13 Dec 2006, Association for Acute CardioVascular Care, European Association of Preventive Cardiology, European Association of Cardiovascular Imaging, European Association of Percutaneous Cardiovascular Interventions, Association of Cardiovascular Nursing & Allied Professions, Working Group on Atherosclerosis and Vascular Biology, Working Group on Cardiac Cellular Electrophysiology, Working Group on Pulmonary Circulation & Right Ventricular Function, Working Group on Aorta and Peripheral Vascular Diseases, Working Group on Myocardial & Pericardial Diseases, Working Group on Adult Congenital Heart Disease, Working Group on Development, Anatomy & Pathology, Working Group on Coronary Pathophysiology & Microcirculation, Working Group on Cellular Biology of the Heart, Working Group on Cardiovascular Pharmacotherapy, Working Group on Cardiovascular Regenerative and Reparative Medicine, E-Journal of Cardiology Practice - Volume 5, e-Journal of Cardiology Practice - Volume 22, Previous volumes - e-Journal of Cardiology Practice, e-Journal of Cardiology Practice - Articles by Theme, novel multiple action antihypertensive agent, The Carvedilol Post-Infarct Survival Control, Evidences for prevention of nitroglycerin tolerance, Nebivolol decreases systemic oxidative stress, Nebivolol, bucindolol, metoprolol and carvedilol, Effects of vasodilatotory B-adrenoceptor antagonists, Effects of nebivolol on human platelet aggregation, Effects of nebivolol on proliferation and apoptosis, Long-term (3 months) effect of new b-blocker (nebivolol) on cardiac performance, Beta blocker treatment of patients with diastolic heart failure and arterial hypertension, The Beta-Blocker Evaluation of Survival Trial Investigators, Evaluation of Survival Trial (BEST) Investigators. A comparative study of carvedilol, slow-release nifedipine, and atenolol in the management of essential hypertension. Vlachopoulos C, Aznaouridis K, Stefanadis C. Prediction of cardiovascular events and all-cause mortality with arterial stiffness: a systematic review and meta-analysis. Lisinopril has an average rating of 5.0 out of 10 from a total of 612 ratings on Drugs.com. A recent meta-analysis on -blocker use in HF patients with reduced ejection fraction (HFrEF) showed that -blocker treatment confers a significant mortality reduction compared with placebo or active comparator (odds ratio [95% confidence interval (CI)]: 0.71 [0.640.80]; p<0.001) [68]. Carella AM, Antonucci G, Conte M, Di Pumpo M, Giancola A, Antonucci E. Curr Diabetes Rev. A meta-analysis. 2006;106(4):199-206. doi: 10.1159/000093060. Side effects include rare vertigo, tiredness and headache. So it's best to check with your healthcare provider first. Effects of nebivolol and atenolol on small arteries and microcirculatory endothelium-dependent dilation in hypertensive patients undergoing isometric stress. Alternatively, as with other -blockers, data do not adequately support the routine use of nebivolol in patients with HFpEF. Placebo-controlled trials of nebivolol monotherapy in specific patient populations include one conducted in younger patients (age range, 1854years; mean age, 45.3years) with stage 1 or stage 2 hypertension in which nebivolol significantly reduced DBP (change from baseline: 11.8mmHg vs 5.5mmHg; p<0.001) and SBP (change form baseline: 13.7mmHg vs 5.5mmHg; p<0.001), compared with placebo [48]. The primary outcome variables were systolic and diastolic blood pressures determined by 24-hour ambulatory blood pressure measurements. The https:// ensures that you are connecting to the If withdrawal symptoms occur, therapy may be temporarily reinstituted. A separate 12-week trial [61] investigated nebivolol (540mg/day) as add-on therapy to lisinopril (1020mg/day) or losartan (50100mg/day) in patients with untreated or uncontrolled hypertension treated with lisinopril or losartan. 0000052566 00000 n Cockcroft JR, Pedersen ME. Abraham WT, Tsvetkova T, Lowes BD, et al. Role of pulse pressure amplification in arterial hypertension: experts opinion and review of the data. The https:// ensures that you are connecting to the Together, these studies show that carvedilol is effective and superior to other -blockers in the treatment of patients following acute myocardial infarction. The antihypertensive efficacy of nebivolol monotherapy has been established in controlled trials with active comparators [24, 2830, 5054]. Nebivolol versus nifedipine in the treatment of essential hypertension: a double-blind, randomized, comparative trial. Liver Dose Adjustments Moderate impairment: Initial dose: 2.5 mg orally once a day; titrate slowly as needed. Pedersen ME, Cockcroft J. Timolol-induced reduction in mortality and reinfarction in patients surviving acute myocardial infarction. Antihypertensive treatment with beta-blockers in the metabolic syndrome: a review. After 10 days of placebo run-in period, they were randomized within the same group as cross-over design to one month carvedilol 25 mg and one month nebivolol 5 mg regimen given once daily in the morning. Lexi-Comp, Inc.; April 10, 2018. Beta Blocker Conversion Table Resident Editor: Patrick Azcarate, MD Faculty Editor: Elisabeth Askin, MD *Disclaimer: These are not typical starting doses. Developed in collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of Intensive Care Medicine (ESICM). Furthermore, treatment with carvedilol achieved more favorable outcomes than bisoprolol. Maitland-van der Zee AH, Klungel OH, Kloosterman JM, et al. Recently, slow-release carvedilol (SR) has been developed. Wiysonge CS, Bradley H, Mayosi BM, et al. Krum H, Hill J, Fruhwald F, et al. Carvedilol inhibits right ventricular hypertrophy induced by chronic hypobaric hypoxia. 0000057866 00000 n After adjusting for heart rate, the mean between-group difference in AIx was 2.4% (p=0.041), with nebivolol increasing AIx to a lesser extent than atenolol [30]. Bouras G, Deftereos S, Tousoulis D, Giannopoulos G, Chatzis G, Tsounis D, et al. Patient education: High blood pressure treatment in adults (Beyond the Basics) available beta blockers include acebutolol, atenolol, betaxolol, bisoprolol, metoprolol, nadolol, nebivolol, pindolol, propranolol, and timolol . Nebivolol: Nebivolol, a beta 1 selective blocker, has been shown to increase portal pressures . endstream endobj 658 0 obj<>/ViewerPreferences<>/Metadata 43 0 R/Pages 42 0 R/StructTreeRoot 45 0 R/Type/Catalog>> endobj 659 0 obj<>/Font<>/ProcSet[/PDF/Text]/Properties<>>>/ExtGState<>>>/Type/Page>> endobj 660 0 obj<> endobj 661 0 obj<> endobj 662 0 obj<> endobj 663 0 obj<> endobj 664 0 obj<> endobj 665 0 obj<> endobj 666 0 obj<>stream Stiles S. Panel to FDA: Nebivolol Shouldnt Be Approved for Chronic Heart Failure. Giugliano D, Acampora R, Marfella R, et al. Clinical efficacy of carvedilol in severe hypertension. Malminiemi K. Association between serum lipids, glucose tolerance, and insulin sensitivity during 12 months of celiprolol treatment. 0000047828 00000 n Unlike traditional beta blockers carvedilol : Its distinctive features allow different applications and usage and there are several trials for various conditions. A large, randomized, placebo-controlled trial in elderly patients with a history of HF [70years of age; 68% with a history of coronary artery disease; N=2128: SENIORS (Study of Effects of Nebivolol Intervention on Outcomes and Rehospitalization in Seniors With Heart Failure)] demonstrated a significantly lower risk of all-cause mortality or cardiovascular hospitalizations in nebivolol-treated patients versus placebo [odds ratio (95% CI): 0.86 (0.740.99); p=0.039] [79]. Prevention of cardiovascular events with an antihypertensive regimen of amlodipine adding perindopril as required versus atenolol adding bendroflumethiazide as required, in the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA): a multicentre randomised controlled trial. (15)Brixius K, Bundkirchen, Bolck B et al. Augmentation index is associated with cardiovascular risk. Meyer-Sabellek W, Schulte KL, Distler A, Gotzen R. Circadian antihypertensive profile of carvedilol (BM 14190). Kveiborg B, Hermann TS, Major-Pedersen A, et al. has a positive effect on renal hemodynamics. Poole-Wilson PA, Swedberg K, Cleland JG, et al. Yancy CW, Jessup M, Bozkurt B, Butler J, Casey DE, Jr, Drazner MH, et al. Effect of antihypertensive treatment on qualitative estimates of microalbuminuria. State of hypertension management in the United States: confluence of risk factors and the prevalence of resistant hypertension. Dawes M, Brett SE, Chowienczyk PJ, Mant TG, Ritter JM. Arzneim Forsch/drug Res 2000;50:973-79. The https:// ensures that you are connecting to the ; otherwise (i.e., for patients receiving low to medium. Rhodes J, Margossian R, Darras BT, et al. Recently, third generation, vasodilating, beta-blockers were introduced into practice. 0000008723 00000 n Efficacy and tolerability of nebivolol monotherapy by baseline systolic blood pressure: a retrospective analysis of pooled data from two multicenter, 12-week, randomized, double-blind, placebo-controlled, parallel-group, dose-ranging studies in patients with mild to moderate essential hypertension. In the Class IV patients bucindolol even increased the composite end point of death and heart failure hospitalisations in six-months follow-up. Nebivolol, but not metoprolol, lowers blood pressure in nitric oxide-sensitive human hypertension. 0000005906 00000 n They differ, though, in beta-selectivity, vasodilation properties, and other ancillary features. Bakris GL, Fonseca V, Katholi RE, et al. Nebivolol decreases systemic oxidative stress in healthy volunteers. 0000007474 00000 n The primary efficacy parameter was change from baseline in mean trough DBP; secondary parameters included change from baseline in mean trough SBP and a response rate at endpoint, defined as the proportion of patients with mean trough DBP <90mmHg or an absolute reduction of 10mmHg from baseline. Grassi G, Trevano FQ, Facchini A, Toutouzas T, Chanu B, Mancia G. Efficacy and tolerability profile of nebivolol vs atenolol in mild-to-moderate essential hypertension: results of a double-blind randomized multicentre trial. Lindholm LH, Carlberg B, Samuelsson O. If a dose is missed, take it as soon as remembered; but if it is close to the next dose, skip the missed dose; do not double the dose. In total, over 2000 patients were included, with one trial consisting of black participants only [43]. Data sources include IBM Watson Micromedex (updated 2 Apr 2023), Cerner Multum (updated 17 Apr 2023), ASHP (updated 10 Apr 2023) and others. In that trial, nebivolol (5mg) but not metoprolol (50mg) lowered night-time SBP (p=0.036) and DBP (p<0.001) versus placebo, effects that were driven by the subgroup of individuals who also responded to sildenafil (25mg) [34]. The contribution of vasodilation to the overall antihypertensive effect of nebivolol was recently assessed in a small, double-blind, placebo-controlled cross-over study of 20 patients with autonomic failure [34], who are devoid of adrenergic input in blood pressure control and are therefore characterized by an impaired baroreceptor function, as manifested through orthostatic hypotension and supine hypertension. Comparing beta-blocking effects of bisoprolol, carvedilol and nebivolol. Methods: Carvedilol: There is both an immediate release and extended release form of carvedilol. In one study, 40 individuals with untreated essential hypertension were randomized to atenolol 50mg/day or nebivolol 5mg/day for 4weeks; treatment with nebivolol reduced aortic PP to a significantly greater extent than atenolol (16 vs 11mmHg; p=0.04) [29]. Albers S, Meibohm B, Mir TS, Ler S. Population pharmacokinetics and dose simulation of carvedilol in paediatric patients with congestive heart failure. The vasodialtor effect of these three agents is obtained via the blockade of the alpha receptors. N Engl J Med 2001;344:1659-67. Labetalol (Normodyne, Trandate) blocks alpha receptors, too. In another 12-week trial of 131 hypertensive men randomized (1:1:1) to receive nebivolol, atenolol, or atenolol and the diuretic chlorthalidone, the mean number of satisfactory sexual intercourses per month declined by 47 and 56% in groups treated with atenolol and atenolol-chlorthalidone, respectively (p<0.01, both), while it remained constant in the group treated with nebivolol [93]. Failure of benefit and early hazard of bucindolol for class IV heart failure. Bristow M, Nelson P, Minobe W, Johnson C. Characterization of 1-adrenergic receptor selectivity of nebivolol and various other beta-blockers in human myocardium. Trends in antihypertensive medication use and blood pressure control among United States adults with hypertension: the National Health And Nutrition Examination Survey, 2001 to 2010. Unable to load your collection due to an error, Unable to load your delegates due to an error. The primary outcome variables were systolic and diastolic blood pressures determined by 24-hour ambulatory blood pressure measurements. Possible tumor or brain cancer possibly MS. D-nebivolol is a selective beta-1 antagonist while L-nebivolol is responsible for the nitric oxide dependent vasodilator effect. Erectile dysfunction may improve by blood pressure control in patients with high-risk hypertension. Dahlf B, Severs PS, Poulter NR, et al. While -blockers are not recommended within the current US guidelines as first-line therapy for treatment of essential hypertension, nebivolol has shown comparable efficacy to currently recommended therapies in lowering peripheral blood pressure in adults with hypertension with a very low rate of side effects. Lainscak M, Moullet C, Schn N, Tendera M. Treatment of chronic heart failure with carvedilol in daily practice: the SATELLITE survey experience. Ritchie LD, Campbell NC, Murchie P. New NICE guidelines for hypertension. Hall S, Prescott RI, Hallman RJ, et al. We also assessed vasodilation induced by these drugs in isolated perfused guinea pig hearts according to Langendorff's procedures. Tual L, Morel OE, Favret F, et al. The, However this particular study had a small number of Class IV patients and the. Connect with thousands of patients and caregivers for support and answers. Factors identified as precipitating hospital admissions for heart failure and clinical outcomes: findings from OPTIMIZE-HF. Relation of early improvement in coronary flow reserve to late recovery of left ventricular function after beta-blocker therapy in patients with idiopathic dilated cardiomyopathy. Current research suggests that nebivolol may be a desirable treatment for specific indications, but further clinical investigation to determine its effects on cardiovascular morbidity and mortality is warranted. Both carvedilol and nebivolol produce hemodynamic and clinical benefits in chronic heart failure, but it is unknown whether their peculiar pharmacologic properties produce different effects on LV function. Objective: Based on findings from this trial, the guidelines now indicate carvedilol in this patient group. Brune S, Schmidt T, Tebbe U, Kreuzer H. Hemodynamic effects of nebivolol at rest and on exertion in patients with heart failure. 34% of reviewers reported a positive effect, while 43% reported a negative effect. J Hypertens. Eichstaedt H, Danne O, Schroeder RJ, Kreuz D. Left ventricular hypertrophy regression during antihypertensive treatment. Discussion of safety and efficacy was limited to hypertension, heart failure (HF), and erectile dysfunction. Are beta-blockers efficacious as first-line therapy for hypertension in the elderly? Regression of carotid atherosclerosis by control of morning blood pressure peak in newly diagnosed hypertensive patients. J Cardiovasc Pharmacol 2001;38:922-29. Moser M, Frishman W. Results of therapy with carvedilol, a beta-blocker vasodilator with antioxidant properties, in hypertensive patients. Treatment with carvedilol is associated with a significant reduction in microalbuminuria: a multicentre randomised study. ESC guidelines for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the diagnosis and treatment of acute and chronic heart failure 2008 of the European Society of Cardiology. Uzunlulu M, Oguz A, Yorulmaz E. The effect of carvedilol on metabolic parameters in patients with metabolic syndrome. However, due to its short half-life, immediate-release carvedilol (IR) needs to be prescribed twice a day. Ler S, Mir TS, Behn F, et al. Guan YY, Ye BH, Lu HH, et al. Addition of HCTZ resulted in an equal additional antihypertensive effect in both groups versus monotherapy (p<0.03) [50]. High blood pressure is a common condition and when not treated, can cause damage . Antihypertensive treatment with beta-blockers in the metabolic syndrome: a review. Similar results were obtained in a randomized, cross-over study of 16 patients with untreated isolated systolic hypertension (ISH) [28] who received atenolol 50mg/day, nebivolol 5mg/day, and placebo for 5 weeks each. The change from baseline in SBP with the nebivolol/lisinopril combination was also significantly reduced compared with placebo (p<0.001) and nebivolol (p<0.05), but not versus lisinopril monotherapy [60]. This eventually leads to lower blood pressure. Overall, 74% of patients treated with nebivolol monotherapy and 65.5% of those treated with nebivolol plus diuretic responded to treatment (DBP 90mmHg or decrease in DBP 10mmHg) [58]. 2010. While -blockers are not recommended as first-line therapy for treatment of essential hypertension, nebivolol has shown comparable efficacy to ACEIs, ARBs, and CCBs in lowering SBP and DBP in adults with mild to moderate hypertension. The absolute bioavailability of nebivolol is unknown. A randomized, controlled trial. De Caterina AR, Leone AM. It has been noted that atenolol, a non-vasodilating 1-selective blocker, was used in the large majority of studies included in these meta-analyses, and the finding therefore may not be generalizable to third-generation, vasodilatory -blockers such as carvedilol and nebivolol [41]. 0 Faculty Editor: Elisabeth Askin, MD, CrCl <40, cirrhosis, heart failure (10mg total daily), Weight <85kg, heart failure (50mg total daily), Contraindicated in severe liver impairment. Herlitz J, Karlson BW, Hjalmarson A. Mazza A, Gil-Extremera B, Maldonato A, Toutouzas T, Pessina AC. MeSH Cardiovasc Drugs Ther. Abbreviations: Carv, carvedilol; Metop, metoprolol. Triposkiadis F, Giamouzis G, Kelepeshis G, Sitafidis G, Skoularigis J, Demopoulos V, et al. After oral administration, absorption is fast and reaches maximum plasma concentration within 1-2 hours. Two such studies compared nebivolol to the non-vasodilatory 1-selective blocker, atenolol, in adults with mild to moderate hypertension [50, 54]. The seventh report of the joint national committee on Prevention, Detection, Evaluation, and Treatment of High Blood pressure: the JNC 7 report. Fonseca VA. Abstract. Edes I, Gasior Z, Wita K. Effects of nebivolol on left ventricular function in elderly patients with chronic heart failure: results of the ENECA study. These receptors affect how tight or relaxed your blood vessels and airways are. 0000001869 00000 n Dobre D, van Veldhuisen DJ, Mordenti G, Vintila M, Haaijer-Ruskamp FM, Coats AJ, et al. Lawless CE, Tamlyn T, Shah R, et al. Interested in more discussions like this? Packer M, Fowler MB, Roecker EB, et al. For metoprolol doses 100 mg (i.e., medium to high doses) and systolic blood pressure >100 mm Hg, carvedilol was started at 12.5 mg b.i.d. Clinical utility of fixed-dose combinations in hypertension: evidence for the potential of nebivolol/valsartan. Finally, in the CARNEBI (Multiparametric comparison of CARvedilol, vs NEbivolol, vs BIsoprolol in moderate heart failure) cardiopulmonary trial, 70 patients with moderate HF who were given carvedilol, nebivolol, and bisoprolol for 2 months each showed improvements on measures of lung diffusion (p0.001) and exercise performance (p<0.0001) with nebivolol and bisoprolol [75]. Fonarow GC, Heywood JT, Heidenreich PA, Lopatin M, Yancy CW. Verza M, Ammendola S, Cambardella A, et al. Kasiske BL, Ma JZ, Kalil RS, et al. Praxis 2001;90:435-441. Lancet 1999;353:2001-2007. However, there was no significant difference in decreasing either systolic or diastolic blood pressure between nebivolol and carvedilol therapies (p>0.05). 0000012469 00000 n Randomized trial to determine the effect of nebivolol on mortality and cardiovascusar hospital admission in elderly patients with heart failure (SENIORS). An official website of the United States government. Did you know that your browser is out of date? This study demonstrates that -blocker therapy combined with a renin-angiotensin system inhibitor is more effective than treatment with a renin-angiotensin system inhibitor alone in patients with acute myocardial infarction. Off-label prescribing of beta-blockers Beta-blockers are sometimes used for "off-label" purposes. Dandona P, Ghanim H, Brooks DP. endstream endobj 702 0 obj<>/Size 657/Type/XRef>>stream 2005 Nov;150(5):985. doi: 10.1016/j.ahj.2005.07.024. It is a prospective; placebo-controlled, cross-over, double-blind, randomized, single-center clinical trial. National Library of Medicine Adding nebivolol to ongoing antihypertensive therapy improves blood pressure and response rates in patients with uncontrolled stage III hypertension. Blood pressure-lowering effect of nebivolol in hypertensive patients with type 2 diabetes mellitus: The YESTONO Study. A small reduction in mean NYHA functional class from baseline was seen in both groups (from 2.5 +/- 0.5 to 2.2 +/- 0.5 for carvedilol [p < 0.05] and from 2.3 +/- 0.4 to 2.2 +/- 0.5 for nebivolol [not significant]). Post-hoc, pooled analyses from the three pivotal trials (N=2016) discussed above were conducted to assess efficacy, safety, and tolerability with a greater statistical power [45], as well as to explore the effects of nebivolol on patients by age [46] and body mass index (BMI) [47]. Nebivolol versus Carvedilol or Metoprolol in Patients Presenting with Acute Myocardial Infarction Complicated by Left Ventricular Dysfunction. Fratta Pasini A, Garbin U, Nava MC, Stranieri C, Davoli A, Sawamura T, et al. (19)Weber MA. The safety of adding carvedilol to hypertensive patients inadequately treated with diuretics. Abrupt discontinuation should be avoided; taper therapy over approximately 1 to 2 weeks. No side effects were recorded during both carvedilol and nebivolol treatments. Tzemos N, Lim PO, MacDonald TM. A meta-analysis. The rationale provided by JNC 8 is based on results from several randomized controlled trials in which either -blockers performed similarly to the recommended therapies of thiazide-type diuretics, calcium channel blockers (CCBs), angiotensin-converting enzyme inhibitors (ACEIs), or angiotensin II receptor blockers (ARBs) or firm conclusions could not be made from the evidence [37]. Mechanism of differential effects of antihypertensive agents on serum lipids. Two-year clinical outcome after carvedilol-loaded stent implantation in patients with coronary artery disease. Titration of carvedilol in elderly heart failure patients. The maximum standardized mean difference of over 20 000 covariates was <0.1 from all 3 databases after PS matching (Figures S1 and S2). Comments: Safety and efficacy have not been established in patients younger than 18 years. Carvedilol has also been shown to inhibit neointimal hyperplasia in patients with coronary artery disease. Efficacy and safety of carvedilol in treatment of heart failure with chronic kidney disease: a meta-analysis of randomized trials. The drug is 98% protein bound, primarily to albumin, and reaches a peak concentration after 1.54h. Nebivolol is metabolized in the liver, mainly via direct glucuronidation and secondarily through cytochrome P450 2D6 (CYP450 2D6). Beta blockade during and after myocardial infarction: an overview of the randomized trials. Carlberg B, Samuelsson O, Lindholm LH. Furthermore, results from a small-scale HF study indicate that, in patients with HFrEF, nebivolol significantly lowers heart rate and SBP and improves stroke volume [72]. 1999;48:4603. Marfella R, Siniscalchi M, Nappo F, et al. Part IV: cardiovascular drugs. This extension of the observation window was interpreted by the advisory panel of the US FDA as a potential source of bias [97]. At baseline and after 6 months of treatment, all patients were assessed clinically and by biochemical and hematological investigation, ECG, 24-hour Holter monitoring, echocardiogram, measurement of ventilatory function, and a 6-minute walk test. Nebivolol (Bystolic) is a beta blocker. Am Heart J. In the case of patients who have left ventricular ejection fraction (LVEF) of 35%, an aldosterone antagonist should be considered [63]. Differential effects of carvedilol and metoprolol on renal function in patients with heart failure. These have a larger effect on lowering blood pressure. Galderisi M, Cicala S, DErrico A, de Divitiis O, de Simone G. Nebivolol improves coronary flow reserve in hypertensive patients without coronary heart disease. Patients with fluid retention can also be given a loop diuretic. 2013 ACCF/AHA guideline for the management of heart failure: a report of the American College of Cardiology Foundation/American Heart Association Task Force on practice guidelines. How it works This drug belongs to a class of drugs. A meta-analysis of 94,492 patients with hypertension treated with beta blockers to determine the risk of new-onset diabetes mellitus. Carvedilol in elderly patients with chronic heart failure, a 12 weeks randomized, placebo controlled open trial. Carvedilol inhibits tumor necrosis factor-alpha-induced endothelial transcription factor activation, adhesion molecule expression, and adhesiveness to human mononuclear cells. Weiss R, Weber M, Carr A, Sullivan W. A randomized, double-blind, placebo-controlled parallel-group study to assess the efficacy and safety of nebivolol, a novel b-blocker, in patients with mild to moderate hypertension. Leonetti Luparini R, Celli V, Piccirillo G, et al. 2005;23:58996. (2)Dunn CJ, Lea AP, Wagstaff AJ. A benefit of nebivolol treatment in HFpEF is less clear than it is in patients with HFrEF. Furthermore, carvedilol appears to be well tolerated in elderly patients with chronic heart failure, although the very elderly (>80 years) tolerate carvedilol less well than their younger counterparts (7079 years). Seventy patients with a LV ejection fraction /Size 657/Type/XRef > > stream 2005 Nov ; (..., Cockcroft J. Timolol-induced reduction in microalbuminuria: a double-blind, randomized comparative... 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