Cardiovascular Research

Analysis of integrated clinical safety data of tadalafil in patients receiving concomitant antihypertensive medications.

Authors: Robert A Kloner|||John B Kostis|||Thomas P McGraw|||Chunfu Qiu|||Alankar Gupta

Affiliations: + Expand

Abstract

This pooled safety analysis assessed the incidence of hypotension-related treatment-emergent adverse events (TEAEs) and major adverse cardiovascular events (MACEs) in patients with concomitant use of tadalafil and antihypertensive medications. Data were pooled from seventy-two Phase II-IV studies conducted on patients with a diagnosis of erectile dysfunction (ED) and/or benign prostate hyperplasia (BPH). Studies were categorized as either All placebo-controlled studies or All studies. The incidences of hypotension-related TEAEs and MACEs were analyzed by indication; by use of concomitant antihypertensive medications; and by the number of concomitant antihypertensive medications. A total of 15 030 and 22 825 patients were included in the analyses for All placebo-controlled studies and All studies, respectively. In the All placebo-controlled studies, the incidence of hypotension-related TEAEs and MACEs was ranging between 0.6-1.5% and 0.0-1.0%, respectively, across all indications. Tadalafil was associated with an increase in hypotension-related TEAEs only in the ED as-needed group not receiving any concomitant antihypertensive medications (p-value = .0070); no significant difference was reported between placebo and tadalafil in the groups of patients receiving ≥1 antihypertensive medication (p-values ≥ .7386). Similarly, no significant differences (p-values≥ .2238) were observed in the incidence of MACEs between tadalafil and placebo treatment groups, with or without concomitant use of antihypertensive medications, and across all indication categories. In the All studies group, results were similar. The pooled analysis showed no evidence that taking tadalafil alongside antihypertensive medications increases the risk of hypotension-related TEAEs or MACEs compared with antihypertensive medications alone.

---

Chemical List

Antihypertensive Agents|||Phosphodiesterase 5 Inhibitors|||Tadalafil

---

Reference List

Kessler A, Sollie S, Challacombe B, Briggs K, Van Hemelrijck M. The global prevalence of erectile dysfunction: a review. BJU International. 2019;124(4):587‐599. 10.1111/bju.14813|||Gratzke C, Angulo J, Chitaley K, et al. Anatomy, physiology, and pathophysiology of erectile dysfunction. J Sex Med. 2010;7(1 Pt 2):445‐475. 10.1111/j.1743-6109.2009.01624.x|||Feldman HA, Goldstein I, Hatzichristou DG, Krane RJ, McKinlay JB. Impotence and its medical and psychosocial correlates: Results of the Massachusetts Male Aging Study. J Urol. 1994;151(1). 10.1016/s0022-5347(17)34871-1|||Kloner R. Erectile dysfunction and hypertension. Int J Impotence Res. 2007;19(3):296‐302. 10.1038/sj.ijir.3901527|||Shin D, Pregenzer G, Gardin JM. Erectile dysfunction: A disease marker for cardiovascular disease. Cardiol Rev. 2011;19(1):5‐11. 10.1097/CRD.0b013e3181fb7eb8|||Huang SA, Lie JD. Phosphodiesterase‐5 (PDE5) inhibitors in the management of erectile dysfunction. P T. 2013;38(7):407‐419.|||Hatzimouratidis K. A review of the use of tadalafil in the treatment of benign prostatic hyperplasia in men with and without erectile dysfunction. Ther Adv Urol. 2014;6(4):135‐147. 10.1177/1756287214531639||| Adis Insight . Tadalafil ‐ Eli Lilly and Company: Springer; 2021. [updated 14 Mar 2021; cited 2021. https://adisinsight.springer.com/drugs/800009738 |||Schwartz BG, Kloner RA. Drug interactions with phosphodiesterase‐5 inhibitors used for the treatment of erectile dysfunction or pulmonary hypertension. Circulation. 2010;122(1):88‐95. 10.1161/CIRCULATIONAHA.110.944603|||Rybalkin SD, Yan C, Bornfeldt KE, Beavo JA. Cyclic GMP phosphodiesterases and regulation of smooth muscle function. Circ Res. 2003;93(4):280‐291. 10.1161/01.RES.0000087541.15600.2B|||Hundemer GL, Knoll GA, Petrcich W, et al. Kidney, cardiac, and safety outcomes associated with α‐blockers in patients with CKD: A population‐based cohort study. Am J Kidney Dis. 2021;77(2):178‐189.e1. 10.1053/j.ajkd.2020.07.018|||Leung AA, Daskalopoulou SS, Dasgupta K, et al. Hypertension Canada's 2017 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults. Can J Cardiol. 2017;33(5):557‐576. 10.1016/j.cjca.2017.03.005|||Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: Executive summary: A report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Circulation. 2018;138(17):e426‐e83. 10.1161/cir.0000000000000597|||Mancia G, Fagard R, Narkiewicz K, et al. 2013 ESH/ESC guidelines for the management of arterial hypertension: the task force for the management of arterial hypertension of the European Society of Hypertension (ESH) and of the European Society of Cardiology (ESC). J Hypertens. 2013;31(7):1281‐1357. 10.1097/01.hjh.0000431740.32696.cc|||Clavijo RI, Miner MM, Rajfer J. Erectile dysfunction and essential hypertension: The same aging‐related disorder?. Rev Urol. 2014;16(4):167‐171.|||Chrysant SG. Antihypertensive therapy causes erectile dysfunction. Curr Opin Cardiol. 2015;30(4):383‐390. 10.1097/hco.0000000000000189|||Patel JP, Lee EH, Mena‐Hurtado CI, Walker CN. Evaluation and management of erectile dysfunction in the hypertensive patient. Curr Cardiol Rep. 2017;19(9):89. 10.1007/s11886-017-0889-z|||Foy CG, Newman JC, Berlowitz DR, et al. Blood pressure, sexual activity, and erectile function in hypertensive men: Baseline findings from the Systolic Blood Pressure Intervention Trial (SPRINT). J Sex Med. 2019;16(2):235‐247. 10.1016/j.jsxm.2018.12.007|||Slag MF, Morley JE, Elson MK, et al. Impotence in medical clinic outpatients. JAMA. 1983;249(13):1736‐1740.|||Curb JD, Borhani NO, Blaszkowski TP, Zimbaldi N, Fotiu S, Williams W. Long‐term surveillance for adverse effects of antihypertensive drugs. JAMA. 1985;253(22):3263‐3268.|||Foy CG, Newman JC, Russell GB, et al. Effect of intensive vs standard blood pressure treatment upon erectile function in hypertensive men: Findings from the Systolic Blood Pressure Intervention Trial. J Sex Med. 2020;17(2):238‐248. 10.1016/j.jsxm.2019.11.256|||Scranton RE, Lawler E, Botteman M, et al. Effect of treating erectile dysfunction on management of systolic hypertension. Am J Cardiol. 2007;100(3):459‐463. 10.1016/j.amjcard.2007.03.045|||McLaughlin T, Harnett J, Burhani S, Scott B. Evaluation of erectile dysfunction therapy in patients previously nonadherent to long‐term medications: A retrospective analysis of prescription claims. Am J Ther. 2005;12(6):605‐611. 10.1097/01.mjt.0000181305.44330.4a|||Whelton PK, Carey RM, Aronow WS, et al. 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. Hypertension (Dallas, Tex : 1979). 2018;71(6):1269‐1324. 10.1161/hyp.0000000000000066|||Kostis JB, Jackson G, Rosen R, et al. Sexual dysfunction and cardiac risk (the Second Princeton Consensus Conference). Am J Cardiol. 2005;96(12b):85m‐93m. 10.1016/j.amjcard.2005.12.018|||Nehra A, Jackson G, Miner M, et al. The Princeton III Consensus recommendations for the management of erectile dysfunction and cardiovascular disease. Mayo Clin Proc. 2012;87(8):766‐778. 10.1016/j.mayocp.2012.06.015|||Kloner RA, Mitchell M, Emmick JT. Cardiovascular effects of tadalafil in patients on common antihypertensive therapies. Am J Cardiol. 2003;92(9a):47m‐57m. 10.1016/s0002-9149(03)00075-4|||Patterson D, McInnes GT, Webster J, Mitchell MM, MacDonald TM. Influence of a single dose of 20 mg tadalafil, a phosphodiesterase 5 inhibitor, on ambulatory blood pressure in subjects with hypertension. Br J Clin Pharmacol. 2006;62(3):280‐287. 10.1111/j.1365-2125.2006.02658.x|||Kloner RA, Jackson G, Hutter AM, et al. Cardiovascular safety update of tadalafil: Retrospective analysis of data from placebo‐controlled and open‐label clinical trials of tadalafil with as needed, three times‐per‐week or once‐a‐day dosing. Am J Cardiol. 2006;97(12):1778‐1784. 10.1016/j.amjcard.2005.12.073|||Montorsi F, Verheyden B, Meuleman E, et al. Long‐Term safety and tolerability of tadalafil in the treatment of erectile dysfunction. Eur Urol. 2004;45(3):339‐345. 10.1016/j.eururo.2003.11.010