Clonidine and Aspirin Fail to Reduce Peri-operative Myocardial Infarction

Myocardial infarction (MI) is the most common major vascular event that occurs after planned non-cardiac surgery.  Multiple strategies have been assessed to try and reduce the rates of peri-operative MI, but few have consistently demonstrated substantial benefit.  With a pro-thrombotic environment and marked sympathetic activation thought to play etiological roles, in the POISE-2 study, the antiplatelet agent aspirin and the alpha-agonist clonidine, were studied in a 2×2 factorial design.   A total of 10,010 patients were randomized in this multi-center, international study to receive a combination of aspirin and clonidine or corresponding placebo.  The trial results from both arms were reported separately, but both arms of the study were neutral for the primary composite outcome of death or nonfatal myocardial infarction at 30 days. The 30-day event rate was 7.0% in patients treated with aspirin and 7.1% in the placebo group (HR, 0.99; 95% CI, 0.86 to 1.15; P=0.92).   Among patients treated with clonidine, 6.6% suffered an event at 30-days compared with 5.9% in the placebo group (HR, 1.11; 95% CI, 0.95 to 1.30; P=0.18).  Aspirin significantly raised the risk of major bleeding (P=0.04) and clonidine increased the risk of clinically significant hypotension (P<0.001).

Conclusion: This large randomized study of aspirin and clonidine in patients undergoing non-cardiac surgery failed to demonstrate benefit from either intervention in comparison to placebo.  Furthermore, both drugs demonstrated evidence of potentially significant side-effects. The need to further define effective agents to reduce peri-operative myocardial infarction risk remains.

Summarized by Steven M. Bradley and Hussain Contractor

  • Devereaux PJ, Mrkobrada M, Sessler DI, Leslie K, Alonso-Coello P, Kurz A, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, VanHelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Baigent C, Chow C, Pettit S, Chrolavicius S and Yusuf S. Aspirin in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1494-503.
  •  Devereaux PJ, Sessler DI, Leslie K, Kurz A, Mrkobrada M, Alonso-Coello P, Villar JC, Sigamani A, Biccard BM, Meyhoff CS, Parlow JL, Guyatt G, Robinson A, Garg AX, Rodseth RN, Botto F, Lurati Buse G, Xavier D, Chan MT, Tiboni M, Cook D, Kumar PA, Forget P, Malaga G, Fleischmann E, Amir M, Eikelboom J, Mizera R, Torres D, Wang CY, Vanhelder T, Paniagua P, Berwanger O, Srinathan S, Graham M, Pasin L, Le Manach Y, Gao P, Pogue J, Whitlock R, Lamy A, Kearon C, Chow C, Pettit S, Chrolavicius S, Yusuf S. Clonidine in patients undergoing noncardiac surgery. N Engl J Med. 2014 Apr 17;370(16):1504-13.

clonidineVSaspirin

Figure: Kaplain-Meier curves for clonidine and aspirin administered in the peri-operative period failed to demonstrate any benefit in reducing myocardial events in comparison with placebo