Clinical InvestigationValvular and Congenital Heart DiseaseShort-term hemodynamic effect of angiotensin-converting enzyme inhibition in patients with severe aortic stenosis: A placebo-controlled, randomized study
Section snippets
Study population
Patients with severe AS, defined as an aortic valve area <1 cm2, being in sinus rhythm and without symptoms at rest, who had been referred for aortic valve replacement were recruited at the Department of Cardiology, Rigshospitalet, Denmark, between November 2005 and December 2009. Patients were grouped as symptomatic or asymptomatic. Symptomatic individuals were those with angina pectoris, dizziness, syncope at exertion, or those who were classified as New York Heart Association (NYHA)
Statistics
It was planned to include 64 patients (32 symptomatic and 32 asymptomatic patients) in this study. However, the enrollment was stopped earlier because of the low recruitment rate. Finally, 32 symptomatic and 12 asymptomatic patients were recruited to the study.
Continuous variables are expressed as the mean ± SD, and categorical variables, as the frequency and percentage. Differences in the hemodynamic variables between the ACE-I and placebo groups were assessed with Student independent-samples t
Ethics
The study was approved by the regional ethics committee (J. nr. 02 269334), and all patients gave their written informed consent before inclusion in the study.
Source of funding
The Danish Heart Foundation supported the research fellowship of Dr Dalsgaard, grant number 06-10-B317-A1186-22339.
Baseline characteristics
Forty-four patients with severe AS were studied (32 symptomatic and 12 asymptomatic), 16 of whom (36%) were women. Mean age was 69.9 ± 8.3 years (range, 55-85 years). Thirty (68%) of the patients had at least 1 of the following conditions: hypertension, ischemic heart disease, or diabetes mellitus. Of these, hypertension was the most common (52%). In patients with a history of hypertension, systolic BP was 158 ± 23 mm Hg versus 136 ± 15 mm Hg in the group without a history of hypertension (P =
Discussion
We investigated the short-term hemodynamic effects and safety of treatment with ACE-I in patients with severe symptomatic and asymptomatic AS. At follow-up, LVESV and NT-proBNP were significantly lower than in placebo, implying hemodynamic improvement with LV unloading. The approximate halving of SVR with exercise emphasizes the potential for medical reduction of afterload in these patients.
In the ACE-I group, we found a decrease in afterload, measured as a drop in SVR and BP, which was
Conclusion
Angiotensin-converting enzyme inhibition in severe AS caused a decrease in LVESV and NT-proBNP with other hemodynamic parameters preserved both at rest and during exercise implying hemodynamic improvement with LV unloading.
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Drugs for Prevention and Treatment of Aortic Stenosis: How Close Are We?
2021, Canadian Journal of CardiologyCitation Excerpt :The Symptomatic Cardiac Obstruction—Pilot Study of Enalapril in Aortic Stenosis (SCOPE-AS) study demonstrated that among those with normal left ventricular systolic function, enalapril appeared to be hemodynamically well tolerated and resulted in significant improvements in 6-minute walk distance, Borg dyspnea index, and functional class at 4 and 12 weeks.126 Another study suggested the beneficial effects of trandolapril in patients with severe AS.127 The Ramipril in Aortic Stenosis (RIAS) trial, comparing ramipril and placebo, showed significant reduction of left ventricular mass with ramipril, and a decreased in the rate of progression of AS (according to aortic valve area and peak velocities), albeit nonsignificantly.
Development of calcific aortic valve disease: Do we know enough for new clinical trials?
2019, Journal of Molecular and Cellular CardiologyCitation Excerpt :Animal studies suggested that administration of ACE inhibitors enalapril and ramipril or angiotensin II receptor blocker olmesartan improves endothelial function and prevents endothelial injury, LDL deposition, macrophage infiltration, and fibrosis [266,269,270]. Randomised clinical trials on use of enalapril, trandolapril (NCT00252317), and ramipril in patients with CAVD demonstrated moderate efficacy including decrease in left ventricular end-systolic volume and left ventricular mass as well as improved effort tolerance [271–273]. However, conflicting results were also reported although in retrospective studies [274,275] which besides pointed on certain therapeutic efficacy of angiotensin II receptor blockers alleviating AV remodeling and decreasing AV weight in patients with CAVD [275–277].
Aortic Stenosis, Left Ventricular Remodeling, and Renin-Angiotensin System Blockade
2018, Journal of the American College of CardiologyEffect of Renin-Angiotensin Blockers on Left Ventricular Remodeling in Severe Aortic Stenosis
2017, American Journal of CardiologyEfficacy and safety of the angiotensin II receptor blocker losartan for hypertrophic cardiomyopathy: The INHERIT randomised, double-blind, placebo-controlled trial
2015, The Lancet Diabetes and EndocrinologyCitation Excerpt :Treatment with losartan in patients with obstructive hypertrophic cardiomyopathy did not cause any haemodynamic compromise. This finding is in agreement with the safety data for ACE inhibitors in patients with aortic stenosis and suggests that losartan should be safe to use for other indications in patients with hypertrophic cardiomyopathy, irrespective of obstructive physiology.31 In our power calculation, we used an SD for change in left ventricular mass of 20 g/m2, but the SD for results was only 12 g/m2.
Aortic stenosis: Diagnosis and treatment
2016, American Family PhysicianCitation Excerpt :Antihypertensive agents should be initiated at low doses and gradually titrated. In addition to being well tolerated, angiotensin-converting enzyme inhibitors improve hemodynamic parameters, augment effort tolerance, and reduce dyspnea in symptomatic patients with severe aortic stenosis.46,48 Second-generation dihydropyridine calcium channel blockers (e.g., amlodipine [Norvasc], felodipine) do not seem to depress LV function as older calcium channel blockers do, and are safe to use in patients with aortic stenosis.
ClinicalTrials.gov Identifier: NCT00252317.
Grants: The Danish Heart Foundation grant no. 06-10-B317-A1186-22339, Copenhagen, Denmark.