Perindopril Remodeling in Elderly With Acute Myocardial Infarction - PREAMI

Description:

The goal of the trial was to evaluate the efficacy of long-term treatment with the angiotensin-converting enzyme (ACE) inhibitor perindopril among elderly patients post-myocardial infarction (MI) with preserved left ventricular (LV) function.

Study Design

Study Design:

Patients Enrolled: 1,252
Mean Follow Up: 12 months
Mean Patient Age: Mean age 73 years
Female: 35
Mean Ejection Fraction: Mean baseline 59%

Patient Populations:

Acute MI in prior 7-20 days, age ≥65 years, LV ejection fraction ≥40%, and good apical views of LV at baseline echo

Exclusions:

Need for urgent revascularization, severe heart failure (NYHA class IV), or creatinine >2.0 mg/dl

Primary Endpoints:

Composite of death, hospitalization for heart failure, or heart remodeling, defined as a >8% increase in LV end-diastolic volume

Secondary Endpoints:

Individual components of the primary endpoint; LV end-diastolic volume; cardiovascular death, hospitalization for reinfarction or angina; and coronary artery bypass grafting or percutaneous coronary intervention

Drug/Procedures Used:

Within 20 days following MI and establishment of preserved LV function, patients were randomized in a double-blind manner to perindopril (4 mg for one month followed by 8 mg for 11 months) (n=631) or placebo (n=621) in addition to standard medical therapy. For patients on an ACE inhibitor initially, a 24-hour washout period was required prior to randomization. Patients underwent echocardiography at six and 12 months. Interpretable LV end-diastolic volume data were available for 455 patients in the perindopril group and 441 patients in the placebo group. The trial enrolled patients over six years.

Concomitant Medications:

Post-MI medications included beta-blockers (71%), ACE inhibitors (78%), and lipid-lowering therapy (50%).

Principal Findings:

Patients were enrolled an average of 11 days post-MI. Mean LV ejection fraction at baseline was 59%. The majority of patients had New York Heart Association (NYHA) heart failure class I (79%) and high LV end-diastolic volume (80 ml). Approximately 24% were diabetics.

The primary composite endpoint of death, hospitalization for heart failure, or heart remodeling was lower in the perindopril group (p<0.001), driven primarily by a reduction in cardiac remodeling (28% for perindopril vs. 51% for placebo, p<0.001). There was no difference in mortality (6% each) or hospitalization for heart failure (4% vs 5%, p=0.24). LV end-diastolic volume was lower at 12 months in the perindopril group compared with placebo (81.8 ml vs. 83.6 ml).

Withdraw from treatment did not differ by treatment group (25.2% in the perindopril group and 24.0% in the placebo group). Cough as an adverse event was reported in 1.6% of the perindopril group.

Interpretation:

Among elderly patients post-MI with preserved LV function, addition of the ACE inhibitor perindopril to conventional therapy was associated with a reduction in the primary composite endpoint of death, hospitalization for heart failure, or heart remodeling, driven by the reduction in remodeling, compared with placebo at 12-month follow-up.

Many prior trials have demonstrated the benefit of ACE inhibitor therapy in patients with coronary artery disease. In the EUROPA trial, benefit of long-term perindopril therapy on cardiovascular death or MI was demonstrated among patients with low-risk, stable coronary artery disease syndromes, including post-MI. The present trial further defines these benefits among a cohort of elderly patients with preserved LV function. While no clinical benefit was observed in PREAMI, the duration of therapy and follow-up was likely insufficient to evaluate such a difference.

Substudies from the EUROPA trial suggested a mechanism of benefit via blood pressure decreases and antiatherosclerotic improvements such as endothelial function and nitric oxide increase. The PREAMI trial suggests cardiac remodeling also plays a role in the mechanism of benefit with perindopril post-MI. The study also demonstrates that LV remodeling can occur post-MI, despite small initial infarct size.

References:

The PREAMI Investigators. Effects of Angiotensin-Converting Enzyme Inhibition With Perindopril on Left Ventricular Remodeling and Clinical Outcome: Results of the Randomized Perindopril and Remodeling in Elderly With Acute Myocardial Infarction (PREAMI) Study. Arch Intern Med 2006;166 659-666.

Presented by Dr. Roberto Ferrari at the European Society of Cardiology Hot Line Session, September 2005.

Clinical Topics: Dyslipidemia, Heart Failure and Cardiomyopathies, Noninvasive Imaging, Atherosclerotic Disease (CAD/PAD), Lipid Metabolism, Statins, Acute Heart Failure, Echocardiography/Ultrasound

Keywords: Perindopril, Myocardial Infarction, Coronary Artery Disease, Follow-Up Studies, Lipids, Blood Pressure, Nitric Oxide, Ventricular Remodeling, Heart Failure, Cough, Diabetes Mellitus, Echocardiography


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