Could a newer diabetes medication provided clinicians with an alternative when managing heart failure? DAPA-HF trial assesses dapagliflozin.
As the number of patients diagnosed with heart failure continues to increase, new strategies are being evaluated to determine how to use alternative drug classes to mitigate exacerbations and decrease heart failure associated with hospitalizations. Sodium-glucose cotransporter two inhibitors, traditionally used for the treatment of diabetes, have shown some good promise in several landmark trials. A recent trial, DAPA-HF, has reported that patients can experience immense benefit from instituting dapagliflozin to current recommended guideline therapies in patients with heart failure and reduced ejection fraction, specifically in older patients within the advanced stages of heart failure. DAPA-HF included patients of all ages and baseline symptoms, which differs from previous trials conducted on this agent. These new results also differ from a recent report which suggested that dapagliflozin was more beneficial in heart failure patients who also had a diagnosis of diabetes.
The major objective in DAPA-HF was to determine if there was a benefit with the use of dapagliflozin in heart failure in both advanced age and disease. The primary outcome was the time to either heart failure associated hospitalization or a heart failure visit that required IV therapy and time to cardiovascular death. DAPA-HF consisted of 4,744 patients with heart failure class II to IV (New York Heart Association). Patients had a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide concentrations. After inclusion, patients were randomly assigned to receive dapagliflozin 10mg once-daily or placebo. In addition to this, all patients were receiving appropriate contemporary therapies. These included renin-angiotensin system inhibitors, mineralocorticoid receptor antagonists, beta-blockers, and even sacubitril/valsartan. Each patients’ additional agents were determined by currently established guidelines as well as tolerability. In both treatment groups, the average ejection fraction was 31%, an average of 41% in each group had chronic kidney disease, and about 45% of participants in each group had diabetes, so the group’s characteristics were very similar.
At the first data collection point, dapagliflozin was shown to have lowered the risk of heart failure associated with exacerbations and hospitalizations by 30%. There was also an 18% drop in the occurrence of mortality in the group that received dapagliflozin. When age analysis was completed, dapagliflozin showed a consistent benefit for those patients who were older as well as for those who were in more severe states of disease. Of the patients who were older than 75, the decline in the risk of the primary endpoints was even higher than the overall group at 32%. After patients received eight months of treatment, about 60% of the who received the dapagliflozin had clinically significant improvement in their symptom scores, which were measured by the Kansas City Cardiomyopathy Questionnaire. This is in contrast to only 50% of patients experiencing this same improvement in the control group. This was determined to be statistically significant. There was also no significant difference in risk reduction when patients with diabetes were compared to those who did not have a diabetes diagnosis. The occurrence of adverse effects was rare but there were fewer reported serious adverse effects with dapagliflozin as compared to placebo. Discontinuation rates were nearly identical for both groups.
All in all, dapagliflozin was shown to be an agent that can have great benefits to patients when it is used adjunctively. Regarding the primary endpoint, those patients who received dapagliflozin had significantly less mortality and exacerbations than those who received a placebo. Diabetes status had no bearing on the heart failure benefit of the agent. The data gathered in this trial also demonstrated that older patients had the same decreases in acute exacerbations and mortality as younger patients did. Older patients also demonstrated the ability to tolerate the agent, as the discontinuation rate for both groups was very similar. This can also be said for those patients in more severe stages of the disease. While more trials would need to be done to determine dapagliflozin’s benefit as monotherapy, there is now data to back using this non-traditional agent as an add-on when other heart failure classes have been exhausted.
- Dapagliflozin, an SGLT-2 Inhibitor, can decrease the risk of mortality and exacerbation when used adjunctively in heart failure.
- Diabetes status, age, and disease severity do not diminish dapagliflozin’s ability to reduce risk.
- Dapagliflozin is a well-tolerated agent with a mild side effect profile and should be considered for add on when managing heart failure.
Mcmurray JJ, Demets DL, Inzucchi SE, et al. The Dapagliflozin And Prevention of Adverse‐outcomes in Heart Failure (DAPA‐HF) trial: baseline characteristics. European Journal of Heart Failure. 2019;21(11):1402-1411. doi:10.1002/ejhf.1548.
DAPA-HF: Dapagliflozin Benefits Regardless of Age, HF Severity. Medscape. https://www.medscape.com/viewarticle/921775#vp_3. Published November 25, 2019.
Jordan Boyd, PharmD. Candidate of Florida Agricultural & Mechanical University School of Pharmacy