the Invasive and Conservative Strategies in Elderly Frail Patients With Non-STEMI

Study Overview
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Brief Summary
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The role of a routine invasive strategy in frail patients with non-ST-segment elevation acute myocardial infarction is currently uncertain. We hypothesize that a routine invasive strategy will improve outcomes. The aim of the trial is to evaluate the efficacy and safety of a routine invasive strategy in increasing the number of days alive at home during the first year and improving cardiovascular outcomes.

Detailed Description
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There is a lack of evidence for the best management of frail patients with non-ST-elevation myoardial infaarction (NSTEMI). Clinical practice guidelines recommend a routine invasive strategy in NSTEMI in the majority of patients (Roffi Eur Heart 2016). Nevertheless, invasive management is underused in frail and patients with comorbidity (Ekerstad Circulation 2011, Sanchis Mayo Clin Proceed 2011, Graham Can J Cardiol 2013,). Furthermore, frail patients undergoing coronary angiography have lower revascularisation rates than non frail counterparts (Ekerstad Circulation 2011, Graham Can J Cardiol 2013). This may be, in part, a reflection of the more complex coronary artery disease, more frequently presenting left main, three vessel disease or proximal coronary artery disease, which may not be amenable to PCI (Singh Circ Cardiovasc Qualit Outco 2011). However, it is also possible that lower rates reflect an aversion to a perceived risk of the intervention in the frail, whereby those with potential to gain benefit may have been deemed not appropriate for coronary intervention. After PCI or cardiac surgery, frailty and comorbidity are associated with adverse long-term outcomes (Singh CircQualitOutco 2011, SundermanEur J Cardio-thoracic Surgery 2011). Comorbid patients, however, could benefit the most from in-hospital revascularization in NSTEMI (Bauer et al Eur Heart J 2007, Palau Clin Cardiol 2012). A few studies addressed the role of invasive strategy in elderly patients. A routine invasive strategy was not statistically superior to a selective invasive strategy in elderly patients with NSTEMI (Savonito JACC CIV 2012) but the study was underpowered due to the small sample size. The After Eighty randomized trial was a proper-sized study which included patients >80 years with NSTEMI and demonstrated the benefit of the invasive strategy in reducing the composite endpoint of death or cardiovascular events at 1.5 years (Tegn Lancet 2016). It is worth noting that no patient underwent cardiac catheterization under any circumstance in the conservative arm of that study. Furthermore, only 23% of the potential candidates for inclusion were finally randomized, suggesting a bias towards lower risk patients, a very restrictive approach. Recently, the MOSCA randomized trial evaluated the efficacy of an invasive strategy in elderly patients with NSTEMI and comorbidities (Sanchis Eur J Intern Med 2016). Although this was a small trial, the invasive strategy reduced the probability of death or ischemic events at 3 months. This benefit, nonetheless, vanished at 2.5-years follow-up. No clinical trials specifically designed to investigate the management of frail patients in NSTEMI have been conducted so far. In fact, frail patients have usually been excluded from randomized clinical trials. The TRILOGY-ACS trial, for instance, included a remarkably low rate (4.7%) of frail patients (White, Eur Heart J ACC 2016). On the other hand, while most of the studies mainly focus on death, myocardial infarction, stroke, need for revascularisation or rehospitalisation, patients are also willing to recover an independent life and return to their usual place for living. The presence of geriatric syndromes (including frailty, cognitive impairment, severe dependence and depression) is not only associated with worse clinical outcomes but with a greater risk of functional decline and need for new social help, that is an increased level of dependence. This has an important impact on the patient quality of life and psychological wellbeing but also frequently becomes a heavy social and economic burden for patients and families. Therefore, one of the real challenges in the management of ACS in very old patients is the prevention of dependence. In this sense, the use of new outcomes especially addressed to measure level of independence and quality of life is especially important (Montilla I, Heart Lung Circ 2016). The role of a routine invasive strategy in frail patients is currently uncertain. We hypothesize that a routine invasive strategy in frail patients with NSTEMI will improve outcomes. The aim of the trial is to evaluate the efficacy and safety of a routine invasive strategy in increasing the number of days alive at home during the first year and improving cardiovascular outcomes. A prespecified subgroup analysis will be conducted according to comorbidities and Charlson index

Official Title
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Randomized Comparison Between the Invasive and Conservative Strategies in Elderly Frail Patients With Non-ST Elevation Myocardial Infarction: The MOSCA-FRAIL Clinical Trial

Conditions
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Non-ST Elevation Myocardial Infarction, Frail Elderly Syndrome

Intervention / Treatment
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* Procedure: Invasive
* Procedure: Conservative


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Non-ST-elevation acute myocardial infarction Age ≥70 years Frailty criteria defined by =>4 points in the Clinical Frailty Scale (Rockwood K CMAJ 2005). Exclusion Criteria: Prior known non-revascularizable coronary artery disease Significant concomitant non-ischemic heart disease (i.e. severe heart valve disease, hypertrophic cardiomyopathy…) Unable to understand/sign informed consent Life expectancy <12 months

Ages Eligible for Study
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Minimum Age: 70 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Invasive<br>In-hospital routine coronary angiogram and revascularization if anatomically feasible | Procedure: Invasive<br>* Coronary angiogram and revascularization if anatomically feasible<br>|
| Active Comparator: Conservative<br>In-hospital coronary angiogram only if poor clinical course | Procedure: Conservative<br>* Conservative<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of days alive out of the hospital | number of days alive out of the hospital | 1 year | 
| major adverse cardiac events | cardiovascular death or myocardial infarction or revascularization | 1 year | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| all-cause death |  | 1 and 3 years | 
| cardiovascular death |  | 1 and 3 years | 
| myocardial infarction |  | 1 and 3 years | 
| rehospitalization for cardiac and extra-cardiac causes |  | 1 and 3 years | 
| bleeding episodes |  | 1 and 3 years | 
| stroke |  | 1 and 3 years |