Current issues of ACP Journal Club are published in Annals of Internal Medicine


Nifedipine delayed the need for valve replacement in aortic regurgitation

ACP J Club. 1995 Jan-Feb;122:13. doi:10.7326/ACPJC-1995-122-1-013

Source Citation

Scognamiglio R, Rahimtoola SH, Fasoli G, Nistri S, Dalla Volta S. Nifedipine in asymptomatic patients with severe aortic regurgitation and normal left ventricular function. N Engl J Med. 1994 Sep 15;331:689-94.



To determine whether vasodilator therapy with nifedipine reduced or delayed the need for aortic valve replacement (AVR) in patients with chronic, severe, isolated aortic regurgitation and normal left ventricular systolic function.


Randomized controlled trial with 6-year follow-up.


University hospital in Italy.


143 patients (mean age 35 y, 85% men) who had chronic, severe, isolated aortic regurgitation and normal left ventricular systolic function. Exclusion criteria were development or worsening of aortic regurgitation within the previous 6 months, diastolic blood pressure > 90 mm Hg, history of coronary artery disease, mixed aortic stenosis and regurgitation, additional valvular or congenital heart disease, absence of high-quality echocardiographic study of the left ventricle, or left ventricular ejection fraction (LVEF) < 50%. Follow-up was 94%.


Patients were allocated to digoxin, 0.25 mg/d (n = 74), or to nifedipine, 20 mg twice daily (n = 69).

Main outcome measure

Progression to AVR. AVR was recommended if any of the following criteria were met: LVEF < 50% confirmed by echocardiography, increase to New York Heart Association functional class II or higher, development of angina, and ≥ 15% increase in left ventricular end-diastolic volume index.

Main results

Rate of progression to AVR was lower in the nifedipine group than in the digoxin group at all times after the first-year evaluation (P < 0.001). At study end, AVR was done in more patients in the digoxin group than in patients in the nifedipine group { P = 0.003}* (Table). LVEF < 50% was the reason for valve replacement in 15 of the 20 patients in the digoxin group and in all 6 patients in the nifedipine group. Side effects occurred in 42% of patients in the nifedipine group (tachycardia and headache most frequent) and 12% of patients in the digoxin group (fatigue most frequent) during the first 3 months (P < 0.001). At study end, the groups did not differ for side effects.


Nifedipine was effective in delaying the need for aortic valve replacement in asymptomatic patients with severe, chronic, isolated aortic regurgitation and normal left ventricular systolic function.

Source of funding: Not stated.

For article reprint: Dr. R. Scognamiglio, Cattedra di Cardiologia, Policlinico, Via Giustiniani, 2, 35100 Padova, Italy. FAX 39-49-875-4179.

* P value calculated from data in article.

Table. Nifedipine vs digoxin in asymptomatic patients with severe aortic regurgitation†

Outcome at 6 y Nifedipine Digoxin RRR (95% CI) NNT (CI)
Progression to aortic valve replacement 9% 27% 68% (28 to 86) 5 (3 to 17)

†Abbreviations defined in Glossary; RRR, NNT, and CI calculated from data in article.


Although vasodilator therapy, including hydralazine (1) and nifedipine (2), has been used successfully in patients with chronic aortic regurgitation, clinical follow-up has been limited (6 mo to 1 y). The study by Scognamiglio and colleagues is the first to examine the effect of long-term vasodilator therapy, in this case with nifedipine. The investigators found that after a mean follow-up of 6 years, patients receiving nifedipine were much less likely to have AVR than were patients receiving digoxin.

These findings represent an important advance in the management of patients with severe, chronic aortic regurgitation. 2 potential concerns should be addressed: 1) Did nifedipine mask progressive left ventricular myocardial damage because of its beneficial vasodilator effects? and 2) Was digoxin a reasonable placebo in this trial? Although a vasodilator such as nifedipine may improve effective ejection fraction (EF) for any level of myocardial contractility, the EF of all 6 patients returned to normal after valve replacement. This strongly suggests that nifedipine was not masking irreversible myocardial damage. Several lines of reasoning suggest that the use of digoxin in the placebo group did not substantially alter the results. First, short-term use of digoxin results in an increase in EF in patients with severe, chronic aortic regurgitation (3). Second, although some positive inotropic agents have an adverse effect on survival, digoxin has not had a detrimental effect in clinical studies of heart failure, and recent withdrawal studies of digoxin suggest that its use may be beneficial (4). Thus, these concerns are more theoretical than real.

These findings strongly support the use of nifedipine in asymptomatic patients with chronic, severe aortic regurgitation.

Robert J. Applegate, MD
Wake Forest UniversityWinston-Salem, North Carolina, USA


1. Scognamiglio R, Fasoli G, Ponchia A, Dalla-Volta S. Long-term nifedipine unloading therapy in asymptomatic patients with chronic severe aortic regurgitation. J Am Coll Cardiol. 1990;16:424-9.

2. Kleaveland JP, Reichek N, McCarthy DM, et al. Effects of six-month afterload reduction therapy with hydralazine in chronic aortic regurgitation. Am J Cardiol. 1986;57:1109-16.

3. Crawford MH, Wilson RS, O'Rourke RA, Vittitoe JA. Effect of digoxin and vasodilators on left ventricular function in aortic regurgitation. Int J Cardiol. 1989;23:385-93.

4. Smith TW. Digoxin in heart failure. N Engl J Med. 1993;329:51-3.