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.
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 )
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 .