STREAM Trial - Statins in Multimorbid Older Adults Without Cardiovascular Disease

NCT ID: NCT05178420

Last Updated: 2025-05-07

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

ACTIVE_NOT_RECRUITING

Clinical Phase

NA

Total Enrollment

1881 participants

Study Classification

INTERVENTIONAL

Study Start Date

2021-11-16

Study Completion Date

2026-11-15

Brief Summary

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Statins are among the most widely used drugs. While they were found to be effective for primary and secondary prevention of cardiovascular disease (CVD) in middle-aged subjects, their benefits for primary prevention in older adults (aged ≥70 years) without CVD are uncertain, particularly for those with multimorbidity. The aim of this randomized controlled trial (RCT) is to provide guidance on the benefits and risks of statin deprescribing in multimorbid older adults.

Detailed Description

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Background:

Until now, no RCT examining the benefits of statins in primary prevention has exclusively recruited multimorbid participants aged 70 years and older (70+), and 70+ participants are under-represented in most RCTs, including those examining statin benefits for primary prevention. However, statin side effects and drug interactions are common in populations of multimorbid older adults and might negatively impact quality of life. The proportion of patients developing myalgia on statins has been shown to be as high as 5-20% in observational studies; older age and polypharmacy are known risk factors for developing muscle problems under statins. Furthermore, multimorbid older adults with polypharmacy are more likely to experience side effects with statins (e.g. elevated liver enzymes, diabetes, myopathy, rhabdomyolysis) and drug-drug interactions (e.g. antibiotics, antifungals), with the potential consequences of drug toxicity, reduced physical activity, sarcopenia and falls. In practice, statins are often discontinued in multimorbid older adults without CVD after side effects. The net clinical benefit of statins for primary prevention in multimorbid 70+ older adults remains unclear, and the effect of multimorbidity might shift the evidence towards favoring no statin treatment, but no large RCT examined this issue.

Design:

The study is a multicenter, randomized, non-inferiority trial conducted in multiple centers in Switzerland, France and the Netherlands. Study subjects are randomly assigned in a 1:1 ratio to either discontinue (intervention arm) or continue (control arm) statin therapy. The study is open-label, with blinded outcome adjudication. After inclusion the study participants will be followed with phone calls, first after 3 months and then yearly for a mean of 24 months (min. follow-up period 12 months, max. follow-up period 48 months). Outcomes are assessed at each study follow-up.

Conditions

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Statin Treatment for Primary Prevention

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Study subjects are randomly assigned in a 1:1 ratio to either discontinue (intervention arm) or continue (control arm) statin therapy
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Outcome Assessors
The study is open-label, with blinded outcome adjudication. Identification of potential outcome events is performed by blinded study team members.

Study Groups

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Statin discontinuation

Discontinuation of statin therapy - statin therapy will be stopped from the next scheduled intake after study inclusion (intervention arm).

Group Type EXPERIMENTAL

Statin discontinuation

Intervention Type OTHER

Statin therapy will be stopped. Additional lipid-lowering medication lowering LDL cholesterol will also be stopped.

Statin continuation

Continuation of statin therapy - no change in the prescribed statin therapy (control arm).

Group Type NO_INTERVENTION

No interventions assigned to this group

Interventions

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Statin discontinuation

Statin therapy will be stopped. Additional lipid-lowering medication lowering LDL cholesterol will also be stopped.

Intervention Type OTHER

Other Intervention Names

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Intervention arm

Eligibility Criteria

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Inclusion Criteria

* Written informed consent
* ≥70 years of age
* Multimorbid with ≥2 coexistent chronic conditions (defined by ICD-10 codes) with an estimated duration of 6 months or more based on clinical decision, besides dyslipidemia treated by statins
* Intake of a statin for ≥80% of the time during the year before enrollment

Exclusion Criteria

1. Cardiovascular secondary prevention setting based on previous large statin trials, defined as:

* History of myocardial infarction type 1 (NSTEMI/STEMI), OR
* History of unstable angina, defined as ACS symptomatic at rest, crescendo or new-onset angina (CCS 2 or 3) without ECG or cardiac biomarker changes (based on available documents), OR
* Stable angina pectoris with a documented ischemia on a stress test or with a significant coronary disease defined as a coronary stenosis \>50%, OR
* History of percutaneous coronary intervention (balloon or stent) or coronary artery bypass graft, OR
* History of Stroke (does not apply to clearly cardio-embolic causes for stroke e.g. due to atrial fibrillation), OR
* History of Transient Ischemic Attack, defined as transient neurological deficit without diffusion restriction in MRI, OR
* History of carotid revascularization (stent, bypass, CEA (carotid thrombendartectomy)), OR
* History of peripheral arterial disease requiring revascularization (e.g. PTA (percutaneous transluminal angioplasty), stent, femoral TEA (thrombendartectomy), bypass; Fontaine IV)
2. Aortic disease that required a vascular repair or aortic aneurysm with a maximum diameter \>5.5 cm (men) or \>5.2 cm (women) based on available documents
3. Diagnosis of familial hypercholesterolemia based on Dutch lipid score ≥6 based on available documents (LDL cholesterol, family history, personal history)
4. Elevated risk of death within 3 months after baseline, defined as:

* Hospitalized patients planned for palliative care within 24h of admission OR
* Hospitalized patients with a Palliative Performance Scale (PPS) level \<30% (based on situation at least 1 month before hospitalization), this corresponds to an estimated survival of 43% after 3 months; OR
* Patients with an advanced metastatic cancer prognosis of ≤20% survival rate within 1 year after baseline (based on: https://cancersurvivalrates.com)
5. Participation to a clinical trial with potential impact on the STREAM cardiovascular endpoints (based on clinical judgment)
Minimum Eligible Age

70 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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University of Bern

OTHER

Sponsor Role collaborator

Insel Gruppe AG, University Hospital Bern

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Nicolas Rodondi, MD, MAS

Role: PRINCIPAL_INVESTIGATOR

University of Bern

Locations

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UNIVERSITY HOSPITAL CENTER of Bordeaux

Bordeaux, Nouvelle Acquitaine, France

Site Status

Leids Universitair Medisch Centrum

Leiden, South Holland, Netherlands

Site Status

Klinik Barmelweid AG

Barmelweid, Canton of Aargau, Switzerland

Site Status

Centre hospitalier Bienne

Biel/Bienne, Canton of Bern, Switzerland

Site Status

Spital Limmattal

Schlieren, Canton of Zurich, Switzerland

Site Status

Kantonsspital Graubünden

Chur, Kanton Graubünden, Switzerland

Site Status

Luzerner Höhenklinik Montana AG

Crans-Montana, Valais, Switzerland

Site Status

Kantonsspital Aarau

Aarau, , Switzerland

Site Status

Kantonsspital Baden

Baden, , Switzerland

Site Status

Universitätsspital Basel

Basel, , Switzerland

Site Status

Ospedale Regionale di Bellinzona e Valli

Bellinzona, , Switzerland

Site Status

Clinic for General Internal Medicine, Bern University Hospital Bern

Bern, , Switzerland

Site Status

Hospital Burgdorf

Burgdorf, , Switzerland

Site Status

HFR Fribourg

Fribourg, , Switzerland

Site Status

Hôpital La Tour

Geneva, , Switzerland

Site Status

Hôpitaux Universitaires de Genève (Geriatrics)

Geneva, , Switzerland

Site Status

Hôpitaux Universitaires de Genève (Internal Medicine)

Geneva, , Switzerland

Site Status

Hospital Langnau

Langnau, , Switzerland

Site Status

CHUV Lausanne

Lausanne, , Switzerland

Site Status

Hôpital Neuchâtelois

Neuchâtel, , Switzerland

Site Status

Hospital St. Gallen (Geriatrics)

Sankt Gallen, , Switzerland

Site Status

Kantonsspital Schaffhausen

Schaffhausen, , Switzerland

Site Status

Stadspital Waid

Zurich, , Switzerland

Site Status

Stadtspital Triemli

Zurich, , Switzerland

Site Status

Countries

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France Netherlands Switzerland

References

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Byrne P, Cullinan J, Smith SM. Statins for primary prevention of cardiovascular disease. BMJ. 2019 Oct 16;367:l5674. doi: 10.1136/bmj.l5674. No abstract available.

Reference Type BACKGROUND
PMID: 31619406 (View on PubMed)

Shepherd J, Blauw GJ, Murphy MB, Bollen EL, Buckley BM, Cobbe SM, Ford I, Gaw A, Hyland M, Jukema JW, Kamper AM, Macfarlane PW, Meinders AE, Norrie J, Packard CJ, Perry IJ, Stott DJ, Sweeney BJ, Twomey C, Westendorp RG; PROSPER study group. PROspective Study of Pravastatin in the Elderly at Risk. Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial. Lancet. 2002 Nov 23;360(9346):1623-30. doi: 10.1016/s0140-6736(02)11600-x.

Reference Type BACKGROUND
PMID: 12457784 (View on PubMed)

Han BH, Sutin D, Williamson JD, Davis BR, Piller LB, Pervin H, Pressel SL, Blaum CS; ALLHAT Collaborative Research Group. Effect of Statin Treatment vs Usual Care on Primary Cardiovascular Prevention Among Older Adults: The ALLHAT-LLT Randomized Clinical Trial. JAMA Intern Med. 2017 Jul 1;177(7):955-965. doi: 10.1001/jamainternmed.2017.1442.

Reference Type BACKGROUND
PMID: 28531241 (View on PubMed)

Cholesterol Treatment Trialists' Collaboration. Efficacy and safety of statin therapy in older people: a meta-analysis of individual participant data from 28 randomised controlled trials. Lancet. 2019 Feb 2;393(10170):407-415. doi: 10.1016/S0140-6736(18)31942-1.

Reference Type BACKGROUND
PMID: 30712900 (View on PubMed)

Ruscica M, Macchi C, Pavanello C, Corsini A, Sahebkar A, Sirtori CR. Appropriateness of statin prescription in the elderly. Eur J Intern Med. 2018 Apr;50:33-40. doi: 10.1016/j.ejim.2017.12.011. Epub 2018 Jan 5.

Reference Type BACKGROUND
PMID: 29310996 (View on PubMed)

van der Ploeg MA, Streit S, Achterberg WP, Beers E, Bohnen AM, Burman RA, Collins C, Franco FG, Gerasimovska-Kitanovska B, Gintere S, Gomez Bravo R, Hoffmann K, Iftode C, Pestic SK, Koskela TH, Kurpas D, Maisonneuve H, Mallen CD, Merlo C, Mueller Y, Muth C, Petrazzuoli F, Rodondi N, Rosemann T, Sattler M, Schermer T, Ster MP, Svadlenkova Z, Tatsioni A, Thulesius H, Tkachenko V, Torzsa P, Tsopra R, Tuz C, Vaes B, Viegas RPA, Vinker S, Wallis KA, Zeller A, Gussekloo J, Poortvliet RKE. Patient Characteristics and General Practitioners' Advice to Stop Statins in Oldest-Old Patients: a Survey Study Across 30 Countries. J Gen Intern Med. 2019 Sep;34(9):1751-1757. doi: 10.1007/s11606-018-4795-x. Epub 2019 Jan 16.

Reference Type BACKGROUND
PMID: 30652277 (View on PubMed)

Kutner JS, Blatchford PJ, Taylor DH Jr, Ritchie CS, Bull JH, Fairclough DL, Hanson LC, LeBlanc TW, Samsa GP, Wolf S, Aziz NM, Currow DC, Ferrell B, Wagner-Johnston N, Zafar SY, Cleary JF, Dev S, Goode PS, Kamal AH, Kassner C, Kvale EA, McCallum JG, Ogunseitan AB, Pantilat SZ, Portenoy RK, Prince-Paul M, Sloan JA, Swetz KM, Von Gunten CF, Abernethy AP. Safety and benefit of discontinuing statin therapy in the setting of advanced, life-limiting illness: a randomized clinical trial. JAMA Intern Med. 2015 May;175(5):691-700. doi: 10.1001/jamainternmed.2015.0289.

Reference Type BACKGROUND
PMID: 25798575 (View on PubMed)

Aebi PS, Adam L, Haller M, Bardoczi JB, Gencer B, Bonnet F, Beer JH, Carballo S, Christ-Crain M, Feller M, Gabutti L, Haynes AG, Moutzouri E, Chocano-Bedoya PO, Bassetti S, Escher R, Egger M, Poortvliet RKE, Schuetz P, Trelle S, Wertli MM, Zekry D, Mean M, Aujesky D, Bauer D, Blum MR, Rodondi N. 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. 2025 May 23;15(5):e093833. doi: 10.1136/bmjopen-2024-093833.

Reference Type DERIVED
PMID: 40409969 (View on PubMed)

Other Identifiers

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STREAM

Identifier Type: -

Identifier Source: org_study_id

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