title: Influence of drugs and gender on the arterial pulse wave and natriuretic peptide secretion in untreated patients with essential hypertension. Bisoprolol, a once‐a‐day beta‐blocking agent for patients with mild to moderate hypertension Effects of Carvedilol on Blood Pressure in Patients with Mild to Moderate Hypertension Bisoprolol and hypertension: effects on sexual functioning in men. Double-blind, placebo-controlled crossover comparison of five classes of antihypertensive drugs Efficacy of a once-daily formulation of carvedilol for the treatment of hypertension. First-line therapy option with low-dose bisoprolol fumarate and low-dose hydrochlorothiazide in patients with stage I and stage II systemic hypertension. Effect of bisoprolol on blood pressure and arterial hemodynamics in systemic hypertension.
abstract: Recent studies have suggested a differential influence of mean pressure and pulse pressure on myocardial infa rct ion and stroke , and differences among the major drugs in their efficacy at preventing these individual endpoints . We hypothesized that antihypertensive drugs have differing influences upon the pulse wave even when their effects on blood pressure are the same . We studied 30 untreated hypertensive patients , aged 28 - 55 years , who were rotated through six 6-week periods of daily treatment with amlodipine 5 mg , doxazosin 4 mg , lisinopril 10 mg , bisoprolol 5 mg , bendrofluazide 2.5 mg or placebo . The best drug was repeated at the end of the rotation . Blood pressure readings and radial pulse tonometry ( by Sphygmocor ) were performed at each visit , and blood was taken for measurement of levels of atrial natriuretic peptide and brain natriuretic peptide ( BNP ) . The Sphygmocor derivation of the central aortic pulse wave was used to measure time for transmission of the reflected wave ( T(R ) ) and the augmentation index ( AI ) , which is the proportional increase in systolic pressure due to the reflected wave . There was a dissociation between the effects of the drugs on blood pressure and pulse wave analysis .  Bisoprolol caused the greatest falls in blood pressure and T(R ) , but was the only drug to increase AI . This paradoxical response to bisoprolol was associated with a 3-fold increase in plasma BNP levels . There was a smaller elevation of BNP in women compared with men , as described previously , and this elevation also was associated with significantly higher values of AI . Other drugs reduced AI , and this was associated with a significant decrease in BNP by amlodipine . In conclusion , antihypertensive drugs differ in their short-term effects on augmentation of the systolic pulse wave and secretion of BNP from the heart , regarded as a sensitive measure of strain on cardiomyocytes . These differences may help to explain cause-specific differences in outcome in recent trials The 24‐h blood pressure control of bisoprolol , a new beta1‐selective , beta‐blocking agent , was studied in 240 mild to moderate hypertensive patients in this 4‐week , r and omized , double‐blind , placebo‐controlled trial . A once‐daily dosing schedule was evaluated by comparing bisoprolol 's antihypertensive effectiveness and safety at 24 h postdose and 3 h postdose , the latter time intended to correspond to peak effectiveness . Results from this trial demonstrated the antihypertensive effectiveness of once‐daily bisoprolol at doses ranging from 5‐20 mg . Mean reductions from baseline diastolic blood pressure , measured 24 h postdose , were 6.3,8.8 , and 10.1 mmHg for patients receiving bisoprolol 5 , 10 , and 20 mg , respectively , compared with 1.6 mmHg for placebo‐treated patients ( p < 0.01 ) ; mean reductions from baseline systolic blood pressure for the bisoprolol groups were 8.6 , 8.6 , and 10.9 mmHg , respectively , versus 3.3 mmHg for placebo ( p≤0.01 ) ; and mean reductions from baseline heart rate for the bisoprolol groups were 5.1,7.1 , and 10.2 beats/min , respectively , compared with a 0.9 beats/min increase in heart rate for the placebo group ( p < 0.01 ) . The response rates  for bisoprolol‐treated patients ranged from 47 to 70 % compared with 18 % for patients on placebo ( p < 0.01 ) . Antihypertensive effects were dose‐related and sustained over the 24‐h dosing interval . Near maximal antihypertensive effects were achieved within 1 week of initiation of therapy with bisoprolol and were sustained over the course of the trial Summary Carvedilol 12.5 , 25 and 50 mg was administered once daily for 4 weeks to patients with mild to moderate hypertension . The purpose of the study was to investigate the antihypertensive action of carvedilol when administered once daily and to investigate the pharmacokinetics of carvedilol in patients with mild to moderate hypertension . Measurable decreases in blood pressure ( BP ) occurred within 1 hour after the first dose . Peak decreases in supine diastolic blood pressure ( DBP ) were 9.0 ± 6.8 , 15.5 ± 6.7 , 14.7 ± 10.6 and 22.5 ± 7.6 mm Hg ( ± SD ) for the placebo , 12.5 , 25 and 50 mg carvedilol groups , respectively , and occurred between 3 and 7 hours after the dose . Administration of carvedilol once daily for 4 weeks kept supine DBP below baseline levels for 24 hours . Trough supine DBP after 4 weeks of treatment were 0.6 ± 6.5 , 7.3 ± 7.9 , 8.8 ± 7.4 and 12.1 ± 3.8 mm Hg ( ± SD ) below baseline . Serum levels of carvedilol were proportional to the dose . Peak serum levels were 39 ± 27 , 75 ± 38 and 161 ± 131 μ/L for carvedilol 12.5 , 25 and 50 mg . The kinetics of carvedilol did not change with repeated administration . Carvedilol was well tolerated ; 2 patients experienced dizziness associated with postural hypotension after administration of the 50 mg dose . Carvedilol 12.5 , 25 and 50 mg effectively reduced BP for 24 hours when administered once daily OBJECTIVES To investigate prospect ively the effects of the selective beta 1 adrenoceptor blocker bisoprolol on sexuality of men with hypertension . DESIGN In newly diagnosed patients ( group I ) : double-blind , crossover , placebo controlled . In men with hypertension on antihypertensive treatment ( group II ) : crossover design . SETTING Large area in and around Rotterdam , The Netherl and s. PATIENTS Twenty-six men ( criteria : between 25 and 70 ; no disease etc . known to affect sexual functioning ) were recruited through their general practitioners . Group I ( n = 13 ) fulfilled the selection criteria , sitting blood pressure systolic > or = 160 mm Hg and /or diastolic > or = 95 mm Hg , measured on 3 different days . Group II ( n = 13 ) patients already on antihypertensive treatment .  MAIN OUTCOME MEASURES Data on blood pressure . Qualitative and quantitative data on sexuality through question naires , including personal and sexual history , sexual functioning , sexual satisfaction and erectile difficulties . RESULTS Bisoprolol is an effective antihypertensive drug with no detrimental effects on sexuality in newly diagnosed men with hypertension . In men already on antihypertensive medication bisoprolol improved sexuality in some parameters , i.e. firmness of erection during coitus , contentedness with sexual functioning and satisfaction with own sexuality . CONCLUSION Bisoprolol is an effective antihypertensive agent with no sexual side effects Objective Hypertension guidelines recommend initial treatment with a β-blocker or diuretic and adding the other drug where blood pressure is not controlled . We hypothesized that systematic rotation through the major classes of antihypertensive drugs would demonstrate substantial differences in the pattern of an individual patient 's response , and suggest a more rational approach to choosing best treatment . Design Thirty-four young hypertensives ( age 28–55 , median 47 ) rotated in a double-blind , Latin-square , crossover fashion through 6 weeks of treatment each with amlodipine , doxazosin , lisinopril , bisoprolol , bendrofluazide and placebo . Blood pressure was measured at each visit . ‘ Best ’ drug , defined by efficacy and tolerability , was repeated at the end . Results Rotation doubled the number of patients reaching target blood pressure ( systolic < 140 mmHg ) on one drug ( P = 0.03 ) . All five drugs were represented among the ‘ best ’ drugs . In six patients , the blood pressure on ‘ best ’ drug was at least 10 mmHg lower than on any other . Response to the ‘ best ’ drug was highly correlated ( r = 0.79 ) with its previous administration . By contrast , there were only weak correlations between responses to pairs of drugs , except for angiotensin-converting enzyme ( ACE ) inhibitor ( A ) with β-blocker ( B ) , and calcium blocker ( C ) with diuretic ( D ) – each r = 0.71 , P < 0.005 ) . In these young patients , the majority of patients ( 23/34 ) responded best to a drug suppressing the renin system ( A and B ) . Conclusions Patients vary reproducibly in their response to initial treatment , and switching among drugs can increase the efficacy of monotherapy . The results support an AB/CD scheme for choosing therapy , in which the first drug is taken from one of these pairs , and uncontrolled patients switch to one of the other pair Beta-blockers with pharmacologic effects that differ from conventional agents might add to antihypertensive treatment options . This study evaluated a new once-daily formulation of the beta-/alpha1-blocker , carvedilol controlled-release ( CR ) , in hypertensive patients off treatment or while still taking up to 2 ( non-beta-blocker ) agents . After a 4-week run-in phase , patients were r and omized either to placebo ( n=76 ) or carvedilol CR 20 mg ( n=82 ) , 40 mg ( n=76 ) , or 80 mg ( n=86 ) once daily . After 6 weeks of treatment , ambulatory blood pressure monitoring was repeated to measure the primary end point of changes in mean 24-hour diastolic blood pressure . During treatment , 24-hour diastolic blood pressure fell in the placebo and carvedilol CR 20-mg , 40-mg , and 80-mg groups by ( mean + /- SE ) 0.4+/-0.9 , 4.4+/-0.9 , 7.9+/-0.9 , and 9.6+/-0.9 mm Hg , respectively ( P < or = .001 , trend test for all carvedilol CR doses with placebo ) . Corresponding 24-hour systolic blood pressure changes were 0.6+/-1.4 , 6.8+/-1.3 , 10.1+/-1.4 , and 12.5+/-1.3 mm Hg , respectively ( P < or = .001 , trend test ) . Diastolic blood pressure trough-to-peak ratios ( placebo-corrected ) based on ambulatory blood pressure monitoring ( trough = mean of 20- to 24-hour post-dose readings ; peak = mean of 3- to 7-hour post-dose readings ) for 20-mg , 40-mg , and 80-mg doses were 0.73 , 0.64 , and 0.65 , respectively . Adverse events , including clinical chemistry values , were similar in the drug-treated and placebo groups . Carvedilol CR has a clinical ly meaningful defined dose-dependent antihypertensive effect that persists throughout a 24-hour period This 30-center , r and omized , double-blind , placebo-controlled , parallel-group study was design ed to ( 1 ) establish that 6.25 mg of hydrochlorothiazide ( HCTZ ) given once daily with 5 mg of bisoprolol fumarate can contribute to antihypertensive effectiveness in patients with stage I and stage II ( mild to moderate ) systemic hypertension ; and ( 2 ) assess whether this formulation was more effective or possessed a safety advantage over st and ard monotherapy with bisoprolol or 25 mg of HCTZ . Results showed that HCTZ 6.25 mg contributed significantly to the antihypertensive effectiveness of bisoprolol 5 mg . Bisoprolol 5 mg/HCTZ 6.25 mg ( B5/H6.25 ) produced significantly greater mean reductions from baseline in sitting systolic and diastolic blood pressure ( -15.8 mm Hg/-12.6 mm Hg ) than bisoprolol 5 mg alone ( -10.0 mm Hg/-10.5 mm Hg ) and HCTZ 25 mg alone ( -10.2 mm Hg/-8.5 mm Hg ) . A 73 % response rate was achieved with the low-dose formulation compared with 61 % for the bisoprolol 5 mg ( B5 ) group and 47 % for the HCTZ 25 mg ( H25 ) group . B5/H6.25 was found to be significantly more effective than B5 or H25 in all subgroups of patients , regardless of gender , race , age , or smoking history . Antihypertensive effects were maintained during the 24-hour dosing interval . The incremental effectiveness of B5/H6.25 was not accompanied by an increase in the frequency or severity of adverse experiences ; the incidence of adverse experiences in the B5/H6.25 group was comparable to that in the placebo group . B5/H6.25 was shown to provide safety advantages over H25 , as shown by less hypokalemia ( < 1 % with B5/H6.25 versus 6.5 % with H25 ) . ( ABSTRACT TRUNCATED AT 250 WORDS Blood pressure , heart rate , common carotid and brachial arterial hemodynamics using pulsed Doppler flowmetry and pulse wave velocity determinations were evaluated using a double-blind crossover design versus placebo in 14 patients with sustained essential hypertension treated by the selective beta 1 blocking agent bisoprolol .  Blood pressure and heart rate significantly decreased after bisoprolol , whereas no significant change occurred in the diameter , the blood flow and in the vascular resistance of the carotid and brachial circulations . Pulse wave velocity significantly decreased in the brachioradial and the carotid femoral areas . The decrease in the latter was -1.6 + /- 0.8 m/s with bisoprolol and -0.06 + /- 0.80 m/s with placebo ( p = 0.001 ) . Brachial artery compliance significantly increased from 117 + /- 49 to 205 + /- 84 cm4 x dynes-1 x 10(9 ) ( p = 0.001 ) , indicating that the antihypertensive effect of beta 1 blockade is associated with an improvement in the viscoelastic properties of the brachial artery wall
target: SBP-lowering effects were significantly increased for bisoprolol compared with placebo .
  In conclusion , current evidence does not support carvedilol or bisoprolol as first-line therapy for adult hypertension without compelling indications
background: Although beta blockers have been used as initial therapy for ischemic heart diseases and heart failure , the beneficial effects of beta blockers are controversial compared with other antihypertensive agents as initial therapy for hypertension without compelling indications .
  Moreover , atenolol has been most commonly used with beta blockers .
  The objective of the present systematic review associated with the Japanese Society of Hypertension ( JSH ) 2019 Hypertension Guideline ( Clinical Question 6 ) was to assess the outcomes ( cardiocerebrovascular mortality , total cause mortality , hypotension , bradycardia , other adverse effects , and changes in systolic blood pressure ( SBP ) ) of currently used carvedilol and bisoprolol as initial therapy for adult hypertension without compelling indications .