Evaluation of the efficacy and tolerability of nitrendipine in reducing both pressure and left ventricular mass in hypertensive type 2 diabetic patients. A randomized, controlled trial comparing diltiazem, hydrochlorothiazide, and their combination in the therapy of essential hypertension. A dose escalation trial comparing the combination of diltiazem SR and hydrochlorothiazide with the monotherapies in patients with essential hypertension. Effect of blood pressure lowering and antihypertensive drug class on progression of hypertensive kidney disease: results from the AASK trial. Amlodipine reduces cyclosporin-induced hyperuricaemia in hypertensive renal transplant recipients. Patterns of compliance with once versus twice daily antihypertensive drug therapy in primary care: a randomized clinical trial using electronic monitoring. Aliskiren, an orally effective renin inhibitor, provides antihypertensive efficacy alone and in combination with valsartan. Antihypertensive efficacy and safety of fixed-dose combination therapy with losartan plus hydrochlorothiazide in Japanese patients with essential hypertension. Study of the efficacy and safety of the combination ramipril 2.5 mg plus hydrochlorothiazide 12.5 mg in patients with mild-to-moderate hypertension. ATHES Study Group.
To evaluate the efficacy and tolerability of nitrendipine in comparison with captopril in hypertensive diabetic patients with left ventricular hypertrophy (LVH).
                A total of 75 patients enrolled in this study presented stable type 2 diabetes (not treated with insulin) and mild-to-moderate hypertension with a left ventricular mass > or = 75 g/m2 by two-dimensional echocardiography. After a 4-week washout period, 38 patients were assigned to treatment with captopril, and 37 patients to nitrendipine (random allocation). The duration of follow-up was 36 weeks.
                Patients of both groups were similar with regard to the duration of diabetes and hypertension, systolic and diastolic blood pressure at rest, degree of LVH, metabolic control, and albumin excretion rate (AER). Both drugs were equally effective in reducing systolic and diastolic blood pressure (captopril: from 165 +/- 13/100 +/- 4 to 147 +/- 11/87 +/- 4 mmHg; nitrendipine: from 167 +/- 17/100 +/- 5 to 143 +/- 9/86 +/- 4 mmHg; P < 0.05) and in reversing LVH (nitrendipine: from 87 +/- 2 to 81 +/- 1 g/m2; captopril: from 89 +/- 2 to 85 +/- 2 g/m2; P = 0.0001). Neither the left ventricular end-diastolic volume index nor the left ventricular ejection fraction changed significantly during the treatment period.
                Nitrendipine is as effective as captopril in reducing both systolic and diastolic blood pressure and in reversing LVH. Neither drug showed any negative side effects on fasting plasma glucose and glycated hemoglobin (HbA1c) levels, and both maintain constant AERs. To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects.
                Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase.
                Private and university-based clinics.
                Subjects of either sex, ranging in age from 18-70 years, with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure (DBP) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm Hg or less after 4-6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria.
                Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily.
                Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p < 0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo.
                The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent. A multicentre, randomised, placebo-controlled parallel group study comparing various doses of the combination diltiazem SR (DTZ SR)/hydrochlorothiazide (HCTZ) with the monotherapies was performed to delineate the optimal antihypertensive dosage of the two drug combinations. The study was carried out in 298 patients with mild to moderate essential hypertension (stable supine diastolic blood pressure, DBP, greater than or equal to 95 and less than or equal to 110 mmHg). After a single-blind placebo lead-in period lasting 4-6 weeks to establish stable baseline BP, the patients were randomised to receive either placebo (n = 75), HCTZ (n = 76), DTZ SR (n = 72), or the combination of DTZ SR/HCTZ (n = 75). There were three 4-week evaluation periods with forced escalation of therapy as follows: HCTZ (6.25, 6.25, 12.5 mg twice daily), DTZ SR (60, 90, 120 mg twice daily), and the combination of DTZ SR/HCTZ (60/6.25, 90/6.25, 120/12.5 mg twice daily). DTZ SR/HCTZ (120/12.5 mg) produced statistically significantly greater reductions in supine DBP compared with each monotherapy and placebo. The lower doses of DTZ SR/HCTZ (60/6.25 mg and 90/6.25 mg) produced statistically significantly greater supine DBP reductions compared with DTZ SR monotherapy and placebo, but not compared with HCTZ monotherapy. A comparison of reduction in supine DBP between evaluation periods demonstrated a dose-response relationship for the combination therapy in reducing BP over the dosage range studied. Adverse clinical and laboratory events were not significantly different between the therapies.(ABSTRACT TRUNCATED AT 250 WORDS) Hypertension is a leading cause of end-stage renal disease (ESRD) in the United States, with no known treatment to prevent progressive declines leading to ESRD.
                To compare the effects of 2 levels of blood pressure (BP) control and 3 antihypertensive drug classes on glomerular filtration rate (GFR) decline in hypertension.
                Randomized 3 x 2 factorial trial with enrollment from February 1995 to September 1998.
                A total of 1094 African Americans aged 18 to 70 years with hypertensive renal disease (GFR, 20-65 mL/min per 1.73 m(2)) were recruited from 21 clinical centers throughout the United States and followed up for 3 to 6.4 years.
                Participants were randomly assigned to 1 of 2 mean arterial pressure goals, 102 to 107 mm Hg (usual; n = 554) or 92 mm Hg or less (lower; n = 540), and to initial treatment with either a beta-blocker (metoprolol 50-200 mg/d; n = 441), an angiotensin-converting enzyme inhibitor (ramipril 2.5-10 mg/d; n = 436) or a dihydropyridine calcium channel blocker, (amlodipine 5-10 mg/d; n = 217). Open-label agents were added to achieve the assigned BP goals.
                Rate of change in GFR (GFR slope); clinical composite outcome of reduction in GFR by 50% or more (or > or =25 mL/min per 1.73 m2) from baseline, ESRD, or death. Three primary treatment comparisons were specified: lower vs usual BP goal; ramipril vs metoprolol; and amlodipine vs metoprolol.
                Achieved BP averaged (SD) 128/78 (12/8) mm Hg in the lower BP group and 141/85 (12/7) mm Hg in the usual BP group. The mean (SE) GFR slope from baseline through 4 years did not differ significantly between the lower BP group (-2.21 [0.17] mL/min per 1.73 m2 per year) and the usual BP group (-1.95 [0.17] mL/min per 1.73 m2 per year; P =.24), and the lower BP goal did not significantly reduce the rate of the clinical composite outcome (risk reduction for lower BP group = 2%; 95% confidence interval [CI], -22% to 21%; P =.85). None of the drug group comparisons showed consistent significant differences in the GFR slope. However, compared with the metoprolol and amlodipine groups, the ramipril group manifested risk reductions in the clinical composite outcome of 22% (95% CI, 1%-38%; P =.04) and 38% (95% CI, 14%-56%; P =.004), respectively. There was no significant difference in the clinical composite outcome between the amlodipine and metoprolol groups.
                No additional benefit of slowing progression of hypertensive nephrosclerosis was observed with the lower BP goal. Angiotensin-converting enzyme inhibitors appear to be more effective than beta-blockers or dihydropyridine calcium channel blockers in slowing GFR decline. Hypertension and hyperuricaemia are common side-effects of cyclosporin A (CsA) treatment in renal transplant recipients. While it is well established that the calcium channel blocker amlodipine can control CsA-induced hypertension effectively in this patient population, recent evidence suggests amlodipine might also reduce hyperuricaemia. The present study was designed to compare the effects of the calcium channel blocker amlodipine (5-10 mg/day) and the beta-adrenoceptor antagonist tertatolol (5-10 mg/day) on CsA-induced hyperuricaemia in post-renal transplant recipients with hypertension.
                Forty-eight hypertensive renal transplant recipients on a stable dose of CsA were randomized in a double-blind, parallel-group manner to receive either amlodipine (n = 24) or tertatolol (n = 24) for 60 days. The primary outcome measure was the change from baseline in serum uric acid concentration. Secondary analyses of efficacy were based on changes in renal function and blood pressure.
                Amlodipine significantly decreased serum uric acid levels from 483 +/- 99 to 431 +/- 110 microM/l (P < 0.001), while tertatolol significantly increased uric acid from 450 +/- 98 to 476 +/-84 microM/l (P = 0.006). Amlodipine also significantly increased glomerular filtration rate (P = 0.0048) and the clearance rate of uric acid (P = 0.023) and it reduced the fractional proximal tubular reabsorption of sodium (P < 0.001), compared with tertatolol. Renal plasma flow and filtered fraction were unaffected by both treatments, as was trough CsA blood concentration. Amlodipine lowered systolic blood pressure to a significantly greater extent than did tertatolol (P = 0.007). The time-dependent profile of diastolic blood pressure did not differ significantly between treatment groups. Both drugs were well tolerated.
                Amlodipine could be more appropriate than tertatolol for CsA-induced hypertension and hyperuricaemia in renal transplant recipients. To evaluate patterns of compliance with once versus twice daily administration of antihypertensive therapy (primary-outcome measure) and relevance of partial compliance for blood pressure control (secondary outcome measure).
                Multicentre, nonblinded, parallel group randomized design.
                Nonacademic primary care practices across Canada.
                Patients with mild essential hypertension (diastolic blood pressure 95 to 110 mmHg) of either sex (40% women), age 18 to 80 years (average 55 years). One hundred and ninety-eight patients were randomized to active treatment; 14 patients discontinued the study because of side effects.
                After a four-week placebo run-in period, patients were randomized to amlodipine 5 mg once-a-day or diltiazem slow release formulation (SR) 90 mg twice daily. Doses were increased to 10 mg and 180 mg to achieve sitting diastolic blood pressure of 90 mmHg or less.
                During 20 weeks on active treatment, compliance was assessed by pill counts and medication event monitoring system (MEMS), assessing percentage of prescribed doses taken, percentage days correct doses taken, percentage prescribed doses taken on time and blood pressure control as determined by office blood pressure measurement.
                The percentage prescribed doses taken (by either pill count of MEMS) showed a high degree of compliance, similar for the two treatments. However, other parameters of compliance were significantly better with once versus twice daily therapy. Partial compliance (less than 80% by pill count) led to less blood pressure control with the short acting diltiazem, but did not affect blood pressure control for the long acting amlodipine. Side effects profiles did not differ between the two treatments.
                Within the constraints of a clinical trial, hypertensive patients in primary care show a high degree of overall compliance with once or twice daily pill-taking, but patterns of pill-taking are more erratic with twice versus once daily medication, particularly in men. The results suggest that the negative consequences of partial compliance for blood pressure control can be offset by choosing agents with a duration of action well beyond the dosing interval. By blocking the renin-angiotensin-aldosterone system (RAAS) at its rate-limiting step, renin inhibition may provide improved RAAS suppression. We investigated the blood pressure (BP)-lowering effects of the oral direct renin inhibitor aliskiren, alone or in combination with the angiotensin receptor blocker valsartan.
                In this multicenter, randomized, placebo-controlled, 8-week trial, 1123 patients with mild-to-moderate hypertension underwent a 3 to 4 week single-blind placebo run-in and were then randomized in a modified factorial study design to receive once-daily, double-blind oral treatment with placebo, aliskiren monotherapy (75, 150, or 300 mg), valsartan monotherapy (80, 160, or 320 mg), aliskiren and valsartan in combination, or valsartan/hydrochlorothiazide (160/12.5 mg). The primary efficacy variable was the change from baseline in mean sitting diastolic BP (DBP) at endpoint.
                Once-daily oral treatment with aliskiren 300 mg significantly (P < .0001) lowered mean sitting DBP and systolic BP (SBP) compared with placebo; aliskiren monotherapy demonstrated a safety and tolerability profile comparable to placebo. Changes in DBP and SBP were fitted to a first-order dose-response surface (lack-of-fit test, P = .65), which showed that aliskiren and valsartan alone and in combination produced dose-related reductions in DBP and SBP. Coadministration of aliskiren and valsartan produced a greater antihypertensive effect than either drug alone, comparable in magnitude to the effect of valsartan/hydrochlorothiazide, with similar tolerability to the component monotherapies and to placebo.
                Aliskiren monotherapy provides antihypertensive efficacy and placebo-like tolerability in patients with hypertension. Aliskiren and valsartan in combination may provide additive BP-lowering effects with maintained tolerability. A randomized, double-blind, placebo-controlled, parallel-group multicenter study was conducted to evaluate the antihypertensive efficacy and safety of 8-week treatment with one of three fixed-dose combinations-losartan 50 mg plus hydrochlorothiazide 12.5 mg, losartan 50 mg plus hydrochlorothiazide 6.25 mg, or losartan 25 mg plus hydrochlorothiazide 6.25 mg-in comparison with those of hydrochlorothiazide 12.5 mg alone, losartan 50 mg alone, or placebo in Japanese patients with essential hypertension. Significant reductions in sitting diastolic blood pressure (DBP) and systolic blood pressure (SBP) were seen in all three combination groups compared with the placebo group (each p<0.001). The greatest reductions in DBP and SBP were observed in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group (12.7 and 18.0 mmHg, respectively). The reductions in the losartan 50 mg plus hydrochlorothiazide 12.5 mg group were significantly greater (each p<0.001) than those in the placebo group and each of the monotherapy groups. There were no significant differences in the incidences of clinical and laboratory drug-related adverse events between any of the combination groups and the placebo group. All combination groups showed improved hypokalemia and hyperuricemia compared to the hydrochlorothiazide 12.5 mg group. These results demonstrated that once-daily, fixed-dose combination therapy with losartan 50 mg plus hydrochlorothiazide 12.5 mg is well tolerated and more efficacious in lowering DBP and SBP than monotherapy in Japanese hypertensive patients. In a double-blind, parallel-group multicentre study, the efficacy and safety of a fixed low-dose combination of ramipril 2.5 mg and hydrochlorothiazide (HCT) 12.5 mg was compared with each of the component drugs when given as monotherapy. After a four-week placebo run-in, patients were randomized to receive either ramipril 2.5 mg (n = 218) or HCT 12.5 mg (n = 220), or the fixed-dose combination of ramipril 2.5 mg and HCT 12.5 mg (n = 222), for a period of eight weeks. At the end of the study, in which 624 patients had completed treatment, it was found that the decrease in supine diastolic blood pressure (the main efficacy parameter) was greater in the ramipril-HCT combination group than in either the ramipril or the HCT monotherapy groups, the difference being statistically significant when compared with the HCT group (-14.3, -13.1 and -12.4 mm Hg, respectively). Reductions in standing DBP and supine and standing systolic blood pressure (SBP) were also greatest in the combination group. The incidence of adverse events was lower in the combination group than in either of the monotherapy groups, and there were no serious clinically significant laboratory abnormalities in the combination group.
Reserpine is effective in reducing SBP roughly to the same degree as other first-line antihypertensive drugs. However, we could not make definite conclusions regarding the dose-response pattern because of the small number of included trials. More RCTs are needed to assess the effects of reserpine on blood pressure and to determine the dose-related safety profile before the role of this drug in the treatment of primary hypertension can be established.