Chronic PDE5i Treatment Found to Improve Cardiac Remodeling in Men, but Not Women, With Diabetic Cardiomyopathy – Endocrinology Advisor

After careful consideration, the Endocrine Society canceled its annual meeting (ENDO 2020), which was set to take place in San Francisco, California, from March 28 to 31, 2020, because of concerns regarding coronavirus disease 2019 (COVID-19). Research findings that were scheduled to be presented at the meeting have been published in a supplemental issue of the Journal of the Endocrine Society.

The society is hosting ENDO Online, a complimentary virtual event featuring on-demand and live programming, from June 8 to 22, 2020, to provide a platform for continued learning and research exhibition. For more information, visit the Endocrine Societys website.

Chronic treatment for diabetic cardiomyopathy with the phosphodiesterase-5 inhibitor (PDE5i) tadalafil resulted in reductions in cardiac torsion and left ventricular strain in men, but not women, with type 2 diabetes (T2D), according to study results intended to be presented at the annual meeting of the Endocrine Society (ENDO 2020).1

Diabetic cardiomyopathy, detected using cardiac magnetic resonance imaging (CMR), is known to progress to heart failure in individuals with T2D. The underlying mechanisms of this progression remain unclear. Chronic treatment of diabetic cardiomyopathy with PDE5i has shown efficacy in men with T2D, regardless of glycemic control. Several animal model studies indicate that PDE5is exert their beneficial effects on heart diseases (eg, chronic mitral regurgitation, doxorubicin-mediated cardiotoxicity, and myocardial ischemia) in an estrogen-dependent manner.2-4 These sex-specific effects of PDE5is had not previously been examined in clinical trials.

In this double-blind interventional study, 108 patients with well-controlled T2D (mean age, 654 years; 47.2% women; mean hemoglobin A1c, 6.8%2.4%) were randomly assigned to receive either 20 mg/d of tadalafil (n=55; women, n=27) or placebo (n=53; women, n=24) for a period of 20 weeks. Study participants were given routine assessment at baseline and at the end of the treatment period, which consisted of metabolic panels, CMR, and renal assessment using Doppler ultrasound, during which the renal resistive index was measured.

After 20 weeks of treatment with tadalafil vs placebo, the diabetic cardiomyopathy of men, but not women, was improved compared with baseline, as assessed by reduced cardiac torsion (mean change: men, -2.28; 95% CI, -4.60 to 0.05; women, 1.13; 95% CI, -0.64 to 2.90; mean change in men vs women: -3.40; 95% CI, -6.05 to -0.76; P =.01) and reduced left ventricular strain (mean change: men, -1.19%; 95% CI, -2.24 to -0.14; women, 0.32%; 95% CI, -0.78 to 1.42; mean change in men vs women: -1.26%; 95% CI, -2.3 to -0.17; P =.05).

The 20-week-long tadalafil treatment was associated with similar improvements in renal function in both sexes compared with placebo, as indicated by reductions in microalbuminuria (change from baseline, -54.36 mg/24 h; 95% CI, -104.52 to -4.21; P =.03) and in the renal resistive index (change from baseline, -3.96%; 95% CI, -7.60 to -0.32; P =.03).

Tadalafil treatment did not affect hemoglobin A1c, body mass index, blood pressure, other parameters of renal function (eg, glomerular filtration rate and creatinine levels), or cardiac morphology (ie, left ventricular mass, end-diastolic volume, and ejection fraction).

The difference between the male-specific cardiac effects and the renal outcomes seen in both sexes after PDE5I suggests that distinctive mechanisms could be involved in the pathogenesis of diabetic complications, noted the study authors. [T]his study adds new insight on complications treatment in [T2D], identifying PDE5I as a possible alternative therapeutic option.

References

1. Pofi R, Giannetta E, Feola T, et al. Chronic inhibition of cyclic phosphodiesterase 5 showed sex-specific improvement on cardiac remodeling in diabetic cardiomyopathy. A randomized controlled trial. J Endocr Soc. 2020;4(suppl 1).

2. Kim KH, Kim YJ, Ohn JH, et al. Long-term effects of sildenafil in a rat model of chronic mitral regurgitation: benefits of ventricular remodeling and exercise capacity. Circulation. 2012;125(11):1390-1401.

3. Fisher PW, Salloum F, Das A, Hyder H, Kukreja RC. Phosphodiesterase-5 inhibition with sildenafil attenuates cardiomyocyte apoptosis and left ventricular dysfunction in a chronic model of doxorubicin cardiotoxicity. Circulation. 2005;111(13):1601-1610.

4. Salloum FN, Chau VQ, Hoke NN, et al. Phosphodiesterase-5 inhibitor, tadalafil, protects against myocardial ischemia/reperfusion through protein-kinase g-dependent generation of hydrogen sulfide. Circulation. 2009;120(11)(suppl 1):S31-S36.

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Chronic PDE5i Treatment Found to Improve Cardiac Remodeling in Men, but Not Women, With Diabetic Cardiomyopathy - Endocrinology Advisor