Vasodilators for Aortic Regurgitation
Abstract & Commentary
By Michael H. Crawford, MD Dr. Crawford is Professor of Medicine, Chief of Clinical Cardiology, University of California, San Francisco and Editor of Clinical Cardiology Alert. Dr. Crawford is on the speaker's bureau for Pfizer.
Synopsis: Long-term vasodilator therapy with either nifedipine or enalapril changed neither the hemodynamic burden of severe aortic regurgitation nor reduce or delay the need for valve replacement surgery in asymptomatic patients with chronic severe aortic regurgitation and normal LV function.
Source: Evangelista A, et al. Long-Term Vasodilator Therapy in Patients with Severe Aortic Regurgitation. N Engl J Med. 2005;353:1342-1349.
The recommendation for the use of vasodilators in the treatment of chronic severe aortic regurgitation in asymptomatic patients with normal left ventricular (LV) function is supported by studies in < 400 patients with short-term follow-up and heterogeneous results. Thus, this long-term study from Barcelona, Spain, is of interest. This was an open label randomized trial of nifedipine vs enalapril vs no treatment in asymptomatic patients with chronic severe aortic regurgitation (AR) and normal systolic LV function enrolled between 1995 and 2000. AR severity was determined by standard echo Doppler methods. Exclusion criteria included LV ejection fraction < 50%, aortic stenosis (mean gradient > 20 mmHg), other significant valve disease, elevated diastolic blood pressure (> 90 mmHg), atrial fibrillation, coronary artery disease, or other longevity-reducing diseases such as Marfan syndrome. The treatment was nifedipine 20 mg every 12 hours, enalapril 20 mg per day, or no treatment. Patient evaluation, including echocardiography was done after 1 month, 6 months, and then yearly for the mean follow-up of 7 years. The recommendation for aortic valve surgery was based upon the development of symptoms or LV dysfunction: EF < 50% or LV enlargement defined as an end-systolic dimension > 50 mm.
Results: Of the 95 patients enrolled, 3 died, one in each group. Chronic vasodilator therapy did not significantly change heart rate or blood pressure between baseline and follow-up, nor was any echocardiographic parameter changed. Aortic valve replacement was recommended in 39% of the control group, 50% of the enalapril group, and 41% of the nifedipine group (P = NS). The reasons for the aortic valve replacement recommendation in 41 of the 95 patients was the development of symptoms in 7, LV dysfunction in 15, and both criteria in 19. Time to valve replacement averaged between 4 and 5 years, and was not different in the 3 groups, nor was the rate of progression to surgery.There was no operative mortality and all operated patients subsequently had decreased LV size and a normal LVEF. During the study, 10 patients dropped out because of adverse effects: 7 in the nifedipine group at a mean of 2 months; 3 in the enalapril group at a mean of 5 months. Evangelista and colleagues concluded that long-term vasodilator therapy with either nifedipine or enalapril did not change the hemodynamic burden of severe aortic regurgitation nor reduce or delay the need for valve replacement surgery in asymptomatic patients with chronic severe aortic regurgitation and normal LV function.
Commentary
This study is in stark contrast to a previous study by Scognamiglio and colleagues (N Engl J Med. 1994;331:689-694), which showed reduced need for surgery and delay of time to surgery with nifedipine vs digoxin. Personally, I am not surprised by these results. After the 1994 paper came out, I tried to treat such patients with nifedipine, only to find that most patients could not tolerate it. Subsequently, I tried amlodipine, which was better tolerated, but like this paper, I noted no change in hemodynamic or echo LV function variables. Angiotensin converting enzyme inhibitors (ACEI) are used by many physicians because of their other beneficial cardiovascular effects, but there is much less data on them, so I was less enthusiastic about them. This study confirms that ACEI are well-tolerated, but not useful. Nifedipine was less well-tolerated, and discontinued in about 8% of those randomized to it by 2 months. Despite my experience, adverse effects of nifedipine do not explain the difference between this study and the prior one.
The major difference between the 2 studies is the percent of patients undergoing surgery for EF < 40% alone. It was 81% in the prior study, 37% in this study, and 17% in a longitudinal follow-up study done by Bonow and colleagues (Circulation. 1991;84:1625-1635). In both these later studies many patients developed symptoms, so the striking lack of symptom development in the earlier study is remarkable and suggests some basic difference in the patient population of that study. Herein lies the problem: This study has 95 patients, the prior one 143; these are small studies in the cardiovascular world. Thus, selection bias in such underpowered studies may explain the discrepant results. So at this point, as Dr. Carabello pointed out in his accompanying editorial (N Engl J Med 2005;353:1400-1402), we can neither confirm nor deny the vasodilator hypothesis. Fortunately, other than side effects in some patients, there seems to be no harm in vasodilator therapy. So the believers will use them and the more skeptical, like me, will not.
Another interesting finding in this study is that the approximately 40% of patients who met criteria for aortic valve surgery did so within 4-5 years, and all improved objectively after surgery, and there were no operative deaths. It is reassuring that we seem to have the appropriate indications for surgery in hand. My focus in such patients has been to be sure I don't miss the indications for surgery.
Long-term vasodilator therapy with either nifedipine or enalapril changed neither the hemodynamic burden of severe aortic regurgitation nor reduce or delay the need for valve replacement surgery in asymptomatic patients with chronic severe aortic regurgitation and normal LV function.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
- Award-winning Medical Content
- Latest Advances & Development in Medicine
- Unbiased Content