Overwhelming evidence indicates that treatment with an aldosterone antagonist, spironolactone or eplerenone, benefits patients with heart failure and left ventricular ejection fraction that’s less than 45%. But few studies have examined these drugs in patients with heart failure and preserved left ventricular function. I have identified three prior studies in the literature, published during 2004-2011, and they include a cumulative total of 98 patients. By assessing the action of spironolactone in a randomized study with 422 patients with diastolic heart failure, Aldo-DHF adds substantial new data to what was previously known about using aldosterone antagonists in this patient population.
| |
Mitchel L. Zoler/IMNG Media MediaDr. John G.F. Cleland |
However, the clinical profile of the patients enrolled in the Aldo-DHF trial suggests that they may be younger and healthier than the typical patient with diastolic heart failure that clinicians usually see. They averaged 67 years old, with only a third of the patients aged 70 years or older. Most of the patients had New York Heart Association class II disease, and hypertension was very prevalent, in more than 90% of patients, but they had remarkably little atrial fibrillation, a 4% prevalence, and remarkably good renal function, with an average estimated glomerular filtration rate at baseline of 79 mL/min.
Another marker of the relatively good health of the enrolled patients in the trial was their median level of NT-proBPN, which was 179 ng/mL in the spironolactone-treated arm and 148 ng/mL in the placebo arm, with nearly half the patients having a level below 125 ng/mL, the minimum for identifying patients with heart failure. The low levels of NT-proBNP are a concern.
Finally, only 1 of the 422 patients in the study died (a patient in the spironolactone arm) during 12 months of follow-up. It is strange that these patients did not have a higher mortality rate.
The overall clinical profile of the patients in this trial indicates that they were at the mild end of the spectrum of diastolic dysfunction.
The results also raise some safety concerns, with the spironolactone-treated patients showing increased levels of anemia and reduced renal function. For efficacy, while spironolactone reduced ventricular and atrial volume and level of NT-proBNP, and also reduced blood pressure, the treatment had no effect on symptoms, exercise capacity, or 6-minute walking distance.
The Aldo-CHF study adds important new information on the progression of diastolic heart failure as seen in the control group. But I do not believe that this really was a study of diastolic heart failure. Few of the patients were on diuretic drugs, at entry they had fairly normal levels of NT-proBNP, they had mild abnormalities detected by echocardiography, and they exhibited mild deficits in cardiopulmonary exercise testing. This was a population of patients with early-phase diastolic dysfunction. That limitation, coupled with the uncertain balance of risks and benefits seen in the outcomes, means that we need to await the results of further studies before deciding how to use aldosterone antagonists when treating diastolic heart failure.
Dr. John G.F. Cleland is a professor of cardiology at the University of Hull, Kingston-upon-Hull, U.K. He said that he has received research funding from Pfizer, the company that markets eplerenone (Inspra). He made these comments as designated discussant for the Aldo-DHR report.
