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Randomized Controlled Trial
. 2018 Jun 8;13(6):e0196962.
doi: 10.1371/journal.pone.0196962. eCollection 2018.

Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial

Marie Mide Michelsen  1 , Anna Bay Rask  1 , Elena Suhrs  1 , Kristoffer Flintholm Raft  1 , Nis Høst  1 , Eva Prescott  1
Affiliations
Randomized Controlled Trial

Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina: A randomized placebo-controlled trial

Marie Mide Michelsen et al. PLoS One. .

Abstract

Objective: Studies have suggested a beneficial effect of angiotensin-converting enzyme (ACE) inhibition. To explore whether the ACE inhibitor ramipril has a direct effect on the microvasculature beyond the blood pressure (BP) lowering effect, we investigated whether ramipril improved coronary microvascular function in normotensive women with coronary microvascular dysfunction (CMD).

Methods: We included 63 normotensive women with angina, no epicardial stenosis>50% and CMD defined as a coronary flow velocity reserve (CFVR)<2.2 assessed by adenosine stress-echocardiography in a randomized double-blinded, superiority trial with 1:1 allocation to placebo or ramipril (maximum dose 10 mg depending on blood pressure) for 24±6 weeks. Primary outcome was CFVR. Secondary outcomes were left ventricular systolic and diastolic function and symptoms evaluated by Seattle Angina Questionnaire (clinicaltrials.gov, NCT02525081).

Results: Follow-up was available on 55 patients. BP remained unchanged during treatment in both groups. CFVR improved in both the ramipril (p = 0.004) and placebo group (p = 0.026) with no difference between groups (p = 0.63). Symptoms improved in both groups with no significant between-group differences. No changes were detected in parameters of systolic and diastolic function. No serious adverse reactions were reported.

Conclusions: In normotensive women with angina and CMD, treatment with ramipril had no significant effect on CFVR or symptoms compared with placebo. The effect of ACE inhibition previously reported may be mediated by blood pressure reduction.

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Conflict of interest statement

The authors have declared that no competing interests exist.

Figures

Fig 1
Fig 1. Up titration of project medication.
Blood pressure (BP) will be controlled after each visit. If possible treatment dose (per day) is increased. If patients have adverse reactions, project medication dose will be reduced. The least acceptable dose for staying in the study is 2.5 mg per day.
Fig 2
Fig 2. General study outline.
CFVR: Coronary flow reserve velocity, LV: Left ventricular, SAQ: Seattle Angina Questionnaire, eGFR: Estimated glomerular filtration rate, BP: blood pressure.
Fig 3
Fig 3. Participant flow-chart.
3 CAD: Coronary artery disease. CFVR: Coronary flow velocity reserve, ACE: Angiotensin-converting enzyme, GFR: Glomerular filtration rate.
See this image and copyright information in PMC

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