Beneficial Effect of Vardenafil on Aortic Stiffness and Wave Reflections

Abstract

Although vardenafil is widely prescribed for erectile dysfunction (ED), its effect on arterial function is not defined. Aortic stiffness, aortic pressures, and wave reflections are predictors of cardiovascular risk. The investigators assessed the hypothesis that vardenafil acutely improves aortic stiffness, aortic pressures, and wave reflections in ED patients. Twelve ED patients (mean age 58 ± 9 years) received vardenafil 20 mg in a randomized, placebo-controlled, double-blind, 2-way crossover design. Aortic stiffness was evaluated with carotid-femoral pulse wave velocity (PWV); wave reflections and aortic pressures were evaluated with augmentation index (AIx) and systolic, diastolic, and pulse pressure of the aortic pressure waveform, respectively. PWV, aortic pressures, and AIx were measured at baseline and for 3 hours after vardenafil intake or placebo. PWV decreased significantly (by 0.7 m/s, P = .001), denoting a decrease in aortic stiffness. AIx decreased significantly (by 7%, P = .008), denoting a decreased effect of wave reflections from the periphery. Aortic pressures decreased significantly (all P < .05). Statin use at baseline significantly interacted with the effects of treatment on both PWV and AIx (P = .003 and P < .001, respectively). This study shows, for the first time, that vardenafil has a favorable acute effect on aortic stiffness and wave reflection in ED patients.

Acute effect of sildenafil on inflammatory markers/mediators in patients with vasculogenic erectile dysfunction

“…PDE-5 inhibitors, in the paradigm of statins, may have a significant impact in stabilizing plaques by decreasing acute inflammatory activation [11,28]. Also, as we and others have shown, they are able to improve endothelial dysfunction [7][8][9][10] and aortic stiffness [12][13][14][15] that are predictors of cardiovascular events [29][30][31]; this may be partially mediated through their antiinflammatory properties [16][17][18]. Such effects are promptly evident, a factor of crucial significance for prevention of events with acute nature such as cardiovascular ones [32,33].…”

“…Furthermore, chronic treatment restores endothelium-dependent relaxations at various sites of the vascular tree, even up to one week after cessation of the treatment [11]. Beneficial acute (sildenafil, vardenafil) and chronic (sildenafil) effects of PDE-5 inhibitors on aortic stiffness and wave reflections in men with ED are also well-known [6,[12][13][14][15].…”

The role of vascular biomarkers for primary and secondary prevention. A position paper from the European Society of Cardiology Working Group on peripheral circulation

“…Anti-inflammatory drugs (corticoids, anti-tumor necrosis factor agents), lipid lowering drugs (statins, ezetimibe) and phosphodiesterase type 5 inhibitors [254,267] can decrease arterial stiffness.…”

“…The opposite was found with beta-blockers, while diuretics appear to be rather neutral [220,254,267,269e271]. Wave reflections measured by AIx were decreased by renin-angiotensin system blockers, calcium channel blockers, nitrates, phosphodiesterase type 5 inhibitors and aldosterone antagonists, while other diuretics did not change AIx [260,261,267,272]. In contrast, a majority of studies with nonvasodilating beta-blockers showed an increase in wave reflection, while vasodilating beta-blockers did not change or decreased AIx [260,273].…”

Future Treatment of Hypertension: Shifting the Focus from Blood Pressure Lowering to Arterial Stiffness Modulation?

“…Direct Treatment of PWV A number of short-term randomised controlled trials investigating the blockade/ inhibition of renin [71], angiotensin converting enzyme/ angiotensin AT1 receptor blockers [72][73][74][75][76][77][78][79][80], endothelin [81], aldosterone [82,83], phosphodiesterase V [84,85], HMGcoA reductase [86][87][88][89][90][91][92] and xanthine oxidase [93] have been shown to reduce aortic PWV. An important randomised trial in patients with early renal impairment showed both PWV and left ventricular mass reduction over 1 year on just 25 mg spironolactone versus placebo, which the authors claimed was independent of BP [94].…”