Six of Seven Guideline-Recommended HF Therapies Lower Mortality at Two Years

February 21, 2012

February 21, 2012 (Los Angeles, California)— The use of clinical guideline-recommended therapies for heart failure is associated with a reduced risk of mortality at two years, with the largest reduction in mortality risk observed among patients treated with cardiac resynchronization therapy (CRT) and beta blockers [1]. The researchers also observed an incremental reduction in mortality with each successive guideline-recommended treatment, although the benefit appeared to plateau once the patient was treated with four or five heart-failure therapies.

"This is all-cause mortality in the 24-month range, and these are really large clinical benefits," Dr Gregg Fonarow (University of California Los Angeles Medical Center) told heartwire . "We're not talking about nonfatal events. From this standpoint, the message of applying the guideline-recommended evidence-based therapies in real-world practice--the cumulative benefit is quite substantial."

The results of the study are published online February 21, 2012 in Cardiovascular and Cerebrovascular Disease, the new open-access journal of the American Heart Association.

The IMPROVE-HF Registry

In IMPROVE-HF, the seven guideline-recommended therapies included the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), beta blockers, aldosterone antagonists, anticoagulation for atrial fibrillation/flutter, cardiac resynchronization therapy (CRT) with a pacemaker or defibrillator, implantable cardioverter defibrillator (ICD or CRT with defibrillator), and patient education about heart failure.

"We were interested in the individual, but more important, the incremental clinical effectiveness of these therapies in the real world," said Fonarow. "While we have randomized clinical trials that have shown the benefit of a number of medications and devices, we know that patients who get involved in clinical trials tend to be younger, have fewer comorbidities, and are followed in a closely monitored environment. So, having evidence in a real-world clinical practice about whether these therapies improve survival is really a fundamental question, and one of the issues that clinicians have had when it comes to implementing these therapies and closely following the guidelines."

In the nested case-control analysis, 1376 patients with heart failure who died (cases) within 24 months were compared with 2752 heart-failure patients who survived beyond two years (controls). Logistic regression analysis was performed, which allowed the researchers to calculate mortality risk from the incomplete use of each evidence-based therapy among the eligible patients.

Six of the seven individual guideline-recommended therapies used by heart-failure patients at baseline significantly reduced the risk of mortality at two years. Use of beta blockers and CRT significantly reduced the risk of death by 58% and 56%, respectively, while educational efforts about heart failure reduced the risk of death by 27%. The use of aldosterone antagonists, however, did not reduce the risk of death at 24 months.

Association Between Treatment With Guideline Therapies at Baseline and Mortality at 24 Months

Guideline-recommended therapy Adjusted odds ratio (95% CI)
ACE/ARB 0.56 (0.47–0.67)
Beta blocker 0.42 (0.34–0.52)
Aldosterone antagonists 1.05 (0.74–1.51)
Anticoagulation for atrial fibrillation 0.73 (0.57–0.95)
ICD 0.62 (0.53–0.73)
CRT 0.44 (0.29–0.67)
Heart-failure education 0.73 (0.62–0.85)

In addition, the researchers also observed an incremental benefit of adding therapies in these heart-failure patients, with the incremental gains plateauing when patients were treated with four to five therapies. For example, beta blockers, ACE inhibitors/ARBs, ICDs, and providing education about heart failure at baseline reduced the risk of death at two years by 81%.

Regarding the magnitude of effect when combining different heart-failure therapies, Fonarow said the results reinforce the importance of adhering to the clinical guidelines, noting there is nowhere else in cardiovascular medicine where clinicians can achieve incremental reductions in the range of 80% to 90%.

Cumulative Effect of Adding Guideline-Recommended Heart Failure Therapies on 24-Month Mortality

Therapy Adjusted odds ratio (95% CI) p (incremental)
Beta blocker 0.61 (0.51–0.72) <0.0001
Beta blocker+ACE/ARB 0.37 (0.29–0.46) <0.0001
Beta blocker+ACE/ARB + ICD 0.24 (0.19–0.32) <0.0001
Beta blocker+ACE/ARB+ICD+HF education 0.19 (0.14–0.25) 0.0038
Beta blocker+ACE/ARB+ICD+HF education+anticoagulation for AF 0.17 (0.12–0.23) 0.1388
Beta blocker+ACE/ARB+ICD+HF education+anticoagulation for AF+CRT 0.19 (0.13–0.28) 0.1208

To heartwire , Fonarow said the lack of mortality benefit in patients treated with aldosterone antagonists was an unexpected finding, especially since a number of clinical trials have shown a benefit. He added that the result might be caused by unmeasured confounding that can occur in these analyses, but "it does raise the question about whether or not we're seeing the same benefits when aldosterone antagonists are used in real-world clinical practice." Further clinical studies about the effect of these drugs are needed, said Fonarow.


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