STREAM Trial - Statins in Multimorbid Older Adults Without Cardiovascular Disease

NCT05178420 | Active Not Recruiting DMC

• 1 other identifier: STREAM
• Study Type: interventional
• Target: 1,880
• Locations: 3 countries
• Sites: 24

Brief Summary

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.

Conditions

Statin Treatment for Primary Prevention

Keywords

Multimorbidity; Primary prevention; Older adults; Deprescribing; Statin

Outcome Measures

Primary Outcomes (1)

• Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)

  The primary endpoint is a composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke). All-cause death (and not CV death only) is chosen to account for a possible shift from CV to other causes of death. The composite endpoint was selected to assess the net clinical benefit in this population with expected high mortality. The clinical event committee which classifies suspected events for the primary and secondary clinical outcomes is blinded. The primary analysis timeframe is at 24 months, and data collection is performed up to 48 months.

  24 months

Secondary Outcomes (11)

• Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)

  up to 48 months

• All-cause death

  up to 48 months

• Non-CV death

  up to 48 months

• Major CV events

  up to 48 months

• Total CV events

  up to 48 months

Study Arms (2)

Statin discontinuation

EXPERIMENTAL

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

Other: Statin discontinuation

Statin continuation

NO INTERVENTION

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

Interventions

Statin discontinuation OTHER

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

Also known as: Intervention arm

Statin discontinuation

Eligibility Criteria

• Age: 70 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)
• 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
• Diagnosis of familial hypercholesterolemia based on Dutch lipid score ≥6 based on available documents (LDL cholesterol, family history, personal history)
• 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)

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead
• University of Bern: collaborator

Study Sites (24)

UNIVERSITY HOSPITAL CENTER of Bordeaux

Bordeaux, Nouvelle Acquitaine, 33404 Talence Cedex, France

Location

Leids Universitair Medisch Centrum

Leiden, South Holland, 2333, Netherlands

Location

Klinik Barmelweid AG

Barmelweid, Canton of Aargau, 5017, Switzerland

Location

Centre hospitalier Bienne

Biel/Bienne, Canton of Bern, 2501, Switzerland

Location

Spital Limmattal

Schlieren, Canton of Zurich, 8952, Switzerland

Location

Kantonsspital Graubünden

Chur, Kanton Graubünden, 7000, Switzerland

Location

Luzerner Höhenklinik Montana AG

Crans-Montana, Valais, 3963, Switzerland

Location

Kantonsspital Aarau

Aarau, Switzerland

Location

Kantonsspital Baden

Baden, Switzerland

Location

Universitätsspital Basel

Basel, Switzerland

Location

Ospedale Regionale di Bellinzona e Valli

Bellinzona, Switzerland

Location

Clinic for General Internal Medicine, Bern University Hospital Bern

Bern, 3010, Switzerland

Location

Hospital Burgdorf

Burgdorf, Switzerland

Location

HFR Fribourg

Fribourg, 1752, Switzerland

Location

Hôpital La Tour

Geneva, Switzerland

Location

Hôpitaux Universitaires de Genève (Geriatrics)

Geneva, Switzerland

Location

Hôpitaux Universitaires de Genève (Internal Medicine)

Geneva, Switzerland

Location

Hospital Langnau

Langnau, Switzerland

Location

CHUV Lausanne

Lausanne, Switzerland

Location

Hôpital Neuchâtelois

Neuchâtel, Switzerland

Location

Hospital St. Gallen (Geriatrics)

Sankt Gallen, Switzerland

Location

Kantonsspital Schaffhausen

Schaffhausen, 8208, Switzerland

Location

Stadspital Waid

Zurich, Switzerland

Location

Stadtspital Triemli

Zurich, Switzerland

Location

Related Publications (8)

• 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.

  PMID: 31619406 BACKGROUND

• 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.

  PMID: 12457784 BACKGROUND

• 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.

  PMID: 28531241 BACKGROUND

• 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.

  PMID: 30712900 BACKGROUND

• 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.

  PMID: 29310996 BACKGROUND

• 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.

  PMID: 30652277 BACKGROUND

• 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.

  PMID: 25798575 BACKGROUND

• 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.

  PMID: 40409969 DERIVED

Study Officials

• Nicolas Rodondi, MD, MAS

  University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Masking Details: The study is open-label, with blinded outcome adjudication. Identification of potential outcome events is performed by blinded study team members.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

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

Study Record Dates

• First Submitted: November 15, 2021
• First Posted: January 5, 2022
• Study Start: November 16, 2021
• Primary Completion: April 30, 2026
• Study Completion (Estimated): November 15, 2026
• Last Updated: May 19, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, SAP, ICF
• Time Frame: Foreseen for one year after publication of the main trial results. Items will be retained indefinitely.
• Access Criteria: All efforts will be made to protect privacy and to de-identify the data. However, datasets contain sensitive data. Therefore, data will be shared on request under the following conditions: * A meaningful study question by the requester * Outline of the planned analyses * Valid methodology Signed data sharing agreement that contains a confidentiality agreement and other obligations to ensure privacy of trial participants

Locations

FR (1); CH (22); NL (1)