Impact of Statin Therapy and Intensity on Postoperative and Mortality and Morbidity: A Prospective Observational Dual-Centre Cohort Study
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 70,000
- 试验地点
- 2
研究概览
简要总结
Statins are among the most widely prescribed drugs worldwide, and their benefits in cardiovascular risk reduction are well established. Beyond lipid lowering, statins exert pleiotropic effects - including anti-inflammatory, antioxidant, and endothelial-stabilizing properties - that have generated longstanding interest in their potential to mitigate perioperative complications.
Major surgery provokes a systemic inflammatory response, endothelial activation, and hemodynamic stress that may precipitate myocardial injury, organ dysfunction, and death, particularly in patients with pre-existing cardiovascular disease.
Therefore, the aim is to examine the association between preoperative statin therapy and its intensity with postoperative all-cause mortality and days at home alive after major non-cardiac surgery in a large, contemporary, dual center-based cohort.
详细描述
Research hypothesis: Preoperative statin use is independently associated with reduced 30-day and 365-day all-cause mortality compared with no statin use. Higher statin intensity (high vs. low or moderate) is independently associated with reduced 30-day and 365-day all-cause mortality. Statin use and intensity are independently associated with greater DAH30 and DAH365, reflecting reduced postoperative morbidity
Background: Early randomised trials suggested that initiating statin therapy before surgery could reduce cardiac complications and mortality. However, several pivotal trials were subsequently retracted following research misconduct, undermining the evidence base for perioperative statin initiation and rendering clinical guidelines equivocal. Importantly, these discredited trials examined de novo short-term statin initiation - a question distinct from whether patients on established, chronic statin therapy experience better postoperative outcomes.
Subsequent observational studies have reported associations between preoperative statin use and reduced postoperative morbidity and mortality, but most have been limited by narrow surgical populations, and an inability to examine dose-response relationships, residual confounding or patient-centred outcomes beyond mortality.
Data collection and analysis: Data is collected prospectively between 2016 and 2023 across two tertiary academic centres - Karolinska University Hospital Solna and Huddinge - from electronic health records. Statin exposure status and intensity were ascertained from based on registered Anatomical Therapeutic Chemical (ATC) classification codes The primary analytical approach uses inverse probability of treatment weighting, implemented across two pre-specified binary analyses - statin use versus no use in the full cohort, and high versus low-moderate intensity within statin users, for more details see attached statistical analysis plan.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults aged ≥ 18 years at the time of surgery
- •Elective (non-emergency) surgical procedure
- •Non-cardiac surgery (all surgical specialties except cardiac surgery)
排除标准
- •Obstetric surgery
- •Transplant surgery
- •Planned day-case surgery (procedures with intended same-day discharge)
- •Anesthetic monitoring episodes not involving a surgical procedure (e.g., anesthetic support for central venous catheter insertion)
- •Urological brachytherapy
- •Stereotactic radiosurgery (Gamma Knife or equivalent)
- •Repeat or subsequent surgical procedures during the study period - only the index (chronologically first eligible) procedure per patient is included in the analysis
研究者
Arman Valadkhani
Consultant in Anaesthesiology and Intensive Care and Postdoctoral Researcher
Karolinska Institutet