CIPLADOC - Cardiology Update - Landmark Trials

CARDIOLOGY UPDATE - Landmark Trials

SECURE Study

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Study to Evaluate Carotid Ultrasound changes in patients treated with Ramipril and vitamin E (SECURE)
(A substudy of the HOPE trial)

Background

Experimental and epidemiological data suggest that activation of the renin angiotensin system and oxidative
modification of LDL cholesterol play important roles in atherogenesis and that prolonged angiotensin converting
enzyme (ACE) inhibition and antioxidant vitamin E therapy may be beneficial.

Aim

To assess the effects of ramipril and vitamin E on atherosclerosis

Patients and Methods

732 patients at high risk for cardiovascular events (>55 years old, had vascular disease or diabetes plus at
least one additional cardiovascular risk factor) were included in the study
Patients were already on effective therapies including aspirin (84%), lipid lowering agents (34%), beta blockers
(43%), diuretics (9%), nitrates (32%) and calcium channel blockers (43%)
Most study patients did not have history of hypertension or had well controlled BP; other antihypertensives and
antianginal drugs were frequently used (>75% of patients)
Patients of heart failure, known left ventricular ejection fraction (<40%), myocardial infarction, unstable angina
or stroke within 1 month of study enrollment, uncontrolled hypertension and overt nephropathy were excluded
Atherosclerosis progression was evaluated by B-mode carotid ultrasound

Study drugs

Patients were randomly assigned to ramipril 10 mg/day or ramipril 2.5 mg/day and to natural-source vitamin E
(RRR-a-tocopheryl acetate) 400 IU/day or their matching placebos

732 patients randomized (3 x 2 factorial design)

Ramipril 10 mg
(n=244)

Ramipril 2.5 mg
(n=244)

Ramipril Placebo
(n=244)

Vitamin E 400 IU
(n=368)

Ramipril 10 mg
Vitamin E 400 IU
(n=121)

Ramipril 2.5 mg
Vitamin E 400 IU
(n=124)

Placebo Ramipril
Vitamin E 400 IU
(n=123)

Vitamin E Placebo
(n=364)

Ramipril 10 mg
Vitamin E Placebo
(n=123)

Ramipril 2.5 mg
Vitamin E Placebo
(n=120)

Ramipril Placebo
Vitamin E Placebo
(n=121)

Study duration
4.5 years

Results

Ramipril slowed the rate of progression of atherosclerosis. Reduction in
mean maximum IMT (initimal medial thickness) was 37% for ramipril 10 mg
versus placebo.

Progression slopes of the mean maximum IMT (in mm/year) in the different treatment groups


Treatment group		Placebo group

	Placebo	0.0205 ± 0.0039

	Vitamin E	0.0229 ± 0.0038

	Ramipril 2.5 mg	1.0184 ± 0.0035

	Ramipril 2.5 mg + Vitamin E	0.0175 ± 0.0039

	Ramipril 10 mg	0.0135 ± 0.0030

	Ramipril 10 mg + Vitamin E	0.01385 ± 0.0038

Vitamin E had a neutral effect on atherosclerosis

Conclusion

Ramipril retards the progression of atherosclerosis

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