Ezetimibe Utilization Early After Acute Myocardial Infarction, "EzAMI Trial"
Status:
Recruiting
Trial end date:
2024-04-01
Target enrollment:
Participant gender:
Summary
Rationale:
Patients with acute coronary syndromes are at an increased risk for recurrent adverse
coronary events, particularly during the early period following their initial presentation.
Early (in-hospital) initiation of high-intensity statins reduces the risk of recurrent events
and is therefore recommended by the best current practice guidelines.(1,2) However, the
delayed onset of action of statin therapy and given the frequent failure of patients to
achieve the recommended LDL-C targets using statins alone (as per the current practice
guidelines recommendations), might be placing large number of patients at increased risk
during such a vulnerable period early after an ACS.(3) More rapid and effective reduction of
LDL-C levels using combination therapy from the outset may therefore be beneficial in these
patients. This hypothesis has been tested with combining Evolocumab and a statin in the
recent EVOPACS study, in which this combination after ACS has shown to be safe and more
effective in achieving LDL-C targets at 6 weeks compared to statin monotherapy.(4) However,
Evolocumab (a PCSK9i) is an expensive drug which is not affordable by many healthcare systems
in low- and middle-income countries. Ezetemibe, on the other hand, is a safe and a cheap drug
that can prove to be extremely cost-effective if a meaningful and timely reduction in LDL-C
levels can be achieved when combined with a statin early after an ACS.
Study population Patients presenting with acute myocardial infarction, with baseline LDL-C
levels not likely to achieve recommended targets on statin monotherapy. This is assumed to be
with LDL-C level > 125 mg/dl for those not on lipid lowering therapy; or with LDL-C > 100
mg/dl on moderate intensity statin therapy at the time of presentation.
Study design Prospective randomized controlled single-blinded trial. A sample size of 500
patients, 250 in each arm, was calculated to provide a power of 0.9 and an adjusted type 1
error as 0.05.
Primary outcomes
- Percentage of patients achieving target LDL-C levels (<70 mg/dl) at 6 weeks interval.
(Efficacy endpoint)
- Freedom from alanine transaminase elevation (ALT) more than 3 folds upper reference
limit "URL" or statin associated muscle symptoms associated with CK elevation more than
4 folds URL. (Safety endpoint) Secondary outcomes
- Percentage of patients achieving > 50% reduction of LDL-C and to levels below 70mg/dl at
6 weeks interval.
- Percentage of LDL-C reduction at 6 weeks interval.
- Reduction of high-sensitive C-reactive protein (hs-CRP) from baseline to 6 weeks
interval.
- Correlating statins efficacy to reduce LDL-C and likelihood to cause statins related
adverse effects to genetic alleles of ABC [ATP Binding Cassette] types A1, G5 and G8,
and of CYP450 isoenzymes.
- MACE free survival at 1 year, (CV death; non fatal-MI; hospitalization for ACS, urgent
unplanned revascularization and stroke).