Diabetic cardiomyopathy is a disease that does not have a defined standard of care or any good treatment options. It is associated with increased incidence of heart failure, even after controlling for coronary artery disease and hypertension. It is sometimes described as being rare, but some cardiology experts say it is just underdiagnosed.
This is why there was a lot of interest in the late-breaking results from the ARISE-HF trial presentd at ACC.24, the annual meeting of the American College of Cardiology (ACC). The Phase 3 randomized, placebo controlled trial enrolled close to 700 patients and examined if a new type of aldose reductase inhibitor (ARI), AT-001, could treat the disease without causing the serious side-effects first generation ARIs caused in these patients. Previous studies showed ARIs could increase exercise tolerance in diabetic cardiomyopathy, but patients had many issues with the earlier drugs.
The trial's primary endpoint was neutral, but the data had positive suggestive findings in select patients.
"We looked at the change in the peak oxygen uptake using cardio-pulmonary testing. What we found was that, among people treated with placebo with diabetic cardiomyopathy from baseline to 15 months, their exercise tolerance worsened significantly. Whereas people treated with high-dose AT-001, there was no significant decline, which is impressive actually. It looked like there was a stabilization. However, the difference between the two did not reach nominal statistical significance," explained James L. Januzzi, Jr. MD, director of the Dennis and Marilyn Barry Fellowship in Cardiology Research at Mass General, the Hutter Family Professor of Medicine at Harvard Medical School and a faculty member at the Harvard Clinical Research Institute.
In a pre-specified subgroup of patients not receiving SGLT2 inhibitors or GLP1 receptor agonists, which was around two thirds of the patient population, there was a statistically significant improvement in the exercise capacity in those treated with AT-001.
"We see a very clear and encouraging signal. Furthermore, cardiovascular events progression to symptomatic heart failure events was reduced in the AT-001 population. So we look at these results and we really think that there's a signal here that needs to be further studied," he explained.
Januzzi said the study showed that a future trial looking at a longer treatment duration might yield better outcomes overall. He said the regulatory requirements for the study also limited enrolled to patients with very well controlled blood glucose.
"Diabetic cardiomyopathy is a byproduct of poorly controlled blood glucose. So the other question is would the drug have been more effective if patients had a more real-world manifestation of diabetes?" Januzzi said.
The study was published online during ACC in the Journal of the American College of Cardiology.[1] Read more
Dave Fornell has covered healthcare for more than 17 years, with a focus in cardiology and radiology. Fornell is a 5-time winner of a Jesse H. Neal Award, the most prestigious editorial honors in the field of specialized journalism. The wins included best technical content, best use of social media and best COVID-19 coverage. Fornell was also a three-time Neal finalist for best range of work by a single author. He produces more than 100 editorial videos each year, most of them interviews with key opinion leaders in medicine. He also writes technical articles, covers key trends, conducts video hospital site visits, and is very involved with social media. E-mail: dfornell@innovatehealthcare.com