Heart Failure With Preserved Ejection Fraction: Current Status and Future Opportunities - Episode 17

Differences in Leading Treatments for Heart Failure

A discussion on the differences of sacubitril-valsartan and spironolactone for the treatment of heart failure.

John McMurray, MBChB: The 2 treatments that may be beneficial for at least in some patients with heart failure and preserved ejection fraction are sacubitril-valsartan and spironolactone. They are quite distinct, but they are also complementary. Sacubitril-valsartan is 2 drugs. Valsartan is an angiotensin receptor blocker that blocks the harmful effects of angiotensin 2 in the heart, the kidneys, and the blood vessels. Sacubitril is a neprilysin inhibitor. Neprilysin is an enzyme that breaks down natriuretic peptides and the other vasoactive substances. We believe that these are beneficial in heart failure, so if you inhibit the enzyme that breaks them down, you increase their levels, and we believe that those peptides bring about beneficial effects, stimulating the kidneys to excrete more sodium in water, thereby inhibiting pathological growth like fibrosis, mycotrophic, for example. On the other hand, spironolactone is a drug that blocks the action of corticosteroids, including aldosterone and its receptor. We believe that aldosterone is harmful in the kidneys and the heart; therefore, you could envision both treatments being used together. They do different things. One would anticipate that their benefits would be additive and incremental because they are in heart failure with reduced ejection fraction.