Perhaps no other disease process has seen so much innovation as heart failure treatment has witnessed in recent years. This article highlights some of such new drugs along with their uses, doses and side effects.

Central to heart failure treatment progress had been newer drugs that have resulted in reduced hospitalisations, cardiovascular death and total mortality.

1. Sacubitril/Valsartan

1. It was Dr John J.V. McMurray 2014 who set the ball rolling. He presented the prestigious paper for the PARADIGM-HF Investigators and Committee at the ESC congress. The results were described as extraordinary, spectacular and path-breaking.
2. For the first time, a new drug Sacubitril/Valsartan had shown a 20% relative risk reduction in the primary endpoints of a composite of death from cardiovascular causes or hospitalisation for heart failure over and above the then best existing treatment.
3. The trial paved the way for the inclusion of the new drug Sacubitril/Valsartan in the modern management of heart failure. 
4. With a series of further trials, the drug is now increasingly being used in acute heart failure, de novo heart failure, early post-discharge heart failure, the first-line drug for heart failure and also in some cases of heart failure with preserved ejection fraction.
5. Today Sacubitril/Valsartan is an established drug in the management of heart failure.

Dose: The dose needs to be carefully escalated to 200 mg twice daily from 50 mg twice daily in a graduated manner.

Side effect:

• Symptomatic hypotension 
• Hyperkalaemia Worsening renal function
• Angioedema 

2. Sodium-glucose co-transporter-2 inhibitors (SGLT2is)

1. Sodium-glucose co-transporter-2 inhibitors (SGLT2is) were a chance discovery for heart failure management.
2. By a decree of the U.S. Food and Drug Administration in 2008 as draft guidance mandated for all new type 2 diabetes therapies, it became essential for the new drugs to be at least not inferior to placebos or even better superior to them.
3. This was to be achieved by large cardiovascular outcomes trials (CVOTs). This had become essential on account of a publication of a meta-analysis of 42 studies suggesting that one of the then Pioglitazone named Rosiglitazone increased the risk of myocardial infarction by 43%, and cardiovascular death by 64%.
4. This paper was published in the June 2007 issue of the New England Journal of Medicine by Nissen SE et. al. The annual sale of Rosiglitazone was approximately $2.5 billion during those days; however, following this meta-analysis it plummeted to just $9.5 million in 2012. The drug's patent got expired in 2012.
5. This riches to rags story of Rosiglitazone however did immense service to mankind as it was observed that SGLT2is, new molecules for diabetes management at that time, in CVOT trials were proved to be extremely beneficial in diabetes patients.  The bulk of this benefit both in the primary and secondary management of diabetes patients was derived from the reduction in the heart failure events. Subsequently, this established the role of SGLT2is in heart failure management.
6. Two large trials were published. Both DAPA-HF (assessing dapagliflozin) and EMPEROR-Reduced (assessing empagliflozin) showed that sodium-glucose co-transporter-2 (SGLT2) inhibition reduced the combined risk of cardiovascular death or hospitalisation for heart failure in patients with heart failure with reduced ejection fraction (HFrEF) with or without diabetes.
7. Dapagliflozin and empagliflozin both are now standard of care treatment for heart failure with reduced ejection fraction.  Additionally, 2 recent trials have also proved their efficacy and safety in heart failure with preserved ejection fraction as well. With this, they become the first drugs to be useful in this disease entity.

Dose:  The dose of Dapagliflozin and Empagliflozin is 10 mg once daily in heart failure.  This is irrespective of the diabetes status of the patient.

Side effects: 

• Diabetic ketoacidosis
• Genital and urinary tract infection
• Increased urination.

3. Vericiugat: Soluble guanylate cyclase stimulator.

1. Soluble guanylate cyclase (sGC) enzymes are intracellular enzymes found in vascular smooth muscle cells and help in the synthesis of cyclic guanosine monophosphate (cGMP).
2. Cyclic GMP acts as a second messenger, activating a number of downstream signalling cascades leading to vasodilation, reduced fibrosis, reduced hypertrophy and increasing renal blood flow.
3. For heart failure patients these diverse physiological effects lead to substantial cellular protective beneficial effects.
4. A recent publication of the VICTORIA trial sought to highlight the role of the novel sGC stimulator, Vericiguat. The trial compared Vericiguat with placebo in 5,050 patients with chronic HF (NYHA class II-IV) with left ventricular ejection fraction (LVEF) <45%. Over a median follow-up of 10.8 months, there was a 10% relative risk reduction in the primary endpoint of cardiovascular death or HF hospitalisation.
5. The target dose was achieved in 89% of these patients, and there was no difference in syncope or hypotension rates. There was a signal for greater benefit in patients with age <75 years, LVEF <40%, renal insufficiency, patients not on an angiotensin receptor neprilysin inhibitor (ARNI), and NYHA class III or IV.

Dose: Vericiguat is available in 2.5, 5 and 10 mg doses.

Side effects:

• Hypotension
• Anaemia 

Summary

Disclaimer- The views and opinions expressed in this article are those of the authors and do not necessarily reflect the official policy or position of M3 India.

The author, Dr Arun Kochar is a Senior Interventional Cardiologist practising in Mohali.