Could thiazolidinediones increase the risk of heart failure in Friedreichs ataxia patients

Garcia–Gimenez JL et al. – The possible fatal consequences must be taken into account when peroxisome proliferator–activated receptor–gamma agonist drugs are considered as possible therapeutic agents for Friedreich's ataxia patients.

• Clinical evidence and the recent decisions of the European Medicines Agency and the Food and Drug Administration challenge the safety of thiazolidinediones treatment.
• Recently, this treatment has been suggested for Friedreich's ataxia because thiazolidinediones improve neurological symptoms.
• Hypertrophic cardiomyopathy is the most prevalent cardiac feature and the cause of premature death in Friedreich's ataxia patients.
• The authors recommend that therapy with peroxisome proliferator–activated receptor–gamma agonists like thiazolidinediones be taken with caution, as they cause a decrease in the number of fast fibers and an increase in mitochondrial biogenesis in cardiac muscle because of the induction of peroxisome proliferator–activated receptor–gamma coactivator–1(alpha).
• The incidence of heart failure may increase when thiazolidinediones are combined with insulin, and moreover, they produce cyclooxygenase 2 inhibition, inducing a thrombotic response.
• Thus, patients are predisposed to adverse cardiovascular outcomes.

[more...]