Perioperative management of oral antiplatelet therapy and clinical outcomes in coronary stent patients undergoing surgery

Summary

The aim was to investigate the perioperative risk of ischaemic and bleeding events in patients with coronary stents undergoing cardiac and non-cardiac surgery and how these outcomes are affected by the perioperative use of oral antiplatelet therapy. This was a multicentre, retrospective, observational study conducted in patients with coronary stent(s) undergoing cardiac or non-cardiac surgery. The primary efficacy endpoint was the 30-day incidence of major adverse cardiac events (MACE), defined as the composite of cardiac death, myocardial infarction (MI) or stroke. The primary safety endpoint was the 30-day incidence of Bleeding Academic Research Consortium (BARC) bleeding ≥ 2. A total of 666 patients were included. Of these, 371 (55.7 %) discontinued their antiplatelet medication(s) (all or partly) before undergoing surgery. At 30 days, patients with perioperative discontinuation of antiplatelet therapy experienced a significantly higher incidence of MACE (7.5 % vs 0.3 %, p < 0.001), cardiac death (2.7 % vs 0.3 %, p=0.027), and MI (4.0 % vs 0 %, p < 0.001). After adjustment, peri-operative antiplatelet discontinuation was the strongest independent predictor of 30-day MACE (odds ratio [OR]=25.8, confidence interval [CI]=3.37–198, p=0.002). Perioperative aspirin (adjusted OR 0.27, 95 % CI 0.11–0.71, p=0.008) was significantly associated with a lower risk of MACE. The overall incidence of BARC ≥ 2 bleeding events at 30-days was significantly higher in patients who discontinued oral antiplatelet therapy (25.6 % vs 13.9 %, p < 0.001). However, after adjustment, antiplatelet discontinuation was not independently associated with BARC ≥ 2 bleeding. In conclusion antiplatelet discontinuation increases the 30-day risk of MACE, in patients with coronary stents undergoing cardiac and non-cardiac surgery, while not offering significant protection from BARC≥ 2 bleeding.

Keywords

Aspirin - antiplatelet therapy - PCI - coronary artery disease - stent - surgery

• References

• 1 Rossini R, Capodanno D, Lettieri C. et al. Prevalence, predictors, and long-term prognosis of premature discontinuation of oral antiplatelet therapy after drug eluting stent implantation. Am J Cardiol 2011; 107: 186-194.
• 2 Ferreira-González I, Marsal JR, Ribera A. et al. Background, incidence, and predictors of antiplatelet therapy discontinuation during the first year after drug-eluting stent implantation. Circulation 2010; 122: 1017-1025.
• 3 Iakovou I, Schmidt T, Bonizzoni E. et al. Incidence, predictors, and outcome of thrombosis after successful implantation of drug-eluting stents. J Am Med Assoc 2005; 293: 2126-2130.
• 4 Spertus JA, Kettelkamp R, Vance C. et al. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation 2006; 113: 2803-2809.
• 5 van Werkum JW, Heestermans AA, Zomer AC. et al. Predictors of coronary stent thrombosis: the Dutch Stent Thrombosis Registry. J Am Coll Cardiol 2009; 53: 1399-1409.
• 6 Savonitto S, Caracciolo M, Cattaneo M. et al. Management of patients with recently implanted coronary stents on dual antiplatelet therapy who need to undergo major surgery. J Thromb Haemost 2011; 09: 2133-2142.
• 7 Wijns W, Kolh P, Danchin N. et al. Task Force on Myocardial Revascularisation of the European Society of Cardiology (ESC) and the European Association for Cardio Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions (EAPCI). Guidelines on myocardial revasculari-sation. Eur Heart J 2010; 31: 2501-2555.
• 8 Eagle KA, Berger PB, Calkins H. et al. ACC/AHA guideline update for perioperative cardiovascular evaluation for noncardiac Surgery-executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1996 Guidelines on Perioperative Cardiovascular Evaluation for Noncardiac Surgery). Anesth Analg 2002; 94: 1052-1064.
• 9 Darvish-Kazem S, Gandhi M, Marcucci M. et al. Perioperative management of antiplatelet therapy in patients with a coronary stent who need noncardiac surgery: a systematic review of clinical practice guidelines. Chest 2013; 144: 1848-1856.
• 10 Rossini R, Musumeci G, Oltrona Visconti L. et al. Perioperative Management Of Antiplatelet Therapy in Patients With Coronary Stents Undergoing Cardiac and nonCardiac surgery: a Consensus Document from Italian Cardiological, Surgical, and Anesthesiological Societies. Eurointervention 2014; 10: 38-46.
• 11 Albaladejo P, Marret E, Samama CM. et al. Noncardiac surgery in patients with coronary stents: the RECO study. Heart 2011; 97: 1566-1572.
• 12 Artang R, Dieter RS. Analysis of 36 reported cases of late thrombosis in drug eluting stents placed in coronary arteries. Am J Cardiol 2007; 99: 1039-1043.
• 13 Schouten O, van Domburg RT, Bax JJ. et al. Noncardiac surgery after coronary stenting: early surgery and interruption of antiplatelet therapy are associated with an increase in major adverse cardiac events. J Am Coll Cardiol 2007; 49: 122-124.
• 14 Anwaruddin S, Askari AT, Saudye H. et al. Characterisation of post-operative risk associated with prior drug-eluting stent use. JACC Cardiovasc Interv 2009; 02: 542-549.
• 15 van Kuijk JP, Flu WJ, Schouten O. et al. Timing of noncardiac surgery after coronary artery stenting with bare metal or drug-eluting stents. Am J Cardiol 2009; 104: 1229-1234.
• 16 Mehran R, Baber U, Steg PG. et al. Cessation of dual antiplatelet treatment and cardiac events after percutaneous coronary intervention (PARIS): 2 year results from a prospective observational study. Lancet. 2013 Epub ahead of print.
• 17 Devereaux PJ, Mrkobrada M, Sessler DI. et al. POISE-2 Investigators. Aspirin in patients undergoing noncardiac surgery. N Engl J Med 2014; 370: 1494-1503.
• 18 Hawn MT, Graham LA, Richman JS. et al. Risk of major adverse cardiac events following noncardiac surgery in patients with coronary stents. J Am Med Assoc 2013; 310: 1462-1472.
• 19 Dripps RD. New classification of physical status. Anesthesiol 1963; 24: 111.
• 20 Mauri L, Hsieh WH, Massaro JM. et al. Stent thrombosis in randomized clinical trials of drug-eluting stents. N Engl J Med 2007; 356: 1020-1029.
• 21 Mehran R, Rao SV, Bhatt DL. et al. Standardized bleeding definitions for cardiovascular clinical trials: a consensus report from the Bleeding Academic Research Consortium. Circulation 2011; 123: 2736-2747.
• 22 van Waes 01 JA, Nathoe HM, de Graaff JC. et al. Myocardial injury after noncar-diac surgery and its association with short-term mortality. Circulation 2013; 127: 2264-2271.
• 23 Brilakis ES, Banerjee S. Patient with coronary stents needs surgery: what to do?. J Am Med Assoc 2013; 310: 1451-1452.
• 24 Cruden NL, Harding SA, Flapan AD. et al. Scottish Coronary Revascularisation Register Steering Committee. Previous coronary stent implantation and cardiac events in patients undergoing noncardiac surgery. Circ Cardiovasc Interv 2010; 03: 236-242.
• 25 Rabbitts JA, Nuttall GA, Brown MJ. et al. Cardiac risk of noncardiac surgery after percutaneous coronary intervention with drug-eluting stents. Anesthesiol-ogy 2008; 109: 596-604.
• 26 Wijeysundera DN, Wijeysundera HC, Yun L. et al. Risk of elective major nonc-ardiac surgery after coronary stent insertion: a population-based study. Circulation 2012; 126: 1355-1362.
• 27 Antithrombotic Trialists’ Collaboration.. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients. Br Med J 2002; 324: 71-86.
• 28 Yusuf S, Zhao F, Mehta SR. et al. Clopidogrel in Unstable Angina to Prevent Recurrent Events Trial Investigators. Effects of clopidogrel in addition to aspirin in patients with acute coronary syndromes without ST-segment elevation. N Engl J Med 2001; 345: 494-502.
• 29 Wiviott SD, Braunwald E, McCabe CH. et al. TRITON-TIMI 38 Investigators. Prasugrel versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2007; 357: 2001-2015.
• 30 Wallentin L, Becker RC, Budaj A. et al. Ticagrelor versus clopidogrel in patients with acute coronary syndromes. N Engl J Med 2009; 361: 1045-1057.
• 31 Fox 01 KA, Mehta SR, Peters R. et al. Benefits and risks of the combination of clopidogrel and aspirin in patients undergoing surgical revascularisation for nonST-elevation acute coronary syndrome: the Clopidogrel in Unstable angina to prevent Recurrent ischaemic Events (CURE) Trial. Circulation 2004; 110: 1202-1208.
• 32 Mehran R, Pocock S, Nikolsky E. et al. Impact of bleeding on mortality after percutaneous coronary intervention results from a patient-level pooled analysis of the REPLACE-2 (randomized evaluation of PCI linking angiomax to reduced clinical events), ACUITY (acute catheterisation and urgent intervention triage strategy), and HORIZONS-AMI (harmonizing outcomes with revascularisation and stents in acute myocardial infarction) trials. JACC Cardiovasc Interv 2011; 04: 654-664.
• 33 Burger W, Chemnitius JM, Kneissl GD. et al. Low-dose aspirin for secondary cardiovascular prevention, cardiovascular risks after its perioperative withdrawal versus bleeding risks with its continuation. Review and meta-analysis. J Intern Med 2005; 257: 399-414.
• 34 Lindblad B, Persson NH, Takolander R. et al. Does low dose acetylsalicylic acid prevent stroke after carotid surgery? A double-blind, placebo-controlled randomized trial. Stroke 1993; 24: 1125-1128.
• 35 Grove EL, Hossain R, Storey RF. Platelet function testing and prediction of procedural bleeding risk. Thromb Haemost 2013; 109: 817-824.
• 36 Savonitto S, Rossini R. The Surgery After Stenting (SAS) Registry (SAS registry). www.ClinicalTrials.gov; #NCT01997242.