AFTER 80 JOSEPHINE MAK WAIKATO CARDIOTHORACIC UNIT JOURNAL

AFTER 80 JOSEPHINE MAK WAIKATO CARDIOTHORACIC UNIT JOURNAL CLUB

INTRODUCTION

BACKGROUND • NSTEMI AND UNSTABLE ANGINA RESULT IN MANY HOSPITAL PRESENTATIONS AND ADMISSIONS • MORTALITY FROM ACS HAS DECREASED OVER THE PAST 20 YEARS WITH THE DEVELOPMENT OF MODERN TREATMENT STRATEGIES SUCH AS REVASCULARISATION AND BETTER MEDICAL TREATMENT • MULTIPLE GUIDELINES NOW EXIST FOR MANAGEMENT OFACS NOW – EG. EUROPEAN SOCIETY OF CARDIOLOGY, AMERICAN HEART ASSOCIATION, AMERICAN COLLEGE OF CARDIOLOGY IN YOUNGER AGE GROUPS • BASED OFF LARGE RCTS – HOWEVER PATIENTS OVER 80 ARE UNDER-REPRESENTED THUS PROPER SUBANALYSIS UNCERTAIN

EVIDENCE • “NON ST-ELEVATIONMI IN THE ELDERLY” ANDA“CUTE CORONARY SYNDROME IN THE ELDERLY” • META-ANALYSIS OF FRISC II, ICTUS, RITA-3 TRIALS SUGGEST THAT PATIENTS > 75 YO BENEFIT FROM INVASIVE STRATEGY BUT UNDERPOWERED FOR >80 YO • ITALIAN ELDERLY ACUTE CORONARY SYNDROME STUDY = S“ YSTEMATIC EARLY INVASIVE APPROACH DOES NOT CONFER SIGNIFICANT CLINICAL ADVANTAGE COMPARED TO AN INITIALLY CONSERVATIVE APPROACH WITH ANGIOGRAPHY AND REVASCULARIZATION ONLY IN THE CASE OF RECURRENT ISCHEMIA” – HOWEVER ALSO UNDERPOWERED

AIMS TO INVESTIGATE IF PATIENTS AGED 80 YEARS OR OLDER WOULD BENEFIT FROM AN EARLY INVASIVE STRATEGY VERSUS A CONSERVATIVE STRATEGY INVASIVE = EARLY CORONARY ANGIOGRAPHY WITH IMMEDIATE ASSESSMENT FOR AD- HOC PERCUTANEOUS CORONARY INTERVENTION, CORONARY ARTERY BYPASS GRAFT, OR OPTIMUM MEDICAL TREATMENT CONSERVATIVE = OPTIMUM MEDICAL TREATMENT

OUTCOMES PRIMARY OUTCOMES • COMPOSITE PRIMARY ENDPOINT OF MYOCARDIAL INFARCTION, NEED FOR URGENT REVASCULARISATION, STROKE, AND DEATH SECONDARY OUTCOMES • DEATH FROM ANY CAUSE

METHODOLOGY

METHODS • 10 DEC 2010 – 21 FEB 2014 • 16 HOSPITALS INSOUTH-EAST HEALTH REGION OF NORWAY WITHOUT PERCUTANEOUS CORONARY INTERVENTION FACILITIES • SEALED OPAQUE ENVELOPES • NON-BLINDED • INTENTION TO TREAT ANALYSIS • MEDIAN FOLLOW-UP OF 1. 53 YEARS • IN 2001 STUDY, >75 YO WITHNSTEMI HAD AN INCIDENCE OF COMPOSITE ENDPOINTS (DEATH AND MYOCARDIAL INFARCTION) OF 21% AT 6 MONTHS, PERCUTANEOUS CORONARY INTERVENTION HAD A LOWER INCIDENCE OF COMPOSITE ENDPOINTS (10· 8%) = 10% IN ABSOLUTE RISK AND 50% IN RELATIVE RISK • ASSUMING A TYPE I ERROR OF 5% AND POWER OF 80% = 206 PATIENTS PER GROUP • 412 PATIENTS WOULD BE NEEDED FOR THE STUDY IN TOTAL -> 450 AT LEAST ENTROLLED

METHODS – INCLUSION CRITERIA • CONSECUTIVE PATIENTS AGED 80 OR OLDER • NSTEMI OR UNSTABLE ANGINAWITH , /WITHOUT ST-SEGMENT DEPRESSION INECG, WITH NORMAL OR RAISED BLOOD CONCENTRATION OF TROPONINT ORI • NO CHEST PAIN OR OTHER ISCHAEMIC SYMPTOMS/SIGNS AFTER MEDICAL TREATMENT AND MOBILIZATION • ASSESSED BY LOCAL CARDIOLOGIST

METHODS – EXCLUSION CRITERIA • CLINICALLY UNSTABLE WITH CONTINUING CHEST PAIN OR OTHER ISCHAEMIC SYMPTOMS OR SIGNS • CARDIOGENIC SHOCK • CONTINUING BLEEDING PROBLEMS • SHORT LIFE EXPECTANCY (<12 MONTHS) BECAUSE OF SERIOUS COMORBIDITY (SUCH AS CHRONIC OBSTRUCTIVE PULMONARY DISEASE, DISSEMINATED MALIGNANT DISEASE, OR OTHER REASONS). • SUBSTANTIAL MENTAL DISORDER

METHODS – STUDY PROTOCOL • RANDOMISED OPEN LABEL CONTROLLED MULTICENTRE TRIAL • PERMUTED BLOCK RANDOMISATION BY CENTRE OF BIOSTATISTICS AND EPIDEMIOLOGY • PATIENTS ASSESSED FOR PARTICIPATION WITHIN 2 DAYS AFTER HOSPITAL ADMISSION • INVASIVE – TRANSFERRED TO OSLO UNIVERSITY THEN TRANSFERRED BACK WITHIN: • 6 -18 HOURS IF UNDERWENT PCI • 4 -6 HOURS IF UNDERWENT ANGIOGRAPHY ALONE • EACH ANGIOGRAM REVIEWED BY AT LEAST 2 INTERVENTIONAL CARDIOLOGISTS BEFORE REVASCULARISATION METHOD DECIDED UPON

METHODS – STUDY PROTOCOL • CONSERVATIVE – MEDICAL TREATMENT IN COMMUNITY HOSPITAL • MEDICALLY TREATED ACCORDING TO “EXISTING GUIDELINES” • IF REINFARCTON, REFRACTORY ANGINA PECTORIS DESPITE OPTIMUM MEDICAL TREATMENT, MALIGNANT VENTRICULAR ARRHYTHMIAS, OR INCREASING SYMPTOMS OF HEART FAILURE, CONSIDERED FOR URGENT INVASIVE CORONARY ANGIOGRAM • DAPT – MOSTLYASPIRIN AND CLOPIDOGREL (ALTHOUGH SOME TICAGRELOR)

RESULTS

DROP-OUTS • WITHIN 24 H AFTER BEING RANDOMLY ASSIGNED, FIVE (2%) PATIENTS DROPPED OUT OF THE INVASIVE GROUP AS DID ONE (<1%) FROM THE CONSERVATIVE GROUP • INVASIVE GROUP BECAUSE OF DISCUSSIONS THE PATIENTS HAD WITH THEIR RELATIVES • CONSERVATIVE GROUP, THE SINGLE DROPOUT WAS BECAUSE OF SEVERE SEPSIS.

RESULTS (BASELINE CHARACTERISTICS)

BASELINE CHARACTERISTICS • BASELINE CHARACTERISTICS AND MEDICAL TREATMENT AT INCLUSION AND DISCHARGE WERE SIMILAR BETWEEN THE GROUPSEXCEPT FOR THE USE OF WARFARIN AND NITRATES

RESULTS • ALL RANDOMLY ASSIGNED PATIENTS WERE ANALYSED AS FAR AS THE OUTCOME AND ADVERSE EVENTS, INCLUDING THE DROPOUTS. • 457 PATIENTS REMAINED IN THE FOLLOW-UP STUDY POPULATION, WITH 229 PATIENTS (MEAN AGE 84· 7 YEARS) IN THE INVASIVE GROUP AND 228 PATIENTS (MEAN AGE 84· 9 YEARS) IN THE CONSERVATIVE GROUP • NO CROSSOVERS BETWEEN THE TWO STRATEGY GROUPS. • REINFARCTION, REFRACTORY ANGINA PECTORIS, DEVELOPMENT OF MALIGNANT VENTRICULAR ARRHYTHMIAS, OR INCREASING SYMPTOMS OF HEART FAILURE WERE DEEMED TO REQUIRE URGENT REVASCULARISATION—IE, AN ENDPOINT

RESULTS

RESULTS • THE RESULTS WERE CONSISTENT WHEN STRATIFYING BY SEX, TYPE 2 DIABETES, CREATININE BLOOD CONCENTRATION OF MORE THAN 103 ΜMOL L/, USE OF WARFARIN, AND AGE OLDER THAN 90 YEARS. • HOWEVER CONFOUNDING EFFECT WITH CREATININE AND AGE >90 INDICATED EFFECT MODIFICATION

AUTHOR’S CONCLUSION • AN INVASIVE STRATEGY IS SUPERIOR TO CONSERVATIVE STRATEGY IN PATIENTS WITH NSTEMI OR UNSTABLE ANGINA WITH A REDUCTION IN COMPOSITE EVENTS • PRIMARY ENDPOINT OCCURRED IN 93 (41%) PATIENTS IN THE INVASIVE GROUP AND IN 140 (61%) PATIENTS IN THE CONSERVATIVE GROUP HR( 0· 53 [95% CI 0· 41– 0· 69], P=0· 0001). • EFFICACY OF INVASIVE STRATEGY WAS DILUTED WITH INCREASING AGE (IN PARTICULAR OVER 90) AFTER ADJUSTING FOR CREATININE AND EFFECT MODIFICATION

DISCUSSION

STRENGTHS OF THE STUDY • RCT • MULTICENTRE • POWER – RECRUITMENT • QUESTION WORTH ANSWERING – RELEVANT • REGISTERED AT CLINICAL TRIALS • UNDER-POWERED FOR OVER 90 GROUP WHICH THEY RECOGNISED • GOOD PROTOCOL FOR HIDING RANDOMISATION – INDEPENDENT

LIMITATIONS OF THE STUDY • OPEN LABEL • AGGRESSIVE EXCLUSION CRITERIA – 10% OF ORIGINAL PATIENTS INCLUDED • PATIENTS THAT DIDN’T MAKE IT INTO TRIAL EG. BECAUSE OF ‘LOGISTICS’ • P VALUES BETWEEN GROUPS CHARACTERISTICS NOT LISTED • QUALITY OF LIFE OUTCOME – LISTED IN ORIGINAL TRIAL REGISTRATION BUT NOT YET DONE

IMPACT OF THE STUDY

HOW HAS THE STUDY IMPACTED ON PRACTICE • IN SELECT GROUPS OF >80 YO AN INVASIVE STRATEGY IS PROBABLY OF BENEFIT • ? APPLICABILITY TO NZ POPULATION • NO QUALITY OF LIFE ANALYSIS YET DONE • MAY BE USEFUL TO DISCUSS WITH CARDIOLOGISTS