Discontinuing Statins in Multimorbid Older Adults Without Cardiovascular Disease (STREAM) - a Randomized Non-inferiority Clinical Trial
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 1,880
- 试验地点
- 36
- 主要终点
- Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
盲法说明
The study is open-label, with blinded outcome adjudication. Identification of potential outcome events is performed by blinded study team members.
入排标准
- 年龄范围
- 70 Years 至 —（Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
- •Participation to a clinical trial with potential impact on the STREAM cardiovascular endpoints (based on clinical judgment)
研究组 & 干预措施
Statin discontinuation
Discontinuation of statin therapy - statin therapy will be stopped from the next scheduled intake after study inclusion (intervention arm).
干预措施: Statin discontinuation (Other)
Statin continuation
Continuation of statin therapy - no change in the prescribed statin therapy (control arm).
结局指标
主要结局
Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)
时间窗: 24 months
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.
次要结局
- Non-CV death(up to 48 months)
- Major CV events(up to 48 months)
- All-cause death(up to 48 months)
- Total CV events(up to 48 months)
- Total composite events(up to 48 months)
- Self-reported falls(12 months)
- Composite endpoint of all-cause death and major non-fatal CV events (non-fatal myocardial infarction, non-fatal ischemic stroke)(up to 48 months)
- EQ-5D questionnaire(3, 12 (primary analysis), 24, 36, 48 months)
- Strength, assistance with walking, rising from a chair, climbing stairs, and falls (SARC-F questionnaire)(12 (primary analysis), 24, 36, 48 months)
- Girerd medication adherence scale(12 (primary analysis), 24, 36, 48 months)
- Verbal numeric pain rating score (VNPRS)(3 months)