In addition to the SGLT-2 inhibitor dapagliflozin, which was also approved by Swissmedic last July for the treatment of heart failure (HFrEF) in non-diabetics, another member of this drug class, empagliflozin, has emerged as a potential treatment option for this indication. The European Society of Cardiology (ESC) has issued an updated recommendation.
In a position paper of the Heart Failure Association (HFA) of the European Society of Cardiology (ESC), cardiology experts advocated therapy with dapagliflozin or empagliflozin in heart failure on the basis of the two studies DAPA-HF and EMPEROR-Reduced [1–3]. Accordingly, dapagliflozin or empagliflozin are recommended to reduce the risk of hospitalization for heart failure and cardiovascular mortality in patients with symptomatic heart failure and reduced ejection fraction (HFrEF), whether or not type 2 diabetes is present.
Study situation strengthens the value of SGLT-2 inhibitors in heart failure
In the EMPEROR-Reduced trial, a significant reduction in the risk of cardiovascular-related death and hospitalization for heart failure in HFrEF patients was achieved with empagliflozin (10 mg/day) compared with placebo [4]. Thus, empagliflozin, a second SGLT-2 inhibitor, has demonstrated that it can significantly reduce clinical events in chronic heart failure in addition to standard therapy*, whether or not type 2 diabetes is present. The data were presented at the 2020 ESC Virtual Congress. During the study follow-up period (median 16 months), the risk of cardiovascular-related death and hospitalization for heart failure in patients with HFrEF was reduced by 25% in the empagliflozin group compared with placebo, reaching the significance level (hazard ratio [HR] 0.75; 95% CI 0.65-0.86; p<0.0001) [4]. Corresponding events occurred in 19.4% of study participants in the empagliflozin group and in 24.7% of those in the placebo group. The relative risk reduction for hospitalization due to heart failure was 31%. For cardiovascular mortality, the empagliflozin group showed a relative decrease of 8% (10.0% vs. 10.8%, HR: 0.92; 95% CI: 0.75-1.12). Thus, in addition to dapagliflozin, there is evidence of efficacy for empagliflozin as the second SGLT-2 inhibitor for the indication of heart failure of the HFrEF phenotype.
* e.g., ACE inhibitors, beta-blockers, aldosterone antagonists, angiotensin II receptor blockers (ARBs), or angiotensin receptor/neprilysin inhibitors (ARNIs).
Dapagliflozin as a concrete therapeutic option in HFrEF patients.
The SGLT-2 inhibitor dapagliflozin (Forxiga®) [5], approved in Switzerland since last year for the treatment of heart failure patients, reduced the risk of the composite endpoint of cardiovascular mortality or worsening of heart failure in patients HFrEF by 26% compared with placebo in the DAPA-HF trial as an add-on to standard therapy [1]. Over a relatively short median study duration of 18.2 months, an NNT (number needed to treat) of only 21 was achieved for the primary endpoint. The safety profile of Forxiga® in the DAPA-HF study was consistent with the already known safety profile of the drug. With a once-daily dosage of 10 mg, without titration, Forxiga® offers seamless integration into any heart failure treatment regimen to optimize therapy [5].
Summary
The current data situation has led the authors of the HFA/ESC position paper update to make a stronger recommendation of the two SGLT-2 inhibitors empagliflozin (Jardiance®) and dapagliflozin (Forxiga®) in manifest heart failure with and without type 2 diabetes. A previous recommendation had already confirmed that dapagliflozin, empagliflozin, canagliflozin, and ertugliflozin have shown consistent efficacy in preventing hospitalizations for heart failure in patients with type 2 diabetes and manifest cardiovascular disease or high cardiovascular risk [3].
Heart failure is a life-threatening condition, with reduced ejection fraction present in about half of cases. For this patient population, SGLT-2 inhibitors are important hopefuls for optimizing treatment options.
Literature:
- McMurray JJV, et al: Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction. N Engl J Med 2019; 381(21): 1995-2008.
- Packer M, et al: Cardiovascular and Renal Outcomes with Empagliflozin in Heart Failure. N Engl J Med 2020; 383: 1413-1424.
- Overbeck P: ESC position paper: SGLT2 inhibitors recommended in heart failure, Oct 27, 2020, www.kardiologie.org, (last accessed, Feb 28, 2021).
- Overbeck P: Empagliflozin also recommended as heart failure therapy, Aug 29, 2020, www.kardiologie.org/esc-kongress-2020, (last accessed Feb 28, 2021).
- Technical Information Forxiga®, www.swissmedicinfo.ch, as of July 2020.
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