The Impact of Preoperative Statin Therapy and and Its Intensity on Postoperative and Mortality and Morbidity (STIMM)

Impact of Statin Therapy and Intensity on Postoperative and Mortality and Morbidity: A Prospective Observational Dual-Centre Cohort Study

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.

Study Overview

• Status: Completed
• Conditions: Perioperative Care

Detailed Description

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.

• Study Type: Observational
• Enrollment (Actual): 70000

Contacts and Locations

Study Locations

• Sweden
  • Stockholm, Sweden
    • Karolinska University Hospital Huddinge
  • Stockholm, Sweden
    • Karolinska University Hospital Solna

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: N/A

• Sampling Method: Non-Probability Sample

Study Population

Adult patients (equal to or over 18 years) undergoing elective non-cardiac surgery

Description

Inclusion Criteria:

• Adults aged ≥ 18 years at the time of surgery
• Elective (non-emergency) surgical procedure
• Non-cardiac surgery (all surgical specialties except cardiac surgery)

Exclusion Criteria:

• 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

Study Plan

How is the study designed?

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
30- and 365-day mortality	Death within the time frames described	30 and 365 days respectively

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DAH30 (Days At Home alive at 30 days) and DAH365 (Days At Home alive at 365 days)	DAH30: Patients who are hospitalized for 14 days postoperatively but are alive on day 30 will have DAH30=16. Patients who are hospitalized for five days, then discharged, but return after 10 days for an additional 11-day stay, will have DAH30=14. Anyone who dies within 30 days will have DAH30=0. This outcome measure is validated in several studies and has a significant advantage in that it correlates well with complications, even better than length of stay (LOS). We will further record DAH365, calculated as described above.	30 and 365 days after index surgery,

Collaborators and Investigators

• Sponsor: Karolinska Institutet

Study record dates

Study Major Dates

• Study Start (Actual): May 14, 2024
• Primary Completion (Actual): February 2, 2026
• Study Completion (Actual): February 2, 2026

Study Registration Dates

• First Submitted: May 4, 2026
• First Submitted That Met QC Criteria: May 4, 2026
• First Posted (Actual): May 8, 2026

Study Record Updates

• Last Update Posted (Actual): May 13, 2026
• Last Update Submitted That Met QC Criteria: May 10, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Other Study ID Numbers: 2024-01664-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED