EVAOLD: Evaluation of a Strategy Guided by Imaging Versus Systematic Coronary Angiography in Elderly Patients With Ischemia

Sponsor

University Hospital, Grenoble (Other)

Overall Status

Recruiting

CT.gov ID

NCT03289728

Collaborator

(none)

1,756

Enrollment

Locations

Arms

67.9

Anticipated Duration (Months)

878

Patients Per Site

12.9

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

The WHO predicts that cardiovascular morbi-mortality will increase by 120-137% within 20 years due to the aging population. Myocardial infarction without ST segment elevation (NSTEMI) is the most common form of infarction. However, its treatment among elderly patients remains a challenging question.

Indeed, the risk benefit balance of revascularization remains unclear, and complications related to revascularization are more frequent in the elderly, including MI, heart failure, stroke, renal failure and bleeding according to National Cardiovascular Network data.The last randomized controlled trial "After Eighty Study", showed a reduction of major cardio-cerebrovascular events (MACCEs) in NSTEMI patients with an invasive strategy (systematic coronary angiography - CA) compared to a conservative strategy (medical treatment alone). Nevertheless, this study presented several limitations of which a major one was the lack of a definition of frailty at inclusion. Moreover, the "After Eighty Study" has shown that percutaneous revascularization in the invasive arm was only performed for 1 in 2 patients showing an inadequacy in the strategy for selecting candidates for revascularization.

Consequently, despite European Society of Cardiology (ESC) guidelines, the management of NSTEMI in elderly patients is not yet evidence based, and current recommendations do not provide any clear clinical decision rule indicating one strategy over another.

For fragile patients, an alternative strategy consists of selecting candidates for a guided CA according to the extent of myocardial ischemia, identified by non-invasive imaging. Single-photon emission computed tomography or dobutamine stress echocardiograms are currently the reference methods with well-defined interpretation of ischemia. According to our experience, this strategy avoids CA for one third of patients and improves the rate of revascularization.

The aim of our study is to compare 1-year morbidity and mortality in NSTEMI patients over 80 years, assigned to guided versus systematic-CA. Our hypothesis is that the guided strategy will not be inferior on MACE rates at 1 year, and will be cost-effective by reducing iatrogenic complications.

Condition or Disease	Intervention/Treatment	Phase
Myocardial Infarction	Other: Stress single photon emission CT (SPECT) or Stress ultrasound with dobutamine (DSE) Procedure: Cornorary angioplasty	N/A

Study Design

Study Type:

Interventional

Anticipated Enrollment :

1756 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Treatment

Official Title:

Evaluation of a Strategy Guided by Imaging Versus Systematic Coronary Angiography in Elderly Patients With Ischemia: a Multicentric Randomized Non Inferiority Trial.

Actual Study Start Date :

Apr 4, 2018

Anticipated Primary Completion Date :

Dec 1, 2023

Anticipated Study Completion Date :

Dec 1, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Strategy guided by ischemia imaging Non-invasive imaging (SPECT or DSE) will be performed. High-risk Patients judged to high risk by imaging (according to ESC guidelines (5)) will undergo coronary angiography aimed at myocardial revascularization and have optimal medical treatment, according to ESC guidelines. - Low or intermediate risk patients will receive optimal medical treatment.	Other: Stress single photon emission CT (SPECT) or Stress ultrasound with dobutamine (DSE) Stress single photon emission CT (SPECT) or Stress ultrasound with dobutamine (DSE), performed using standard protocol. Patients with ≥ moderate ischemia observed by SPECT (≥ 10% of the myocardium or transient ischaemic dilatation or reduced post-stress ejection fraction (EF)) or abnormal movements of the myocardial walls observed during a stress echocardiogram (≥ 3/17 segments) will benefit from coronary angiography. Depending on the results of coronary angiography and on the coronary anatomy and other clinical and para-clinical considerations (territory of myocardial ischemia) revascularisation will be performed (REVASC). Patients with < moderate ischemia will receive medical treatment only (MT).
Active Comparator: Systematic coronary angioplasty Patients will routinely undergo invasive coronary angiography aimed at myocardial revascularization.	Procedure: Cornorary angioplasty Participants randomized to the SCA group, will benefit from a coronary angiography within 24 to 72 hours after the diagnosis of NSTEMI; without any preliminary ischemia imaging.

Arm

Intervention/Treatment

Experimental: Strategy guided by ischemia imaging

Non-invasive imaging (SPECT or DSE) will be performed. High-risk Patients judged to high risk by imaging (according to ESC guidelines (5)) will undergo coronary angiography aimed at myocardial revascularization and have optimal medical treatment, according to ESC guidelines. - Low or intermediate risk patients will receive optimal medical treatment.

Other: Stress single photon emission CT (SPECT) or Stress ultrasound with dobutamine (DSE)

Stress single photon emission CT (SPECT) or Stress ultrasound with dobutamine (DSE), performed using standard protocol. Patients with ≥ moderate ischemia observed by SPECT (≥ 10% of the myocardium or transient ischaemic dilatation or reduced post-stress ejection fraction (EF)) or abnormal movements of the myocardial walls observed during a stress echocardiogram (≥ 3/17 segments) will benefit from coronary angiography. Depending on the results of coronary angiography and on the coronary anatomy and other clinical and para-clinical considerations (territory of myocardial ischemia) revascularisation will be performed (REVASC). Patients with < moderate ischemia will receive medical treatment only (MT).

Active Comparator: Systematic coronary angioplasty

Patients will routinely undergo invasive coronary angiography aimed at myocardial revascularization.

Procedure: Cornorary angioplasty

Participants randomized to the SCA group, will benefit from a coronary angiography within 24 to 72 hours after the diagnosis of NSTEMI; without any preliminary ischemia imaging.

Outcome Measures

Primary Outcome Measures

Rate of MACCE [12 months]
Rate of MACCE (defined as all-cause death, non-fatal myocardial infarction, non-fatal stroke)

Secondary Outcome Measures

Rate of MACCEs and each component of the MACCEs criteria during index hospitalization [1, 6 and 12 months]
MACCE (defined as all-cause death, non-fatal myocardial infarction, non-fatal stroke)
Incremental cost-effectiveness ratio (ICER) expressed as the extra cost for a QALY (quality adjusted life year) gained by the strategy guided by ischemia imaging compared to the systemic coronary angioplasty strategy [12 months]
The annual financial impact of implementing the strategy guided by ischemia imaging will be calculated from the French Health Insurance System perspective over three years [12 months]
Quality of life using standardized scale : EQ5D-5L [1, 6 and 12 months]
Frailty assessment [1 week]
Multiple assessment are necessary to evaluate patient frailty: ADL, IADL, CAM, MNA, Charlson score, SEGA, MMSE, Time up and go test, mini GDS, history of fall
Dependency (ADL) [1, 6, 12 months]
Autonomy (IADL) [1, 6, 12 months]
Incidence of bledding events as defined by the Bleeding Research Consortium (BARC) score [1. 6, 12 months]
Rate of MACCE according to sub-group analysis [1. 6, 12 months]
Sub group : age, gender, diabetes, renal failure and frailty
Create prognostic model with multivariate survival analysis : [1. 6, 12 months]
Risk Algorithm, setting up a score to choose an invasive strategy or not based on analysis of different score (for example geriatric score)

Eligibility Criteria

Criteria

Ages Eligible for Study:

80 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Patients aged 80 years or older
Hospitalized for NSTEMI with or without ST-segment depression on electrocardiogram (ECG), and with raised blood concentration of troponin T or I. Raised troponin was defined as a value exceeding the 99th percentile of a normal population at the local laboratory at each participating site. A local cardiologist assessed patient eligibility and clinical condition compatible with a doubt for systematic coronary angiography due to a frailty.
Written informed consent by the patient or the next of kin in case of incapacity.

Non-inclusion criteria:

Recurrent or ongoing chest pain refractory to medical treatment
Haemodynamic instability or cardiogenic shock
Life-threatening arrhythmias or cardiac arrest
Contra-indication to CA: Renal failure (creatinine clearance <15 mL/min by Modification of the Diet in Renal Disease (MDRD)), continuing bleeding problems
Mechanical complications of MI
Severe aortic stenosis
Medical history of severe dementia (documented for more than 3 months)
Patient under administrative or judicial control
Patient who are protected under the act
No health care insurance