Utility of Biomarkers With Statin Therapy in Multimorbid Older Adults - An Ancillary Study Nested Within a Randomized Trial
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 500
- 试验地点
- 2
- 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. Older patients with elevated biomarkers associated with cardiovascular (CV) risk might benefit from continuing statins to prevent CV outcomes, but this hypothesis has not been rigorously tested in randomized clinical trials (RCTs). To address these questions, the investigators conduct a RCT in 500 multimorbid adults ≥70 years old taking statins for primary prevention who will be randomized to statin continuation vs. statin discontinuation, and measure baseline biomarkers to determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs among those with baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes.
详细描述
Background & rationale: The benefit of statin use for primary prevention is uncertain in older adults with multimorbidity, while harms such as side effects may be more common in this population. Therefore, the 2018 AHA/ACC cholesterol guidelines mention that it may be reasonable to discontinue statins in multimorbid older adults without cardiovascular disease (CVD). Older patients with elevated biomarkers associated with cardiovascular (CV) risk might benefit from continuing statins to prevent CV outcomes, but this hypothesis has not been rigorously tested in randomized clinical trials (RCTs). To address this question, the investigators conduct a RCT in 500 multimorbid adults ≥70 years old taking statins for primary prevention who will be randomized to statin continuation vs. statin discontinuation, and measure baseline biomarkers to determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs among those with baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes.
Specific aim:
To determine if the risk of a composite outcome of CV events and all-cause mortality after statin discontinuation differs according to the baseline levels of previously validated blood biomarkers associated with increased risk of CV outcomes (lipoprotein(a), inflammatory markers [high-sensitivity C-reactive Protein], myocardial damage/wall strain [NT-proBNP, troponin]).
Design:
The study is a multicenter, randomized, non-inferiority trial conducted in multiple centers in Switzerland. 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. We will measure previously validated biomarkers at baseline.
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. Participants, care providers, investigators and outcomes assessors are blinded to the baseline biomarker levels.
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
- •≥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
- •Taking a statin for ≥80% of the time during the year before baseline
- •Exclusion criteria:
- •Secondary prevention based on previous large statin trials, defined as:
- •History of myocardial infarction type 12 (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 ischemic stroke OR
- •History of Transient Ischemic Attack, defined as transient neurological deficit without diffusion restriction in MRI OR
- •History of carotid revascularization (stent or bypass) OR
- •History of peripheral arterial disease requiring revascularization (stent or 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-c, 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 an online tool: https://cancersurvivalrates.com)
排除标准
- 未提供
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: Up to 48 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.
次要结局
- Total composite events(Up to 48 months)
- Total CV events(Up to 48 months)
- Non-CV death(Up to 48 months)
- Major CV events(Up to 48 months)
- Verbal numeric pain rating score (VNPRS)(3 months)
- Girerd medication adherence scale(12 (primary analysis), 24, 36, 48 months)
- All-cause death(Up to 48 months)
- Self-reported falls(Up to 12 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)