Scope of the Problem: DAPT and Triple Therapy after Stenting Kurt Huber, MD, FESC, FACC 3 rd Medical Department Cardiology & Emergency Medicine Wilhelminenhospital Vienna, Austria Session, August 30, 2010, 08:30-10:00, Budapest - Zone A: Antiplatelet and antithrombotic therapy in patients referred for coronary artery bypass grafting
Coronary Interventions Duration of dual antiplatelet therapy stable Angina (elective) NSTE-ACS (UA/NSTEMI) STEMI BMS DES PPCI 24 (-48) h urgent PCI PPCI 1 month (6-)12 mo (9-)12 months DAPT
Discontinuation of Thienopyridine and Risk of Stent Thrombosis: Milan-Siegburg Cohort Study Airoldi F et al. Circulation 2007;116:745-54 3,021 patients with 5,389 lesions treated with DES (2002-2004) HR=13.7 4.0-47 P<0.001 HR=0.94 0.30-3.0 P=0.92
STENTING IN PATIENTS ON ORAL ANTICOAGULATION ESC STEMI Guidelines. Eur Heart J 2008;29:2909-2945
bleeding free survival Bleeding over time % 100 95.1 % 90 95.1 % 80 70 60 Double therapy Triple therapy with INR < 2.6 66.7 % Triple therapy with INR 2.6 50 0 200 300 450 600 days p <0.0001 vs double therapy p <0.0001 vs triple with INR <2.6 Rossini R. Am J Cardiol 2008; 102: 1618-1623
STENTING IN PATIENTS ON ORAL ANTICOAGULATION STEMI Focused update. Circulation 2008;117:296-328
Management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary intervention/ stenting. Lip GY, Huber K, Andreotti F et al. Thromb Haemost 2010;103:13 Antithrombotic management of atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing coronary stenting: executive summary--a Consensus Document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association (EHRA) and the European Association of Percutaneous Cardiovascular Interventions (EAPCI). Lip GY, Huber K, Andreotti F et al. Eur Heart J 2010;31:1311
Current Recommendations Hem. Risk Clinical Setting Stent Type Recommendation Low to intermediate Elective DES Triple Rx for 3-6 mo (INR 2,0-2,5+ASA 100+Clopi 75) Dual Rx until 12 mo (INR 2,0-2,5+Clopi or ASA) ACS BMS/ DES Lifelong: warfarin (INR 2,0-3,0) Triple Rx for 6 mo, then Dual Rx until 12 mo, then lifelong warfarin Lip GY, Huber K, Andreotti F, et al. Thromb Haemost 2010;103:13 and Eur Heart J 2010;31:1311
Hem. Risk Current Recommendations Clinical Setting Stent Type Recomm High Elective BMS Triple Rx for 2-4 weeks (INR 2,0-2,5+ASA 100+Clopi 75) Dual Rx until 12 mo (INR 2,0-2,5+Clopi or ASA) Lifelong: warfarin (INR 2,0-3,0) ACS BMS Triple Rx for 4 weeks, then Dual Rx until 12 mo, then lifelong warfarin Lip GY, Huber K, Andreotti F, et al. Thromb Haemost 2010;103:13 and Eur Heart J 2010;31:1311
Combination Therapy with Aspirin, Clopidogrel and Warfarin following Coronary Stenting is Associated with a significant Risk of Bleeding Stent implantation: 107 consecutive patients on chronic warfarin therapy 107 contemporary patients with dual antiplatelet therapy Major bleeding: significantly disabling, intraocular or 2 U PRC Minor bleeding: bleed that led to interruption of medication Major bleeding Minor bleeding Triple Tx 6.6 % 14.9 % Dual Tx 0 % 3.8 % p = 0.03 p = 0.01 INR or aspirin dose did not correlate to the bleeding rate Khurram Z. et al, J Invas Cardiol 2006
Ngyen MC. Eur Heart J 2007;28:1717-1722
TRIPLE ANTITHROMBOTIC TREATMENT IN PATIENTS ON WARFARIN * Karthikeyan G. Eur Heart J 2008;29:Abstr Suppl:745 * p < 0.001 vs OAC
Triple versus dual therapy % (n =102) (n =102) p = 0.1 p = 0.6 Rossini R. Am J Cardiol 2008; 102: 1618-1623
Predictors of increased bleeding in patients under DAPT older age Diabetes mellitus female gender low body weight renal dsyfunction co-treatment with anticoagulants (AFib, artificial valves) invasive procedures
Hazards with withdrawal of ASA or DAPT 3-fold increase in MACE rate within 10 days after withdrawal of ASA Biondi-Zoccai G. et al. Eur Heart J 2006;27:2667 (discontinuing aspirin; 50.279 pts) 2-fold increase in MACE rate within 90 days after withdrawal of DAPT Ho P. et al JAMA 2008;299:532 (premature stop after ACS; 3.137 pts) deleterious (re-mi and CV death) when DAPT is stopped after recent stenting King S. at al. J Am Coll CArdiol 2008;51:172 (updated ACC/AHA guidelines for PCI)
How to prevent premature stop of DAPT or triple therapy Avoid DES in patients under A/C or if surgical procedures are planned within 12 months (POBA or BMS should be preferred) Avoid DES in patients likely not to comply with 12 months of thienopyridine therapy Only important surgical procedures, which cannot be delayed, should be performed during the phase of dual antiplatelet Rx Adequate information and education of the patient is mandatory Health care providers should contact the patient s cardiologist before discontinuing antiplatelet therapy Drug costs should not lead to early discontinuation of DAPT
Algorithm for Preoperative Management of Patients after PCI with Dual Antiplatelet Drug Therapy Cardiac/Non-Cardiac Surgery Emergency Semi-elective and urgent Elective Proceed to surgery Case-by-case decision Wait until completion of the mandatory dual antiplatelet regime Risk of thrombosis Continue aspirin + clopidogrel Continue aspirin stop clopidogrel Risk of bleeding stop aspirin stop clopidogrel Metzler H, Kozek-Langenecker S, Huber K. Best Pract Res Clin Anaesthesiol 2008;22:81
PATIENT S THROMBOTIC RISK SURGICAL BLEEDING RISK LOW: >9-12 months after uncomplicated ACS, DES, POBA, BMS, CABG. MEDIUM: 7 weeks to 9-12 months after uncomplica-ted ACS, POBA, BMS, CABG. 7-12 months after DES or high risk stent. HIGH: 6 weeks after ACS, POBA, BMS, CABG, or <9-12 months after their complications 6 months after DES or high risk stent. LOW (transfusion usually not needed): General biopsies. Skin, dental, anterior eye, minor general, minor orthopedic, minor ENT surgery. Endoscopy. Maintain lowdose aspirin (and clopidogrel if prescribed). Maintain low dose aspirin (and clopidogrel if prescribed). Maintain low dose aspirin (and clopidogrel if prescribed). MEDIUM (transfusion often required): Cardiovascular, visceral, ENT, reconstructive, major orthopedic, endoscopic urological surgery. Maintain lowdose aspirin. Withdraw clopidogrel (if prescribed) for 5 days. Maintain low dose aspirin (and clopidogrel if prescribed). Maintain low dose aspirin (and clopidogrel if prescribed). HIGH: Intracranial, spinal canal, posterior eye surgery. Possible bleed in closed space. Large expected blood loss. Withdraw aspirin (and clopidogrel if prescribed) for 3-5 days, respectively. Postpone elective surgery. If urgent, maintain low dose aspirin for all but intracranial surgery. Withdraw clopidogrel (if prescribed) for 5 days. Postpone non-vital surgery. If vital, maintain low dose aspirin. Withdraw clopidogrel (if prescribed) for 5 days. Consider bridging with small molecule iv GPI. Patrono C., Andreotti F. et al. on behalf of the WG on Thrombosis, 2010, in preparation
Perioperative Strategies in Patients on ASA or on DAPT Korte W. et al. on behalf of the working group on Perioperative Haemostasis of the Society on Thrombosis- and Haemostasis Research (GTH), Thromb Haemost 2010, submitted