{MP Test LMU-MY} New heart failure drug shows promise

A new first-in-class drug for the treatment of systolic heart failure may provide local cardiologists with another welcome tool in the battle against the condition, says a prominent cardiologist.

In the extensive PARADIGM-HF* study, which compared valsartan/sacubitril  against enalapril, the combination drug valsartan/sacubitril was shown to reduce the risk of death from cardiovascular (CV) complications by 20 percent and hospitalizations for heart failure by 21 percent. [N Engl J Med 2014;doi:10.1056/NEJMoa1409077] Enalapril is currently one of the first line therapeutic agents used in the treatment of heart failure.  

“The trial’s encouraging results of survival advantage for (valsartan/sacubitril) gives cardiologists an option to provide better quality care … (the drug) is expected to change the management of heart failure in the years to come,” said Datuk Dr. Aizai Azan Abd. Rahim, head of cardiology and senior consultant cardiologist at the National Heart Institute Malaysia (IJN).

The PARADIGM-HF trial was conducted over a 5-year period with a sample of 8,399 patients from 47 countries including Malaysia. Patients were first screened for acceptable side effect profiles in response to both enalapril and valsartan/sacubitril before being randomly assigned at a 1:1 ratio to either enalapril at 10 mg twice daily, or valsartan/sacubitril at 200 mg twice daily.

Over a median treatment period of 27 months, death from CV causes or hospitalization for heart failure—the primary end point—occurred in 914 patients (21.8 percent) in the valsartan/sacubitril group, and 1117 patients (26.5 percent) in the enalapril group (p<0.001). Of these, 558 deaths (13.3 percent) in the valsartan/sacubritril group and 693 (16.5%) in the enalapril group were due to CV causes (p<0.001).

Overall, treatment with valsartan/sacubritil conferred an additional 3.7 percent reduction of CV-related deaths and heart failure hospitalizations compared to enalapril, according to the authors. In addition, overall mortality was reduced by an additional 3.2 percent.

The valsartan/sacubitril combination forms a new class of drugs known as angiotensin receptor neprilysin inhibitors (ARNI), intended as an alternative to angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARBs – such as valsartan by itself) as the primary mode of treatment for heart failure. The sacubitril component inhibits the enzyme neprilysin to prevent the breakdown of natriuretic and other vasoactive peptides, while the valsartan component simultaneously blocks angiotensin II receptors; in combination, the salt complex of both was shown during the PARADIGM-HF trial to significantly increase sodium excretion and vasodilatation, as well as reduce blood pressure.

According to the Ministry of Health, heart failure accounts for 6 to 10 percent of all severe hospital admissions in Malaysia as of 2014. Overall prevalence of heart failure ranges from 0.3 percent to 2 percent of the general population, or as much as 10 percent in those over 65 years of age.

Speaking at the launch of IJN’s “Keep It Pumping” heart failure awareness campaign, Aizai highlighted that heart failure mortality and morbidity remained substantial worldwide, with an estimated 26 million adults living with differing forms of the condition.

*A Multicenter, Randomized, Double-blind, Parallel Group, Active-controlled Study to Evaluate the Efficacy and Safety of LCZ696 Compared to Enalapril on Morbidity and Mortality in Patients With Chronic Heart Failure and Reduced Ejection Fraction