ACE Inhibitor Therapy in Patients with Severe Aortic Stenosis Appears Safe

NEW ORLEANS, LA—There are theoretical concerns that arterial vasodilatation and fixed valve obstruction might result in a severe fall in blood pressure (BP) if patients with severe aortic stenosis (AS) are treated with angiotensin-converting enzyme (ACE) inhibitors. Until now, there has been a lack of clinical randomized trials to confirm these potential risks or benefits. But Morten Dalsgaard, MD from Copenhagen University Hospital, Denmark, and colleagues evaluated the hemodynamic effect of ACE inhibitors in the treatment of severe AS in a placebo-controlled, randomized study and reported on their findings at ACC.11, the American College of Cardiology's 60th Annual Scientific Session. No adverse effects due to ACE inhibitor therapy occurred during the trial and no episodes of symptomatic hypotension were noted.

Forty-four patients with severe AS (aortic valve area <1 cm2), 32 symptomatic and 12 asymptomatic, were randomized to treatment with trandolapril 2mg daily/placebo (1:1). Patients performed a symptom-limited exercise test at baseline and at Day 3. Measurements of cardiac output (CO), systemic vascular resistance (SVR), and pulmonary capillary wedge pressure (PCWP) by a Swan-Ganz catheter and left ventricular end-systolic volume (LVESV) by echocardiography were performed at rest and at peak exercise. Follow-up was performed until valve replacement or a maximum of 8 weeks where exercise echocardiography was repeated. NT-proBNP was measured at baseline and at follow-up.

The study investigators reported that at baseline, exercise caused a drop in SVR from 1399±414 to 776±278 DS/cm5. ACE-I caused a drop in resting systolic BP (148±24 to 136±24mmHg), SVR (1358±408 to 1196±267 DS/cm5) and heart rate (72±11 to 68±10bpm), p<0.05 for all, while CO and PCWP remained unchanged (5.6±1.1 to 5.6±0.9 L/min and 18±8 to 17±6mmHg), both NS. ACE inhibitors did not affect BP, SVR, PCWP or CO during exercise. At follow-up (median time: 49 days) LVESV at rest and during exercise and NT-proBNP decreased in the ACE inhibitor group (56±21 to 46±15mL, 61±29 to 39±14mL and 69±79 to 50±54pmol/L, respectively, P<0.05 for all), while these values remained unchanged in the placebo group.

Exercise dramatically decreases SVR in patients with severe AS, and ACE inhibitors do not reduce SVR further during peak exercise. ACE inhibitors do, however, reduce SVR at rest. And ACE inhibition appears to be safe in patients with severe AS.

“A decrease in left ventricular end-systolic volume and NT-proBNP at follow-up indicates a beneficial effect of the ACE inhibitor-induced LV unloading,” Dalsgaard concluded during the presentation of his research at ACC.11.