Ezetimibe Utilization Early After Acute Myocardial Infarction, "EzAMI Trial"

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).

Conditions

• Acute Myocardial Infarction
• Dyslipidemias

Interventions

DRUG

Ezetimibe 10mg

comparing upfront use of Ezetimibe (added to high intensity statins) after acute myocardial infarction versus selective Ezetimibe initiation to those failing to achieve LDL-C targets when assessed in follow up visit.

Sponsors & Collaborators

• Aswan Heart Centre

  collaborator OTHER

• Cairo University

  lead OTHER

Principal Investigators

• Ahmad Samir, MD · Cairo University

Study Design

Allocation

RANDOMIZED

Purpose

TREATMENT

Masking

TRIPLE

Model

PARALLEL

Eligibility

Min Age

18 Years

Max Age

100 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2021-03-24

Primary Completion

2025-12-31

Completion

2025-12-31

Countries

• Egypt

Study Locations