STOPPING VS CONTINUING ASPIRIN BEFORE CORONARY ARTERY SURGERY

STOPPING VS. CONTINUING ASPIRIN BEFORE CORONARY ARTERY SURGERY VAAIGA AUTAGAVAIA WAIKATO CARDIOTHORACIC UNIT JOURNAL CLUB

QUESTIONS 1. WHAT ARE THE RISKS AND BENEFITS OF STOPPING OR CONTINUING ASPIRIN PRIORTO CABG? 1. DOES ASPIRIN REDUCE THE RISK OF POST-OPERATIVE THROMBOTIC EVENTS? PARTICULARLY GRAFT THROMBOSIS? 2. DOES ASPIRIN INCREASE THE RISK OF POST-OPERATIVE BLEEDING? 2. WHAT ARE THE CURRENT INTERNATIONAL GUIDELINES? 3. WHAT ARE THE CURRENT GUIDELINES IN THE CTS DEPARTMENT ATWAIKATO HOSPITAL?

INTRODUCTION

BACKGROUND • COMMON RECURRING CLINICAL QUESTION – AS PER WKT. CO. NZ, 857 INPATIENTS FOR WAIKATO CTS IN 2016 • ? ELECTIVE PROPORTION THAT ARE CABG • ? INCIDENCE OF THROMBOTIC EVENTS VS INCIDENCE OF POST-OPERATIVE BLEEDING

ASPIRIN – ANTI-THROMBOTIC EFFECT

META-ANALYSIS • 2015, ASPIRIN AND CORONARY ARTERY SURGERY: A SYSTEMATIC REVIEW AND METAANALYSIS • S HASTINGS, P MYLES, D MCILROY • 13 RANDOMISED TRIALS • N = 2399 • PREOPERATIVE ASPIRIN IN PATIENTS UNDERGOINGCABG: • REDUCTION IN MI, NO REDUCTION IN MORTALITY • INCREASED BLEEDING – CHEST DRAIN OUTPUTRBC , TRANSFUSION, SURGICAL EXPLORATION

OBJECTIVE ‘…TO DETERMINE WHETHER ASPIRIN WOULD REDUCE THE OCCURRENCE OF DEATH AND THROMBOTIC COMPLICATIONS IN AT-RISK PATIENTS WHO WERE UNDERGOING CORONARY SURGERY. ’ PRIMARY OUTCOMES • COMPOSITE OF DEATH AND THROMBOTICEVENTS, 30 DAYS POST-OP SECONDARY OUTCOMES • DEATH, NONFATAL MYOCARDIAL INFARCTION, MAJOR HAEMORRHAGE, CARDIAC TAMPONADE, AND A REQUIREMENT FOR TRANSFUSION, 30 DAYS POST-OP

METHODOLOGY

METHODS – ENTRY CRITERIA • ELECTIVE ON-PUMP OR OFF-PUMP CORONARY ARTERY SURGERYAT RISK FOR MAJOR COMPLICATIONS…

METHODS – INCLUSION CRITERIA • MEN AND WOMEN, AGED ≥ 18 Y • ANY OF THE FOLLOWING RISK FACTORS: • AGE ≥ 70 Y • LV IMPAIRMENT • CONCOMITANT VALVULAR OR AORTIC SURGERY • LV ANEURYSMECTOMY • REPEATED CARDIAC SURGERY (“RE-DO”) • COPD • RENAL IMPAIRMENT • OBESITY • PULMONARY HTN • PVD

METHODS – EXCLUSION CRITERIA • • • • POOR (ENGLISH) LANGUAGE COMPREHENSION CLINICIAN PREFERENCE FOR ANTIFIBRINOLYTIC THERAPY URGENT SURGERY FOR UNSTABLE CORONARY SYNDROMES ACTIVE PEPTIC ULCERATION ALLERGY OR CONTRAINDICATION TO ASPIRIN ORTXA ASPIRIN THERAPY WITHIN 5 D OF SURGERY WARFARIN OR CLOPIDOGREL THERAPY WITHIN 7 D OFSURGERY GLYCOPROTEIN IIB/IIIA ANTAGONISTS WITHIN 24 H OF SURGERY THROMBOCYTOPENIA OR ANY OTHER KNOWN HISTORY OF BLEEDING DISORDER SEVERE RENAL IMPAIRMENT RECENT HEMATURIA THROMBOEMBOLIC DISEASE PREGNANCY

METHODS – STUDY PROTOCOL • ASPIRIN AND TRANEXAMIC ACID FOR CORONARY ARTERY SURGERY (ATACAS) TRIAL • MULTI-CENTRE – AUSTRALIA, NEW ZEALAND, ASIA, EUROPE • TESTING WHETHER ASPIRIN, TRANEXAMIC ACID T ( XA), OR BOTHREDUCE , MORTALITY AND/OR MAJOR MORBIDITY AFTER ELECTIVE CABG SURGERY • 4 GROUPS: ASPIRIN 1. ASPIRIN 2. TXA Y N Y ASPIRIN Tx. A (+asp pl) N ASPIRIN (+Tx. A pl) PLACEBO (x 2) 3. ASPIRIN WITH TXA 4. PLACEBO • RANDOMIZED, BLINDED • 2 -BY-2 FACTORIAL Tx. A

METHODS – SURGICAL DETAILS • ELECTIVE CABG, ON- OR OFF-PUMP • INCLUDING: • ANEURYSMECTOMY • CONCOMITANT VALVULAR OR AORTIC SURGERY • REDO • NB: EXCLUDING URGENT SURGERY FOR UNSTABLE CORONARY SYMPTOMS • STANDARD SURGICAL/PERIOPERATIVE CARE – INCL. SELECTION OF VEIN/ARTERY CONDUIT HARVESTING • HEPARIN

ASPIRIN AND PLACEBO • ASPIRIN, ORAL, ENTERIC-COATED: 100 MILLIGRAMS • PLACEBO • (BOTHPROVIDED BY BAYER PHARMA) • ADMINISTERED 1 -2 HR BEFORE SURGERY • (HAVING HAD NO ASPIRIN FOR 5 DAYS PRIOR TO SURGERY) • NO LIMITATION OF POST-OPERATIVE USE OF ASPIRIN/OTHER ANTI-PLATELET THERAPY

METHODS – PRIMARY ENDPOINTS • WITHIN 30 DAYS OF SURGERY • COMPOSITE: • DEATH • THROMBOTIC EVENTS: • NON-FATAL MI • STROKE • PE • ACUTE RENAL FAILURE • BOWEL INFARCTION

METHODS – SECONDARY ENDPOINTS • WITHIN 30 DAYS OF SURGERY • DEATH • NON-FATAL MI • MAJOR HAEMORRHAGE • CARDIAC TAMPONADE • BLOOD TRANSFUSION

METHODS – STATISTICAL ANALYSIS • PRIMARY OUTCOME: • ESTIMATED SAMPLE SIZE: 4484 PATIENTS • 30% OR MORE REDUCTION IN PRIMARY OUTCOME (7% VS 10%) • 90% POWER • RECRUITMENT GOAL: 1150 PER GROUP • SECONDARY OUTCOMES: ESTIMATED 60— 85% POWER • INTENTION TO TREAT ANALYSIS • SUBGROUP SECONDARY ANALYSIS

RESULTS

RESULTS

RESULTS

RESULTS

RESULTS

AUTHOR’S CONCLUSION • THE FINDINGS CONTRADICT THOSE OF THE MOST RECENT META-ANALYSIS • ABSENCE OF BLEEDING EFFECT: • ? ASPIRIN – DOSE-RELATED? , RESISTANCETO ANTI-PLATELET EFFECT • ? TXA – REDUCES BLEEDING IN ASPIRIN (AND PLACEBO) • AFTER CABG: NO EVIDENCE TO PROVE ASPIRIN • DECREASES RISK OF DEATH AND THROMBOTIC EVENTS, OR • INCREASES RISK OF BLEEDING

DISCUSSION

STRENGTHS OF THE STUDY • INCLUSION OF HIGH RISK GROUPS/FACTORS • ADEQUATE SAMPLE SIZE AND POWER • SOMEWHAT GENERISABLE WITH SIMILAR POPULATIONS

LIMITATIONS OF THE STUDY • ENDPOINTS: • PRIMARY AS A COMPOSITE • MI INCLUDED AS PRIMARY AND SECONDARY ENDPOINT • EFFECT OF EARLY DISCONTINUATION ON OVERALL TRIAL OUTCOME • POTENTIAL INTERACTION BETWEEN ASPIRIN ANDTXA IN THIS STUDY

GENERAL DISCUSSION POINTS • NO FIRM CONCLUSIONS DRAWN FROM A REASONABLY LARGERCT • SIGNIFICANCE OF THE HIGHER 30 -DAY MORTALITY IN MALES • RECENT AUDIT OF POST-OPERATIVEDAPT PRESCRIBING/PRACTICE W ATAIKATO CTS • ? PRE AND POST- OPERATIVE BENEFITS • SIGNIFICANCE AND RELEVANCE OF TXA AND ITS EFFECT ON THIS STUDY

IMPACT OF THE STUDY

HOW HAS THE STUDY IMPACTED ON PRACTICE • SOCIETY OF THORACIC SURGEONS GUIDELINES • ? REFLECTION OF THE CURRENT LITERATURE • ? WAIKATO CTS CONSENSUS • FURTHER CONSIDERATION AT ELECTIVE ADMISSION • ALSO HESITANT IN LIGHT OF UNCERTAINTY

ENDING QUESTION FOR AUDIENCE 1. HOW TO CLARIFY THE UNCERTAIN BENEFITS AND RISKS IN LIGHT OF THE CURRENT LITERATURE? 2. WAIKATO CTS ALIGNMENT WITH INTERNATIONAL GUIDELINES +/- DEPARTMENT CONSENSUS?

REFERENCES • MYLES PS, ET AL. STOPPING VS. CONTINUING ASPIRIN BEFORE CORONARY ARTERY SURGERY. N ENGL J MED 2016; 374: 728 -37. • FERRARIS VA, ET AL. 2012 UPDATE TO THE SOCIETY OF THORACIC SURGEONS GUIDELINE ON USE OF ANTIPLATELET DRUGS IN PATIENTS HAVING CARDIAC AND NONCARDIAC OPERATIONS. ANN THORAC SURG 2012; 94: 176 -81. • WWW. WKT. CO. NZ/HOME • AWTRY EH, LOSCALZO J. ASPIRIN. CIRCULATION 2000; 101: 1206 -18. • HASTINGS SLM, MYLES P, MCILROY D. ASPIRIN AND CORONARY ARTERY SURGERY: A SYSTEMATIC REVIEW AND META-ANALYSIS. BR J ANAESTH 2015; 115: 376 -85. • KELLEHER R, ET AL. POST-OPERATIVE ANTIPLATELET THERAPY FOLLOWING CORONARY ARTERY BYPASS GRAFT SURGERY -AN AUDIT OF PRACTICE. WKT. CO. NZ/WAIKATO-GRAND -ROUND. HTML.