Cardiovascular Parameter Changes in Patients With Erectile Dysfunction Using Pde‐5 Inhibitors: A Study With Sildenafil and Vardenafil

Abstract

Sildenafil is the most prescribed oral agent for patients with erectile dysfunction (ED). Vardenafil is a new phosphodiesterase type 5 (Pde-5) inhibitor that was approved by the US Food and Drug Administration last year to treat patients with ED of various causes. Both of these Pde-5 inhibitors have vasodilating properties and effects on blood pressure (BP), and like nitrates, they work through the nitric oxide cyclic guanosine monophosphate pathway. The aim of this study was to investigate the influence of these Pde-5 inhibitors on BP and heart rate (HR) in normotensive men with ED by a crossover comparison. Thirty-five patients with ED were enrolled to evaluate and compare the effect of sildenafil (50 mg) and vardenafil (10 mg) on BP and HR. At the screening (baseline [B]) visit, sitting systolic blood pressure (B-SBP), diastolic blood pressure (B-DBP), and HR were measured. We performed a multiple administration for both drugs and, therefore, multiple measurements of BP and HR changes, 3 doses a week, on alternate days, late in the afternoon, and on an empty stomach. B-SBP, B-DBP, and HR were recorded before each 50-mg sildenafil dosing and after 30, 60, 120, and 240 minutes. Data were averaged over the 4 time points and compared with the baseline values obtained before each dosing. After a 3-week wash-out period, patients were crossed over to vardenafil (10 mg) with the same study design. After administration of both drugs, we observed a statistically significant decrease of BP and an increase of HR. On average, sildenafil caused a decrease of SBP ranging from 5.1 +/- 3.9 mm Hg during the first dosing to 4.7 +/- 4.2 mm Hg during the third dosing, DBP ranged from 4.4 +/- 4.9 to 4 +/- 4.1 mm Hg, and HR increased 1.8 +/- 2.0 bpm (first dose) and 1.2 +/- 0.9 bpm (third dose). With vardenafil, we recorded a greater variation for SBP and DBP. SBP decreased from 8.02 +/- 8.0 mm Hg during the first dosing to 5.4 +/- 5.5 mm Hg during the third dosing, whereas DBP decreased from 6.6 +/- 7.2 to 5.0 +/- 5.3 mm Hg, respectively. Recorded HR showed an increase of 3.1 +/- 3.2 bpm (first dose) and 2.4 +/- 2.3 bpm (third dose). After the first vardenafil administration, we recorded fainting episodes in 3 patients because of a decrease in BP greater than 20 mm Hg. Two of the patients were in therapy with doxazosin for benign prostatic hyperplasia (BPH). Cardiovascular response was not significantly different after the first dose between the 2 treatments. Vardenafil demonstrated clinically significant differences (fainting) with respect to sildenafil only during the first doses. We suggest that before starting therapies with Pde-5 inhibitors, particularly with the newer ones, that baseline cardiovascular parameters are measured and monitored, especially during the first dose, because of the presence of a "first dose effect." Moreover, it is necessary to pay particular attention to those patients in treatment with other drugs that could have a synergistic hypotensive effect as a result of vasodilation potentiation.

Phosphodiesterase inhibitors for the treatment of pulmonary hypertension

“…In a cross-over study in males with erectile dysfunction, both sildenafil 50 mg and vardenafil 10 mg produced significant reductions in systemic blood pressure. Greater variability in response was noted with vardenafil, with three patients reporting fainting following the first dose [59]. Little change in systemic blood pressure was observed in healthy volunteers treated with tadalafil 20 mg or in males aged .45 yrs with erectile dysfunction treated daily for 26 weeks [60].…”

The effects of chronic phosphodiesterase-5 inhibitor use on different organ systems

“…In a study involving the use of 10 or 20 mg tadalafil in healthy patients there was a small but statistically significant reduction in systolic and diastolic pressure without adverse effects on hemodynamics. 48 In a crossover study comparing sildenafil (50 mg) and vardenafil (10 mg 49 PDE-5i have been shown to be tolerated with a wide range of concomitant antihypertensive drugs, such as b-adrenergic receptor blockers, calcium channel blockers, and angiotensin converting enzyme inhibitors (ACEi). However, PDE-5i should be used with caution in patients receiving a blocking agents since the combination of both might lead to excessive vasodilatation and hypotension.…”

Phosphodiesterase type 5 inhibitors and kidney disease

“…A crossover study compared the hypotensive effects of sildenafil and vardenafil in normotensive men with erectile dysfunction: Sildenafil (50 mg) and vardenafil (10 mg) were given on alternate days. Sildenafil caused a lower mean decrease in systolic and diastolic BP (5/4 mmHg) than vardenafil (8/6 mmHg) [19]. The long-acting PDE5 inhibitor PF-00489791 administered once daily for 28 days decreased blood pressure to a greater extent on day 1 than on days 14 and 28, but the response was sustained between days 14 and 28.…”