Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial

Maura Marcucci; Emmanuelle Duceppe; Yannick Le Manach; Clive Kearon; John W Eikelboom; Kayla Pohl; Jessica Vincent; Saeed Darvish-Kazem; Sadeesh K Srinathan; John D D Neary; Joel L Parlow; Andrea Kurz; Peter L Gross; Marko Mrkobrada; Kumar Balasubramanian; Daniel I Sessler; P J Devereaux

doi:10.1186/s40814-020-00643-9

Tranexamic acid and rosuvastatin in patients at risk of cardiovascular events after noncardiac surgery: a pilot of the POISE-3 randomized controlled trial

Pilot Feasibility Stud. 2020 Jul 21:6:104. doi: 10.1186/s40814-020-00643-9. eCollection 2020.

Authors

Maura Marcucci^{1

2

3}, Emmanuelle Duceppe^{1

3

4}, Yannick Le Manach^{1

3

5}, Clive Kearon^{1

2}, John W Eikelboom², Kayla Pohl³, Jessica Vincent³, Saeed Darvish-Kazem^{2

6}, Sadeesh K Srinathan⁷, John D D Neary², Joel L Parlow⁸, Andrea Kurz⁹, Peter L Gross⁴, Marko Mrkobrada¹⁰, Kumar Balasubramanian³, Daniel I Sessler⁹, P J Devereaux^{1

2

3}

Affiliations

¹ Department of Health Research Methods, Evidence, and Impact, McMaster University, Hamilton, ON Canada.
² Department of Medicine, McMaster University, Hamilton, ON Canada.
³ Population Health Research Institute, Hamilton, ON Canada.
⁴ Department of Medicine, University of Montreal, Montreal, QC Canada.
⁵ Department of Anesthesia, McMaster University, Hamilton, ON Canada.
⁶ William Osler Health System, Brampton, ON Canada.
⁷ Department of Surgery, University of Manitoba, Winnipeg, MB Canada.
⁸ Department of Anesthesiology and Perioperative Medicine, Kingston General Hospital and Queen's University, Kingston, ON Canada.
⁹ Department of Outcomes Research, Anesthesiology Institute, Cleveland Clinic, Cleveland, OH USA.
¹⁰ Department of Medicine, University of Western Ontario, London, ON Canada.

Abstract

Background: Surgical bleeding is associated with postoperative cardiovascular complications. The efficacy and safety of tranexamic acid (TXA) in noncardiac surgery are still uncertain. Statins may prevent perioperative cardiovascular complications. We conducted a pilot to assess the feasibility of a perioperative trial of TXA and rosuvastatin.

Methods: Using a factorial design, we randomized patients at cardiovascular risk undergoing noncardiac surgery to intravenous TXA (1 g at the start and end of surgery) or placebo, and oral rosuvastatin (40 mg before and 20 mg daily for 30 days after surgery) or placebo. Feasibility outcomes included recruitment rates, follow-up, and compliance to interventions. Clinical outcomes were secondarily explored.

Results: After 3 months, we changed the design to a partial factorial due to the difficult recruitment of statin-naive patients. Over 6 months, 100 patients were randomized in the TXA trial (49 TXA, 51 placebo), 34 in the rosuvastatin trial (18 rosuvastatin, 16 placebo). Ninety-two percent (95% CI 80-98) of TXA and 86% (95% CI 74-94) of TXA-placebo patients received the 2 study doses. Thirty-three percent (95% CI 13-59) of rosuvastatin patients and 37% (95% CI 15-65) of rosuvastatin-placebo patients discontinued the study drug. A major cardiovascular complication occurred at 30 days in 1 TXA and 6 TXA-placebo patients, and 1 rosuvastatin and no rosuvastatin-placebo patients.

Conclusions: Our pilot study supports the feasibility of a perioperative TXA trial in noncardiac surgery. Feasibility of a perioperative rosuvastatin trial is uncertain because of a high prevalence of statin use in the target population and concerns about compliance.

Trial registration: ClinicalTrials.govNCT02546648.

Keywords: Feasibility; Noncardiac surgery; Pilot; Rosuvastatin; Tranexamic acid.

Associated data

ClinicalTrials.gov/NCT02546648