Does ivabradine exhibit a role in the reduction of bladder overactivity?

Abstract

Dear Editor, Ivabradine is a novel selective and specific inhibitor of the sinus node If current that induces heart rate reduction in a dose-dependent manner, with no direct hemodynamic effects [1, 2]. Moreover, it has been proved that it improves LV systolic function, reduces collagen density in the non-infarcted myocardium, and improves myocardial perfusion and the coronary reserve [3, 4]. It is less than a decade since it was first used for the treatment of chronic stable angina. Our anecdotal experience, however, suggests that it could possibly play a role in the reduction of bladder overactivity. Three months ago, a patient with lower urinary tract symptoms (LUTS), suggestive for benign prostatic hyperplasia treated with an a-blocker (AB), reported a significant reduction of storage symptoms after the introduction of ivabradine therapy for the treatment of co-morbitant chronic stable angina. In order to verify if the above-mentioned observation is a correlation or a coincidence, we asked five more patients with diagnosed benign prostatic hyperplasia suffering from storage LUTS (daytime urinary frequency, nocturia and urgency) and chronic stable angina to complete the International Prostate Symptom Score (IPSS) questionnaire prior and after ivabradine treatment. Surprisingly four out of five patients reported a significant reduction of storage LUTS (especially nocturia), resulting in an overall reduction of symptom bothersomeness (from moderately symptomatic to mildly symptomatic). In contrast, the IPSS of the remaining patient remained unchanged. Current knowledge on bladder patho-physiology does not allow for the evaluation of the abovementioned observation. However, the failure of prostate-directed treatments to help all men or all symptoms has led investigators to question the longstanding assumption that the prostate is at the root of all male urinary symptoms [5]. It is now widely recognized that bladder dysfunction plays a role in some, if not most, cases, and recent prospective studies and post-hoc analyses have suggested that pharmacotherapies that target the bladder, such as antimuscarinics, may improve storage urinary symptoms [6]. Indeed, the current mainstays of overactive bladder (OAB) pharmacotherapy are antimuscarinic agents, with mixed actions, including musculotropic (calcium antagonistic) activity [7, 8]. Although the exact mechanism is not clearly understood it could be assumed that it involves interplay between several ionic currents: whole-cell patch clamp studies showed that acetylcholine causes an outward K + current, presumably mediated through Ca 2+ -activated K + channels. Muscarinic M3 receptors are thought to act through increased polyphosphoinositide hydrolysis, inositol 1,4,5-triphosphate (IP 3) K. Stamatiou (&) I. Heretis Faculty of Medicine, Urology Department, University of Crete, Voutes Point, Iraklio, Crete 71110, Greece e-mail: stamatiouk@yahoo.com; stamatiouk@gmail.com