Treatment with trimetazidine in patients with wild-type transthyretin amyloid cardiomyopathy (ATTR-CM) did not result in significant improvements in heart function, exercise capacity or mitochondrial performance when compared to a placebo, according to a study published recently in ESC Heart Failure.
The randomized, double-blind, placebo-controlled trial highlighted that the antianginal agent offered no measurable benefit for managing wild-type ATTR-related cardiomyopathy.
What are the types of ATTR-CM?
There are two variants of ATTR-CM, with some associated differences in patient population, symptoms and life expectancy. Wild-type ATTR-CM (wATTR-CM) can occur with age, particularly in men, after the age of 60. It is the most common type of ATTR-CM. Hereditary ATTR-CM (hATTR-CM) occurs in both men and women and is passed down from a family member. It results from the mutation of the transthyretin gene.
“In the study, there was no significant effect of [trimetazidine] treatment on myocardial injury or loading conditions, as cardiac troponins and NT-proBNP were comparable with placebo,” the study authors said. “Furthermore, no improvement was noted with respect to LV [left ventricular] systolic function.”
Read more about ATTR-CM therapies
This study included 22 male patients with a mean age of 79.7 years, all diagnosed with wild-type ATTR-CM. Over two four-week treatment periods, patients alternated between trimetazidine and placebo, with invasive tests such as right heart catheterization and myocardial biopsies conducted after each phase.
Researchers focused on the mean pulmonary artery wedge pressure during exercise as the primary endpoint and cardiac mitochondrial oxidative phosphorylation as a secondary measure.
Results showed no differences between trimetazidine and placebo in mean pulmonary artery wedge pressure during peak exercise or in oxidative phosphorylation capacity. Trimetazidine also did not improve other markers of heart function, such as ejection fraction, global longitudinal strain or levels of NT-proBNP. Exercise tolerance, measured as metabolic equivalents and VO2 max, and quality of life scores remained unchanged.
Some minor effects were noted, including a decrease in resting stroke volume and cardiac output. But the changes were not clinically significant and did not indicate therapeutic benefit.
The treatment was well-tolerated, with mild side effects such as dizziness and abdominal discomfort reported by a small percentage of patients. These did not lead to treatment discontinuation.
Overall, trimetazidine did not provide functional or symptomatic relief for patients with wildATTRwt. The results underscored the need for further research into effective therapies for this challenging condition.