No Change in Patients with Heart Failure with the Introduction of Aliskiren

Study finds a limit to the benefits of renin-angiotensin system blockers for heart failure.

After the successful introduction of angiotensin receptor blockers (ARBs) to existing treatments for heart failure, researchers were hopeful that an additional drug, aliskiren, would benefit patients even further.

Originally, patients were treated with just the angiotensin-converting enzyme (ACE) inhibitor, enalapril. Then, research suggested that adding an ARB could increase the patient’s likelihood of survival.

This combination of ACEs and ARBs became known as the “gold standard” for treatment. These 2 drugs both block the body’s renin-angiotensin system (RAS), but each does this in a different way.

In a study reported at the American College of Cardiology's 65th Annual Scientific Session, researchers believed that adding another type of RAS blocker would benefit patients. This time, they added aliskiren, a direct renin inhibitor.

The study enrolled 7016 patients who all had heart failure and are unable to pump blood normally. These patients were treated with enalapril or a different ACE inhibitor plus a beta blocker.

Patients in the study had to take either enalapril monotherapy, aliskiren monotherapy, or both drugs. The endpoint of this study was death due to cardiovascular problems or hospitalization due to heart failure.

Death from cardiovascular causes or hospitalization for heart failure was seen in 34.6% of patients in the group that received enalapril monotherapy and 33.8% in the group treated with aliskiren monotherapy.

The cohort that received both drugs had the lowest mortality and hospitalization rates at 32.9%. The researchers also found that this group was at a higher risk for low blood pressure and elevated serum creatinine concentration than the group that received enalapril alone.

The differences between the groups were not considered statistically significant.

"There seems to be a ceiling to the benefit that can be obtained with renin-angiotensin system blockers," John JV McMurray, MD said in a press release. "Above a certain level of blockade, there are more adverse effects and no additional benefit. These findings also tell us that it is very hard to improve on the results obtained with ACE inhibitors."

According to Murray, the findings show the importance of a similar study he conducted called PARADIGM-HF. This study showed that patients responded better to a sacubitril and valsartan combination than to enalapril.

Considering both of these studies, once the maximum benefits from ACE inhibitors are reached, patients should be switched to sacubitril and valsartan.