TY - JOUR
T1 - Effect of ACE-inhibition on coronary microvascular function and symptoms in normotensive women with microvascular angina
T2 - A randomized placebo-controlled trial
AU - Michelsen, Marie Mide
AU - Rask, Anna Bay
AU - Suhrs, Elena
AU - Raft, Kristoffer Flintholm
AU - Høst, Nis
AU - Prescott, Eva
PY - 2018/6
Y1 - 2018/6
N2 - 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.
AB - 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.
KW - Aged
KW - Angiotensin-Converting Enzyme Inhibitors/administration & dosage
KW - Blood Flow Velocity/drug effects
KW - Blood Pressure/drug effects
KW - Coronary Circulation/drug effects
KW - Double-Blind Method
KW - Female
KW - Follow-Up Studies
KW - Humans
KW - Microcirculation/drug effects
KW - Microvascular Angina/drug therapy
KW - Middle Aged
KW - Ramipril/administration & dosage
U2 - 10.1371/journal.pone.0196962
DO - 10.1371/journal.pone.0196962
M3 - Journal article
C2 - 29883497
SN - 1932-6203
VL - 13
JO - PLOS ONE
JF - PLOS ONE
IS - 6
M1 - e0196962
ER -