ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. A 16-week, randomized, double-blind, placebo-controlled, crossover trial to quantify the combined effect of an angiotensin-converting enzyme inhibitor and a beta-blocker on blood pressure reduction. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Partial regression of vascular structural alterations in hypertensive patients treated with alpha-beta-blocker, labetalol. Atenolol and bendrofluazide in hypertension. Effect of different antihypertensive drug classes on central aortic pressure. [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring]. Nutritional dose of magnesium in hypertensive patients on beta blockers lowers systolic blood pressure: a double-blind, cross-over study. Beta-blockade in heart failure: a comparison of carvedilol with metoprolol. To compare the effect of Telmisartan with Metoprolol on arterial stiffness in hypertension: prospective randomized parallel group trial. Antihypertensive efficacy and side effects of three beta‐blockers and a diuretic in elderly hypertensives: a report from the STOP‐Hypertension study Plasma renin activity predicts blood pressure responses to beta-blocker and thiazide diuretic as monotherapy and add-on therapy for hypertension. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. The Losartan Intervention For Endpoint reduction (LIFE) in Hypertension study: rationale, design, and methods. The LIFE Study Group. The 2001 Canadian recommendations for the management of hypertension: Part two--Therapy. Antihypertensive effect of alpha- and beta-adrenergic blockade in obese and lean hypertensive subjects. Behavioral and physiological effects of a beta blocker and relaxation therapy on mild hypertensives. Initial blood pressure as a predictor of the response to antihypertensive therapy. Relaxation therapy for hypertension. Comparison of effects with concomitant placebo, diuretic, and beta-blocker. The effects of selective and non-selective adrenoceptor blockade on the portal blood flow in patients with liver cirrhosis. A nurse-led up-titration clinic improves chronic heart failure optimization of beta-adrenergic receptor blocking therapy - a randomized controlled trial Crossover design to test antihypertensive drugs with self-recorded blood pressure. The efficacy and tolerability of nebivolol in hypertensive African American patients.
The objective of this study was to determine which of the common groups of antihypertensive drugs is most effective at lowering systolic blood pressure ( SBP ) in elderly patients with previously untreated hypertension and the percentage of patients controlled with single or sequential monotherapy . Subjects were recruited from patients attending other outpatient clinics and entered into the study if their SBP was more than 150 mm Hg after three visits . Patients were given a low and high dose of each of the main classes of drugs or placebo for 1 month each . The study was a balanced , r and omized crossover design with five periods : placebo ; angiotensin converting enzyme inhibitors ; beta-blocking drugs ; calcium-blocking drugs ; and thiazide diuretics .  Blood pressure ( BP ) was measured 24 to 26 h after the previous dose . A question naire for side effects was administered at each visit . Seventy-four patients entered the study . beta-Blockers could not be used in 15 patients because of asthma or bronchospasm and these had two placebo periods . There were 9 of 66 patients on P , 9 of 46 on beta-blockers , 4 of 65 on calcium-blocking drugs , 4 of 65 on diuretic , and 1 of 62 patients on ACE inhibitors who did not progress to the higher dose because of side effects . Decreases in SBP compared to r and omized placebo were calcium-blocking drugs 15 mm Hg = diuretic 13 mm Hg > ACE inhibitors 8 mm Hg = beta-blockers 5 mm Hg . Blood pressure decrease correlated with placebo BP ( P < .0005 , r = 0.53 to 0.70 ) . When corrected for placebo , target SBP ( < 140 mm Hg ) was reached in between 6 % to 15 % of patients on monotherapy . Sequential monotherapy achieved target in 29 % . Angiotensin converting enzyme inhibitors , calcium-blocking drugs , and diuretics had no more side effects than placebo . Patients on beta-blockers had more side effects and the well-being score was reduced . Diuretics and calcium-blocking drugs are more effective in elderly patients at lowering SBP pressure . beta-Blockers were relatively ineffective , were frequently contraindicated , and had more side effects . Monotherapy achieved control in only a small number of patients . In elderly people with essential hypertension , therapy should be instituted with diuretics or calcium-blocking drugs , but combination therapy will usually be required to achieve goal BACKGROUND Although beta-blockers and angiotensin-converting enzyme ( ACE ) inhibitors are often used together , there is a lack of quantitative evidence for the efficacy of this combination in reducing  blood pressure ( BP ) .  OBJECTIVE The aim of this r and omized , double-blind , placebo-controlled , crossover study was to quantify the combined effect of a beta-blocker ( atenolol ) and an ACE inhibitor ( lisinopril ) in lowering BP . METHODS Participants who were > or = 40 years of age and enrolled in the hypertension or anticoagulation clinics at St. Bartholomew 's Hospital , London , United Kingdom , were r and omized to 3 consecutive 4-week treatments consisting of atenolol 25 mg plus placebo , lisinopril 5 mg plus placebo , and atenolol 25 mg plus lisinopril 5 mg , plus a period of 2 placebos . At the end of each period , seated BP was measured in the right arm using electronic monitors . RESULTS The mean  placebo-adjusted peak BP reductions among the 47 participants ( mean age , 62 [ range 42 - 82 ] years ; 75 % male ; 70 % white/30 % Asian ; mean baseline BP , 145/82 mm Hg ) who completed all 4 periods were significantly greater with the combination of both drugs than with either drug alone ( P < 0.001 ) . The systolic reductions were 22.9 mm Hg with combination treatment , 16.1 mm Hg with atenolol treatment , and 12.5 mm Hg with lisinopril treatment , and the diastolic reductions were 13.9 , 9.8 , and 6.8 mm Hg , respectively . The BP-lowering effect of the 2 drugs together was similar to that expected from the sum of each alone , allowing for the reduced effect of 1 drug given the lower pretreatment BP due to the other . The incremental systolic BP reduction from the 2 drugs together compared with 1 alone was 79 % ( 95 % CI , 54%-126 % ) of the expected additive effect , 88 % ( 95 % CI , 58%-130 % ) for diastolic BP , and 84 % ( 95 % CI , 65%-118 % ) for the mean of systolic and diastolic BP . CONCLUSIONS The combination of the beta-blocker atenolol 25 mg plus the ACE inhibitor lisinopril 5 mg was associated with a significantly greater decrease in BP compared with either alone . The BP reduction with the combination treatment was similar to and statistically consistent with the 2 drugs having additive effects . Clinical Trials Identification Number : IS RCT N97280940 A large-scale , 8-week , open-label , clinical experience trial evaluated the efficacy of the angiotensin II receptor ( AT1 subtype ) blocker c and esartan cilexetil ( 16 to 32 mg once daily ) either alone or as add-on therapy in 6465 hypertensive patients . The study population was 52 % female and 16 % African American with a mean age of 58 years . It included 5,446 patients who had essential hypertension ( HBP ) and 1,014 patients who had isolated systolic hypertension ( ISH ) . These patients had either untreated or uncontrolled hypertension ( systolic blood pressure [ SBP ] 140 to 179 mm Hg or diastolic blood pressure [ DBP ] 90 to 109 mm Hg inclusive at baseline ) despite a variety of antihypertensive medications including diuretics , calcium antagonists , angiotensin converting enzyme ( ACE ) inhibitors , and alpha- or beta-blockers , either singly or in combination . The mean baseline blood pressure for the HBP group was 156/97 mm Hg . C and esartan cilexetil as monotherapy ( in 51 % of HBP patients ) reduced mean SBP/DBP by 18.7/ 13.1 mm Hg . As add-on therapy ( in 49 % of HBP patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.8/11.3 mm Hg ) , calcium antagonists ( 16.6/11.2 mm Hg ) , beta-blockers ( 16.5/ 10.4 mm Hg ) , ACE inhibitors ( 15.3/10.0 mm Hg ) , alpha-blockers ( 16.4/10.4 mm Hg ) . The mean baseline blood pressure for the ISH group was 158/81 mm Hg . C and esartan cilexetil , as monotherapy ( in 34 % of ISH patients ) , reduced SBP/DBP by 17.0/4.4 mm Hg . As add-on therapy ( in 66 % of ISH patients ) to various background therapies , c and esartan cilexetil consistently reduced mean SBP/DBP further , irrespective of the background therapy : diuretics ( 17.4/5.1 mm Hg ) , calcium antagonists ( 15.6/3.6 mm Hg ) , beta-blockers ( 14.0/4.8 mm Hg ) , ACE inhibitors ( 13.4/4.3 mm Hg ) , and alpha-blockers ( 11.6/4.5 mm Hg ) . The further blood pressure lowering effects of c and esartan cilexetil as add-on therapy were seen regardless of age , sex , and race . Overall , 6.8 % of the 6465 patients withdrew because of adverse events , most commonly headache ( 6.3 % ) and dizziness ( 5.0 % ) . Orthostatic hypotension was infrequent ; 0.2 % with c and esartan cilexetil alone , and 0.8 % with c and esartan cilexetil as add-on therapy . Thus , c and esartan cilexetil either alone or as add-on therapy was highly effective for the control of systolic or diastolic hypertension regardless of demographic background when used in typical clinical practice setting We studied the structural and functional characteristics of the vascular bed at calf level in 46 middle aged hypertensive patients ( 20 males and 26 females ) treated with different beta-blockers . After one week of placebo , the patients were divided into three groups : group 1 was treated with labetalol , an alpha-beta-blocker ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 2 was treated with acebutolol , a cardioselective beta-blocker with intrinsic sympathomimetic activity ( ISA ) ( 200 mg t.t.d . ) ; group 3 was treated with metoprolol , a cardioselective beta-blocker without ISA ( 100 mg t.t.d . ) . Before and after placebo , and after three months of active drug treatment , we measured blood pressure , and rest and peak flow at the calf level by strain gauge plethysmography . Basal and minimal vascular resistances were calculated as the ratio between mean blood pressure and rest or peak flow , respectively . A significant decrease in blood pressure was observed in each group . However , basal and minimal vascular resistances decreased only in the labetalol-treated group . These observations indicate that antihypertensive agents that have similar effects on blood pressure , may have different effects on minimal vascular resistance . Therefore , maximum vasodilation of arterioles improves , suggesting that long term treatment with labetalol , but not with other beta-blockers is able to induce a partial regression of vascular structural alterations in hypertensive patients The effect of atenolol , a new beta-1-adrenergic receptor blocking agent , was studied in a double-blind cross-over trial in 24 carefully selected hypertensive out patients . After a four-week run-in period on matching placebo each patient received atenolol 200 mg/day , atenolol 400 mg/day , a combination of atenolol 200/mg day with bendrofluazide 5 mg/day , and bendrofluazide 5 mg/day alone , according to a r and om sequence . Atenolol at either dose produced a significantly greater reduction in all blood pressure levels except st and ing systolic pressure than bendrofluazide alone . There was no statistically significant difference between the effects of the two atenolol doses on either blood pressure or pulse rate . The addition of bendrofluazide to atenolol result ed in a further significant lowering of the blood pressure . A significant effect of thiazide on weight was noted . The study shows that atenolol , a cardioselective beta-blocker of similar potency to propranolol in animals but without membrane-stabilizing or partial agonist acitivity , is an effective and well-tolerated hypotensive agent Central aortic systolic blood pressure ( BP ) is an important determinant of cardiac workload and cardiac hypertrophy . The relationship of central aortic systolic BP and brachial BP varies depending on the stiffness of blood vessels . It is not certain whether the different drug classes affect the brachial and aortic systolic BP in a similar manner . In a double-blind crossover study , we measured the effects of the four major drug classes compared with placebo on central aortic pressure . Central aortic pressure and various indices were determined using the Sphygmo Cor apparatus . The study was undertaken in patients aged 65 to 85 years with systolic BP > 150 mm Hg at study entry . Results are reported for 32 patients who had satisfactory applanation tonometry in all five periods .  Calcium channel blockers and diuretics caused a greater fall in brachial artery systolic BP than angiotensin-converting enzyme ( ACE ) inhibitors or beta-blocking drugs . On placebo , central aorta augmentation pressure and index were 23 mm Hg and 33.3 % ; on ACE inhibitors the values were 18 mm Hg and 30 % ; on beta-blockers , 26 mm Hg and 38.5 % ; on calcium channel blockers , 16 mm Hg and 28 % ; and on diuretics , 17 mm Hg and 28.8 % . The augmentation pressure on beta-blocking drugs was greater than on the other three drug classes ( P < .05 ) , and augmentation pressures on ACE inhibitors , calcium channel blockers , and diuretics were less than on placebo ( P < .05 ) . The lowest central aortic pressures were achieved with calcium blocking drugs and diuretics . Therapy based on brachial artery recordings may thus overestimate the effect of beta-blocking drugs on central aortic systolic BP and underestimate the effectiveness of ACE inhibitors and calcium blocking drugs . The clinical importance of this discrepancy needs to be evaluated OBJECTIVE To evaluate the efficacy of the monotherapy of 15 agents in treating essential hypertension . METHODS After 2-week wash-out , a total of 370 patients with seated diastolic blood pressure 95 - 114 mmHg and seated systolic blood pressure < 180 mmHg were r and omized to different therapeutic groups .  24-hour ambulatory blood pressure monitoring was performed before medication and at the end of 8 weeks . RESULT All the agents significantly reduced the 24 hour mean blood pressures after treatment except doxazosin , terazosin , and torasemide . CONCLUSION The result suggested that the angiotensin-converting enzyme inhibitors , angiotensin II receptor blockers , beta-blockers and long-acting calcium antagonists were effective in treating essential hypertension , while the low-dose doxazosin , terazosin and torasemide can be used for combination therapy but not for monotherapy OBJECTIVES To evaluate if magnesium alters blood pressure in hypertensive patients treated with beta blockers and if such effect can be coupled to a change in potassium and magnesium levels in muscle , serum and urine . DESIGN A r and omized double-blind , cross-over study with magnesium and placebo taken orally , each for 8 weeks . SETTING Outpatient clinic , University Hospital , Umeå , Sweden . SUBJECTS Thirty-nine patients aged 26 - 69 years with moderate essential hypertension , treated before entry and during the study with continuous , unchanged beta blockers completed the study . INTERVENTIONS R and om allocation to receive magnesium aspartate or placebo . Daily magnesium dose was 15 mmol ( 365 mg ) distributed three times a day over 8 weeks . MAIN OUTCOME MEASURES Blood pressure , serum , urine and muscle magnesium and potassium . Measurements performed at the start , after 8 and 16 weeks . RESULTS Systolic supine and st and ing blood pressure significantly decreased when magnesium was supplemented following placebo but not when magnesium was given at start . When magnesium and placebo groups were independently compared there was no significant change in supine and st and ing systolic and diastolic pressure . Serum and urine magnesium and serum potassium were significantly higher after magnesium treatment , whilst no change was present in urine potassium or in muscle magnesium and potassium . CONCLUSIONS This study showed that 15 mmol magnesium day-1 given to mild to moderate hypertensive patients treated with beta blockers could be the cause of a significant decrease in supine and st and ing systolic blood pressure OBJECTIVES This study was performed to compare the long-term clinical efficacy of treatment with metoprolol versus carvedilol in patients with chronic heart failure . BACKGROUND Beta-adrenergic blockade is of proven value in chronic heart failure .  Metoprolol , a selective beta-blocker , is widely used , but recent trials suggest carvedilol , a nonselective beta-blocker with alpha-1-receptor antagonist activity and antioxidant activities , is also effective . It is uncertain , however , if these additional properties of carvedilol provide further clinical benefit compared with metoprolol . METHODS In this r and omized double-blind control trial , 51 patients with chronic heart failure and mean left ventricular ( LV ) ejection fraction of 26 % + /- 1.8 % were r and omly assigned treatment with metoprolol 50 mg twice daily or carvedilol 25 mg twice daily in addition to st and ard therapy after a four-week dose titration period for a total of 12 weeks . Response was assessed by a quality of life question naire , New York Heart Association class , exercise capacity ( 6-min walk test ) , radionucleotide ventriculography for LV ejection fraction , two-dimensional echocardiography measurement of LV dimensions and diastolic filling and 24-h electrocardiograph monitoring to assess heart rate variability . RESULTS Both carvedilol and metoprolol produced highly significant improvement in symptoms ( p < 0.001 ) , exercise capacity ( p < 0.05 ) and LV ejection fraction ( p < 0.001 ) , and there were no significant differences between the two drugs . Carvedilol had a significantly greater effect on sitting and st and ing blood pressure , LV end-diastolic dimension and normalized the mitral E wave deceleration time . CONCLUSIONS Both metoprolol and carvedilol were equally effective in improving symptoms , quality of life , exercise capacity and LV ejection fraction , although carvedilol lowers blood pressure more than metoprolol BACKGROUND Hypertension is often complicated by increased arterial stiffness and is an independent predictor of adverse cardiovascular ( CV ) outcome . Beta blockers and angiotensin receptor blockers ( ARBs ) are commonly used antihypertensive agents . The effect of beta blockers and ARBs on arterial stiffness has not been compared adequately . The aim of the present study is to compare the effect of telmisartan with metoprolol on arterial stiffness in hypertensive patients in prospect i ve open label r and omized parallel group intervention study . METHODS 100 patients of hypertension , not on any antihypertensive agents , were enrolled after obtaining informed consent . Baseline recording of data related to demographics , CV risk factors , anthropometry and BP were made . Arterial stiffness was measured noninvasively by recording pulse wave velocity ( PWV ) using periscope ( Genesis medical system ) . Left ventricular ( LV ) mass was measured using 2D guided M-mode echocardiography . Blood sugar , renal function , lipids and uric acid estimations were done in fasting state . Patients were r and omized to receive metoprolol and telmisartan using stratified r and omization technique . Dose of the study drugs were titrated to achieve target BP of < 140/90 mmHg . Data related to PWV , BP , anthropometry and blood biochemistry was repeated after 6 months of treatment with study drugs . RESULTS Telmisartan result ed in significantly greater reduction in arterial stiffness index ( ASI ) in left and right lower limb arterial bed ( 39.9 ± 11.7 vs. 46.8 ± 17.0 m/s , p < 0.02 ) and ( 36.4 ± 9.6 vs. 44.86 ± 15.1 m/s , p < 0.002 ) respectively and systolic blood pressure ( SBP ) ( -4.9 mmHg with 95 % C.I. of -8.0 - 1.7 mmHg , p < 0.003 ) compared to metoprolol . Reduction in diastolic blood pressure ( DBP ) in telmisartan and metoprolol groups was not different statistically ( -1.0 mmHg with 95 % C.I. of -3.3 - 1.2 mmHg , p < 0.3 ) . The change in LV mass was not significantly different between the study groups ( 135.5 ± 37.6 vs. 143.2 ± 41.5 , p < 0.3 ) Objective : To compare the blood pressure‐lowering efficacy , the frequency of side effects and changes in laboratory values of three & bgr;‐blockers and a potassium‐sparing diuretic combination in elderly hypertensive patients . Design : The Swedish Trial in Old Patients with Hypertension ( STOP‐Hypertension ) was a prospect i ve , r and omized , double‐blind , multicentre trial comparing active antihypertensive treatment with placebo in patients aged 70‐84 years . Methods : The study group consisted of 1627 elderly hypertensive patients ( mean ± SD age 75.7 ± 3.7 years ; 37 % males , 63 % females ) . Supine and st and ing blood pressure , heart rate and side effects were recorded at each visit . Blood was drawn for routine analysis . The mean length of follow‐up was 25 months ( range 6‐65 ) . No patient was lost to follow‐up . Results : After 2‐months ' single‐drug therapy , all four active drugs were found to be equally effective in reducing diastolic blood pressure ( DBP ) . However , there were differences in their efficacy in reducing systolic blood pressure ( SBP ) ; the diuretic was significantly more effective than the & bgr;‐receptor blockers . The results of a series of multiple linear regression analyses showed that the observed differences in effect on SBP could not be explained by the different effects of the drugs on heart rate . More than two‐thirds of the patients were given supplementary treatment , most of them already by the 2‐month visit , after which there was no significant difference in blood pressure among the treatment regimens . The changes in laboratory values and in the prevalence of symptoms were minor for all four regimens . Conclusion : Metoprolol ( controlled release ) , atenolol , pindolol and the combination hydrochlorothiazide + amiloride were equally effective as single drugs in reducing DBP . There were differences in their efficacy in reducing SBP , the diuretic being more effective than the & bgr;‐blockers . After addition of supplementary treatment ( & bgr;‐blocker to diuretic , or vice versa ) there were no significant differences in blood pressure reduction among the groups . The changes in laboratory values and in the prevalence of symptoms were minor for all active treatment regimens . Thus , the satisfactory effect on cardiovascular morbidity and mortality was not impaired by low tolerability of the drugs BACKGROUND Age and race categories or renin profiling have been recommended to predict blood pressure responses to monotherapy with a beta-blocker or thiazide diuretic . Whether these or other characteristics predict blood pressure responses when the drugs are administered as add-on therapy is uncertain . METHODS We evaluated predictors of blood pressure response in 363 men and women < or = 65 years of age with primary hypertension ( 152 blacks , 211 whites ) , 86 of whom ( 24 % ) were untreated and 277 of whom ( 76 % ) were withdrawn from previous antihypertensive drugs before r and omization to either atenolol followed by addition of hydrochlorothiazide ( N = 180 ) or hydrochlorothiazide followed by addition of atenolol ( N = 183 ) . Responses were determined by home blood pressure averages before and after each drug administration . Race , age , plasma renin activity , and other characteristics including pretreatment blood pressure levels were incorporated into linear regression models to quantify their contributions to prediction of blood pressure responses . RESULTS Plasma renin activity and pretreatment blood pressure level consistently contributed to prediction of systolic and diastolic responses to each drug administered as mono- and as add-on therapy . Higher plasma renin activity was consistently associated with greater blood pressure responses to atenolol and lesser responses to hydrochlorothiazide . The predictive effects of plasma renin activity were statistically independent of race , age , and other characteristics . CONCLUSIONS Plasma renin activity and pretreatment blood pressure level predict blood pressure responses to atenolol and hydrochlorothiazide administered as mono- and as add-on therapy in men and women < or = 65 years of age Men aged 40 - 64 years with mild to moderate hypertension [ diastolic blood pressure ( DBP ) 100 - 130 mmHg ] were r and omized to treatment with a  diuretic ( n = 3272 ) or a  beta-blocker ( n = 3297 ) , with additional drugs if necessary , to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease ( CHD ) events and death .  Patients with previous CHD , stroke or other serious diseases , or with contraindications to diuretics or beta-blockers were excluded . If normotension ( DBP less than 95 mmHg ) was not achieved by monotherapy , other antihypertensive drugs were added , but the two basic drugs were not crossed over . Patients were assessed at 6-monthly intervals . The mean follow-up for end-points was 45.1 months . Blood pressure ( BP ) side effects and end-points were recorded in a st and ardized manner . Entry characteristics and the BP reduction achieved were very similar in both treatment groups . All analyses were made on an intention-to-treat basis . The incidence of CHD did not differ between the two treatment groups . The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group . Total mortality and the total number of end-points were similar in both groups . The percentage of patients withdrawn due to side effects was similar , whereas the number of reported symptoms , according to a question naire , was higher for patients on beta-blockers . The incidence of diabetes did not differ between the two groups . Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers , and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD . Beta-blockers and thiazide diuretics were approximately equally well tolerated . The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group . Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications , including CHD , to a different extent The treatment of hypertension mainly with diuretics and beta blockers reduces cardiovascular mortality and morbidity , largely due to a decreased incidence of stroke , whereas the beneficial effects of antihypertensive therapy on the occurrence of coronary events have been less than expected from epidemiological studies . Furthermore , treated hypertensive patients still have a higher cardiovascular complication rate , compared with matched normotensives . This is particularly evident in patients with left ventricular hypertrophy ( LVH ) , a major independent risk indicator for cardiovascular disease . In addition to elevating blood pressure , angiotensin II ( A-II ) exerts an important influence on cardiac structure and function , stimulating cell proliferation and growth . Thus , to further reduce morbidity and mortality when treating hypertensive patients , it may be important to effectively block the effects of A-II . This can be achieved directly at the A-II receptor level by losartan , the first of a new class of antihypertensive agents . It therefore seems pertinent to investigate whether selective A-II receptor blockade with losartan not only lowers blood pressure but also reduces LVH more effectively than current therapy , and thus improves prognosis . The Losartan Intervention For Endpoint reduction ( LIFE ) in Hypertension study is a double-blind , prospect i ve , parallel group study design ed to compare the effects of losartan with those of the beta-blocker atenolol on the reduction of cardiovascular morbidity and mortality in approximately 8,300 hypertensive patients ( initial sitting diastolic blood pressure 95 to 115 mm Hg or systolic blood pressure 160 to 200 mm Hg ) with electrocardiographically documented LVH . The study , which will continue for at least 4 years and until 1,040 patients experience one primary endpoint , has been design ed with a statistical power that will detect a difference of at least 15 % between groups in the incidence of combined cardiovascular morbidity and mortality . It is also the first prospect i ve study with adequate power to link reversal of LVH to reduction in major cardiovascular events . The rationale of the study , which will involve more than 800 clinical centers in Sc and inavia , the United Kingdom , and the United States , is discussed , and the major features of its design and general organization are described . On April 30 , 1997 , when inclusion was stopped , 9,218 patients had been r and omized OBJECTIVE To provide up date d , evidence -based recommendations for the therapy of hypertension in adults . OPTIONS For patients with hypertension , a number of antihypertensive agents may control blood pressure . R and omized trials evaluating first-line therapy with thiazides , beta-adrenergic antagonists , angiotensin-converting enzyme inhibitors , calcium channel blockers , alpha-blockers , central ly acting agents or angiotensin II receptor antagonists were review ed . OUTCOMES The health outcomes that were considered were changes in blood pressure , cardiovascular morbidity , and cardiovascular and /or all-cause mortality rates . Economic outcomes were not considered due to insufficient evidence . EVIDENCE MEDLINE was search ed for the period March 1999 to October 2001 to identify studies not included in the 2000 revision of the Canadian Recommendations for the Management of Hypertension . Reference lists were scanned , experts were polled , and the personal files of the subgroup members and authors were used to identify other published studies . All relevant articles were review ed and appraised , using prespecified levels of evidence , by content experts and method ological experts . VALUES A high value was placed on the avoidance of cardiovascular morbidity and mortality . BENEFITS , HARMS AND COSTS Various antihypertensive agents reduce the blood pressure of patients with sustained hypertension . In certain setting s , and for specific classes of drugs , blood-pressure lowering has been associated with reduced cardiovascular morbidity and /or mortality . RECOMMENDATIONS The present document contains detailed recommendations pertaining to treatment thresholds , target blood pressures , and choice of agents in various setting s in patients with hypertension . The main changes from the 2000 Recommendations are the addition of a section on the treatment of hypertension in patients with diabetes mellitus , the amalgamation of the previous sections on treatment of hypertension in the young and old into one section , increased emphasis on the role of combination therapies over repeated trials of single agents and expansion of the section on the treatment of hypertension after stroke . Implicit in the recommendations for therapy is the principle that treatment for an individual patient should take into consideration global cardiovascular risk , the presence and /or absence of target organ damage , and comorbidities . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the Canadian Hypertension Recommendations Working Group . Individuals with potential conflicts of interest relative to any specific recommendation were excluded from voting on that recommendation . Only those recommendations achieving high levels of consensus are reported here . These guidelines will continue to be up date d annually The purpose of this study was to determine the contribution of the adrenergic system in mediating hypertension in obese and lean patients . Thirteen obese , hypertensive patients with a body mass index ( BMI ) > or = 28 kg/m2 ( obese ) and nine lean patients with a BMI < or = 25 kg/m2 ( lean ) were recruited . After a 1-week washout period , participants underwent daytime ambulatory blood pressure monitoring  ( ABPM ) . Participants were then treated with the alpha-adrenergic antagonist doxazosin , titrating to 4 mg QHS in 1 week . In the next week , the beta-adrenergic antagonist atenolol was added at an initial dose of 25 mg/day and titrated to 50 mg/day within 1 week . One month after the addition of atenolol , all patients underwent a second ABPM session . There were no differences between the obese and lean subjects in baseline systolic ( SBP ) , diastolic ( DBP ) , or mean arterial pressures ( MAP ) measured by office recording or ABPM . However , obese subjects had higher heart rates than lean subjects ( 87.5+/-2.4 v 76.8+/-4.9 beats/min ) . After 1 month of treatment with the adrenergic blockers , obese patients had a significantly lower SBP ( 130.0+/-2.5 v 138.9+/-2.1 mm Hg , P = .02 ) and MAP ( 99.6+/-2.3 v 107.0+/-1.5 mm Hg , P = .02 ) than lean patients . Obese patients also tended to have a lower DBP than lean patients ( 84.3+/-2.5 v 90.9+/-1.6 mm Hg , P = .057 ) , but there was no significant difference in heart rate after 1 month of adrenergic blockade . These results indicate that blood pressure is more sensitive to adrenergic blockade in obese than in lean hypertensive patients and suggest that increased sympathetic activity may be an important factor in the maintenance of hypertension in obesity & NA ; In this industrial‐based study we compared the blood pressure (BP)‐lowering effectiveness of relaxation , a beta blocker , and the combined use of these two treatments in 47 untreated , mildly hypertensive blue collar steel workers . Using a r and omized two by two factorial design , patients received either nadolol or placebo drug daily , and either a relaxation training or an education program , each lasting 8 weeks . A pre‐intervention and post‐intervention stress test measured response of heart rate and BP to mental and physical tasks . BP assessment s were done at baseline , post‐intervention , 1 month , and 3 month follow‐up . Change in several self‐report measures was determined . Results showed that beta blocker was more effective in lowering BP than placebo , but relaxation was not more effective in lowering BP than health education . The combined effect of beta blocker and relaxation was not superior to beta blocker alone . Compliance with relaxation practice was not superior to compliance with medication . We conclude that pharmacologic treatment is superior to the relaxation therapy tested 1 . The relationship between fall in systolic blood pressure and initial systolic blood pressure has been investigated in 255 mixed normotensive and hypertensive subjects given placebo or one of five types of antihypertensive drug ( ACE inhibitors , calcium antagonists , direct vasodilators , alpha-adrenoceptor blocker , beta-adrenoceptor blocker ) .  2 . In all cases there was a significant correlation between the change in blood pressure and initial blood pressure . When Oldham 's transformation was used ( replacing the initial blood pressure by the mean of the initial and minimum pressures ) the correlation coefficients were all reduced , although five out of six were still statistically significant . 3 . In a subset of 43 hypertensive subjects given four antihypertensive agents , concentration-effect analysis was carried out . For three of the agents a linear model was used to relate effect to concentration ; for the remaining agent a Langmuir type model was used . 4 . For all four sets of data for which concentration-effect analysis was carried out , there was a significant correlation between the sensitivity of response and the initial blood pressure . 5 . The observed relationships between initial blood pressure , change in blood pressure and sensitivity of response can be qualitatively explained by postulating a general form of dose-response relationship for all antihypertensive agents We compared the effects of relaxation therapy in hypertensive patients taking placebo , a beta-blocker ( atenolol , 100 mg/d ) , or a diuretic ( chlorthalidone , 50 mg/d ) , and we also compared the effects of relaxation therapy with the effects of the latter two drugs alone . Blood pressures were measured not only in the relaxation therapists ' office and at a hypertension clinic , but also in the patient 's environment by means of 24-hour ambulatory blood pressure recordings . The effect of relaxation therapy , while statistically significant , was modest . There was no generalization of effect to ambulatory blood pressure .  Atenolol was significantly more effective than  relaxation  in reducing both systolic and diastolic pressure .  Chlorthalidone was significantly more effective than relaxation in reducing systolic but not diastolic pressure in the hypertension clinic only . The long-term effects of relaxation were independent of concomitant drug use , but within the actual relaxation sessions blood pressure dropped further during chlorthalidone than during placebo or atenolol treatment The effects of different types of adrenoceptor blocking agents on portal venous blood flow were studied in 10 patients with liver cirrhosis by using a duplex Doppler system . Oral atenolol ( selective beta 1 blocker ) , propranolol ( non-selective beta blocker ) , and labetalol ( non-selective adrenoceptor blocker ) were compared . The drugs were administered at r and om at an interval of 3 days or more . Hemodynamic measurements were done before and after 1 h , 2 h , and 3 h of therapy .  Atenolol and propranolol  produced significant decrease in the portal vein cross-sectional area , portal blood velocity , and estimated volume of the portal blood flow . The portal blood velocity decreased by 13.1 + /- 7.2 % 3 h after atenolol and by 16.2 + /- 6.5 % 3 h after propranolol administration ( p less than 0.05 ) . Labetalol had no significant influence on portal venous hemodynamics . These results support the hypothesis that a decrease in portal venous flow induced by beta blockers is at least partly mediated with alpha-adrenergic receptors Background Beta-adrenergic blockade has been shown to improve left ventricular function , reduce hospital admissions and improve survival in chronic heart failure with reduced ejection fraction ( HFrEF ) , with mortality reduction starting early after beta-adrenergic receptor blocker initiation and being dose-related . The aim of this pilot study was to determine the effectiveness of a nurse-led titration clinic in improving the time required for patients to reach optimal doses of the beta-adrenergic receptor blocking agents . Method We conducted a prospect i ve pilot r and omized controlled trial . Twenty eight patients with CHF were r and omized to optimisation of beta-adrenergic receptor blocker therapy over six months by either a nurse-led titration ( NLT ) clinic , led by a nurse specialist with the support of a cardiologist in a CHF clinic , or by their primary care physician ( usual care ( UC ) ) . The primary endpoint was time to maximal beta-adrenergic receptor blocker dose . The secondary end-point was the proportion of patients reaching the target dose of beta-adrenergic receptor blocker by six months . Results The patients were predominantly men ( 72 % ) , age 67 ± 16 years ; New York Heart Association ( NYHA ) functional class I ( 32 % ) , II ( 44 % ) and III ( 20 % ) ; baseline left ventricular ejection fraction 33 ± 10 % , and a low mean Charlson co-morbidity score of 2.5 ± 1.4 .  The time to maximum dose was shorter in the NLT group compared to the UC group ( 90 ± 14 vs 166 ± 8 days , p < 0.0005 ) . At six months , in the NLT group there were nine patients ( 82 % ) on high dose and one patient ( 9 % ) on low dose beta-adrenergic receptor blocker compared to the UC group with five ( 42 % ) patients reaching maximum dose and five ( 42 % ) patients on low dose ( p = 0.04 ) . The patients allocated to the NLT group also had significantly less worsening of depression between baseline and six months ( p = 0.006 ) . Conclusion A NLT clinic improves optimisation of beta-adrenergic receptor blocker therapy through increasing the proportion of patients reaching maximal dose and facilitating rapid up-titration of beta-adrenergic receptor blocker agents in patients with chronic HFrEF.Trial registration Australian Clinical Trials Registry ( ACTRN012606000383561 ) In a double-blind , within-patient study , blood pressure was measured at regular intervals at the clinic by the physician and each day at home by the patient . Both methods of blood pressure measurement demonstrated an antihypertensive effect of the diuretics chlorthalidone ( 25 mg ) and triamterene ( 50 mg ) and the beta-blocker oxprenolol ( 160 mg ) and the greater efficacy of the combination of the two therapies . During placebo , as well as during active treatment , blood pressure values were higher at the clinic than at home , except when the patients were taking the beta-blocker , which minimized the arousal response during blood pressure measurements in the clinic . With 2-week treatment periods , separated by 2 weeks of placebo administration , blood pressure returned toward its initial level after each of the three treatments and none of the carryover effects was significant at the 5 % level . This methodology was intended to make it possible to demonstrate in 27 patients at the clinic and in 20 patients with measurements made at home , at the usual statistical risks ( alpha = 5 % , beta = 10 % ) , a fall of 5 mm Hg in diastolic blood pressure in comparison with a placebo . Moreover , at the end of this 3-month follow-up , each patient could continue to receive the treatment that was the most effective and the best tolerated . In conclusion , the use of a within-patient trial design , with a 15-day washout period between active treatments and careful recording of blood pressure values , can minimize the number of patients included in hypertension trials and offer to each patient the possibility of individualization of treatment Hypertensive African Americans often respond poorly to beta-blocker monotherapy , compared with whites . There is evidence , however , that suggests that this response may be different if beta-blockers with vasodilating effects are used . This 12-week , multi-center , double-blind , r and omized placebo-controlled study assessed the antihypertensive efficacy and safety of nebivolol , a cardioselective , vasodilating beta1-blocker , at doses of 2.5 , 5 , 10 , 20 , or 40 mg once daily in 300 African American patients with stage I or II hypertension ( mean sitting diastolic blood pressure [ SiDBP ] > or = 95 mm Hg and < or = 109 mm Hg ) . The primary efficacy end point was the baseline-adjusted change in trough mean SiDBP . After 12 weeks , nebivolol significantly reduced least squares mean SiDBP ( P < or = .004 ) at all doses of 5 mg and higher and sitting systolic blood pressure ( P < or = .044 ) at all doses 10 mg and higher , compared with placebo . The drug was safe and well-tolerated , with no significant difference in the incidence of adverse events compared with placebo . Nebivolol monotherapy provides antihypertensive efficacy , with few significant adverse effects , in hypertensive African Americans
Carvedilol , within the recommended dose range , did not show a significant dose response effect for SBP or DBP .
Carvedilol had little or no effect on pulse pressure ( -1 mm Hg ) and did not change BP variability .
Due to the larger sample size from the two unpublished studies , carvedilol provided a better estimate of BP lowering effect than labetalol .
Doses higher than the recommended starting dose did not provide additional BP reduction .
Higher doses of dual receptor blockers caused more bradycardia than lower doses .
Based on indirect comparison with other classes of drugs , the blood pressure lowering effect of dual alpha- and beta-receptor blockers is less than non-selective , beta1 selective and partial agonist beta blockers , as well as thiazides and drugs inhibiting the renin angiotensin system .
Dual blockers also had little or no effect on reducing pulse pressure , which is similar to the other beta-blocker classes , but less than the average reduction of pulse pressure seen with thiazides and drugs inhibiting the renin angiotensin system .
Patients taking dual receptor blockers  were not more likely to withdraw from the study compared to patients taking placebo
BACKGROUND Drugs with combined alpha and beta blocking activity are commonly prescribed to treat hypertension .
However , the blood pressure ( BP ) lowering efficacy of this class of beta blockers has not been systematic ally review ed and quantified .
OBJECTIVES To quantify the dose-related effects of various types of dual alpha and beta adrenergic receptor blockers ( dual receptor blockers ) on systolic and diastolic blood pressure versus placebo in patients with primary hypertension .