Effect of sacubitril/valsartan and dapagliflozin on athletic performance; can the popular cardiac medications of recent years be used as doping agents?

Abstract

Abstract Background/Introduction Recent guidelines have highlighted the positive impacts of sacubitril/valsartan and dapagliflozin on heart failure management [1]. Given their potential misuse as doping agents in professional sports, this study evaluates their effects on athletic performance. Purpose To investigate the effects of sacubitril/valsartan and dapagliflozin on athletic performance and cardiac functions in a rodent model. Methods The study had a randomized double-blind design. 24 Sprague-Dawley male rats aged 4 months, divided into control, sacubitril/valsartan, and dapagliflozin groups. The rats were weighed at the start of the experiment. The medications (dapagliflozin 1,5 mg/kg/1 ml/once a day, sacubitril/valsartan 60 mg/kg/1 ml/once a day to their respective groups, and normal saline for control group) were administered via gastric gavage for 30 days. The rats were weighed, examined with transthoracic echocardiography and put on rotarod at the start of the experiment, and on 15th and 30th days. The rats were put on forced swimming tests for 20 days. Exhaustion, loss of coordinated movements and failure to surface for 3 seconds after submersion in the water were defined as indications for ending the test as per the guidelines regarding rat exercise testing [2]. M-mode and Doppler measurements, forced swimming test durations, rotarod durations and weight were recorded on 0th, 15th and 30th days. Results Initial performance metrics, including echocardiography, weight, and rotarod tests, showed no significant differences among the groups at baseline. The distributions in data were non-normal. Over the course of the study, median swimming times significantly differed from the 9th session, with dapagliflozin-treated rats exhibiting a substantial increase in endurance. Specifically, dapagliflozin group's swimming times increased to a median of 3580 seconds by the 20th session, compared to 2382 seconds in the control group and 2591 seconds in the sacubitril/valsartan group, indicating a pronounced improvement in exercise capacity (P<0.0001)(Figure-1). Echocardiographic assessments revealed enhanced cardiac output and ejection fraction, particularly in the sacubitril/valsartan group, suggesting increased cardiac efficiency and potential athletic performance enhancement. Conclusion(s) The study demonstrates a significant improvement in athletic performance with dapagliflozin compared to sacubitril/valsartan. These findings suggest a potential for misuse in sports doping, emphasizing the need for stringent regulation and monitoring within competitive athletics.Figure-1