ACE inhibitors, beta-blockers, calcium blockers, and diuretics for the control of systolic hypertension. Partial regression of vascular structural alterations in hypertensive patients treated with alpha-beta-blocker, labetalol. Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. Differential effects of beta-adrenoreceptor antagonists on central and peripheral blood pressure at rest and during exercise. Beta-blockers do not impair the cardiovascular benefits of endurance training in hypertensives Beta-blocker/thiazide combination for treatment of hypertensive children: a randomized double-blind, placebo-controlled trial. Effect of different antihypertensive drug classes on central aortic pressure. A multicenter, randomized, double-blind comparison of the efficacy and safety of irbesartan and enalapril in adults with mild to moderate essential hypertension, as assessed by ambulatory blood pressure monitoring: the MAPAVEL Study (Monitorización Ambulatoria Presión Arterial APROVEL). Adjusted Drug Treatment Is Superior to Renal Sympathetic Denervation in Patients With True Treatment-Resistant Hypertension Behavioral and physiological effects of a beta blocker and relaxation therapy on mild hypertensives. Blood pressure response under chronic antihypertensive drug therapy: the role of aortic stiffness in the REASON (Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind) study. Efficacy of candesartan cilexetil as add-on therapy in hypertensive patients uncontrolled on background therapy: a clinical experience trial. ACTION Study Investigators. Blood Pressure Control with a Single-Pill Combination of Indapamide Sustained-Release and Amlodipine in Patients with Hypertension: The EFFICIENT Study Treatment of hypertension with dihydropyridine calcium antagonists and aspirin. Ambulatory Blood Pressure and Left Ventricular Changes During Antihypertensive Treatment: Perindopril Versus Isradipine A selective endothelin-receptor antagonist to reduce blood pressure in patients with treatment-resistant hypertension: a randomised, double-blind, placebo-controlled 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 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 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 Dihydropyridine and nondihydropyridine calcium channel blockers ( CCB ) differ in pharmacologic characteristics . Few clinical studies distinguish effects of CCB as monotherapy . We conducted a comprehensive comparison of two CCB on patients with moderate to severe hypertension . Thirty patients with pretreatment diastolic blood pressures > or = 100 mm Hg were r and omly assigned to either nifedipine-GITS or verapamil-SR . Dose titration achieved a diastolic blood pressure of < or = 95 mm Hg or a decrease of > or = 15 mm Hg over 4 weeks . Clinic blood pressure ( BP ) , 24-h ambulatory BP , exercise BP , left ventricular mass , systolic and diastolic function by echocardiography , and coronary flow reserve by split-dose thallium-201 imaging  with adenosine were assessed at baseline , end of titration , 3 months and 6 months of treatment . Plasma renin activity , atrial natriuretic peptide , norepinephrine , and epinephrine were assayed . Both drugs caused similar reductions in clinic and 24-h ambulatory BP and similar reductions in left ventricular mass index . Compared to nifedipine-GITS , verapamil-SR produced a significantly lower resting and peak exercise heart rate .  Nifedipine-GITS elicited a lower peak exercise systolic BP . At end titration nifedipine-GITS produced lower plasma atrial natriuretic peptide levels , no longer apparent by 6 months . Plasma norepinephrine was lower with verapamil-SR , also at end titration and at 3 months , but not at 6 months . Plasma epinephrine and plasma renin activity were unchanged by either drug . There was no difference for systolic or diastolic left ventricular function or coronary flow reserve between the two treatments . Once daily nifedipine-GITS and verapamil-SR are equally effective for reduction of arterial pressure in moderate to severe hypertension . Differences in their hemodynamic profiles and neurohormonal responses are consistent with pre clinical pharmacologic characteristics . The clinical implication s of their similarities and differences remain to be fully evaluated in outcome studies BACKGROUND Differential effects of beta-adrenoreceptor antagonists ( beta-ARB ) on central and peripheral blood pressure may relate to change in heart rate and /or vasodilator tone and thus be exaggerated during exercise . AIMS To examine acute effects of selective and nonselective beta-ARB on central and peripheral blood pressure , cardiac output and peripheral vascular resistance during exercise . METHODS Healthy volunteers ( n= 20 , 18 men , 19 - 54 years ) received propranolol 80 mg , bisoprolol 20 mg , and placebo 1 h before bicycle ergometry ( 50 , 75 and 100 W each for 3 min ) in a r and omized , cross-over study . Cardiac output was determined by pulmonary uptake of soluble and inert gas tracers ( InnoCor , Innovision ) . Central systolic blood pressure ( SBP ) was determined from the late systolic shoulder of the digital artery pressure waveform ( Finometer , Finopres ) . RESULTS At rest , both beta-ARB reduced brachial but not central SBP ( compared with placebo ) . During exercise , beta-ARB reduced brachial SBP ( reductions of 19.9 + /- 4.3 mmHg and 23.2 + /- 2.7 mmHg for propranolol and bisoprolol , respectively , at 100 W , each P < 0.0001 ) but not central SBP . The difference between peripheral and central SBP was reduced , relative to that during placebo , by 21.5 mmHg ( 95 % confidence interval 8.8 , 34.1 ) and 26.4 mmHg ( 18.1 , 34.8 ) for propranolol and bisoprolol , respectively , at 100 W ( each P < 0.01 ) . There was no significant effect of beta-ARB on diastolic blood pressure or peripheral vascular resistance . CONCLUSIONS Despite reducing brachial blood pressure , acute beta-adrenoreceptor blockade in man at rest and during exercise does not reduce central blood pressure Aerobic physical exercise is broadly recommended as a helpful adjunct to obtain blood pressure control in hypertension . Beta-blockade interacts with heart rate , sympathetic tone , maximal workload and local lactate production . In the present r and omized-controlled study , we compared the cardiovascular effects of an endurance training programme in elderly hypertensives with or without beta-blockers and developed a first approach to determine a lactate-based training heart rate in presence of beta-blockade . Fifty-two patients ( 23 with beta-blocker , 29 without beta-blocker ) ⩾60 years with systolic 24-h ambulatory blood pressure ( ABP ) ⩾140 mm Hg and /or antihypertensive treatment were r and omly assigned to sedentary activity or a heart-rate controlled 12-week treadmill exercise programme ( lactate 2.0 mmol/l ) . In the exercise group , the training significantly decreased systolic and diastolic 24-h ABP , blood pressure on exertion ( 100 W ) and increased endothelium-dependent vasodilation ( flow-mediated vasodilation , FMD ) and physical performance both in the presence and absence of beta-blockade ( P<0.05 each ) . The extent of ABP reduction did not significantly differ in the presence or absence of beta-blockade ( Δ systolic ABP 10.6±10.5 vs 10.6±8.8 mm Hg , Δ diastolic ABP 5.7±8.6 vs 5.8±4.0 mm Hg ) . Mean training heart rate was significantly lower in the patients on beta-blockers ( 97.2±7.7 vs 118.3±7.5/min , P<0.001 ) . Lactate-based aerobic endurance training evokes comparable cardiovascular benefits in the presence and absence of beta-blockade including a marked improvement of endothelial function . In the present study , target training heart rate with beta-blockers is about 18 % lower than without Antihypertensive medications are used extensively in children despite a paucity of r and omized , placebo-controlled trials . This study was among the first r and omized , controlled pediatric antihypertensive medication trials , in which the combination drug bisoprolol fumarate/hydrochlorothiazide ( B/HT ) was compared with placebo . The study comprised a 2-week single-blind placebo screening period , a 6-week double-blind dose titration period , a 4-week double-blind dose maintenance period , and a 2-week double-blind dose-tapering period . One hundred and forty subjects were enrolled to achieve 94 r and omized subjects treated either with B/HT ( n=62 ) or placebo ( n=32 ) . B/HT induced significant reductions compared with placebo for average sitting systolic blood pressure ( SiSBP ) ( 9.3 vs. 4.9 mmHg , P<0.05 ) and sitting diastolic blood pressure ( SiDBP ) ( 7.2 vs. 2.7 mmHg , P<0.05 ) . The placebo-subtracted BP reductions were greater in younger children and those with more-severe baseline hypertension . The percentage of subjects with BP less than the 90th percentile at study completion was 45 % for B/HT and 34 % for placebo ( P = NS ) . Although the study demonstrated that B/HT  reduced BP safely compared with placebo , the large placebo effect and failure of most subjects to achieve target BP control make it uncertain whether B/HT is appropriate first-line therapy for pediatric hypertension , particularly in adolescents with mild-to-moderate BP elevation 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 BACKGROUND When blood pressure (BP)-lowering efficacy is assessed by measurements taken in a clinic setting , angiotensin II-receptor antagonists show similar efficacy to angiotensin-converting enzyme inhibitors and better tolerability . A search of MEDLINE to date , however , reveals no r and omized , double-blind studies using ambulatory BP monitoring ( ABPM ) to compare the BP-lowering efficacy of irbesartan and enalapril in a large number of patients ( > 200 ) with essential hypertension . OBJECTIVE This study compared 24-hour BP reduction and BP control , as assessed by ABPM , in patients with mild to moderate essential hypertension treated with irbesartan or enalapril .  The relative tolerability of the 2 treatments was also evaluated . METHODS This was a multicenter , r and omized , double-blind study in patients with mild to moderate essential hypertension ( office diastolic BP [ DBP ] 90 - 109 mm Hg or systolic BP [ SBP ] 140 - 179 mm Hg ) . After a 3-week , single-blind placebo washout phase , patients with a mean daytime DBP > or = 85 mm Hg , as measured by ABPM between 10 AM and 8 PM , were r and omized to 12 weeks of active treatment with irbesartan or enalapril . Starting doses were 150 and 10 mg/d , respectively , with titration to 300 or 20 mg/d if clinic DBP was > or = 90 mm Hg at week 4 or 8 . Based on clinic measurements , BP control was defined as a BP reading < 140/90 mm Hg after 12 weeks of treatment ; patients achieving a reduction in DBP of > or = 10 mm Hg at 12 weeks were considered responders . The ABPM criterion for BP control , independent of clinic values , was achievement of a daytime BP < 130/85 mm Hg after 12 weeks of treatment ; patients achieving a reduction in 24-hour DBP > or = 5 mm Hg at 12 weeks were considered responders , in dependent of clinic values . RESULTS A total of 238 patients were r and omized to treatment , 115 to irbesartan and 123 to enalapril . The study population was approximately 52.0 % female and 48.0 % male , with a mean ( + /- SD ) age of 52.7 + /- 10.6 years . The study was completed by 111 patients in the irbesartan group ( dose titrated to 300 mg/d in 72.0 % of patients ) and 115 patients in the enalapril group ( dose titrated to 20 mg/d in 76.5 % of patients ) . BP reductions were similar in the 2 groups , both as measured in the clinic ( DBP , 12.7 + /- 8.8 mm Hg irbesartan vs 12.4 + /- 7.4 mm Hg enalapril ; SBP , 19.0 + /- 14.1 mm Hg vs 17.5 + /- 14.0 mm Hg ) and by 24-hour ABPM ( DBP , 9.4 + /- 8.5 mm Hg vs 8.8 + /- 8.5 mm Hg : SBP , 14.7 + /- 14.7 mm Hg vs 12.6 + /- 13.1 mm Hg ) . As assessed by ABPM , rates of BP control were 40.5 % ( 45/111 ) for irbesartan and 33.9 % ( 39/115 ) for enalapril , and the response rates were a respective 71.2 % ( 79/111 ) and 71.3 % ( 82/115 ) . The overall incidence of adverse events ( 40.0 % irbesartan , 51.2 % enalapril ) was not statistically different between groups , although the incidence of adverse events considered probably related to antihypertensive treatment was significantly higher with enalapril than with irbesartan ( 24.6 % vs 9.2 % , respectively ; P = 0.026 ) , essentially because of the higher incidence of cough ( 8.1 % vs 0.9 % ) . CONCLUSIONS As assessed by ABPM , irbesartan 150 to 300 mg/d was as effective in lowering BP and achieving BP control as enalapril 10 to 20 mg/d . Based on the number of treatment-related adverse events , irbesartan was better tolerated than enalapril & NA ; We aim ed to investigate for the first time the blood pressure (BP)–lowering effect of renal sympathetic denervation ( RDN ) versus clinical ly adjusted drug treatment in true treatment-resistant hypertension ( TRH ) after excluding patients with confounding poor drug adherence . Patients with apparent TRH ( n=65 ) were referred for RDN , and those with secondary and spurious hypertension ( n=26 ) were excluded . TRH was defined as office systolic BP ( SBP ) > 140 mm Hg , despite maximally tolerated doses of ≥3 antihypertensive drugs including a diuretic . In addition , ambulatory daytime SBP > 135 mm Hg after witnessed intake of antihypertensive drugs was required , after which 20 patients had normalized BP and were excluded . Patients with true TRH were r and omized and underwent RDN ( n=9 ) performed with Symplicity Catheter System versus clinical ly adjusted drug treatment ( n=10 ) . The study was stopped early for ethical reasons because RDN had uncertain BP-lowering effect . Office SBP and diastolic BP in the drug-adjusted group changed from 160±14/88±13 mm Hg ( ±SD ) at baseline to 132±10/77±8 mm Hg at 6 months ( P<0.0005 and P=0.02 , SBP and diastolic BP , respectively ) and in the RDN group from 156±13/91±15 to 148±7/89±8 mm Hg ( P=0.42 and P=0.48 , SBP and diastolic BP , respectively ) . SBP and diastolic BP were significantly lower in the drug-adjusted group at 6 months ( P=0.002 and P=0.004 , respectively ) , and absolute changes in SBP were larger in the drug-adjusted group ( P=0.008 ) . Ambulatory BPs changed in parallel to office BPs . Our data suggest that adjusted drug treatment has superior BP lowering effects compared with RDN in patients with true TRH . Clinical Trial Registration — URL : http://www . clinical trials.gov . Unique identifier : & 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 OBJECTIVES We sought to evaluate the role of arterial stiffness on  blood pressure ( BP ) response to drug treatment . BACKGROUND Increased arterial stiffness ( pulse wave velocity [ PWV ] ) is associated with increased systolic blood pressure ( SBP ) . Antihypertensive drug therapy achieves better control of diastolic blood pressure ( DBP ) than SBP does , implying that increased PWV might be a predictor of the SBP response to treatment . METHODS The REASON ( Preterax in Regression of Arterial Stiffness in a Controlled Double-Blind ) study is a r and omized , double-blind trial comparing atenolol versus perindopril/indapamide ;  375 patients with hypertension , with BP and PWV measurements at baseline and after 12 months of treatment , were divided into 3 tertiles according to baseline PWV and included in a post-hoc analysis . RESULTS After 12 months of treatment , BP differed significantly between PWV tertiles ( the third having the lowest response , p < 0.05 ) . Factors related to smaller BP decline were low baseline BP , high baseline PWV , need for a double dose of treatment , use of atenolol ( only for SBP response ) , and age ( only for DBP ) . Although DBP control did not differ in the PWV tertiles , SBP control was significantly associated with PWV level ( p = 0.001 ) as well as with the use of perindopril/indapamide ( p < 0.001 ) . The predictive value of PWV on BP response was independent of age , sex , mean BP , and cardiovascular risk factors . CONCLUSIONS Baseline PWV is a significant predictor of BP response to antihypertensive treatment , independent from age , the need for increasing drug dosage , and the presence of cardiovascular risk factors . Achievement of SBP control appears to be influenced by aortic stiffness as well as by angiotensin-converting enzyme inhibition 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 Objective Despite antihypertensive treatment , most hypertensive patients still have high blood pressure ( BP ) , notably high systolic blood pressure ( SBP ) . The EFFICIENT study examines the efficacy and acceptability of a single-pill combination of sustained-release ( SR ) indapamide , a thiazide-like diuretic , and amlodipine , a calcium channel blocker ( CCB ) , in the management of hypertension . Methods Patients who were previously uncontrolled on CCB monotherapy ( BP≥140/90 mm Hg ) or were previously untreated with grade 2 or 3 essential hypertension ( BP≥160/100 mm Hg ) received a single-pill combination tablet containing indapamide SR 1.5 mg and amlodipine 5 mg daily for 45 days , in this multicenter prospect i ve phase 4 study . The primary outcome was mean change in BP from baseline ; percentage of patients achieving BP control ( BP<140/90 mm Hg ) was a secondary endpoint . SBP reduction ( ΔSBP ) versus diastolic BP reduction ( ΔDBP ) was evaluated ( ΔSBP/ΔDBP ) from baseline to day 45 . Safety and tolerability were also assessed . Results Mean baseline BP of 196 patients ( mean age 52.3 years ) was 160.2/97.9 mm Hg . After 45 days , mean SBP decreased by 28.5 mm Hg ( 95 % CI , 26.4 to 30.6 ) , while diastolic BP decreased by 15.6 mm Hg ( 95 % CI , 14.5 to 16.7 ) . BP control ( < 140/90 mm Hg ) was achieved in 85 % patients . ΔSBP/ΔDBP was 1.82 in the overall population . Few patients ( n = 3 [ 2 % ] ) reported side effects , and most ( n = 194 [ 99 % ] ) adhered to treatment . Conclusion In patients who were previously uncontrolled on CCB monotherapy or untreated with grade 2 or 3 hypertension , single-pill combination indapamide SR/amlodipine  reduced BP effectively — especially SBP— over 45 days , and was safe and well tolerated . Trial Registration Clinical Trial Registry – India The effects of dihydropyridine calcium antagonists on blood pressure and platelets , and the effects of aspirin on the circadian antihypertensive efficacy of dihydropyridines and on the 24-h platelet-activity profile , were the focus of a double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine focus of double-blind study . Patients with essential hypertension were treated for 8 weeks with either isradipine ( 2.5 mg/day ) or nitrendipine ( 10 mg/day ) . Aspirin ( 100 mg/day ) was added to both treatment groups for a further 8 weeks . Measurements were taken after 4 weeks of placebo , after 8 weeks of dihydropyridine treatment , and after 8 weeks of treatment combined with aspirin .  Plasma levels of beta-thromboglobulin ( beta-TG ) and platelet aggregation induced by serotonin were measured six times during 24 h. Both dihydropyridines significantly lowered systolic and diastolic blood pressure . The addition of aspirin to dihydropyridine treatment had no significant effects on systolic or diastolic blood pressure .  Dihydropyridine treatment lowered the increased 24-h plasma beta-TG profile and inhibited platelet aggregability .  Aspirin added to nitrendipine led to a further significant decrease in beta-TG levels whereas its addition to isradipine was accompanied by a partial increase in plasma beta-TG . It is concluded that increases in platelet activity in hypertensive patients can be prevented with either isradipine alone or nitrendipine plus aspirin . Aspirin in a daily dose of 100 mg does not affect the antihypertensive efficacy of calcium antagonists Using digitized M-mode echocardiograms and 24-h ambulatory blood pressure ( BP ) monitoring , we compared the effects on left ventricle ( LV ) and BP of 6-month treatment with a calcium antagonist or an angiotensin-converting enzyme ( ACE ) inhibitor in 36 hypertensive patients with LV hypertrophy ( group 1 , 18 subjects treated with sustained-release isradipine ; group 2 , 18 subjects treated with perindopril ) . At the basal evaluation , the two groups had comparable BP and LV parameters . After treatment , both groups showed a similar and significant reduction in 24-h , day- and night-systolic and diastolic BP ( SBP , DBP ) . The reduction in LV mass index was greater ( p < 0.01 ) in group 2 . In group 1 , percentage of decrease of LV mass correlated significantly with percentage of decrease in 24-h and daytime BP ; this was not true of group 2 . Together with the reduction in LV hypertrophy , there was a significant increase of peak lengthening rate of LV diameter that was greater ( p < 0.01 ) in group 1 . Both drugs can reduce LV hypertrophy and improve diastolic function . The reduction of hypertrophy induced by perindopril appears to be partly independent of BP decrease and therefore partly related to a direct action of perindopril on the myocardium BACKGROUND Hypertension can not always be adequately controlled with available drugs . We investigated the blood-pressure-lowering effects of the new vasodilatory , selective endothelin type A antagonist , darusentan , in patients with treatment-resistant hypertension . METHODS This r and omised , double-blind study was undertaken in 117 sites in North and South America , Europe , New Zeal and , and Australia . 379 patients with systolic blood pressure of 140 mm Hg or more ( > /=130 mm Hg if patient had diabetes or chronic kidney disease ) who were receiving at least three blood-pressure-lowering drugs , including a diuretic , at full or maximum tolerated doses were r and omly assigned to 14 weeks ' treatment with placebo ( n=132 ) or darusentan 50 mg ( n=81 ) , 100 mg ( n=81 ) , or 300 mg ( n=85 ) taken once daily . R and omisation was made central ly via an automated telephone system , and patients and all investigators were masked to treatment assignments . The primary endpoints were changes in sitting systolic and diastolic blood pressures . Analysis was by intention to treat . The study is registered with Clinical Trials.gov , number NCT00330369 . FINDINGS All r and omly assigned participants were analysed . The mean reductions in clinic systolic and diastolic blood pressures were 9/5 mm Hg ( SD 14/8 ) with placebo , 17/10 mm Hg ( 15/9 ) with darusentan 50 mg , 18/10 mm Hg ( 16/9 ) with darusentan 100 mg , and 18/11 mm Hg ( 18/10 ) with darusentan 300 mg ( p<0.0001 for all effects ) . The main adverse effects were related to fluid accumulation . Oedema or fluid retention occurred in 67 ( 27 % ) patients given darusentan compared with 19 ( 14 % ) given placebo . One patient in the placebo group died ( sudden cardiac death ) , and five patients in the three darusentan dose groups combined had cardiac-related serious adverse events . INTERPRETATION Darusentan provides additional reduction in blood pressure in patients who have not attained their treatment goals with three or more antihypertensive drugs . As with other vasodilatory drugs , fluid management with effective diuretic therapy might be needed . FUNDING Gilead Sciences
Pindolol , celiprolol and alprenolol  lowered SBP and DBP compared to placebo .
Acebutolol  lowered SBP but there was no clear evidence that it lowered DBP .
There was no clear evidence that pindolol and  oxprenolol lowered SBP or DBP .
Higher dose partial agonists did not appear to provide additional BP lowering effects compared to lower dose .
There was no evidence of a greater effect at doses higher than the initial doses .
Based on the indirect comparison of the results in this review and two Cochrane review s on angiotensin-converting-enzyme ( ACE ) inhibitors and angiotensin receptor blockers ( ARBs ) , which also used similar inclusion criteria as this review , the BP lowering effect appeared to be less than the effect in patients with mild to moderate elevated BP who were taking ACE inhibitors  and ARBs based on an indirect comparison .
Withdrawals due to adverse effects were only reported in one trial so it is impossible to assess the harm of these drugs
BACKGROUND Partial agonists are a subclass of beta blockers used to treat hypertension in many countries .
Partial agonist act by stimulating beta receptors when they are quiescent and blocking beta receptors when they are active .
The blood pressure ( BP ) lowering effect of partial agonist beta blockers has not been quantified .
OBJECTIVES To quantify the dose-related effects of various partial agonists beta blockers on systolic blood pressure ( SBP ) , diastolic blood pressure ( DBP ) and heart rate versus placebo in patients with primary hypertension .