Study on propionyl-L-carnitine in chronic heart failure

Aims In patients with chronic heart failure, fatigue is independentof haemodynamic and neuroendocrine changes and possibly maybe due to impaired muscle metabolism. Propionyl-L-carnitine,a carnitine derivative, was shown in previous studies to improvemuscle metabolism. The objective of this study was to evaluatethe effect of propionyl-L-carnitine on exercise capacity inmild–moderate chronic heart failure patients, treatedwith ACE inhibitors and diuretics. Methods and Results This was a phase III, double-blind, randomized, parallel, multicentrestudy. The primary objective was the evaluation of the effectof propionyl-L-carnitine vs placebo on maximum exercise durationusing a bicycle exercise test. The primary analysis performedin the intention-to-treat population (271 and 266 patients inpropionyl-L-carnitine and placebo), showed no statisticallysignificant difference between treatments. A difference of 15sin favour of propionyl-L-carnitine was observed in the completer/complierpopulation (P=0·092). An a priori specified subgroupanalysis on patients stratified by baseline maximum exerciseduration showed a trend of improvement in propionyl-L-carnitinepatients with shorter maximum exercise duration. A non a priorispecified analysis in patients stratified by ejection fraction(30% vs 30–40%), showed a statistically significant differencein maximum exercise duration in favour of propionyl-L-carnitinein those patients with a higher ejection fraction (40s,P<0·01).There were no safety issues. Conclusion The study fails to meet the primary objective, but confirmsthe good safety profile of propionyl-L-carnitine. An exploratorynon-prespecified analysis suggests that propionyl-L-carnitineimproves exercise capacity in patients with preserved cardiacfunction. This hypothesis needs to be confirmed by a specifictailored study.