Antihypertensive effects of parenteral nicardipine alone and in combination with captopril

We studied the safety and efficacy of intravenous nicardipine alone and in combination with oral captopril. Sixteen patients with essential hypertension received a single oral dose of captopril, 50 mg, to be certain that excessive hypotension would not occur. Nicardipine was given intravenously as a 2 mg bolus, followed by an infusion at a rate designed to lower the supine diastolic blood pressure at least 10 mm Hg; then oral captopril, 50 mg, or placebo was given. The next week, nicardipine was again infused, but the alternate oral treatment was given. Intravenous nicardipine reduced blood pressure from 156 +/- 15/101 +/- 5 mm Hg (mean arterial blood pressure 120 +/- 6 mm Hg) to 140 +/- 11/88 +/- 4 mm Hg (mean arterial blood pressure 105 +/- 5 mm Hg). When captopril was added to nicardipine, the mean arterial blood pressure fell an additional 8 mm Hg but the heart rate did not increase. The combination of angiotensin-converting enzyme inhibition and calcium channel blockage produces additive antihypertensive effects without additional reflex tachycardia.     

Comparison of the efficacy and tolerability of Prinivil and Procardia XL in black and white hypertensive patients.

The efficacy and tolerability of Prinivil and Procardia XL were compared in 135 (67 black, 68 white) patients with mild to moderate uncomplicated essential hypertension. The goal of therapy was to achieve and maintain a supine diastolic blood pressure (SDBP) of > 90 mmHg or a decrease in SDBP > or = 10 mmHg. Patients received Prinivil 10 to 40 mg once daily or Procardia XL 30 to 120 mg once daily during a titration period of 2 to 8 weeks to achieve the goal blood pressure before a 4-week maintenance period. The mean baseline supine systolic/diastolic blood pressures were 151/97 mmHg in patients receiving Prinivil and 153/99 mmHg in patients receiving Procardia XL. Ninety-one percent of patients receiving Prinivil and 95% of those receiving Procardia XL achieved SDBP control at the end of titration therapy. At the end of the maintenance treatment period, 79% of patients receiving Prinivil and 80% of those receiving Procardia XL had SDBP control. Mean decreases in SDBP from baseline were comparable for both treatment groups. At the end of the titration period, mean decreases were 9.6 mmHg in patients receiving Prinivil and 11.3 mmHg in patients receiving Procardia XL; at the end of the maintenance period, mean decreases were 10.8 mmHg and 12.1 mmHg, respectively. There were no differences in treatment responses in either the black or white hypertensive subgroups. Thus both drugs were equally effective in black and white patients with mild to moderate essential hypertension. Both drugs were generally well tolerated, but the number of adverse experiences requiring discontinuation of therapy was significantly higher (P = 0.03) in patients receiving Procardia XL.     

Comparison of the efficacy and tolerability of lisinopril and sustained-release verapamil in older patients with hypertension.

The efficacy and tolerability of lisinopril and sustained release (SR) verapamil hydrochloride were compared in 68 patients (mean age, 60 years) with mild to moderate uncomplicated essential hypertension. The goal of therapy was to achieve and maintain a supine diastolic blood pressure (SDBP) of less than 90 mmHg or a fall in SDBP greater than or equal to 10 mmHg. Patients received lisinopril (10 to 40 mg QD) or verapamil SR (120 to 480 mg QD) during a variable titration period (two to eight weeks) to achieve goal blood pressure prior to a four-week maintenance treatment period. Among the 62 patients who completed the titration period, the mean baseline supine systolic/diastolic blood pressures were 155/97 mmHg for the lisinopril group and 150/95 mmHg for the verapamil SR group. Ninety-seven percent of patients in the lisinopril group and 100% of patients in the verapamil SR group achieved SDBP control at the end of titration therapy. At the end of the maintenance treatment period, 82% of the lisinopril-treated patients and 81% of the verapamil SR-treated patients had SDBP control. Mean decreases in SDBP from baseline were comparable for both treatment groups. At the end of titration, mean decreases were 11.3 mmHg for the lisinopril group and 10.7 mmHg for the verapamil SR group; at the end of maintenance treatment, mean decreases were 10.5 mmHg and 8.5 mmHg. Thus both drugs were equally effective in older patients with mild to moderate essential hypertension. Both drugs were generally well tolerated. One patient in the lisinopril group and four patients in the verapamil SR group experienced adverse effects that required withdrawal from the study.     

Comparison of 26-week efficacy and tolerability of telmisartan and atenolol, in combination with hydrochlorothiazide as required, in the treatment of mild to moderate hypertension: a randomized, multicenter study

OBJECTIVE: This study was undertaken to compare the efficacy and tolerability of telmisartan, a novel antihypertensive agent, and atenolol, a well-established beta-blocker, in the treatment of mild to moderate hypertension. METHODS: This 26-week, multicenter, randomized, double-blind, double-dummy, parallel-group, titration-to-response study compared doses of telmisartan (40 mg titrated to 80 mg titrated to 120 mg) with atenolol (50 mg titrated to 100 mg) required to achieve diastolic blood pressure (DBP) control (< or = 90 mm Hg or a decrease from baseline of > or = 10 mm Hg). Open-label hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added if needed according to a prespecified titration rule. Men and women aged > 18 years with mild to moderate hypertension (morning mean supine DBP [SDBP] > or = 95 mm Hg and < or = 114 mm Hg) were eligible to participate. Patients with significant cardiovascular, metabolic, hepatic, or renal dysfunction or chronic obstructive pulmonary disease were excluded. The primary efficacy end point was trough SDBP response at 26 weeks; secondary efficacy end points included changes from baseline at trough in both standing and supine DBP and systolic blood pressure (SBP), and heart rate after 4, 8, 16, and 26 weeks; SBP control (reduction from baseline of > or = 10 mm Hg); normalization of supine SDBP to < or = 90 mm Hg; and the need for add-on HCTZ. Changes in quality of life were also examined. Adverse events were obtained from spontaneous reporting and recorded. Serious adverse events were reported to the sponsor according to predefined timelines. RESULTS: A total of 533 patients from 49 centers participated. Patients' mean age was 57.9 years (range, 22-79 years); 55.9% (298/533) of the population was male and 98.1% (523/533) was white. Of the 533 patients randomly assigned to treatment and included in the safety analysis, 520 (97.6%) were included in the efficacy analysis; 346 received telmisartan and 174 received atenolol. A total of 489 patients (91.7%) completed the study (325 [93.9%], telmisartan; 164 [94.2%], atenolol). Full SDBP response (trough SDBP < or = 90 mm Hg and/or a reduction from baseline of > or = 10 mm Hg) was observed in 84% and 78% of telmisartan- and atenolol-treated patients, respectively; this difference was not statistically significant. Final SBP/DBP reductions of 20.9/14.4 mm Hg were observed for the telmisartan regimen versus 16.7/13.3 mm Hg for the atenolol regimen; only the difference in SBP was significant (P = 0.005). Reduction from baseline in SBP of > or = 10 mm Hg was achieved by 80% of telmisartan-treated and 68% of atenolol-treated patients (P = 0.003). Adverse events were reported by 52.7% of patients given telmisartan and 61.2% of patients given atenolol; this difference was not statistically significant. Most events were mild or moderate. Although fatigue and male impotence were more common in atenolol-treated patients (3.4% and 4.0%, respectively), the incidence of these adverse events was too low to differentiate statistically. CONCLUSIONS: Telmisartan appears to be at least as effective as atenolol in the treatment of mild to moderate hypertension and may be better tolerated.     

Antihypertensive effectiveness of very low doses of hydrochlorothiazide: results of the PHICOG Trial

A large, multicenter, randomized, placebo-controlled, double-blind trial was carried out to determine the effects of the lowest dose of commercially available hydrochlorothiazide. Thus, Dyazide (which contains 25 mg of hydrochlorothiazide and 50 mg of triamterene in an approximately 50% bioavailable form), one capsule, was given daily to patients with either mild or moderate hypertension (supine diastolic blood pressure of 95 to 115 mmHg) for eight weeks. At the end of this eight-week period, supine diastolic blood pressure (SDBP) fell by 11.3 +/- 6.7 mmHg (mean +/- SD) in the Dyazide-treated compared to 4.6 +/- 6.9 mmHg in the placebo-treated group (P less than 0.001). In two thirds of the patients receiving active treatment the fall in SDBP was more than 10 mmHg, and in over half SDBP was completely normalized (ie, SDBP less than 90 mmHg). Supine systolic blood pressure fell by 14.7 +/- 12.3 mmHg in the Dyazide-treated group compared to 5.3 +/- 11.6 mmHg in the placebo-treated group (P less than 0.001). Approximately 80% of the antihypertensive effect occurred within two weeks and after four weeks there was no further significant reduction. Mildly (SDBP = 95 to 104 mmHg) and moderately (SDBP = 105 to 115 mmHg) hypertensive patients responded similarly to treatment. All studied subpopulations responded to treatment with a reduction of SDBP of at least an average of 10 mmHg; the best responders were blacks, women, the elderly (greater than 65 years old), and patients weighing less than 170 lbs. Side effects were mild and infrequent. In conclusion, by examining the effects of Dyazide (one capsule/day), this investigation demonstrated the effectiveness of low-dose hydrochlorothiazide in antihypertensive therapy and quantified it both in the general population and in clinically relevant subpopulations.     

Population dose versus response of betaxolol and atenolol: a comparison of potency and variability

The dose-response curves of betaxolol and atenolol were compared in 140 patients with mild to moderate essential hypertension. Patients with a supine diastolic blood pressure of 95 to 115 mm Hg at the end of a 4-week single-blind placebo washout phase were randomized (double-blind) to receive either betaxolol or atenolol in a dose-escalation manner. The dose (5 mg, 10 mg, and 20 mg betaxolol; 25 mg, 50 mg, and 100 mg atenolol) was increased if the supine diastolic blood pressure remained greater than 90 mm Hg after 4 weeks at each level. The final dose in the escalation phase was continued for an additional 12 weeks and then followed by a 2-week placebo phase. The data were analyzed with a population model using the program NONMEM (nonlinear mixed effects model). Atenolol exhibited a graded dose-response curve, whereas the lowest dose of betaxolol produced maximum or near-maximum effect. The estimated maximum effect (drug plus possibly unmeasured placebo effect) was similar for both treatments, about 13 mm Hg (95% confidence interval, 10 to 15 mm Hg). A trend toward less interindividual variability (coefficient of variation) was apparent for betaxolol compared to atenolol, 19% (95% confidence interval, 0% to 29%) versus 31% (95% confidence interval, 0% to 47%). The intraindividual variability (standard deviation) in supine diastolic blood pressure, 5.9 mm Hg (95% confidence interval, 5.2 to 6.5 mm Hg), did not differ significantly between drugs despite significantly greater intraindividual variability (coefficient of variation) in atenolol concentrations, 62% (95% confidence interval, 48% to 73%) versus 26% (95% confidence interval, 22% to 29%) for betaxolol.     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, combination therapy of verapamil SR 240 mg plus indapamide 2.5 mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg daily, those patients with diastolic blood pressures of <95 mm Hg were excluded from further study; 137 remaining patients with sitting diastolic blood pressure of 95--115 mm Hg, representing "incomplete" responders to verapamil SR 240 mg, were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. Efficacy was assessed after 16 weeks of double-blind therapy or at end point. All three treatments significantly reduced sitting diastolic and systolic blood pressure from baseline levels. Compared with Group I (verapamil SR 240 mg daily), there was a significant reduction (p < 0.05) in Group II combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction (p < 0.05) in Group II (verapamil SR 480 mg daily) of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Patients who had the least change in blood pressure (diastolic blood pressure decreases of <5 mm Hg) to lead-in verapamil SR 240 mg daily, prior to randomization, tended to have a greater response to combination therapy than to verapamil SR 480 mg. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving verapamil SR 480 mg daily (Group II). There was a significantly greater withdrawal from Group II than the other two treatment groups (8.5% from Group III and 4% from Group I). This trial demonstrated that adding indapamide 2.5 mg to the incomplete responders of verapamil SR 240 mg enhances efficacy and was well tolerated.     

Combined alpha/beta-blockade versus beta 1-selective blockade in essential hypertension in black and white patients

The purpose of this multicenter investigation was to determine the efficacy and safety of the alpha/beta-blocker labetalol versus the beta 1-selective beta-blocker atenolol in white and black patients with essential hypertension. Equal numbers of black and white patients were enlisted to form four treatment groups (white patients taking either labetalol or atenolol and black patients taking either labetalol or atenolol). Two hundred ninety-two patients (152 white and 140 black patients) with essential hypertension characterized by a standing diastolic blood pressure of 105 to 119 mm Hg (inclusive) were recruited for this trial. Patients were randomized to either labetalol (dosage titrated from 200 to 1600 mg/day) or atenolol (dosage titrated from 50 to 100 mg/day). The therapeutic goal was achievement of a standing diastolic blood pressure of 90 mm Hg or less or a fall of 15 mm Hg in diastolic pressure from baseline value at the end of the placebo run in period. At the end of the study there were no significant differences in blood pressure or heart rate changes in the supine position between the labetalol and atenolol groups. In contrast, labetalol produced greater reduction in both the standing systolic and diastolic blood pressure (-12/-13 mm Hg, respectively) compared with atenolol (-7/-9 mm Hg; p less than 0.05; p less than 0.005, respectively). The greatest decrease in blood pressure was observed in white patients receiving labetalol. In black patients the decrease in blood pressure was greater in those treated with labetalol compared with atenolol, particularly with respect to the systolic blood pressure. We conclude that the alpha 1-blocking property of labetalol provides an additional lowering of the blood pressure over that seen with beta 1-blockade alone, especially in the standing position, and this enhanced efficacy is not confined to one radical group.     

The renin-angiotensin system during converting enzyme inhibition with captopril in patients with severe treatment-resistant hypertension

Abstract. The effect of captopril on blood pressure (BP) and various components of the renin-angiotensin system was assessed in ten severely hypertensive patients. Captopril acutely reduced the BP with a maximum decrease of 23% at 90–120 min.
Maintenance treatment with captopril alone could not control the BP in any of the patients. Addition of hydrochlorothiazide markedly reduced the BP, while supplementation with propranolol caused no consistent changes.
Three patients attained a supine diastolic blood pressure (SDBP) ≤90 mmHg. Only two patients had a fall in SDBP less than 10 mmHg. One patient stopped because of taste disturbances.
Monitoring the renin-angiotensin system showed suppressed plasma concentrations of angiotensin II and increased levels of angiotensin I and renin, indicating the inhibition of converting enzyme activity. Plasma concentration of renin substrate decreased significantly. This observation has important implications for the methodology of renin assays.
Captropril is an effective alternative in the treatment of hypertensive patients not readily controlled with conventional therapy.     

Combination Treatment with Sustained-Release Verapamil and Indapamide in the Treatment of Mild-to-Moderate Hypertension

A multicenter study of the treatment of mild and moderate hypertension compared three once-daily regimens for efficacy and safety: Group I, verapamil sustained release (SR) 240 mg; Group II, verapamil SR 480 mg; and Group III, verapamil SR 240 mg plus indapamide 2.5. mg. After a 3-week placebo washout period and a 2-week preliminary treatment period with verapamil SR 240 mg, patients with sitting diastolic blood pressures of 95--115 mm Hg were randomized in a double-blind fashion to one of the three treatment groups for a duration of 16 weeks. (Patients with diastolic BP < 95 mm Hg on this initial treatment were excluded from further study.) Efficacy assessed after 16 weeks or at the end point showed all three treatments significantly reduced sitting diastolic blood pressure from baseline levels. Compared with Group I (low-dose) verapamil SR treatment, there was a reduction in Group III combination therapy of 8.6 mm Hg systolic and 3.0 mm Hg diastolic and a significant reduction in Group II high-dose verapamil SR therapy of 7.6 mm Hg systolic and 3.9 mm Hg diastolic BP. Efficacy results were independent of age or body weight. Patients who were poor responders to lead-in verapamil SR 240 mg daily prior to randomization tended to have a greater response to combination therapy than to high-dose verapamil SR. Adverse experiences leading to withdrawal from the study occurred in 21% of patients receiving high-dose verapamil (Group II), exceeding the withdrawal from the other two treatment groups (8.5% from Group II and 4% from Group I). The most frequent adverse experiences in Group II were constipation and peripheral edema; headache was most common in Groups I and III. This trial demonstrates that adding indapamide to low-dose verapamil SR enhances efficacy and is well tolerated.     

Telmisartan plus hydrochlorothiazide versus telmisartan or hydrochlorothiazide monotherapy in patients with mild to moderate hypertension: a multicenter, randomized, double-blind, placebo-controlled, parallel-group trial.

BACKGROUND: Recent surveys reveal continuing deficiencies in the awareness, treatment, and control of hypertension. In many cases, failure to achieve blood pressure targets may be attributable to the use of antihypertensive monotherapy. OBJECTIVES: This study was undertaken to identify combinations of telmisartan, a new oral angiotensin II type 1-receptor antagonist, and hydrochlorothiazide (HCTZ) that might provide greater antihypertensive efficacy than monotherapy with either agent in the treatment of mild to moderate hypertension. It also examined the dose-response surface for the 2 drugs alone and in combination. METHODS: This was a multicenter, randomized, double-blind, placebo-controlled, parallel-group study that employed all cells of a 4 x 5 factorial design. After a 4-week, single-blind, placebo run-in period, men and women between 18 and 80 years of age with mild to moderate hypertension (defined as mean supine diastolic blood pressure [DBP] between 95 and 114 mm Hg during the last 2 weeks of the placebo run-in period and systolic blood pressure [SBP] between 114 and 200 mm Hg immediately before randomization) were eligible to enter the 8-week, double-blind, double-dummy treatment period. Study comparisons were between once-daily telmisartan monotherapy (20, 40, 80, or 160 mg), HCTZ monotherapy (6.25, 12.5, or 25 mg), 12 combinations of these telmisartan/HCTZ doses, and placebo. The focus was on 2 combinations: telmisartan 40 mg/HCTZ 12.5 mg and telmisartan 80 mg/HCTZ 12.5 mg. The primary efficacy variable was change in supine trough DBP from baseline to the last evaluable measurement during double-blind treatment. Plasma renin activity and safety parameters, including treatment-emergent adverse events, physical findings, electrocardiograms, and serum electrolyte levels (which are known to increase with HCTZ treatment), were also assessed. RESULTS: Of 1293 patients screened, 818 (63.3%) were enrolled at 47 centers. Of these 818, 749 (91.6%) completed the study. The intent-to-treat population (randomized with > or = 1 postrandomization blood pressure measurement) consisted of 807 patients (98.7%). Telmisartan 80 mg/HCTZ 12.5 mg significantly decreased mean supine trough SBP/DBP by 23.9/14.9 mm Hg, a benefit of 8.5/3.4 mm Hg compared with telmisartan 80 mg and of 17.0/7.6 mm Hg compared with HCTZ 12.5 mg (both comparisons, P < 0.01). Telmisartan 40 mg/HCTZ 12.5 mg significantly reduced mean supine SBP by 18.8 mm Hg, a benefit of 6.6 mm Hg compared with telmisartan 40 mg and 11.9 mm Hg compared with HCTZ 12.5 mg (both, P < 0.01). This same combination significantly reduced mean supine DBP by 12.6 mm Hg, a benefit of 5.3 mm Hg compared with HCTZ 12.5 mg (P < 0.01), but was not significantly different from telmisartan 40 mg. Telmisartan 80 mg/HCTZ 12.5 mg was significantly more effective than telmisartan 40 mg/HCTZ 12.5 mg in reducing mean supine DBP and SBP (both, P < 0.05). The response surface and responder analyses confirmed the additive antihypertensive efficacy of the combination of telmisartan and HCTZ. All regimens were well tolerated. CONCLUSIONS: Once-daily telmisartan 80 mg/HCTZ 12.5 mg was effective and well tolerated when used to reduce SBP and DBP in patients with mild to moderate hypertension. In addition to enhancing efficacy, this combination protected against potassium depletion, a common side effect of thiazide monotherapy.     

The impact of arm position on the measurement of orthostatic blood pressure

Blood pressure is a standard vital sign in patients evaluated in an Emergency Department. The American Heart Association has recommended a preferred position of the arm and cuff when measuring blood pressure. There is no formal recommendation for arm position when measuring orthostatic blood pressure. The objective of this study was to assess the impact of different arm positions on the measurement of postural changes in blood pressure. This was a prospective, unblinded, convenience study involving Emergency Department patients with complaints unrelated to cardiovascular instability. Repeated blood pressure measurements were obtained using an automatic non-invasive device with each subject in a supine and standing position and with the arm parallel and perpendicular to the torso. Orthostatic hypotension was defined as a difference of ≥ 20 mm Hg systolic or ≥ 10 mm Hg diastolic when subtracting standing from supine measurements. There were four comparisons made: group W, arm perpendicular supine and standing; group X, arm parallel supine and standing; group Y, arm parallel supine and perpendicular standing; and group Z, arm perpendicular supine and parallel standing. There were 100 patients enrolled, 55 men, mean age 44 years. Four blood pressure measurements were obtained on each patient. The percentage of patients meeting orthostatic hypotension criteria in each group was: W systolic 6% (95% CI 1%, 11%), diastolic 4% (95% CI 0%, 8%), X systolic 8% (95% CI 3%, 13%), diastolic 9% (95% CI 3%, 13%), Y systolic 19% (95% CI 11%, 27%), diastolic 30% (95% CI 21%, 39%), Z systolic 2% (95% CI 0%, 5%), diastolic 2% (95% CI 0%, 5%). Comparison of Group Y vs. X, Z, and W was statistically significant (p < 0.0001). Arm position has a significant impact on determination of postural changes in blood pressure. The combination of the arm parallel when supine and perpendicular when standing may significantly overestimate the orthostatic change. Arm position should be held constant in supine and standing positions when assessing for orthostatic change in blood pressure.     

Comparison of the effectiveness of a beta blocker (atenolol) and a diuretic (chlorthalidone) in black hypertensive patients

A double-blind crossover trial of atenolol and chlorthalidone was done in black Jamaican hypertensive patients. After an initial four weeks of single drug therapy, the beta blocker and thiazide diuretic were used in combination. Chlorthalidone at a daily dose of 25 mg produced a significant (P less than .05) fall in the mean systolic and diastolic pressures (19.4 mm Hg and 12.2 mm Hg, respectively); atenolol produced a significant fall in the diastolic blood pressure (6.5 mm Hg); and combination therapy produced a reduction in systolic and diastolic blood pressures (27.8 mm Hg and 17.8 mm Hg, respectively). The study showed that combination therapy using a low dose of thiazide diuretic and a beta blocker was synergetic, but that a thiazide was more effective than a beta blocker in lowering the blood pressure in black hypertensive patients.     

Efficacy and tolerability of enalapril (20 mg)/hydrochlorothiazide (12.5 mg) combination therapy in essential hypertension.

The efficacy and tolerability of a preconstituted formulation combining enalapril (20 mg) and hydrochlorothiazide (12.5 mg) were evaluated in patients with essential hypertension unresponsive to enalapril monotherapy (20 mg/day). The duration of this open-lable, multicenter, noncomparative trial was 12 weeks: a two-week washout period followed by ten weeks of active treatment. During the active treatment period, patients received enalapril alone (up to 20 mg/day) for six weeks. At the end of week 6, patients with supine diastolic blood pressure greater than 90 mmHg were treated with the enalapril/hydrochlorothiazide combination therapy (EN/HCTZ). Of the 147 patients who were entered into the study, 81 were not normalized with enalapril alone. At the end of the study period, blood pressure was normalized (supine diastolic blood pressure less than or equal to 90 mmHg) in 60 (74%) of the 81 patients who had received the EN/HCTZ combination. Overall, 86% of the patients achieved satisfactory blood pressure control with this therapeutic regimen. Adverse reactions were mild and transient. Six patients experienced undesirable effects, the most frequent of which was coughing (2 cases). Neither enalapril (20 mg/day) alone nor the EN/HCTZ combination had any significant influence on any of the metabolic parameters evaluated. No hypokalemia and no significant changes in serum lipids occurred in the course of the study.     

Comparison of a fixed-dose combination of 40 mg telmisartan plus 12.5 mg hydrochlorothiazide with 40 mg telmisartan in the control of mild to moderate hypertension

This study investigated whether a fixed-dose combination of 40 mg of the angiotensin II antagonist telmisartan plus 12.5 mg of the diuretic hydrochlorothiazide (HCTZ) was superior to 40 mg telmisartan in patients with mild to moderate hypertension who failed to respond adequately to 40 mg telmisartan monotherapy. One hundred forty-six patients were withdrawn before randomization. Nonresponders (n = 327) were double blind and randomized to 40 mg telmisartan + 12.5 mg HCTZ (n = 160) or 40 mg telmisartan (n = 167). After 8 weeks of treatment, 40 mg telmisartan + 12.5 mg HCTZ lowered diastolic blood pressure (DBP) by an additional 3.5 mm Hg (P <.01) and systolic blood pressure (SBP) by 7.4 mm Hg (P <.01) compared with 40 mg telmisartan. Most of the additional effect of the combination was seen after 4 weeks of treatment. At week 8, blood pressure was normalized (SBP <140 mm Hg and DBP <90 mm Hg) in 51.6% of patients on 40 mg telmisartan + 12.5 mg HCTZ compared with 23.5% on 40 mg telmisartan (P <.05). The combination of 40 mg telmisartan + 12.5 mg HCTZ normalized DBP in 64.8% of patients, whereas 40 mg telmisartan normalized DBP in 40.1% (P <.05). SBP decreased by > or =10 mm Hg from baseline in 63.5% of patients receiving the fixed-dose combination compared with 42.6% of those receiving 40 mg telmisartan (P <.05). Both treatments were well tolerated. Adverse events were predominantly mild, transient, and considered unrelated to therapy. These findings indicate that a fixed-dose combination of 40 mg telmisartan + 12.5 mg HCTZ is clinically and statistically superior to 40 mg telmisartan in patients with mild to moderate hypertension failing to respond to 40 mg telmisartan alone.     

Effects of delapril in combination with indapamide on blood pressure and left ventricular mass in elderly hypertensive patients

We present a single-blinded, placebo-controlled trial of the effects on blood pressure and left ventricular mass and of the safety of a combined antihypertensive treatment with delapril, a new nonsulfhydryl angiotensin-converting enzyme inhibitor, and indapamide, a sulfonamide diuretic. We studied 28 elderly patients aged 65-85 years (mean age, 69 +/- 1) with sitting systolic/diastolic blood pressure of 160-200/95-115 mm Hg (at the end of the placebo period). After a 2-week placebo run-in, patients took 30 mg delapril in combination with 1.25 mg indapamide once daily for 24 weeks. Twenty-four-hour ambulatory blood pressure was monitored and M- and B-mode echocardiography were performed before and after 24 weeks of treatment. Blood pressure decreased from 156 +/- 1.5/101 +/- 1 mm Hg before treatment to 133 +/- 1/73 +/- 1 mm Hg after treatment. The total blood pressure burden also decreased; the percentage of measurements with a systolic blood pressure > or = 140 mm Hg and a diastolic blood pressure > or = 90 mm Hg decreased from 48.7% +/- 5%/31.5% +/- 4.3% to 23.5% +/- 4%/20.5% +/- 2.9% (p < 0.0005 and p < 0.05). The area under the curve of the 24-hour blood pressure decreased from 250 +/- 41/103 +/- 21 mm Hg to 97 +/- 21/37 +/- 8.5 mm Hg (p < 0.001 and p < 0.005). The left ventricular mass index (LVMI) in the 15 patients with pretreatment left ventricular hypertrophy was reduced after therapy from 167.5 +/- 8.5 g/m 2 to 152.2 +/- 7.6 g/m 2 (p < 0.05). A positive correlation was observed between percent changes of the area under the curve of the 24-hour diastolic blood pressure and percent changes of LVMI (r = 0.6; p < 0. 05) in the 15 patients with left ventricular hypertrophy. Only 2 patients reported side effects: 1 developed skin rash and 1 developed headache. The safety of the treatment was confirmed by laboratory tests. In elderly hypertensive patients, the combination of delapril and indapamide at low doses reduced blood pressure and had favorable effects on LVMI with few side effects.     

Safety and Efficacy of Once-Daily Captopril Plus Hydrochlorothiazide versus Nifedipine Gastrointestinal Therapeutic System in Black Patients with Mild to Moderate Hypertension

The safety and efficacy of captopril plus hydrochlorothiazide (HCTZ) were compared to nifedipine gastrointestinal therapeutic system (GITS) in 145 randomly assigned black patients with mild to moderate hypertension. Following a 4-week placebo lead-in, patients received captopril plus HCTZ 25/15 mg or nifedipine GITS 30 mg for up to 12 weeks. Upward dose titration was permitted at weeks 3 and 6. Mean seated systolic and diastolic blood pressures decreased 16.1 ± 13.5 mm Hg and 11.5 ± 7.4 mm Hg, respectively, with captopril plus HCTZ. Statistically similar decreases were observed with nifedipine GITS: systolic, 19.3 ± 12.2 mm Hg; diastolic, 13.8 ± 7.2 mm Hg. There were no clinically significant between-group differences in serum chemistries. Edema was reported in 20.3% of nifedipine GITS patients versus 1.4% of captopril plus HCTZ patients (p = 0.001). The two regimens were equally effective in controlling blood pressure in black patients; however, a higher incidence of edema occurred with nifedipine GITS compared to captopril plus HCTZ.     

Comparison of the efficacy and tolerability of lisinopril and sustained-release verapamil in black patients with hypertension.

In this clinical study the efficacy and tolerability of lisinopril and sustained-release (SR) verapamil hydrochloride were compared in black patients with mild-to-moderate uncomplicated essential hypertension. The goal of therapy was to achieve a supine diastolic blood pressure (SDBP) of less than 90 mmHg or a greater than or equal to 10-mmHg fall in SDBP. Forty-three patients completed the titration phase, 23 in the lisinopril group and 20 in the verapamil SR group. The mean baseline supine systolic/diastolic blood pressures were 147/98 mmHg for the lisinopril group and 155/100 mmHg for the verapamil SR group. At the end of a two- to eight-week titration period, 87% of the lisinopril-treated patients and 90% of the verapamil SR-treated patients had achieved SDBP control. Six patients were excluded from maintenance therapy: four in the lisinopril group (one because of urticaria and three because of failure to reach goal blood pressure) and two in the verapamil SR group (because of failure to reach goal blood pressure). After eight weeks of maintenance therapy, 68% of the lisinopril-treated patients and 72% of the verapamil SR-treated patients had achieved SDBP control. The mean decreases in SDBP were comparable for both treatment groups. At the end of titration, the mean decreases from baseline were 10.5 mmHg for the lisinopril group and 12.6 mmHg for the verapamil SR group. At the end of maintenance, the mean decreases from baseline were 7.8 mmHg for the lisinopril group and 9.2 mmHg for the verapamil SR group. Adverse experiences were few.(ABSTRACT TRUNCATED AT 250 WORDS)     

A comparison of valsartan and captopril in patients with essential hypertension in Indonesia

Adult Indonesian outpatients were randomised to receive either valsartan 80 mg once daily or captopril 25 mg twice daily for 8 weeks. The main criterion for tolerability was the incidence of adverse events. The primary efficacy variable was the change in mean sitting diastolic blood pressure (SDBP) from baseline to endpoint. No valsartan patients experienced dry cough, which was reported by 22 captopril patients (21.6%). Both drugs reduced mean SDBP and SSBP, with a trend in favour of valsartan. The percentage of valsartan patients whose BP normalised was higher than in captopril patients at week 4 (37% and 22%) and week 8 (45% and 34%), the difference being statistically significant at week 4 (p < 0.05). Valsartan 80 mg once daily is as effective as captopril 25 mg twice daily in reducing blood pressure in Indonesian patients, and has a better tolerability profile in respect of dry cough.     

Evaluation of isradipine (PN 200-110) in mild to moderate hypertension

The efficacy and safety of isradipine (PN 200-110), a new dihydropyridine calcium antagonist, was evaluated in 87 hypertensive patients in a placebo-controlled, double-blind, randomized multicenter trial. After a 3-week single-blind washout phase, isradipine (or matching placebo) was administered for 4 weeks, beginning at 2.5 mg b.i.d. with increments of 2.5 mg b.i.d. at weekly intervals if supine diastolic blood pressure remained greater than or equal to 90 mm Hg. At the end of 1 week average supine blood pressure in the isradipine group (n = 45) fell from a baseline of 156 +/- 13/104 +/- 4 mm Hg to 146 +/- 14/97 +/- 7 mm Hg. By week 4 blood pressure was reduced by 19/14 mm Hg compared with 4/5 mm Hg in the placebo group (P less than 0.001 between groups). Supine and standing pulse rates were slightly increased initially with isradipine therapy but returned to baseline with increasing isradipine doses. Blood pressure responses at week 4 were good or excellent (supine diastolic less than or equal to 90 mm Hg or greater than or equal to 10 mm Hg decrease from baseline) in 87% of isradipine-treated patients and in 26% of placebo-treated patients. Headache, edema, abdominal discomfort, and constipation occurred slightly more frequently in isradipine-treated patients than in placebo-treated control subjects. The results indicate that isradipine, administered as monotherapy in doses of 2.5 to 10 mg b.i.d., is safe and effective in patients with mild to moderate essential hypertension.