SEATTLE – Aldosterone antagonists can be used safely and effectively to treat heart failure in real-world practice, and their underuse likely accounts for a sizable share of deaths in this patient population, according to Dr. Gregg C. Fonarow, cochief of the division of cardiology at the University of California, Los Angeles.
These agents are among six heart failure therapies having a class I (highest) recommendation in national guidelines for managing heart failure, he said at the annual meeting of the Heart Failure Society of America. Yet, nearly 68,000 patients with heart failure and reduced left ventricular ejection fraction (LVEF) die each year in the United States because they do not receive these therapies (Am. Heart J. 2011;161:1024-30).
Dr. Gregg C. Fonarow
"If we bridged that gap, and assuming the efficacy and effectiveness match, you can see the potential number of lives saved each year. ... And, in fact, the greatest number of lives saved [roughly 21,400] could result from the improved use of aldosterone antagonists, if there were optimal implementation," he said.
Indeed, analyses show that only about one-third of eligible heart failure outpatients (Circ. Heart Fail. 2008;1:98-106) and inpatients (JAMA 2009;302:1658-65) in real-world U.S. practice receive drugs in this class.
Some resistance to the use of aldosterone antagonists – such as spironolactone (brand name Aldactone) and eplerenone (Inspra) – has stemmed from uncertainty as to whether the risk-benefit profile in clinical trials translates to real-world practice, according to Dr. Fonarow.
A recent analysis suggests that among patients with heart failure and reduced LVEF, aldosterone antagonist therapy decreases the risk of death by about 30% and the risk of hospitalization by 35% (Am. Heart J. 2011;161:1024-30). The number needed to treat to prevent a single death in a 36-month period is just eight, and the benefit is incremental to that of other standard therapies.
"There was just a moderate increase in the risk of hyperkalemia and increased creatinine, but overall, safe and well tolerated," he said. "They were shown to be highly cost effective even with fully branded medications at full cost, and the benefits greatly outweighed the potential risks."
However, an analysis of Canadian administrative data showed that after publication of the Randomized Aldactone Evaluation Study (RALES), which found significant benefit of spironolactone in heart failure, there was an increase in prescriptions for the drug but also a concomitant increase in hyperkalemia-related hospitalizations and deaths (N. Engl. J. Med. 2004;351:543-51).
The analysis did not assess benefits and had some limitations, according to Dr. Fonarow. "But after that publication and a few others, a number of notable heart failure experts stated pretty strong viewpoints that aldosterone antagonists are really not safe in real-world clinical practice, the risks outweigh any potential benefits, and they should be reserved only for the most severe heart failure patients and only after all other therapies have been tried and failed."
Yet, other studies have suggested, for example, that every 10% increase in aldosterone antagonist use among hospitalized patients is associated with a 6% reduction in all-cause mortality over the following year (Am. Heart J. 2010;159:406-13). Furthermore, in the context of careful monitoring, with increasing use of spironolactone, hyperkalemia is not problematic (BMJ 2010;340:c1768).
"Certainly, some of the data have had a number of individuals saying, ‘We need to get away from evidence guidelines and performance measures, and individualize therapy,’ and ‘I should pick and choose therapy as I think,’ and ‘Findings from clinical trials are not applicable to my patients, they are much more complex, and I know my patients are going to do well because I give them highly personalized care rather than cookbook medicine,’" Dr. Fonarow commented. "That is certainly not a very scientific or satisfying type of approach."
Experience from IMPROVE HF suggests that a performance improvement program can safely and effectively increase the use of aldosterone antagonists for heart failure in a real-world setting (Circulation 2010;122:585-96). The program led to a near doubling of use of these agents over 2 years. "At the same time, did we see any increase in inappropriate or ineligible patients being treated? No, the rates for patients with absolute contraindications or relative contraindications was very small, below 1%, and did not increase," he said.
"Treatment gaps between guidelines and practice exist for heart failure and, as a result, large numbers of patients are having hospitalizations and fatal events that could have been prevented. This is particularly true for aldosterone antagonists," Dr. Fonarow concluded. "Bridging the gap between evidence and clinical practice systems is needed, and by applying these evidence-based therapies with the appropriate monitoring and the appropriate selection of patients, we can do this in a way that truly will improve outcomes."