Heart failure, characterized by chronic dysfunction of the cardiac muscle, stands as the most prevalent cardiac condition globally. A groundbreaking study published in the esteemed New England Journal of Medicine introduces new hope for a subset of patients with this ailment. In Israel alone, tens of thousands of patients who previously had only one treatment option may now have an alternative. The study demonstrated that a medication, initially used for kidney disease, significantly reduces hospitalization rates and mortality risk while enhancing patients' quality of life.
The study involved approximately 6,000 heart failure patients with preserved ejection fraction, examining the effects of a drug from a different class, known as Nonsteroidal Mineralocorticoid Receptor Antagonists (MRA). This drug acts by inhibiting a hormonal pathway involved in cardiac muscle activity, thereby reducing inflammation and fibrosis of the heart muscle. Half of the participants received the new medication, while the other half were given a placebo.
After a 32-month follow-up, the study revealed that the treatment led to nearly a 20% reduction in a composite measure of hospitalizations and deaths from cardiovascular events in the drug-treated group compared to the control. Moreover, the study indicated that the drug also improved patients' quality of life and well-being, as assessed through self-reported questionnaires.
The reality of heart failure
In both heart failure types, symptoms such as dyspnea and fluid retention causing edema are similar; however, the etiologies and affected populations differ. In the reduced ejection fraction group, the primary causes are myocardial infarctions and ischemic heart disease. Conversely, in the preserved ejection fraction group, uncontrolled hypertension is the leading cause.
Diabetes medications mitigate disease severity
A significant gap exists in treatment options for both heart failure phenotypes. Although heart failure remains a chronic, largely incurable condition, numerous drugs now substantially alter the disease course in reduced ejection fraction heart failure, significantly decreasing hospitalizations and mortality risk.
Just three years ago, a new class of medications demonstrated significant efficacy in treating heart failure with preserved ejection fraction. Originally developed for diabetes treatment, these SGLT-2 inhibitors lower blood glucose levels and have proven effective in reducing cardiac complications in diabetic patients. Recent studies have shown their effectiveness in lessening heart failure severity, even in non-diabetic individuals. Until the latest publication, two drugs from this class were the only ones proven effective in reducing hospitalizations and mortality in heart failure with preserved ejection fraction.
These medications have side effects, and given the large patient population, additional treatment options are necessary for those who respond inadequately to initial therapy, as this drug class alone does not suffice for such a vast patient group.
The link to renal failure
Another avenue explored today involves treating these patients, who also suffer from obesity, with anti-obesity medications. These have been found to alleviate disease symptoms but are suitable only for patients with both heart failure and obesity, limiting their applicability. Therefore, the research effort to discover additional effective treatments continues.
Prof. Avishai GroperThe drug examined in the study was previously approved for other conditions—specifically, diabetic nephropathy—and showed significant efficacy in reducing cardiovascular complications and heart failure in these patients. There is a well-documented link between kidney and heart failure, as heart failure patients are at increased risk of renal complications and vice versa, underscoring the need for an integrated treatment approach to improve patients' health outcomes. The unique mechanism of this drug makes it suitable for both conditions, preventing the exacerbation of heart failure in patients with renal failure.
Two other drugs from the same class have previously demonstrated efficacy in treating reduced ejection fraction heart failure. However, this study marks the first instance of a drug from this class significantly improving the health status of heart failure patients with preserved ejection fraction. Given the limited treatment options, this new study represents a significant breakthrough, offering a promising new therapeutic avenue for these patients.
- Professor Avishai Groper is head of the cardiac transplants clinics and acute heart failure hospitalization at Sheba Medical Center
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