics and dissemination The trial protocol has received approval from the local ethics committees in Switzerland, France and the Netherlands. Results will be published in a peer-reviewed journal.Trial registration number Clinicaltrials.gov: NCT05178420; BASEC (Swiss Ethics Commission): 2021-01513; FOPH (Swiss national portal): SNCTP000005172; Netherlands Trial Register: NL83907.058.23; France Trial Register: 22.04747.000158– IDRCB 2022-A02481-42. |
| format | Article |
| id | doaj-art-3afe27d582764701be5caaf8cfbc2e9f |
| institution | DOAJ |
| issn | 2044-6055 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Open |
| spelling | doaj-art-3afe27d582764701be5caaf8cfbc2e9f2025-08-20T03:08:55ZengBMJ Publishing GroupBMJ Open2044-60552025-05-0115510.1136/bmjopen-2024-093833Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trialMirjam Christ-Crain0Manuel R Blum1Philipp Schuetz2Luise Adam3Elisavet Moutzouri4Martin Feller5Drahomir Aujesky6Sven Trelle7Nicolas Rodondi8Marie Méan9Rosalinde K E Poortvliet10Jürg-Hans Beer11Stefano Bassetti12Fabrice Bonnet13Sebastian Carballo14Baris Gencer15Robert Escher16Dina Zekry17Maria M Wertli18Luca Gabutti19Philipp Stefan Aebi20Moa Haller21Julia Bianca Bardoczi22Alan G Haynes23Patricia Orializ Chocano-Bedoya24Martin Egger25Douglas Bauer26Department of Endocrinology, Diabetology and Metabolism, University Hospital Basel, Basel, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDivision of Internal Medicine, Kantonsspital Aarau, Aarau, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandCTU Bern, Department of Clinical Research, University of Bern, Bern, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDivision of Internal Medicine, Department of Medicine, Lausanne University Hospital, Lausanne, SwitzerlandDepartment of Public Health and Primary Care, Leiden University Medical Center, Leiden, The NetherlandsDepartment of Internal Medicine, Cantonal Hospital of Baden, Baden, SwitzerlandDivision of Internal Medicine, University Hospital Basel, Basel, SwitzerlandService de Médecine Interne et Maladies Infectieuses, Hôpital Saint-André, CHU de Bordeaux, and INSERM U1219, Bordeaux Population Health, Université de Bordeaux, Bordeaux, FranceDivision of General Internal Medicine, Hôpitaux Universitaires Genève, Geneva, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandDepartment of Internal Medicine, Spital Emmental, Burgdorf, SwitzerlandDivision of Internal Medicine for the Aged, Hôpitaux Universitaires Genève, University of Geneva, Geneva, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandDepartment of Internal Medicine, Repubblica e Cantone Ticino Ente Ospedaliero Cantonale, Bellinzona, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandDepartment of General Internal Medicine, Inselspital, Bern University Hospital, University of Bern, Bern, SwitzerlandCTU Bern, Department of Clinical Research, University of Bern, Bern, SwitzerlandInstitute of Primary Health Care (BIHAM), University of Bern, Bern, SwitzerlandClinic of Internal Medicine, Spital Emmental, Langnau, SwitzerlandDepartment of Medicine, University of California, San Francisco, San Francisco, California, USAIntroduction Statins are among the most widely used drugs. While they are effective for primary and secondary prevention of cardiovascular (CV) disease in middle-aged subjects, their benefits for prevention in older adults (aged ≥70 years) without CV disease are uncertain, particularly for those with multimorbidity. Statin side effects and drug interactions are common in older patients and may negatively impact quality of life. To date, the only randomised controlled trial (RCT) investigating statin discontinuation in older adults has demonstrated no difference in survival but did note a small improvement in quality of life for those who discontinued statins. However, this trial exclusively enrolled patients with a life expectancy <1 year. Therefore, the present RCT aims to assess the safety and potential benefits of statin discontinuation in primary prevention for the ever-growing population of multimorbid older adults.Methods and analysis This study is a multicentre, randomised, non-inferiority trial conducted in both inpatient and outpatient settings in Switzerland, France and the Netherlands, targeting patients using statins for primary prevention. 1800 participants are randomly assigned 1:1 to either discontinue (intervention arm) or continue (control arm) statin therapy. The primary objective is to compare the primary composite endpoint of major CV events (non-fatal myocardial infarction or non-fatal ischaemic stroke) and all-cause death between the control and intervention groups over a follow-up duration of up to 48 months. We hypothesise that discontinuing statins does not result in shorter event-free survival, with a non-inferiority margin set at 5.2 weeks over a 2-year observation period. Secondary objectives are to compare patient-centred outcomes (health-related quality of life, muscle pain symptoms, falls and sarcopenia) and all-cause death, non-CV death, major CV events and coronary and peripheral artery revascularisation. The study is open-labelled, with blinded outcome adjudication of the primary endpoints.Ethics and dissemination The trial protocol has received approval from the local ethics committees in Switzerland, France and the Netherlands. Results will be published in a peer-reviewed journal.Trial registration number Clinicaltrials.gov: NCT05178420; BASEC (Swiss Ethics Commission): 2021-01513; FOPH (Swiss national portal): SNCTP000005172; Netherlands Trial Register: NL83907.058.23; France Trial Register: 22.04747.000158– IDRCB 2022-A02481-42.https://bmjopen.bmj.com/content/15/5/e093833.full |
| spellingShingle | Mirjam Christ-Crain Manuel R Blum Philipp Schuetz Luise Adam Elisavet Moutzouri Martin Feller Drahomir Aujesky Sven Trelle Nicolas Rodondi Marie Méan Rosalinde K E Poortvliet Jürg-Hans Beer Stefano Bassetti Fabrice Bonnet Sebastian Carballo Baris Gencer Robert Escher Dina Zekry Maria M Wertli Luca Gabutti Philipp Stefan Aebi Moa Haller Julia Bianca Bardoczi Alan G Haynes Patricia Orializ Chocano-Bedoya Martin Egger Douglas Bauer Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial BMJ Open |
| title | Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial |
| title_full | Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial |
| title_fullStr | Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial |
| title_full_unstemmed | Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial |
| title_short | Rationale and design of ‘discontinuing statins in multimorbid older adults without cardiovascular disease (STREAM)’: study protocol of a randomised non-inferiority clinical trial |
| title_sort | rationale and design of discontinuing statins in multimorbid older adults without cardiovascular disease stream study protocol of a randomised non inferiority clinical trial |
| url | https://bmjopen.bmj.com/content/15/5/e093833.full |
| work_keys_str_mv | AT mirjamchristcrain rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT manuelrblum rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT philippschuetz rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT luiseadam rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT elisavetmoutzouri rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT martinfeller rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT drahomiraujesky rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT sventrelle rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT nicolasrodondi rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT mariemean rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT rosalindekepoortvliet rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT jurghansbeer rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT stefanobassetti rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT fabricebonnet rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT sebastiancarballo rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT barisgencer rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT robertescher rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT dinazekry rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT mariamwertli rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT lucagabutti rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT philippstefanaebi rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT moahaller rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT juliabiancabardoczi rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT alanghaynes rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT patriciaorializchocanobedoya rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT martinegger rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial AT douglasbauer rationaleanddesignofdiscontinuingstatinsinmultimorbidolderadultswithoutcardiovasculardiseasestreamstudyprotocolofarandomisednoninferiorityclinicaltrial |