Treatment of mild-to-moderate hypertension with calcium channel blockers: a multicentre comparison of once-daily nifedipine GITS with once-daily amlodipine Twenty-four hour ambulatory blood pressure in the Hypertension Optimal Treatment (HOT) study The 2007 Canadian Hypertension Education Program recommendations for the management of hypertension: part 2 - therapy. A comparison of the antihypertensive efficacy and safety of felodipine IV and nifedipine IV in patients with hypertensive crisis or emergency not responding to oral nifedipine Effects of different ACE inhibitor combinations on albuminuria: results of the GUARD study. Effect of indomethacin on blood pressure control during treatment with nitrendipine. Follow-up of renal function in treated and untreated older patients with isolated systolic hypertension Additional Antihypertensive Effect of Drugs in Hypertensive Subjects Uncontrolled on Diltiazem Monotherapy: A Randomized Controlled Trial Using Office and Home Blood Pressure Monitoring Interaction between nonsteroidal anti-inflammatory drug intake and calcium-channel blocker-based antihypertensive treatment in the Syst-Eur trial Combinations of olmesartan and a calcium channel blocker or a diuretic in elderly hypertensive patients: a randomized, controlled trial1 Comparison of two calcium blockers on hemodynamics, left ventricular mass, and coronary vasodilatory in advanced hypertension. Treatment of hypertension with dihydropyridine calcium antagonists and aspirin. Rationale, design, methods and baseline demography of participants of the Anglo-Scandinavian Cardiac Outcomes Trial Better renoprotective effect of angiotensin II antagonist compared to dihydropyridine calcium channel blocker in childhood. Calcium channel blockade and cardiovascular prognosis in the European trial on isolated systolic hypertension. Nifedipine in acute hypertensive emergencies in pregnancy. A Comparative Study of the Management of Stage 2 hypertension by Combined therapy with Losartan, Amlodipine and Hydrochlorothiazide Antihypertensive efficacy and safety of olmesartan medoxomil compared with amlodipine for mild-to-moderate hypertension Combination of antihypertensive therapy in the elderly, multicenter investigation (CAMUI) trial. Calcium supplementation in patients with essential hypertension: Assessment by office, home and ambulatory blood pressure Cardiovascular events in elderly patients with isolated systolic hypertension. A subgroup analysis of treatment strategies in STOP‐Hypertension‐2 [Efficacy of monotherapy with 15 antihypertensive agents in treating essential hypertension assessed by 24-hour ambulatory blood pressure monitoring]. The antihypertensive efficacy and tolerability of a low dose combination of ramipril and felodipine ER in mild to moderate essential hypertension.
SUMMARY Background : Hypertension is one of the most important causes of cardiovascular disease , and treatment of hypertension leads to a significant reduction in cardiovascular mortality and morbidity . Although calcium channel blockers are regarded as an important part of the therapeutic armamentarium against cardiovascular diseases , and are among the most frequently prescribed antihypertensive medications , concern has been aroused about these drugs , particularly the short-acting dihydropyridine derivatives . However , the value of nifedipine GITS ( Adalat-Crono * ) , the long-acting dihydropyridine , is in need of being re-established . * Adalat-Crono is a registered tradename of Bayer AG , Leverkusen , Germany Objective : To compare the effectiveness , safety and tolerability of once-daily nifedipine and amlodipine treatment in patients with mild-to-moderate essential hypertension . Design : R and omised multicentre trial with an open comparison of treatments for 12 weeks , with a preceding placebo run-in period of 2 weeks ( patients on beta-blockers at the time of enrolment entered a m and atory 2-week wash-out period before being allowed in the placebo run-in period ; this wash-out period was one week for patients using any antihypertensive medication other than beta-blockers ) . Setting : Nine centres ( all university hospitals ) in Turkey . Patients : 155 patients with essential hypertension ( diastolicblood pressure 95 - 109 mmHg ) . Interventions : Initial treatment ( step 1 ) consisted of 30 mg nifedipine GITS ( n = 76 ; ( Adalat-Crono tablets ) , or 5 mg amlodipine ( n = 79 ; Norvasc * 5-mg tablets ) , either administered once daily , as a morning dose , or if the blood pressure was not below 140/90 mmHg , or the reduction in diastolic blood pressure was lower than 10 mmHg after a treatment period of 6 weeks , the dose was increased ( Step 2 ) to 60 mg once daily in the nifedipine group , or 10 mg once daily in the amlodipine group . Main efficacy parameter : Diastolic blood pressure at trough after 12 weeks of active compound therapy adjusted to baseline . Results : After 12 weeks of treatment , the mean diastolic blood pressure was 83.1 and 81.9 mmHg , in the nifedipine and amlodipine groups , respectively ( p = 0.436 ) . The mean decrease in systolic blood pressure ( 28.5 ± 11.9 and 28.2 ± 11.2 mmHg in the nifedipine and amlodipine groups , respectively ) and the mean decrease in diastolic blood pressure ( 16.4 ± 7.0 and 17.5 ± 6.9 mmHg in the nifedipine and amlodipine groups , respectively ) , as well as the responder rates ( 88.1 % and 92.1 % , in the nifedipine and amlodipine groups , respectively ) were comparable at the end of the study . No significant differences between groups were detected in the efficacy parameters assessed in this study . Both drugs were well tolerated . The overall incidence of adverse events was 7.9 % in the nifedipine group and 10.1 % in the amlodipine group . However , more patients discontinued treatment prematurely in the amlodipine group ( 13 patients ; 19.7 % ) , than in the nifedipine group ( four patients ; 5.6 % ) . Conclusions : The results of this study demonstrated that once-daily nifedipine in GITS formulation and amlodipine are comparably safe and effective treatment options in patients with mild-to-moderate essential hypertensi on Background and aims The Hypertension Optimal Treatment ( HOT ) study showed that when antihypertensive treatment reduces diastolic blood pressure well below 90 mmHg , there can be a further reduction of cardiovascular events , particularly myocardial infa rct ion , with no evidence of a J-shaped curve at lower pressures . Office measurement , however , gives no information about blood pressure outside the office . This paper describes a HOT sub study in which patients underwent both office measurement and 24 h ambulatory blood pressure monitoring . Methods The mean age of the sub study population was 62 ± 7 years . Sub study patients were treated for a median period of 2 years . All received the dihydropyridine calcium antagonist felodipine , while some also received an ACE-inhibitor , a beta-blocker or a diuretic .  Average 24 h , day and night ambulatory blood pressure values were computed at baseline ( n = 277 ) and during treatment ( n = 347 ) : 112 patients had been r and omized to a target office diastolic blood pressure ⩽ 90 mmHg , 117 to ⩽ 85 mmHg and 118 to ⩽ 80 mmHg . Additional analyses included computation of : ( 1 ) trough-to-peak ratio and ( 2 ) the smoothness index ( the ratio between the average of the 24 hourly blood pressure reductions after treatment and its st and ard deviation ) . Results Taking the subgroup as a whole , baseline 24 h average blood pressures ( 146 ± 18/90 ± 10 mmHg ) were significantly and markedly lower than office blood pressures ( 170 ± 14/105 ± 3 mmHg , P < 0.01 ) . Office , 24 h , day and night blood pressures were all significantly reduced by treatment , but there was a smaller fall in ambulatory , than in office pressures . The between group differences in office blood pressure were smaller than those observed in the overall HOT sample . Between-group differences in 24 h blood pressure were even smaller . Trough-to-peak ratios and smoothness indices were lowest in the highest blood pressure target group and highest in the lowest blood pressure target group . Office and ambulatory blood pressures were similar in the groups r and omized to placebo ( n = 170 ) or acetylsalicylic acid ( n = 177 ) . Conclusion In conclusion , in the HOT study , treatment reduced not only office but also ambulatory blood pressure throughout the 24 h. The reduction was less marked for ambulatory than for office blood pressure OBJECTIVE To provide up date d , evidence -based recommendations for the prevention and management of hypertension in adults . OPTIONS AND OUTCOMES For lifestyle and pharmacological interventions , evidence was review ed from r and omized controlled trials and systematic review s of trials . Changes in cardiovascular morbidity and mortality were the primary outcomes of interest . However , for lifestyle interventions , blood pressure lowering was accepted as a primary outcome given the lack of long-term morbidity and mortality data in this field . For treatment of patients with kidney disease , the progression of kidney dysfunction was also accepted as a clinical ly relevant primary outcome . EVIDENCE A Cochrane collaboration librarian conducted an independent MEDLINE search from 2005 to August 2006 to up date the 2006 Canadian Hypertension Education Program recommendations . In addition , reference lists were scanned and experts were contacted to identify additional published studies . All relevant articles were review ed and appraised independently by both content and method ological experts using prespecified levels of evidence . RECOMMENDATIONS Dietary lifestyle modifications for prevention of hypertension , in addition to a well-balanced diet , include a dietary sodium intake of less than 100 mmol/day . In hypertensive patients , the dietary sodium intake should be limited to 65 mmol/day to 100 mmol/day . Other lifestyle modifications for both normotensive and hypertensive patients include : performing 30 min to 60 min of aerobic exercise four to seven days per week ; maintaining a healthy body weight ( body mass index of 18.5 kg/m2 to 24.9 kg/m2 ) and waist circumference ( less than 102 cm in men and less than 88 cm in women ) ; limiting alcohol consumption to no more than 14 units per week in men or nine units per week in women ; following a diet reduced in saturated fat and cholesterol , and one that emphasizes fruits , vegetables and low-fat dairy products , dietary and soluble fibre , whole grains and protein from plant sources ; and considering stress management in selected individuals with hypertension . For the pharmacological management of hypertension , treatment thresholds and targets should take into account each individual 's global atherosclerotic risk , target organ damage and any comorbid conditions : blood pressure should be lowered to lower than 140/90 mmHg in all patients and lower than 130/80 mmHg in those with diabetes mellitus or chronic kidney disease . Most patients require more than one agent to achieve these blood pressure targets . In adults without compelling indications for other agents , initial therapy should include thiazide diuretics ; other agents appropriate for first-line therapy for diastolic and /or systolic hypertension include angiotensin-converting enzyme ( ACE ) inhibitors ( except in black patients ) , long-acting calcium channel blockers ( CCBs ) , angiotensin receptor blockers ( ARBs ) or beta-blockers ( in those younger than 60 years of age ) . First-line therapy for isolated systolic hypertension includes long-acting dihydropyridine CCBs or ARBs . Certain comorbid conditions provide compelling indications for first-line use of other agents : in patients with angina , recent myocardial infa rct ion , or heart failure , beta-blockers and ACE inhibitors are recommended as first-line therapy ; in patients with cerebrovascular disease , an ACE inhibitor plus diuretic combination is preferred ; in patients with nondiabetic chronic kidney disease , ACE inhibitors are recommended ; and in patients with diabetes mellitus , ACE inhibitors or ARBs ( or , in patients without albuminuria , thiazides or dihydropyridine CCBs ) are appropriate first-line therapies . All hypertensive patients with dyslipidemia should be treated using the thresholds , targets and agents outlined in the Canadian Cardiovascular Society position statement ( recommendations for the diagnosis and treatment of dyslipidemia and prevention of cardiovascular disease ) . Selected high-risk patients with hypertension who do not achieve thresholds for statin therapy according to the position paper should nonetheless receive statin therapy . Once blood pressure is controlled , acetylsalicylic acid therapy should be considered . VALIDATION All recommendations were grade d according to strength of the evidence and voted on by the 57 members of the Canadian Hypertension Education Program Evidence -Based Recommendations Task Force . All recommendations reported here achieved at least 95 % consensus . These guidelines will continue to be up date d annually Abstract Objective : A clinical definition of a hypertensive emergency is excessively high blood pressure in the presence of symptoms indicating end organ damage . Equally high blood pressure without symptoms is called a hypertensive crisis . Patients with hypertensive crisis or emergency need prompt , effective , and specific therapy and a controlled reduction of blood pressure . Methods : We performed a r and omized , double-blind multi-centre study , to compare the safety , efficacy and tolerability of an intravenous ( IV ) infusion of two dihydropyridine calcium channel blockers ( either nifedipine or felodipine ) in 122 patients , of whom 63 were diagnosed as hypertensive emergencies and 59 as hypertensive crisis , who had not reacted adequately ( diastolic blood pressure < 115 mmHg ) to 5 mg of nifedipine PO . Results : Both drugs lowered blood pressure adequately in more than 90 % of the patients and were well tolerated . Only one patient had to be withdrawn , because of an excessive decrease in blood pressure . Conclusion : Patients with excessively high blood pressure who do not react to oral nifedipine can be treated equally effectively with felodipine and nifedipine IV . Felodipine is easier to h and le because of its lack of light sensitivity Clinical practice guidelines recommend blockers of the renin-angiotensin system alone or in combination with other agents to reduce blood pressure and albuminuria in patients with type 2 diabetes .  Dihydropyridine calcium channel blockers , however , may lower blood pressure but not albuminuria in these patients . Here we tested the hypothesis that combining an ACE inhibitor with either a thiazide diuretic or a calcium channel blocker will cause similar reductions in blood pressure and albuminuria in hypertensive type 2 diabetics . We conducted a double blind r and omized controlled trial on 332 hypertensive , albuminuric type 2 diabetic patients treated with benazepril with either amlodipine or hydrochlorothiazide for 1 year . The trial employed a non-inferiority design . Both combinations significantly reduced the urinary albumin to creatinine ratio and sitting blood pressure of the entire cohort . The percentage of patients progressing to overt proteinuria was similar for both groups . When we examined patients who had only microalbuminuria and hypertension we found that a larger percentage of the diuretic and ACE inhibitor normalized their albuminuria . We conclude that initial treatment using benzaepril with a diuretic result ed in a greater reduction in albuminuria compared to the group of ACE inhibitor and calcium channel blocker . In contrast , blood pressure reduction , particularly the diastolic component , favored the combination with amilodipine . The dissociation between reductions in blood pressure and albuminuria may be related to factors other than blood pressure This study tested the hypothesis that treatment with a nonsteroidal anti-inflammatory drug will not alter the hypotensive effect of a dihydropyridine calcium channel antagonist .  Fifteen essential hypertensives ( ages 58 - 80 years ) had a supine diastolic blood pressure ( DBP ) < 100 mmHg after 4 weeks monotherapy with nitrendipine 5 - 20 mg twice daily . They entered a double-blind r and omised crossover study in which the addition of indomethacin 25 mg three times daily was compared with placebo in treatment phases each of 4 weeks duration . Subjects were seen weekly and measurements in the last 2 weeks of each phase were compared . Supine blood pressure ( mean + /- SE ) was higher in the indomethacin phase ( 158 + /- 4/80 + /- 2 ) than in the placebo phase ( 154 + /- 4/76 + /- 3 ) ( p < 0.01 for DBP ) . In 6/15 ( 40 % ) of subjects the increase in supine diastolic blood pressure with indomethacin was > 5 mmHg . Plasma urea was also increased in the indomethacin phase : 7.6 + /- 0.6 mmol/l compared with placebo : 6.3 + /- 0.5 mmol/l ( p < 0.001 ) . The study has demonstrated that concurrent treatment with the NSAID indomethacin impairs the blood pressure lowering effect of the dihydropyridine calcium channel antagonist nitrendipine . This increase in blood pressure with indomethacin in subjects treated with nitrendipine may represent either an independent pressor effect of indomethacin or a reduced vasodilator prostanoid contribution to the hypotensive effect of nitrendipine . This blood pressure increase may be sufficient to interfere significantly with clinical blood pressure control in some subjects Background In the outcome trials that provided information on renal function in older hypertensive patients , diuretics and β-blockers were mostly used as first-line drugs . The long-term renal effects of calcium-channel blockers remain unclear . Objective To compare the changes in renal function in 2258 treated and 2148 untreated patients with isolated systolic hypertension , of whom 455 had diabetes mellitus and 390 had proteinuria . Methods We performed a post-hoc analysis of the double-blind placebo-controlled Systolic Hypertension in Europe ( Syst-Eur ) Trial . Active treatment was initiated with nitrendipine ( 10–40 mg/day ) with the possible addition of enalapril ( 5–20 mg/day ) , hydrochlorothiazide ( 12.5–25 mg/day ) , or both , titrated or combined to reduce the sitting systolic blood pressure by at least 20 mmHg , to less than 150 mmHg . The main outcome measures were serum creatinine concentration and creatinine clearance calculated by the formula of Cockroft and Gault . Results Serum creatinine concentration at the time when participants were r and omly allocated to study groups was less than 176.8 μmol/l ( 2.0 mg/dl ) , averaging 88 μmol/l . At the time of the last serum creatinine measurement , the blood pressure difference ( P < 0.001 ) between the two groups was 11.6/4.1 mmHg . In the intention-to-treat analysis ( 11 427 patient – years ) , serum creatinine and the calculated creatinine clearance were not influenced by active treatment . However , in the patients assigned r and omly to receive active treatment , the incidence of mild renal dysfunction ( serum creatinine at least 176.8 mmol/l ) decreased by 64 % ( P = 0.04 ) and that of proteinuria by 33 % ( P = 0.03 ) . Active treatment reduced the risk of proteinuria more in diabetic than in non-diabetic patients : by 71 % , compared with 20 % ( P = 0 . 04 ) . In non-proteinuric patients , active treatment did not influence serum creatinine , whereas in patients with proteinuria at entry to the study , serum creatinine decreased on active treatment ( P < 0 . 001 ) . Furthermore , in on-r and omized treatment comparison stratified for risk at baseline , serum creatinine concentration did not change ( P = 0.98 ) in patients continuing to receive monotherapy with nitrendipine , whereas it increased by 6.73 mmol/l ( P < 0.001 ) in patients who received hydrochlorothiazide alone or in combination with other study medication ( P < 0.001 for difference in trends ) . Conclusions In older patients with isolated systolic hypertension , antihypertensive treatment starting with the dihydropyridine calcium-channel blocker , nitrendipine , did not decrease blood pressure at the expense of renal function and prevented the development of proteinuria , especially in diabetic patients The purpose of this study was to compare several diltiazem-based antihypertensive drug combinations and assess the usefulness of home blood pressure monitoring in the evaluation of the efficacy of combination pharmacotherapy . Sixteen general practitioners recruited hypertensive subjects uncontrolled on diltiazem monotherapy , who were r and omized to receive eight weeks of add-on therapy with a diuretic ( chlorthalidone ) , a dihydropyridine calcium antagonist ( felodipine ) , an ACE inhibitor ( lisinopril ) , or an angiotensin blocker ( valsartan ) .  Sitting office and home blood pressure was measured using electronic devices A&D 767 . A total of 211 patients were r and omized , and 185 completed the study . Of 52 subjects r and omized to felodipine  , 15 were withdrawn due to ankle edema . The additional antihypertensive effect of the second drug was smaller in 18 subjects with a white coat effect ( p < 0.01 ) . All combinations produced a significant decline in office ( 21.2 ± 14.8 / 7.7 ± 9.7 mmHg ) and home ( 17.1 ± 11.9 / 6.0 ± 7.0 ) blood pressure ( systolic / diastolic , p < 0.001 ) . There were no differences in the efficacy of the four combinations assessed using office or home blood pressure monitoring . These data suggest that diuretics , dihydropyridines , ACE inhibitors , and angiotensin receptor blockers provide significant additional antihypertensive effects in hypertensive patients uncontrolled on diltiazem monotherapy . The diltiazem-dihydropyridine combination is often intolerable because of ankle edema . Home blood pressure monitoring is useful in the assessment of the efficacy of combination pharmacotherapy and also allows for the detection of subjects who do not require treatment intensification Objective : To assess the relationship between chronic intake of nonsteroidal anti-inflammatory drugs ( NSAID ) and outcome , in particular ( gastrointestinal ) bleeding and to investigate whether the effect of chronic NSAID intake was similar in untreated and treated elderly hypertensives . Methods : Eligible patients ( ⩾60 years , with systolic blood pressure 160–219 mm Hg and diastolic blood pressure < 95 mm Hg ) were r and omised to active treatment or placebo . Active treatment consisted of nitrendipine , with the possible addition of enalapril , hydrochlorothiazide , or both , titrated or combined to reduce the sitting systolic blood pressure by at least 20 mm Hg to below 150 mm Hg . Patients never taking NSAIDs ( n = 2882 ) were compared with patients on chronic NSAID intake ( n= 861 ) , defined as reporting NSAID intake on at least 50 % of the patient forms . Results : There was a tendency towards lower mortality ( relative hazard rate ( 95 % confidence interval ( CI ) , 0.77 ( 0.56–1.06 ) ) and higher incidence of bleeding ( 1.13 ( 0.63–2.05 ) with chronic NSAID intake . Although there was no significant interaction between calcium-channel blocker (CCB)-based treatment and chronic NSAID intake for any of the end points , chronic NSAID intake tended to be associated with a lower incidence of bleeding on active treatment as compared to placebo ( P-value of the interaction term = 0.07 ) . Conclusion : The effect of chronic NSAID intake on outcome was similar in patients on active treatment based on a dihydropyridine CCB or on placebo . However , chronic NSAID intake might have a less deleterious effect on bleeding on active treatment as compared to placebo Objective : The aim of the present study was to compare the cardiovascular effects of olmesartan , an angiotensin II receptor blocker , combined with a calcium channel blocker ( CCB ) or a diuretic , in a prospect i ve , r and omized , open-label , blinded endpoint trial . Methods : Japanese hypertensive patients aged at least 65 to less than 85 years with SBP at least 140 mmHg and /or DBP at least 90 mmHg with antihypertensive treatment , or SBP at least 160 mmHg and /or DBP at least 100 mmHg without antihypertensive treatment were r and omized to receive olmesartan with either a dihydropyridine CCB or a low-dose diuretic . If SBP and /or DBP remained at least 140 and /or at least 90 mmHg , the other antihypertensive drug was added . The primary endpoint was a composite of fatal and nonfatal cardiovascular events . The median follow-up time was 3.3 years . Results : Blood pressure decreased similarly in both groups . The primary endpoint occurred in 116/2568 patients ( 4.5 % ) in the olmesartan plus CCB group and in 135/2573 patients ( 5.3 % ) in the olmesartan plus diuretic group [ hazard ratio 0.83 , 95 % confidence interval ( CI ) 0.65–1.07 , P = 0.16 ] . Rates of all-cause death and cardiovascular deaths were similar . Among patients aged at least 75 years , the incidence of stroke tended to be lower in the olmesartan plus CCB group than in the olmesartan plus diuretic group ( hazard ratio 0.63 , 95 % CI 0.38–1.02 , P = 0.059 , interaction P = 0.019 ) . Fewer patients in the olmesartan plus CCB group ( 8.2 % , 211/2568 ) than in the olmesartan plus diuretic group ( 9.8 % , 253/2573 ; P = 0.046 ) experienced serious adverse events . Conclusion : Despite no significant difference in cardiovascular events , the different safety profiles suggest that the combination of olmesartan and CCB may be preferable to that of olmesartan and diuretic 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 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 Objective To test the primary hypothesis that a newer antihypertensive treatment regimen ( calcium channel blocker ± an angiotensin converting enzyme inhibitor ) is more effective than an older regimen ( β-blocker ± a diuretic ) in the primary prevention of coronary heart disease ( CHD ) . To test a second primary hypothesis that a statin compared with placebo will further protect against CHD endpoints in hypertensive subjects with a total cholesterol ⩽ 6.5 mmol/l . Design Prospect i ve , r and omized , open , blinded endpoint trial with a double-blinded 2 × 2 factorial component . Setting Patients were recruited mainly from general practice s. Patients Men and women aged 40–79 were eligible if their blood pressure was ⩾160 mmHg systolic or ⩾ 100 mmHg diastolic ( untreated ) or ⩾140 mmHg systolic or ⩾ 90 mmHg diastolic ( treated ) at r and omization . Interventions Patients received either amlodipine ( 5/10 mg ) ± perindopril ( 4/8 mg ) or atenolol ( 50/100 mg ) ± bendroflumethiazide ( 1.25/2.5 mg ) + K+ with further therapy as required to reach a blood pressure of ⩽140 mmHg systolic and 90 mmHg diastolic . Patients with a total cholesterol of ⩽ 6.5 mmol/l were further r and omized to receive either atorvastatin 10 mg or placebo daily . Main outcome measure Non-fatal myocardial infa rct ion ( MI ) and fatal coronary heart disease ( CHD ) . Results 19 342 men and women were initially r and omized , of these 10 297 were also r and omized into the lipid-lowering limb . All patients had three or more additional cardiovascular risk factors . Conclusions The study has 80 % power ( at the 5 % level ) to detect a relative difference of 20 % in CHD endpoints between the calcium channel blocker-based regimen and the β-blocker-based regimen . The lipid-lowering limb of the study has 90 % power at the 1 % level to detect a relative difference of 30 % in CHD endpoints between groups BACKGROUND The dihydropyridine calcium channel blocker amlodipine and the angiotensin II antagonist irbesartan effectively reduce blood pressure in hypertensive children . METHODS Eligible for the open-label , r and omized study were nephropathic children between 6.0 and 18 years of age with plasma creatinine < 177 micromol/L , overt proteinuria , untreated arterial hypertension ( systolic , 5 to 30 mm Hg ; and diastolic , 1 to 15 mm Hg;>95th centile ) and stable immunosuppressive treatment . The initial dose of amlodipine was 5 mg ( body weight , 20 to 40 kg ) and 10 mg ( body weight,>40 kg ) , respectively , that of irbesartan , which was 75 mg ( body weight , 20 to 40 kg ) and 150 mg ( body weight,>40 kg ) , respectively . The dosage was doubled if necessary . RESULTS A total of 26 children aged 6.1 to 17 years were allocated to receive either amlodipine ( N = 13 ) or irbesartan ( N = 13 ) for 16 weeks . Severe edema and headache occurred in two patients on amlodipine who withdrew from the study . No adverse experiences were noted in patients given irbesartan . Amlodipine [ by 12 ( 10 to 14)/7 ( 5 to 10 ) mm Hg ; median and interquartile range , respectively ] and irbesartan [ by 13 ( 9 to 16)/9 ( 7 to 11 ) mm Hg , respectively ] reduced blood pressure ( P < 0.01 ) in a similar fashion . Heart rate , plasma sodium , and creatinine did not change . Irbesartan slightly increased plasma potassium [ by 0.1 ( 0.0 to 0.2 ) mmol/L ; P < 0.05 ] . Plasma albumin and the urinary albumin/creatinine ratio were similar before and with amlodipine . On the contrary , irbesartan increased plasma albumin [ by 4 ( 3 to 5 ) g/L ; P < 0.03 ] and decreased the urinary albumin/creatinine ratio [ by 242 ( 68 to 312 ) mg/mmol ; P < 0.03 ] . CONCLUSION The study demonstrates that in children the effect of angiotensin II antagonists on proteinuria is better than that of dihydropyridine calcium channel blockers In the double-blind Systolic Hypertension in Europe ( Syst-Eur ) Trial , active treatment was initiated with nitrendipine ( 10 to 40 mg/d ) with the possible addition of enalapril ( 5 to 20 mg/d ) and /or hydrochlorothiazide ( 12.5 to 25 mg/d ) titrated or combined to reduce sitting systolic blood pressure by at least 20 mm Hg to < 150 mm Hg . In the control group , matching placebos were used similarly . In view of persistent concerns about the use of calcium channel blockers as first-line antihypertensive drugs , this report explored to what extent nitrendipine , administered alone , prevented cardiovascular complications .  Age at r and omization averaged 70.2 years and systolic/diastolic blood pressure 173.8/85.5 mm Hg . Of 2398 actively treated patients , 1327 took only nitrendipine ( average dose , 23.4 mg/d ) , and 1042 progressed to other treatments including nitrendipine ( n=757 ; 35.7 mg/d ) , enalapril ( n=783 ; 13.4 mg/d ) , and /or hydrochlorothiazide ( n=294 ; 21.0 mg/d ) . Compared with the whole placebo group ( n=2297 ) , patients receiving monotherapy with nitrendipine had 25 % ( P=0.05 ) fewer cardiovascular end points , and those progressing to other active treatments showed decreases ( P</=0 . 01 ) in total mortality ( 40 % ) , stroke ( 59 % ) , and all cardiovascular end points ( 39 % ) . Among the control patients , 863 used only the first-line placebo . Compared with this subgroup , patients receiving monotherapy with nitrendipine showed a nearly 50 % ( P</=0.004 ) reduction of all types of end points , including total and cardiovascular mortality . The full relative benefit from nitrendipine was seen as early as 6 months after r and omization . To ascertain that the benefit conferred by the dihydropyridine was not due to selection bias , the 1327 patients remaining on monotherapy with nitrendipine  were matched by gender , age , previous cardiovascular complications , and systolic blood pressure at entry with an equal number of placebo patients . In this analysis , nitrendipine reduced ( P</=0.05 ) cardiovascular mortality by 41 % , all cardiovascular end points by 33 % , and fatal and nonfatal cardiac end points by 33 % . Despite the limitations inherent in post hoc analyses , the present findings suggest that the calcium channel blocker nitrendipine , given as a single antihypertensive medication , prevents cardiovascular complications in older patients with isolated systolic hypertension The effect of nifedipine ( Adalat ; Bayer-Miles)--a calcium channel blocker , which has a well-established place in nonobstetric hypertension -- was compared with dihydralazine in 33 primigravidas with severe hypertension of pregnancy . Patients with a diastolic blood pressure greater than 110 mmHg before drug administration were r and omly assigned to treatment with either nifedipine or dihydralazine . Both drugs were found to be equally efficacious .  Nifedipine , however , showed an earlier onset of action in lowering systolic blood pressure and had the advantage of oral administration Background The most effective and accurate treatment of hypertensive patients  reduces cardiovascular events and improves the quality of life . Objective This study compared the efficacy and safety of combined ( combination therapy ) with an angiotensin-receptor blocker ( ARB ) a calcium-channel blocker ( CCB ) ( Losartan / Amloidipine 50/10 mg ) vs maximal combination doses of ARB with hydrochlorothiazide ( Losartan /HCTZ 100/25 mg ) and maximal combination doses of CCB with HCTZ ( Amlodipine /HCTZ 10/25 mg ) in the management of stage 2 hypertension . Methods This r and omized clinical trial ( RTC ) comprised 478 hypertensive patients with mean age 50.5±5.21 years , and took place between January 2010 and December 2011 in Vasei Hospital clinic in Sabzevar . Antihypertensive drugs were washed out after 5 days of discontinuation of drugs and the patients with mean blood pressure in sitting position ≥ 160 and < 200 mmHg in systole and ≥ 100 and < 110 mmHg in diastole were r and omized into three groups : Losartan / Amlodipine 50/10 mg ( n = 164 ) , Losartan / HCTZ 100/25 mg ( n = 155 ) and Amlodipine / HCTZ 10/25 mg ( n = 159 ) . The end point was reaching the blood pressure below 140/90 within 56 days of treatment in each group . Results There was a significant difference in systolic blood pressure reductions between treatment groups ( P<0.001 ) and also there was a significant difference between groups in reducing diastolic blood pressure ( P<0.01 ) . The highest systolic and diastolic blood pressure reduction respectively was found in Amlodipine/losartane and losartane/HTCZ group . The ANCOVA analysis revealed that only treatment regimen had a significant effect ( P=0.01 ) and other factor including Age , Gender , Diabetes Mellitus , Smoking and High serum cholesterol did n’t have significant effect on blood pressure reduction . Conclusion ARB/CCB combination therapy reduced blood pressure more effectively than the maximal doses of ARB or CCB with HCTZ in stage 2 hypertensive patients within this period of study The antihypertensive efficacy of the angiotensin II receptor blocker olmesartan medoxomil has been shown to compare favourably with that of other antihypertensive agents . This r and omized , double-blind study compared the antihypertensive efficacy of the starting dose of olmesartan medoxomil with that of the calcium channel blocker amlodipine besylate ( amlodipine ) in subjects with mild-to-moderate hypertension . Following a 4-week , single-blind , placebo run-in period , 440 subjects aged ⩾18 years were r and omized to the starting dose of olmesartan medoxomil ( 20 mg/day ) , amlodipine ( 5 mg/day ) , or placebo for 8 weeks . Subjects were evaluated by  24-h ambulatory blood pressure monitoring ( ABPM ) and by seated cuff blood pressure ( BP ) measurements at trough . The primary end point was the change from baseline in mean 24-h diastolic blood pressure ( DBP ) by ABPM at Week 8 . Secondary end points included change from baseline in mean 24-h ambulatory systolic blood pressure ( SBP ) at 8 weeks , change from baseline in mean seated trough cuff DBP and SBP measurements , and response and control rates for DBP < 90 and < 85 mmHg . Control rates for SBP < 140 and < 130 mmHg were also calculated . Olmesartan medoxomil and amlodipine produced significantly greater reductions in ambulatory and seated DBP and SBP compared with placebo . Mean reductions in ambulatory and seated BP were similar between the two active agents ; however , in the olmesartan medoxomil group , significantly more patients achieved the SBP goal of < 130 mmHg and the DBP goal of < 85 mmHg . Both drugs were well tolerated at the recommended starting dose . Although amlodipine was associated with a higher incidence of oedema , this did not reach statistical significance . Olmesartan medoxomil is an effective antihypertensive agent , with BP-lowering efficacy at the starting dose similar to that of amlodipine , and is associated with more patients achieving the rigorous BP goals of SBP < 130 mmHg and DBP < 85 mmHg Angiotensin receptor blockers ( ARBs ) with calcium channel blockers ( CCBs ) or diuretics are a widely used combination therapy for hypertensive patients . The present study aim ed to determine which combination was better for elderly hypertension patients aged ≧ 65 years . We design ed a multicentre , r and omized , open-label , parallel comparison study . Hypertensive out patients aged ≧ 65 years who did not achieve the target blood pressure ( BP < 140/90 mmHg ) with usual dosages of ARBs  were r and omly assigned to switch treatment to losartan 50 mg/hydrochlorothiazide 12.5 mg or amlodipine 5 mg in addition to ARBs . The primary endpoint was a change in the systolic blood pressure ( SBP ) and diastolic blood pressure ( DBP ) after the 3-month treatment period , while secondary endpoints were changes in the BP , albuminuria , laboratory values , and cognitive function with the mini-mental state examination ( MMSE ) at baseline and after one year . The results from the CAMUI trial should provide new evidence for selecting optimal combination therapies for elderly hypertensive patients Objective To study the effects of a high calcium intake in hypertensive patients by blood pressure monitoring . Design In a r and omized crossover study , patients were assigned to an 8-week calcium supplementation period and an 8-week control period . The subjects were given 25 mmol/day ( 1 g/day ) of calcium as calcium carbonate during the intervention period . Setting A hypertension clinic in a tertiary teaching hospital . Patients Sixty untreated or treated hypertensive patients ( 35 men and 25 women , mean age 58 years ) with office systolic/diastolic blood pressure ≥ 140/90 mmHg . Main outcome measures Office blood pressure , home blood pressure ( last 7 days ) , and ambulatory 24 h blood pressure ( every 30 min using TM-2421 ) . Results The serum calcium concentration and urinary calcium excretion increased significantly with calcium supplementation . Office , home and 24 h blood pressure were lower in the calcium period than in the control period , although the differences were small ( mean ± SEM office blood pressure : 1.2 ± 1.2/1.1 ± 0.7 mmHg ; home blood pressure : 1.9 ± 0.7/1.3 ± 0.6 mmHg ; 24 h blood pressure : 1.2 ± 0.8/0.9 ± 0.5 mmHg , ) , and significant only for home systolic and diastolic blood pressures . The difference in home systolic blood pressure was inversely correlated with the level of home blood pressure in the control period and with the difference in urinary calcium . The difference in 24 h systolic blood pressure was positively correlated with the control level of urinary calcium . Age , sex , antihypertensive medication , drinking habit , sodium intake or order of treatment did not significantly influence the effects of calcium supplementation . Conclusions An increase in calcium intake tends to lower office , home and ambulatory blood pressure in hypertensive patients . However , the antihypertensive effect is too small to support the general application of a high calcium intake in the treatment of hypertension Objective : To perform a subgroup analysis on those patients in STOP‐Hypertension‐2 who had isolated systolic hypertension . Design and methods : The STOP‐Hypertension‐2 study evaluated cardiovascular mortality and morbidity in elderly hypertensives comparing treatment with conventional drugs ( diuretics , beta‐blockers ) with that of newer ones [ angiotensin‐converting enzyme ( ACE ) inhibitors , calcium antagonists ] . In all , 6614 elderly patients with hypertension ( mean age 76.0 years , range 70–84 years at baseline ) were included in STOP‐Hypertension‐2 . In the present subgroup analysis of STOP‐Hypertension‐2 , isolated systolic hypertension was defined as systolic blood pressure at least 160 mmHg and diastolic blood pressure below 95 mmHg , in accordance with the Syst‐Eur and Syst‐China study criteria . In total , 2280 patients in STOP‐Hypertension‐2 met these criteria . In the study , patients were r and omized to one of three treatment groups : “ conventional ” antihypertensive therapy with beta‐blockers or diuretics ( atenolol 50 mg , metoprolol 100 mg , pindolol 5 mg , or fixed‐ratio hydrochlorothiazide 25 mg plus amiloride 2.5 mg daily ) ; ACE inhibitors ( enalapril 10 mg or lisinopril 10 mg daily ) ; or calcium antagonists ( felodipine 2.5 mg or isradipine 2.5 mg daily ) . Analysis was by intention to treat . Results : The blood pressure lowering effect in patients with systolic hypertension was similar with all three therapeutic regimens : 35/13 mmHg in the conventional group ( n = 717 ) , 34/12 mmHg in the ACE inhibitor group ( n = 724 ) , and 35/13 mmHg in the calcium antagonist group ( n = 708 ) . Prevention of cardiovascular mortality , the primary endpoint of the study , did not differ between the three treatment groups . All stroke events , i.e. fatal and non‐fatal stroke together , were significantly reduced by 25 % in the newer‐drugs group compared with the conventional group ( 95 % CI 0.58–0.97 ; p = 0.027 ) . This difference was attributable to reduction of non‐fatal stroke while fatal stroke events did not differ between groups . New cases of atrial fibrillation were significantly increased by 43 % ( 95 % CI 1.02–1.99 ; p = 0.037 ) on “ newer ” drugs compared with “ conventional ” therapy , mainly attributable to the calcium antagonists . There were no significant differences between the three treatment groups with respect to the risks of myocardial infa rct ion , sudden death or congestive heart failure . Conclusions : The analysis demonstrated that “ newer ” therapy ( ACE inhibitors/calcium antagonists ) was significantly better ( 25 % ) than “ conventional ” ( diuretics/beta‐blockers ) in preventing all stroke in elderly patients with isolated systolic hypertension 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 1 . The antihypertensive efficacy and tolerability of a low dose combination of the angiotensin converting enzyme inhibitor ramipril ( 2.5 mg ) and the extended release formulation of the dihydropyridine calcium channel antagonist felodipine ( 5 mg ) were assessed in a double-blind , double dummy placebo controlled , r and omised , crossover study in 20 patients ( mean age 55.4 years ; range 46 - 69 ) with uncomplicated mild to moderate hypertension ( supine diastolic > 90 mmHg < 115 mmHg after 4 weeks of single-blind wash-out on placebo ) . The four r and omised , double-blind , crossover study phases evaluated the response to 4 weeks of once daily treatment with placebo , monotherapy with each drug and the combination .  Noninvasive ambulatory blood pressure monitoring ( Spacelabs 90207 ) was performed for 24 h at the end of each phase . 2 . The mean 24 h ambulatory blood pressure ( mmHg ) was 147.9/92.0 following placebo , 141.3/87.8 following monotherapy with ramipril 2.5 mg , 136.8/85.8 following monotherapy with felodipine ER 5 mg and 131.1/82.6 following the combination of ramipril 2.5 mg and felodipine ER 5 mg . All active treatment phases significantly reduced mean 24 h ambulatory diastolic pressure by comparison with placebo . The antihypertensive efficacy of the combination was additive . 3 . The coadministration of ramipril did not attenuate the incidence of headache attributable to felodipine ER
Once-daily dihydropyridine calcium channel blockers appeared to lower blood pressure by a relatively constant amount throughout the 24-hour dosing interval .
Six dihydropyridine calcium channel blockers studied in this review lowered blood pressure by a relatively similar amount each hour over the course of 24 hours .
BACKGROUND Calcium channel blockers are a heterogeneous class of drugs , including dihydropyridine and non-dihydropyridine subgroups , commonly used in the treatment of hypertension .
A systematic review of the 24-hour time course of the blood pressure-lowering effect has not been published .
OBJECTIVES To assess how much variation there is in hourly systolic and diastolic blood pressure lowering by dihydropyridine calcium channel blockers over a 24-hour period in people with hypertension aged 18 years or over , with baseline systolic blood pressure of at least 140 mmHg or diastolic blood pressure of at least 90 mmHg , or both .