It is more or less clear that an SGLT2 inhibitor will significantly reduce hospitalisation or cardiovascular mortality in patients both with reduced or preserved ejection fraction. We have the Emperor Reduced, Emperor Preserved, Data HF, and Deliver Trials to confirm this. We also know that there are lakhs of patients with heart failure, with half of them havingĀ  preserved ejection fraction. The Deliver Trial reported efficacy of dapapgliflozin in ejection reactions more or less than 60%, the DAPA heart failure trial had shown efficacy in an ejection fraction less than 40%. But there is one important point very few patients were on ARNI class of medicine in the SGLT2 trials, just around 15%. I will come to ARNI very soon.



Sadly heart failure is a progressive disease with 50% patients needing re-hospitalisation in a month and 20% dying in 2 years. This is despite therapy. We have a huge problem on our hands. Over the years multiple randomised trials showed that certain drugs significantly reduce mortality in heart failure patients. Beta blockers reduced death by 30%, a mineralocorticoid receptor blocker by 30%, and an ACE inhibitor by 25%.



Against this background the PARADIGM heart failure trial presented in 2014 was a landmark study that included more than 8400 patients with heart failure and median ejection fraction of only 29%. Around 22% were in NYHA class II, 80% were men, average age was 67 years. Follow up was for 27 months. The study randomised patients to an ARNI or an ACE inhibitor called enalapril. An ARNI is an angiotensin receptor neprilysin inhibitor with sacubitril and valsartan. Sacubitril is the neprilysin blocker and valsartan the AT receptor blocker.



By 27 months the ARNI treated group had a significant 20% reduction in cardiovascular death or hospitalisation for heart failure as compared with the enalapril group. This was a robust difference as these patients were already on a beta blocker, a diuretic, an MRA and 7% had a biventricular pace-maker.



Another trial called PROVE followed 800 patients with an ARNI for one year. There was a significant fall in NTproBNP levels that started falling as early as 2 weeks from treatment onset, and crucially the ejection fraction increased on an average by 9.5% at one year. Such a rise in ejection fraction compares with that of a biventricular pacemaker treatment.



So in conclusion a chronic heart failure patient should be ideally treated with an ARNI, a beta blocker, an MRA and an SGLT2 inhibitor.

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