- Email: [email protected]
Carvedilol for the Treatment of Benign Prostatic Hypertrophy in Patients With Heart Failure?
Journal of Cardiac Failure Vol. 17 No. 10 2011
Case Report
Carvedilol for the Treatment of Benign Prostatic Hypertrophy in Patients With Heart Failure? COLLEEN K. ROHRER, MS, ANP-BC,1 ROBERT LEE PAGE II, PharmD, MSPH,2 SIMON F. SHAKAR, MD,3,4 AND JOANN LINDENFELD, MD3,4 Aurora, Colorado
ABSTRACT Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only b-adrenergic blocker approved for HF that also has additional a1-adrenergic blockade. As a1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient’s symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an a1-adrenergic blockers. (J Cardiac Fail 2011;17:875e877) Key Words: Benign prostatic hypertrophy, heart failure, adrenergic a-antagonists, adrenergic b-antagonists.
This case suggests that carvedilol might be considered for the management of HF with systolic dysfunction in patients with BPH, potentially eliminating the need for a1-adrenergic blockers.
As both heart failure (HF) and benign prostatic hypertrophy (BPH) affect O10% of men O60 years old, it comes as no surprise that these two diagnoses may coexist and b-adrenergic blocking agents are prescribed frequently in men with BPH.1,2 Carvedilol is the only b-adrenergic blocker approved for HF that also has additional a1-adrenergic blockade. Because a1-adrenergic blockers are commonly used to treat BPH, one might expect that carvedilol would improve symptoms of BPH compared with other b-adrenergic blockers used in HF.3 We present an interesting case where carvedilol was replaced with bisoprolol resulting in acute urinary retention.
Case Report The patient was a 69-year old man who was admitted for signs and symptoms consistent with an exacerbation of both heart failure and chronic obstructive pulmonary disease (COPD) after an acute upper respiratory infection. His medical history was notable for nonischemic dilated cardiomyopathy with an estimated ejection fraction of w35%, COPD with pulmonary function tests showing a severe obstructive pattern, chronic atrial fibrillation, hyperlipidemia, and hypothyroidism. The patient had no history suggestive of BPH; specifically, he had no nocturia and no difficulty in intitiating the urinary stream. On physical exam, the patient appeared in mild respiratory distress with scattered wheezes throughout bilateral lung fields and diminished breath sounds at the bilateral bases, as well as bilateral lower extremity edema and elevated jugular venous distention. Initially, the patient had no evidence of urinary retention on exam with no percussible bladder noted. The patient’s medications on admission included: carvedilol 25 mg in the morning and 50 mg in the evening, eplerenone, lisinopril, furosemide, atorvastatin, warfarin, levothyroxine, and albuterol-ipratropium inhaler as needed. He had been taking this stable medication regimen for w18 months with no symptoms of BPH.
From the 1Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado; 2Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, Colorado; 3Heart Failure Program, Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado and 4Cardiac Transplant Program, Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado. Manuscript received March 11, 2011; revised manuscript received May 12, 2011; revised manuscript accepted May 16, 2011. Reprint requests: JoAnn Lindenfeld, MD, Professor of Medicine, Medical Director, Cardiac Transplant Program, University of Colorado, 1635 Aurora Court, F749, Room 7083, Aurora, CO 80045. Tel: 720-8482258; Fax: 720-848-0851. E-mail: [email protected] See page 876 for disclosure information. 1071-9164/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.cardfail.2011.05.009
875
876 Journal of Cardiac Failure Vol. 17 No. 10 October 2011 All home medications were continued at the same doses and intervals with the exception of the following medications. For his acute COPD exacerbation, a 5-day course of oral prednisone and azithromycin was administered, in addition to inhaled levalbuterol as needed for respiratory distress. To manage his acute decompensated heart failure, intravenous furosemide (40 mg daily) was administered for the first 3 days, which was then transitioned back to his oral home dose of 40 mg daily. On hospital day 2, the patient’s carvedilol was changed to a more selective b1-blocker, bisoprolol (10 mg daily) in an attempt to reduce wheezing due to b2-adrenergic blockade with carvedilol. The patient received his last dose of carvedilol (50 mg) on hospital day 1 in the evening and was administered his first dose of bisoprolol (10 mg) on hospital day 2 in the morning. Twelve hours after stopping the carvediolol, the patient reported a moderate improvement in his wheezing but now complained of significant urinary retention. With a straight catheterization, O1,000 mL was emptied from his bladder. All potential medical and mediation-related causes were initially ruled out, and the urinary retention was thought to be due to BPH. On hospital day 5, the medical team suspected that the conversion from carvedilol to bisoprolol could have led to exacerbation of underlying BPH. Therefore, bisoprolol was discontinued and the patient restarted carvedilol (25 mg twice daily). Within 12 hours of receiving the first dose of carvediolol, the patient began to experience improvement in his urine stream when voiding. However, due to his initial complaints of urinary retention, the patient was discharged on hospital day 6 with an indwelling catheter, which was removed 3 days after discharge. One week after discharge, after removal of the indwelling urinary catheter the patient was diagnosed by digital rectal exam with BPH by his primary care provider. Six months after discharge, the patient remained on carvedilol (25 mg twice daily) with no active symptoms of BPH or need for additional BPH medications.
Discussion Carvedilol is a nonselective b-blocker with additional a1-adrenergic receptor blockade. The drug has an affinity for the a1a, a1b, and a1d receptors that predominate in the prostate similar to that of doxazosin.3 Compared with terazosin, carvedilol has a greater affinity for the same a receptors but a much lower affinity than prazosin or tamsulosin.3 In a single-dose study, carvedilol’s a-adrenergic receptor blockade appeared to be dose dependent, with the greatest a-blockade effects seen with a single 25 mg dose.4 In the present patient, the clinical presentation of acute urinary retention became apparent within 12 hours of removing the a-blocking effects of carvedilol. This finding is consistent with pharmacodynamic and kinetic studies that suggest that carvedilol occupies the a-receptor for $3.5e8 hours.5,6 Labetalol is also a nonselective a-b-adrenergic receptor blocker which varies from carvediolol in that it exhibits a higher ratio of a-blockade to b-blockade.7 In a singledose study, Tomlinson et al7 found the a-blockade of 100 mg carvedilol to be slightly less than that of 400 mg labetalol, attributing this finding to carvedilol’s lower ratio of a-blockade to b-blockade. Nonetheless, labetalol is not approved or recommended for the treatment of systolic HF.8
Based on carvedilol’s pharmacologic profile, we hypothesized that the patient already suffered from underlying BPH which was being controlled by the carvedilol.9 After reinstitution of carvedilol and discontinuation of bisoprolol, the patient experienced no further urinary symptoms and no need for additional BPH medications. It is important to note that our patient was receiving an anticholinergic medication, ipratropium, which could lead to urinary retention. However, he had been taking stable doses of the inhaler for 18 months prior to this hospitalization and remained on the same doses throughout his admission and after discharge. Of note, the use of use a1-adrenergic blockers may have hazardous effects in patients with cardiovascular disease.10,11 In a retrospective cohort analysis of 388 veterans with HF, Dhaliwal et al10 found an increase in HF hospitalizations (hazard ratio 1.94, confidence interval 1.14e3.32; P 5 .015) in those patients taking an a1-adrenergic blocker for BPH without a b-blocker. Additionally, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attach Trial found that the risk of development of HF doubled in patients with hypertension who received doxazosin compared with chlorthalidone.11 It has been hypothesized that unopposed a1-adrenergic blockade without b-blockade may lead to increased b1-receptor stimulation.9 Such stimulation could in turn increase plasma renin activity with subsequent increases in angiotensin II and aldosterone concentrations leading to weight gain and edema. In conclusion, the present case suggests that in patients with HF and BPH, withdrawal of carvedilol may be associated with acute symptoms of BPH. Additionally, it is possible that carvedilol might be used to control BPH symptoms in patients who require a b-blocker without an additional a1-adrenergic blocker, thus reducing the total number of medications for individual patients. Because the majority of patients O65 years old consume $5 prescription and over-the-counter medications annually, medication consolidation in this population is of paramount importance.12 Disclosures None.
References 1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statisticsd2011 update: a report from the American Heart Association. Circulation 2010; 123:e18e209. 2. Hoke GP, McWilliams GW. Epidemiology of benign prostatic hyperplasia and comorbidities in racial and ethnic minority populations. Am J Med 2008;121:S3e10. 3. Hieble JP. Adrenoceptor subclassification: an approach to improved cardiovascular therapeutics. Pharm Acta Helv 2000;74:163e71. 4. Tham TC, Guy S, McDermott BJ, Shanks RG, Riddell JG. The dose dependency of the alpha- and beta-adrenoceptor antagonist activity of carvedilol in man. Br J Clin Pharmacol 1995;40:19e23.
Carvedilol, Heart Failure, and BPH 5. Beermann C, Schloos J, Belz GG. Oral administration of carvedilol and prazosin inhibits the prostaglandin F2 alphae and noradrenaline-induced contraction of human hand veins in vivo. Clin Investig 1992;70:S13e9. 6. Giannattasio C, Cattaneo BM, Seravalle G, Carugo S, Mangoni AA, Grassi G, et al. Alpha 1eblocking properties of carvedilol during acute and chronic administration. J Cardiovasc Pharmacol 1992; 19(Suppl 1):S18e22. 7. Tomlinson B, Bompart F, Graham BR, Liu JB, Prichard BN. Vasodilating mechanism and response to physiological pressor stimuli of acute doses of carvedilol compared with labetalol, propranolol, and hydralazine. Drugs 1988;36(Suppl 6):37e47. 8. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, et al. Heart Failure Society of America 2010 comprehensive heart failure practice guideline. J Card Fail 2010;16:e1e194.
Rohrer et al
877
9. Frishman WH. Carvedilol. N Engl J Med 1998;339:1759e65. 10. Dhaliwal AS, Habib G, Deswal A, Verduzco M, Souchek J, Ramasubbu K, et al. Impact of alpha 1eadrenergic antagonist use for benign prostatic hypertrophy on outcomes in patients with heart failure. Am J Cardiol 2009;104:270e5. 11. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2000;283:1967e75. 12. Page RL 2nd, Linnebur SA, Bryant LL, Ruscin JM. Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions. Clin Interv Aging 2010;5: 75e87.
Erratum The article ‘‘Effects of Sertraline on Circulating Markers of Oxidative Stress in Depressed Patients With Chronic Heart Failure: A Pilot Study,’’ by Michalakeas et al (J Card Fail 2011;17:748-54), was published with a misspelling to an author’s name. The correct spelling of the author’s name is Elefterios Lykouras.
Case Report
Carvedilol for the Treatment of Benign Prostatic Hypertrophy in Patients With Heart Failure? COLLEEN K. ROHRER, MS, ANP-BC,1 ROBERT LEE PAGE II, PharmD, MSPH,2 SIMON F. SHAKAR, MD,3,4 AND JOANN LINDENFELD, MD3,4 Aurora, Colorado
ABSTRACT Heart failure (HF) and benign prostatic hypertrophy (BPH) are two conditions that commonly coexist in men 60 years and older. Carvedilol is the only b-adrenergic blocker approved for HF that also has additional a1-adrenergic blockade. As a1-adrenergic blockers are used in the treatment of BPH, it is intuitive that carvediolol could improve BPH symptoms. We present a case where carvedilol was replaced with bisoprolol resulting in acute urinary retention. When carvediolol was reinstituted, the patient’s symptoms of BPH resolved. Benign prostatic hypertrophy was later diagnosed by digital rectal exam. Six month after reinstituting the carvediolol, the patient remains free of his BPH symptoms. This case suggests that carvedilol may be considered for the management of HF with systolic dysfunction in patients with concomitant BPH thus eliminating the need for an a1-adrenergic blockers. (J Cardiac Fail 2011;17:875e877) Key Words: Benign prostatic hypertrophy, heart failure, adrenergic a-antagonists, adrenergic b-antagonists.
This case suggests that carvedilol might be considered for the management of HF with systolic dysfunction in patients with BPH, potentially eliminating the need for a1-adrenergic blockers.
As both heart failure (HF) and benign prostatic hypertrophy (BPH) affect O10% of men O60 years old, it comes as no surprise that these two diagnoses may coexist and b-adrenergic blocking agents are prescribed frequently in men with BPH.1,2 Carvedilol is the only b-adrenergic blocker approved for HF that also has additional a1-adrenergic blockade. Because a1-adrenergic blockers are commonly used to treat BPH, one might expect that carvedilol would improve symptoms of BPH compared with other b-adrenergic blockers used in HF.3 We present an interesting case where carvedilol was replaced with bisoprolol resulting in acute urinary retention.
Case Report The patient was a 69-year old man who was admitted for signs and symptoms consistent with an exacerbation of both heart failure and chronic obstructive pulmonary disease (COPD) after an acute upper respiratory infection. His medical history was notable for nonischemic dilated cardiomyopathy with an estimated ejection fraction of w35%, COPD with pulmonary function tests showing a severe obstructive pattern, chronic atrial fibrillation, hyperlipidemia, and hypothyroidism. The patient had no history suggestive of BPH; specifically, he had no nocturia and no difficulty in intitiating the urinary stream. On physical exam, the patient appeared in mild respiratory distress with scattered wheezes throughout bilateral lung fields and diminished breath sounds at the bilateral bases, as well as bilateral lower extremity edema and elevated jugular venous distention. Initially, the patient had no evidence of urinary retention on exam with no percussible bladder noted. The patient’s medications on admission included: carvedilol 25 mg in the morning and 50 mg in the evening, eplerenone, lisinopril, furosemide, atorvastatin, warfarin, levothyroxine, and albuterol-ipratropium inhaler as needed. He had been taking this stable medication regimen for w18 months with no symptoms of BPH.
From the 1Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado; 2Department of Clinical Pharmacy, School of Pharmacy, University of Colorado, Aurora, Colorado; 3Heart Failure Program, Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado and 4Cardiac Transplant Program, Division of Cardiology, Department of Medicine, School of Medicine, University of Colorado, Aurora, Colorado. Manuscript received March 11, 2011; revised manuscript received May 12, 2011; revised manuscript accepted May 16, 2011. Reprint requests: JoAnn Lindenfeld, MD, Professor of Medicine, Medical Director, Cardiac Transplant Program, University of Colorado, 1635 Aurora Court, F749, Room 7083, Aurora, CO 80045. Tel: 720-8482258; Fax: 720-848-0851. E-mail: [email protected] See page 876 for disclosure information. 1071-9164/$ - see front matter Ó 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.cardfail.2011.05.009
875
876 Journal of Cardiac Failure Vol. 17 No. 10 October 2011 All home medications were continued at the same doses and intervals with the exception of the following medications. For his acute COPD exacerbation, a 5-day course of oral prednisone and azithromycin was administered, in addition to inhaled levalbuterol as needed for respiratory distress. To manage his acute decompensated heart failure, intravenous furosemide (40 mg daily) was administered for the first 3 days, which was then transitioned back to his oral home dose of 40 mg daily. On hospital day 2, the patient’s carvedilol was changed to a more selective b1-blocker, bisoprolol (10 mg daily) in an attempt to reduce wheezing due to b2-adrenergic blockade with carvedilol. The patient received his last dose of carvedilol (50 mg) on hospital day 1 in the evening and was administered his first dose of bisoprolol (10 mg) on hospital day 2 in the morning. Twelve hours after stopping the carvediolol, the patient reported a moderate improvement in his wheezing but now complained of significant urinary retention. With a straight catheterization, O1,000 mL was emptied from his bladder. All potential medical and mediation-related causes were initially ruled out, and the urinary retention was thought to be due to BPH. On hospital day 5, the medical team suspected that the conversion from carvedilol to bisoprolol could have led to exacerbation of underlying BPH. Therefore, bisoprolol was discontinued and the patient restarted carvedilol (25 mg twice daily). Within 12 hours of receiving the first dose of carvediolol, the patient began to experience improvement in his urine stream when voiding. However, due to his initial complaints of urinary retention, the patient was discharged on hospital day 6 with an indwelling catheter, which was removed 3 days after discharge. One week after discharge, after removal of the indwelling urinary catheter the patient was diagnosed by digital rectal exam with BPH by his primary care provider. Six months after discharge, the patient remained on carvedilol (25 mg twice daily) with no active symptoms of BPH or need for additional BPH medications.
Discussion Carvedilol is a nonselective b-blocker with additional a1-adrenergic receptor blockade. The drug has an affinity for the a1a, a1b, and a1d receptors that predominate in the prostate similar to that of doxazosin.3 Compared with terazosin, carvedilol has a greater affinity for the same a receptors but a much lower affinity than prazosin or tamsulosin.3 In a single-dose study, carvedilol’s a-adrenergic receptor blockade appeared to be dose dependent, with the greatest a-blockade effects seen with a single 25 mg dose.4 In the present patient, the clinical presentation of acute urinary retention became apparent within 12 hours of removing the a-blocking effects of carvedilol. This finding is consistent with pharmacodynamic and kinetic studies that suggest that carvedilol occupies the a-receptor for $3.5e8 hours.5,6 Labetalol is also a nonselective a-b-adrenergic receptor blocker which varies from carvediolol in that it exhibits a higher ratio of a-blockade to b-blockade.7 In a singledose study, Tomlinson et al7 found the a-blockade of 100 mg carvedilol to be slightly less than that of 400 mg labetalol, attributing this finding to carvedilol’s lower ratio of a-blockade to b-blockade. Nonetheless, labetalol is not approved or recommended for the treatment of systolic HF.8
Based on carvedilol’s pharmacologic profile, we hypothesized that the patient already suffered from underlying BPH which was being controlled by the carvedilol.9 After reinstitution of carvedilol and discontinuation of bisoprolol, the patient experienced no further urinary symptoms and no need for additional BPH medications. It is important to note that our patient was receiving an anticholinergic medication, ipratropium, which could lead to urinary retention. However, he had been taking stable doses of the inhaler for 18 months prior to this hospitalization and remained on the same doses throughout his admission and after discharge. Of note, the use of use a1-adrenergic blockers may have hazardous effects in patients with cardiovascular disease.10,11 In a retrospective cohort analysis of 388 veterans with HF, Dhaliwal et al10 found an increase in HF hospitalizations (hazard ratio 1.94, confidence interval 1.14e3.32; P 5 .015) in those patients taking an a1-adrenergic blocker for BPH without a b-blocker. Additionally, the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attach Trial found that the risk of development of HF doubled in patients with hypertension who received doxazosin compared with chlorthalidone.11 It has been hypothesized that unopposed a1-adrenergic blockade without b-blockade may lead to increased b1-receptor stimulation.9 Such stimulation could in turn increase plasma renin activity with subsequent increases in angiotensin II and aldosterone concentrations leading to weight gain and edema. In conclusion, the present case suggests that in patients with HF and BPH, withdrawal of carvedilol may be associated with acute symptoms of BPH. Additionally, it is possible that carvedilol might be used to control BPH symptoms in patients who require a b-blocker without an additional a1-adrenergic blocker, thus reducing the total number of medications for individual patients. Because the majority of patients O65 years old consume $5 prescription and over-the-counter medications annually, medication consolidation in this population is of paramount importance.12 Disclosures None.
References 1. Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, et al. Heart disease and stroke statisticsd2011 update: a report from the American Heart Association. Circulation 2010; 123:e18e209. 2. Hoke GP, McWilliams GW. Epidemiology of benign prostatic hyperplasia and comorbidities in racial and ethnic minority populations. Am J Med 2008;121:S3e10. 3. Hieble JP. Adrenoceptor subclassification: an approach to improved cardiovascular therapeutics. Pharm Acta Helv 2000;74:163e71. 4. Tham TC, Guy S, McDermott BJ, Shanks RG, Riddell JG. The dose dependency of the alpha- and beta-adrenoceptor antagonist activity of carvedilol in man. Br J Clin Pharmacol 1995;40:19e23.
Carvedilol, Heart Failure, and BPH 5. Beermann C, Schloos J, Belz GG. Oral administration of carvedilol and prazosin inhibits the prostaglandin F2 alphae and noradrenaline-induced contraction of human hand veins in vivo. Clin Investig 1992;70:S13e9. 6. Giannattasio C, Cattaneo BM, Seravalle G, Carugo S, Mangoni AA, Grassi G, et al. Alpha 1eblocking properties of carvedilol during acute and chronic administration. J Cardiovasc Pharmacol 1992; 19(Suppl 1):S18e22. 7. Tomlinson B, Bompart F, Graham BR, Liu JB, Prichard BN. Vasodilating mechanism and response to physiological pressor stimuli of acute doses of carvedilol compared with labetalol, propranolol, and hydralazine. Drugs 1988;36(Suppl 6):37e47. 8. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, et al. Heart Failure Society of America 2010 comprehensive heart failure practice guideline. J Card Fail 2010;16:e1e194.
Rohrer et al
877
9. Frishman WH. Carvedilol. N Engl J Med 1998;339:1759e65. 10. Dhaliwal AS, Habib G, Deswal A, Verduzco M, Souchek J, Ramasubbu K, et al. Impact of alpha 1eadrenergic antagonist use for benign prostatic hypertrophy on outcomes in patients with heart failure. Am J Cardiol 2009;104:270e5. 11. ALLHAT Officers and Coordinators for the ALLHAT Collaborative Research Group. Major cardiovascular events in hypertensive patients randomized to doxazosin vs chlorthalidone: the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). JAMA 2000;283:1967e75. 12. Page RL 2nd, Linnebur SA, Bryant LL, Ruscin JM. Inappropriate prescribing in the hospitalized elderly patient: defining the problem, evaluation tools, and possible solutions. Clin Interv Aging 2010;5: 75e87.
Erratum The article ‘‘Effects of Sertraline on Circulating Markers of Oxidative Stress in Depressed Patients With Chronic Heart Failure: A Pilot Study,’’ by Michalakeas et al (J Card Fail 2011;17:748-54), was published with a misspelling to an author’s name. The correct spelling of the author’s name is Elefterios Lykouras.