1. Josephine Mak Waikato Cardiothoracic Unit Journal Club
After 80
Josephine Mak
Waikato Cardiothoracic Unit Journal Club

3. INTRODUCTION

4. 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

5. 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

6. 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

7. Outcomes Primary Outcomes
composite primary endpoint of myocardial infarction, need for urgent revascularisation, stroke, and death
Secondary Outcomes
Death from any cause

8. Methodology

9. 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

10. 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

11. 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

12. 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

13. 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)

14. Results

16. 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.

17. Results (Baseline Characteristics)

18. Baseline Characteristics
baseline characteristics and medical treatment at inclusion and discharge were similar between the groups Except for the use of warfarin and nitrates

19. 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

22. Results

23. 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

25. 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

26. Discussion

27. 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

28. 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

29. Impact of the study

30. 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