There was a time when antibiotics and prolactin-lowering molecules were repurposed for use as antidiabetic drugs. Today, glucose-lowering drugs are proving their mettle in non-diabetic indications as well. This phenomenon is known as endocrine exaptation.

Empagliflozin may become the first and only clinically proven therapy to improve outcomes for the full spectrum of heart failure patients with either preserved or reduced ejection fraction. Results from the EMPEROR-Preserved trial released earlier this week show great promise. In the trial, empagliflozin significantly reduced the risk of cardiovascular death or hospitalization for heart failure in adults, with or without diabetes, who live with heart failure with preserved ejection fraction (HFpEF).

EMPagliflozin outcomE tRial in Patients With chrOnic heaRt Failure with Preserved Ejection Fraction (EMPEROR-Preserved) is a phase III randomised, double-blind trial to evaluate efficacy and safety of once daily empagliflozin 10 mg compared to placebo, in 5988 HF patients with preserved ejection fraction. The primary endpoint of the study was a composite of time to first event of adjudicated CV death or Hospitalisation for Heart Failure over a time period of 38 months.

Although no specific results have been released for now except that the EMPEROR-Preserved Phase III trial had met its primary endpoint, they are comparable to the findings of the EMPEROR-Reduced trial published last year in the New England Journal of Medicine (N Engl J Med. 2020 Oct 8;383(15):1413-1424). In this trial, once-daily empagliflozin had significantly reduced the combined relative risk of CV death or HF hospitalization by 25% compared with placebo in 3,730 patients of HF with reduced ejection fraction (HFrEF). These patients also had a slower decline in renal function. .

The efficacy of empagliflozin was first demonstrated in the EMPA-REG OUTCOME trial (Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes). It provided strong evidence not only for its cardioprotective effect (reducing cardiovascular risk in type 2 diabetes patients at high risk for cardiovascular events), but also its beneficial effect on heart failure hospitalization and CV death.

HFpEF patients have not been easy to manage on account of their age (most are elderly), presence of comorbidities and diverse etiopathogenesis. Comorbidities are significant and equally important contributors to the hospitalizations and mortality in these patients as is the heart failure. Also, the heterogeneous etiology has precluded an effective treatment. Treatment of HFpEF therefore mainly involves the management of associated conditions and symptoms and mortality remains considerably high in these patients.

Given the rising prevalence and challenges encountered in the treatment of HFpEF, the success of empagliflozin has come as a breakthrough for the treating physician. The EMPEROR-Preserved has now offered, for the first time, empagliflozin as a therapeutic option for these patients.

Taken together, both EMPEROR trials showcase the efficacy of empagliflozin across patients with heart failure regardless of the ejection fraction.

The complete results of EMPEROR-Preserved are scheduled for presentation August 27 during the European Society of Cardiology (ESC) Congress 2021.

(Source:  Boehringer Ingelheim Press Release, July 6, 2021)

Dr Sanjay Kalra, DM, Bharti Hospital, KarnalImmediate Past President, Endocrine Society of India