What is the clinical evidence from this study?

Study design: RCT. Population: Stable ischaemic heart disease (n=389). Intervention: Ramipril vs. Placebo. Primary outcome: Change in duration of ST-segment depression, total ischaemic burden, and maximum ST-segment depression over 6 months (p=>0.05).

April 1, 2001Open Access

No effects on myocardial ischaemia in patients with stable ischaemic heart disease after treatment with ramipril for 6 months

Key Result

Ramipril at doses of 1.25 mg/day or 5 mg/day for 6 months did not significantly reduce the duration of ST-segment depression, total ischaemic burden, or maximum ST-segment depression compared to placebo in patients with stable ischaemic heart disease.

Study Design

Type

RCT (n=389)

Blinding

Double-blind

Randomization

1:1:1

Multicenter

Structured PICO

Does ramipril reduce myocardial ischaemia on ambulatory electrocardiography in patients with stable ischaemic heart disease and preserved left ventricular systolic function?

Population

389 patients (aged 30-80 years) with stable symptomatic or asymptomatic ischaemic heart disease (history of myocardial infarction or typical angina pectoris, with positive exercise test and/or a pathological coronary angiogram) and preserved left ventricular systolic function, showing at least 10 min ST-segment depression of at least 0.1 mV during 48 h. Excluded: symptomatic heart failure, left ventricular systolic dysfunction, ACE inhibitor contraindication or recent use, continuing digitalis treatment, non-sinus rhythm, or unstable angina.

Intervention

Ramipril 5 mg or 1.25 mg oral once daily, added to baseline medication, for 24 weeks (6 months).

Comparator

Matching placebo, added to baseline medication, for 24 weeks (6 months).

Outcome

Relative decrease in duration of ST-segment depression (STD), total ischaemic burden, and maximum STD on 48-h ambulatory electrocardiography from baseline to 6 months.surrogate

In patients with stable ischemic heart disease and preserved left ventricular function, 6 months of ramipril therapy did not significantly reduce myocardial ischemia as assessed by ambulatory electrocardiography.

Main Result

p-value: p=>0.05

Limitations

The doses of ramipril might have been too low.
Ambulatory electrocardiography might overlook myocardial ischaemia in patients who predominantly develop ischaemia at high exercise loads.
High use of concomitant medications like acetylsalicylic acid and statins may have blunted any beneficial effect of ramipril.
The study duration of 6 months may have been too short to demonstrate beneficial effects.
Some included patients might have had unspecific ST-segment depression due to left ventricular hypertrophy rather than true myocardial ischaemia.

Abstract

OBJECTIVE: To assess the effects of a 6-month angiotensin-converting enzyme (ACE) inhibitor intervention on myocardial ischaemia. METHOD: We randomized 389 patients with stable coronary artery disease to double-blind treatment with ramipril 5 mg/day (n = 133), ramipril 1.25 mg/day (n = 133), or placebo (n = 123). Forty-eight-hour ambulatory electrocardiography was performed at baseline, and after 1 and 6 months. RESULTS: Relevant baseline variables were similar in all groups. Changes over 6 months in duration of >/= 1 mm ST-segment depression (STD), total ischaemic burden and maximum STD did not differ significantly between the treatment groups. There was no difference in the frequency of adverse events between the groups. CONCLUSION: ACE inhibitor treatment has little impact on incidence and severity of myocardial ischaemia in patients with stable ischaemic heart disease.

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