Verapamil reduces penile curvature, plaque size in Peyronie’s disease

Use of the calcium channel blocker verapamil is both safe and effective for the treatment of Peyronie’s disease, as proven by a decrease in penile curvature, reduction in plaque size, and improvement in erectile dysfunction, with minimal to mild side effects, relative to placebo, according to the results of a systematic review and meta-analysis.

Lead researcher Alvin Christopher Lavidia from St. Luke’s Medical Center in Quezon City, Philippines, presented the study at the 37th Annual European Association of Urology Congress (EAU 2022).

“Current literature on the use of verapamil for the treatment of Peyronie’s disease is conflicting,” the researchers said. “Hence, we performed a systematic review and meta-analysis to determine the efficacy of verapamil compared to placebo as well as other current accepted treatments in the management of Peyronie’s disease.”

Lavidia and his team searched the databases of Medline, Embase, and the Central Register of Controlled Trials for relevant studies through January 2021, with no language restriction, and supplemented the retrieved records with cross-referencing and search on trial registries. They assessed study quality by using RoBINS-I and RoB2.

The systematic review was done in compliance with the Cochrane Collaboration Recommendations on Review for Interventions. For the meta-analysis, the following outcomes were examined: decrease in penile curvature, plaque size, patient-reported outcome regarding improvement of erectile dysfunction, pain related to Peyronie’s disease, and adverse effects.

The researchers then extracted effect estimates as risk ratios (RRs) and standardized mean difference (SMD). They also pooled corresponding 95 percent confidence intervals (CIs) using inverse variance method with random effect model. Finally, study reporting was accomplished in accordance with the PRISMA guideline.

A total of 379 relevant records were identified, of which 16 comparative studies met the eligibility criteria. The researchers noted varied study quality and design.

In pooled effect estimates, treatment with verapamil resulted in a significantly better outcome in reducing penile curvature compared with placebo (RR, 1.78, 95 percent CI, 1.05‒3.01; p=0.03) and other active agents (RR, 1.40, 95 percent CI, 1.07‒1.84; I², 33 percent). [EAU 2022, abstract A0407]

Verapamil also substantially reduced plaque size relative to placebo (RR, 1.82, 95 percent CI, 1.46‒2.28; p<0.001), but no significant difference was noted in comparison with other active agents (SMD, ‒0.77, 95 percent CI, ‒1.57 to 0.02; p=0.06; I², 87 percent).

Likewise, patient-reported outcomes of improvement in erectile dysfunction were much better with verapamil than with placebo (RR, 3.01, 95 percent CI, 1.32‒6.84; p=0.009), whereas no statistically significant difference was observed when compared to other active agents (RR, 1.10, 95 percent CI, 0.96‒1.25; p=0.16; I², 0 percent).

In addition, “[t]here was no significant difference in post-treatment improvement on the patient perceived pain related to the disease between verapamil and placebo (RR, 1.85, 95 percent CI, 0.80‒4.26; p=0.05) nor between verapamil and other active agents (RR, 1.04, 95 percent CI, 0.93‒1.15; p=0.49; I², 46 percent),” the researchers said.

“Adverse effects were minimal and mostly transient,” they added.

In vitro and in vivo studies have shown the benefits of calcium channel blockers, such as verapamil, in inhibiting the synthesis and secretion of extracellular matrix molecules, as well as in boosting collagenase activity. Patients with localized plaque will benefit the most from intralesional injections of verapamil. [Arch Ital Urol Androl 2020;doi:10.4081/aiua.2020.3.253]