After examining two heart failure treatments, scientists found conflicting results concerning improvement in survival in two different reports in JAMA.

The clinical benefits of aldosterone antagonist therapy was observed in one study by a team led by Adrian F. Hernandez, M.D., M.H.S., of the Duke Clinical Research Institute, Durham, N.C. The researchers also analyzed the associations with long-term results of older patients with heart failure who were discharged from a hospital.

The background information in the report stated:

“Aldosterone antagonist therapy [a diuretic drug] for heart failure and reduced ejection fraction [a measure of how well the left ventricle of the heart pumps with each contraction] has been highly efficacious in randomized trials. However, questions remain regarding the effectiveness and safety of the therapy in clinical practice.”

Utilizing data from the clinical registry that was associated with Medicare claims from 2005 to 2010, the experts observed the outcomes of patients that were in the hospital with heart failure and reduced ejection fraction.

The primary outcomes that were evaluated were:

  • cardiovascular readmission
  • readmission linked to hyperkalemia, greater than average levels of potassium in the circulating blood, at 30 days and one year
  • heart failure readmission at 3 years
  • all-cause mortality

There were 5,887 subjects, 78 years old on average, who reached the inclusion standards from 246 medical centers. An authorization to take an aldosterone antagonist was given to 18.2% (1,070) of the patients when they were discharged from a hospital.

Results showed that at 3 years, the treatment groups showed comparable rates of all-cause mortality (49.9% vs. 51.2%) and cardiovascular readmission (63.8% vs. 63.9%).

The therapy group had higher cumulative prevalence rates of arrhythmia (5.4 percent vs. 3.9 percent) and elective readmission for an arrhythmia control apparatus (6.5% vs. 4.2%).

There were no notable differences in mortality and cardiovascular readmission, according to the authors. They also discovered that the treated group had a considerably lower cumulative incidence of the first heart failure readmission (38.7% vs. 44.9%).

The treatment group had higher hyperkalemia readmission rates at 30 days (2.9% vs. 1.2%) and at 1 year (8.9% vs. 6.3%). Hyperkalemia, however, was rarely the main diagnosis for being readmitted.

According to the experts, this research may suggest that aldosterone antagonists are not very effective among older patients regarding mortality in the real-world environment.

The authors concluded:

“One potential reason for limited effectiveness may be a lack of adherence to or persistence with therapy. … Our findings highlight the importance of conducting clinical trials that can be easily generalized to real-world practice and in which the most vulnerable patient groups are well represented.”

The other research, conducted by scientists led by Lars H. Lund, M.D., Ph.D., of the Karolinska Institutet, Stockholm, Sweden, set out to determine whether RAS antagonists – i.e. ACE (angiotensin-converting enzyme) inhibitors, or ARBs (angiotensin receptor blockers) – are linked to lower death rates among heart failure patients with preserved ejection fraction.

Background information in the report stated:

“Up to half of patients with heart failure have normal or near-normal ejection fraction, termed heart failure with preserved ejection fraction (HFPEF) or diastolic heart failure. The mortality in HFPEF may be as high as in heart failure with reduced ejection fraction (HFREF) or systolic heart failure, but there is no proven therapy.”

Between 2000 and 2011, the researchers analyzed 41,791 patients in the Swedish Heart Failure Registry from 64 hospitals and 84 outpatient clinics. There were 16,216 patients with HFPEF (ejection fraction of 40% or greater) who were 75 years old on average and 46% were women. The patients were either treated with RAS antagonists (n = 12,543) or did not receive treatment (n = 3,673).

The experts analyzed the data in order to identify the link between RAS antagonists and all-cause mortality by using of a matched cohort. For the HFREF consistency evaluation, the team included 20,111 people with ejection fraction of less than 40%.

Results from analysis of the overall HFPEF group showed:

  • Crude 1-year survival was 86% for patients taking RAS antagonists compared to 69% for subjects not taking the treatment.
  • 5-year survival was 55% for patients taking RAS antagonists compared to 32% for those not receiving treatment.

Results of the matched HFPEF cohort showed:

  • 1-year survival was 77% for treated patients compared to 72% for those that didn’t receive treatment.
  • Five-year survival was 36% for treated patients compared to 34% for those not treated.

The experts concluded:

“There is currently no consensus on the use of RAS antagonists in patients with HFPEF. In our study, use of RAS antagonists was associated with reduced all-cause mortality in a broad unselected population of patients with HFPEF. Our results together with the signal toward benefit in randomized controlled trials suggest that RAS antagonists may be beneficial in patients with HFPEF, but this should be confirmed in an appropriately powered randomized trial.”

James C. Fang, M.D., of University Hospitals Case Medical Center, Cleveland, wrote an accompanying editorial to observe the conclusion that clinicians should take from these 2 studies that would seem to conflict with the clinical trial evidence.

“If all of the evidence is carefully considered in its totality, it would be sound to conclude that (1) renin-angiotensin system antagonists are reasonable agents to control hypertension in heart failure with preserved ejection fraction, and (2) aldosterone antagonists are effective drugs in heart failure with reduced ejection fraction but should be used carefully and selectively.

Although clinical trials should remain the gold standard for testing hypotheses, observational studies bridge the gap from the scientific rigor of clinical trials to real-world experience. Clinical trials are a reminder of the rigor of medicine as a science; observational studies are a reminder that medicine is still an art.”

Written by Sarah Glynn