Josephine Mak Waikato Cardiothoracic Unit Journal Club 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 of ACS 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-elevation MI in the elderly” and “Acute coronary syndrome in the elderly” Meta-analysis of FRISC II, ICTUS, RITA-3 trials suggest that patients > 75yo benefit from invasive strategy but underpowered for >80yo Italian Elderly Acute Coronary syndrome study = “systematic 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 in South-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, >75yo with NSTEMI 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 angina, with/without ST-segment depression in ECG, with normal or raised blood concentration of troponin T or I 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 – mostly Aspirin 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 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 groups Except 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 >80yo 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