A single-blind study of doxazosin in the treatment of essential hypertension when added to nonresponders to angiotensin-converting enzyme inhibitor therapy

Doxazosin, a selective α₁-inhibitor, was assessed in hypertensive patients with sitting diastolic blood pressures (DBPs) of 95 to 114 mm Hg while receiving a stable dose of captopril or enalapril. Fifty-six patients were entered into the study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of doxazosin treatment, 95% of the patients were therapy successes (sitting DBP either ≤90 mm Hg with ≥5 mm Hg reduction or ≥10 mm Hg reduction) at a mean daily dose of 2.4 mg. Ninety-three percent achieved blood pressure control (sitting DBP ≤90 mm Hg) at a mean dose of 2.3 mg once daily. By the final treatment visit, systolic/diastolic sitting blood pressures for efficacy evaluable patients were reduced by $\text{16}\text{17}\text{mm Hg}$ from a mean baseline of $\text{158}\text{101}\text{mm Hg}$ to a final value of $\text{143}\text{84}\text{mm Hg}$. Throughout the study (2 to 14 weeks), all blood pressure reductions from baseline were significant (p < 0.05). There was only one side effect (vertigo) that warranted dose reduction, and only one patient was withdrawn from therapy (nausea). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 94% of patients and fair or poor for 6% of patients. The investigators' global assessment of patient toleration of doxazosin treatment was excellent or good for 93% of the 56 patients evaluated and fair or poor for 7% of patients. Total cholesterol was significantly decreased (p = 0.03), and the ratio of high-density lipoprotein to total cholesterol was significantly increased (p = 0.02) after doxazosin therapy. From baseline to final visit there was a highly significant reduction of 24% (p < 0.001) in calculated coronary heart disease risk score on the basis of the Framingham equation.     

Doxazosin in the treatment of mild and moderate essential hypertension in general medical practice

Doxazosin, a selective α₁-inhibitor, was assessed in 34 patients with mild and moderate hyportension. This study involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received 1 to 8 mg of doxazosin once dally, and (3) a 4-week maintenance period. After 12 weeks, 77% of the efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either ≤90 mm Hg with ≥5 mm Hg reduction or ≥10 mm Hg reduction) at a mean daily dose of 4.3 mg. Sixty-one percent achieved blood pressure control (sitting diastolic blood pressure ≤90 mm Hg) at a mean dose of 3.7 mg once daily. By the final treatment visit, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by $\text{17}\text{12}$ and $\text{17}\text{11}\text{mm Hg}$ from a mean baseline of $\text{160}\text{100}$ and $\text{156}\text{101}\text{mm Hg}$ in the sitting and standing positions, respectively (p < 0.05). Of the 34 patients, nine (26%) reported 12 adverse experiences, of which only one was severe. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigator's global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 85% of patients and fair for 15% of patients. The investigator's global assessment of toleration was excellent or good for 91% of patients and fair for 9% of patients. The overall lipid profile indicated a decrease in total cholesterol and triglycerides. From baseline to final visit there was a highly significant reduction of 24% (p < 0.001) in calculated coronary heart disease risk score, which was based on the Framingham equation.     

The addition of doxazosin to the treatment regimen of hypertensive patients not responsive to nifedipine

The efficacy and safety of doxazosin, a selective α₁-inhibitor, were assessed in hypertensive patients who failed to respond to nifedipine. Fifty patients were entered into a study that involved three phases: (1) a 2-week baseline period, (2) a 10-week period in which patients received doxazosin, 1 to 8 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks, all 43 efficacy evaluable patients were considered therapy successes (sitting diastolic blood pressure either ≤90 mm Hg or ≥10 mm Hg reduction) at a mean daily dose of 3.1 mg. Ninety-three percent achieved blood pressure control (sitting diastolic blood pressure ≤90 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, sitting systolic and diastolic blood pressures of efficacy evaluable patients were reduced (p < 0.05) by $\text{16}\text{18}\text{mm Hg}$ from a mean baseline of $\text{157}\text{103}\text{mm Hg}$ to a final value of $\text{141}\text{85}\text{mm Hg}$. The most prevalent side effect was vertigo (six patients). Most side effects were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. The investigators' global assessment was excellent or good for 98% of patients for both efficacy and toleration. From baseline to final visit there was a highly significant reduction of 17% (p < 0.001) in the calculated coronary heart disease risk score, which was based on the Framingham equation.     

Clinical experience with doxazosin in general medical practice

The antihypertensive efficacy, lipid effects, and safety of doxazosin, a selective α₁-inhibitor for the reduction of coronary heart disease (CHD) risk in hypertensive patients, was assessed in a general medical practice setting. Seven hundred seventy-one patients were entered into the study, which involved three phases: (1) a 2-week baseline period, (2) an 8-week period in which patients received doxazosin, 1 to 8 mg once daily, and (3) a 4-week maintenance period. From baseline to final visit there was a highly significant 27% reduction (p <0.001) in calculated CHD risk based on the Framingham equation as a consequence of doxazosin's favorable effects on both blood pressure and serum lipid levels. Efficacy and toleration of doxazosin therapy were good to excellent in most patients. The investigators' global assessment of efficacy of once-daily doxazosin therapy was excellent or good for 82% of patients and fair or poor for only 18% of patients. After 12 weeks, 83% of the patients were considered therapy successes (sitting diastolic blood pressure either ≤90 mm Hg or ≥ 10 mm Hg reduction not reaching ≤90 mm Hg) at a mean daily dose of 3.5 mg. Seventy-one percent achieved “normalized” blood pressure control (sitting diastolic ≤90 mm Hg with a decrease of ≥5 mm Hg) at a mean dose of 3.1 mg once daily. By the final treatment visit, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by $\text{20.6}\text{15.3}$ and $\text{21.0}\text{15.4}\text{mm Hg}$ from a mean baseline of $\text{166}\text{104}$ and $\text{165}\text{104}\text{mm Hg}$ in the sitting and standing positions, respectively (p < 0.05). Total cholesterol was significantiy decreased (p < 0.01). Most side effects were mild or moderate and disappeared with or were tolerated on continued therapy. The investigators' global assessment of patient toleration of doxazosin treatment was excellent or good for 89% of the 763 patients evaluated and fair or poor for only 11% of patients. The most commonly reported side effects were headache (8%) and dizziness (7%). No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment.     

A multicenter study of doxazosin in the treatment of severe essential hypertension

The antihypertensive efficacy and safety of doxazosin, a selective α₁-inhibitor, were assessed in 33 severely hypertensive patients. The study involved three phases: a 1-day baseline period, a 32-day period in which patients received doxazosin, 1 to 16 mg, once daily, and a 4-week maintenance period. All patients were considered therapy successes (sitting diastolic blood pressure either ≤90 mm Hg or ≥10 mm Hg reduction) at a mean daily dose of 8.1 mg. Twenty-seven patients (82%) achieved good blood pressure control (sitting diastolic blood pressure ≤90 mm Hg) at a mean dose of 6.7 mg once daily. By the final treatment visit, mean systolic/diastolic blood pressures in the sitting and supine positions were significantly reduced by $\text{40}\text{29}$ and $\text{37}\text{28}\text{mm Hg}$ from a mean baseline of $\text{180}\text{121}$ and $\text{181}\text{121}\text{mm Hg}$ to final visit values of $\text{140}\text{91}$ and $\text{144}\text{92}\text{mm Hg}$, respectively (p < 0.05). Eleven patients experienced one or more side effects that were mild or moderate and disappeared or were tolerated with continued therapy. During the study no abnormal laboratory test findings were identified by the investigators. The investigators' global assessment of the efficacy and toleration of once-daily doxazosin therapy was excellent or good for 31 (94%) patients and fair for the remaining two patients.     

Doxazosin in the treatment of patients with mild or moderate hypertension and mild or moderate renal insufficiency

The antihypertensive efficacy and safety of doxazosin, a selective α₁-inhibitor, were assessed in 23 hypertensive patients with renal insufficiency. The study involved three phases: (1) a 2-week baseline period, (2) a 10-week period during which patients received doxazosin, 1 to 16 mg, once daily, and (3) a 4-week maintenance period. After 14 weeks of active treatment, systolic/diastolic blood pressures of efficacy evaluable patients were reduced by $\text{8.9}\text{9.2}$ and $\text{4.6}\text{9.1}\text{mm Hg}$ to final values of $\text{153}\text{90}$ and $\text{149}\text{91}\text{mm Hg}$ in the supine and standing positions, respectively. The mean dose of the efficacy evaluable patients was 9.8 mg/day. Eleven patients experienced one or more side effects, most of which were mild or moderate and disappeared or were tolerated with continued therapy. No clinically significant laboratory changes were apparent, and no trends were observed with regard to organ systems or correlations with dose or duration of treatment. There were no significant differences in serum creatinine levels between baseline and final visits. The overall lipid profile indicated a decrease in total cholesterol with increases in high-density lipoprotein cholesterol and the high-density lipoprotein/total cholesterol ratio. From baseline to final visit there was highly significant reduction of 19% (p < 0.05) in calculated risk scores for coronary heart disease on the basis of the Framingham equation.     

A double-blind comparative study of doxazosin and nitrendipine in patients with mild-to-moderate essential hypertension

The antihypertensive efficacy and safety of doxazosin, a selective α₁-inhibitor, were compared with nitrendipine. Seventy-two hypertensive patients were entered into the 18-week, double-blind parallel group study, which involved three phases: a 4-week baseline period, a 10-week period in which patients received 1 to 8 mg of doxazosin or 10 and 20 mg of nitrendipine once daily, and a 4-week maintenance period. For all patients, the mean final daily doses were 2.5 mg for doxazosin and 13.9 mg for nitrendipine. In efficacy evaluable patients the percentages of therapy successes (standing diastolic blood pressure ≤90 mm Hg with ≥5 mm Hg reduction or ≥10 mm Hg decrease) were comparable for doxazosin (94%) and nitrendipine (91%), as was the proportion in whom blood pressure was “normalized” (standing diastolic blood pressure ≤90 mm Hg). 91% and 85, respectively. Blood pressures (diastolic and systolic in supine and standing positions) were significantly reduced (p < 0.05) at all visits in both treatment groups. Ten patients (28%) in each treatment group experienced at least one adverse event. No clinically significant laboratory changes were apparent in either the doxazosin or nitrendipine groups, and no trends were observed with regard to organ systems or correlations with dose or duration of treatments. The investigators' global assessment of efficacy was rated excellent or good for all doxazosin-treated patients and excellent or good for 32 and fair for four in the nitrendipine group. The investigators' global assessment of patient toleration of doxazosin was excellent or good for 34 patients and poor for two. Toleration of nitrendipine was excellent or good in 33 patients and fair in three. Lipid parameters did not differ significantly between groups. From baselline to final visit there were highly significant reductions (p < 0.001) in the calculated coronary heart disease risk scores on the basis of the Framingham equation, for both treatment groups.     

A comparison of doxazosin and enalapril in the treatment of mild and moderate essential hypertension

The antihypertensive efficacy and safety of doxazosin, a selective α₁-adrenoceptor antagonist, were compared with that of the angiotensin-converting enzyme inhibitor enalapril in an 18-week double-blind, parallel-group trial. Sixty-seven hypertensive patients entered the three-phase study, which involved a 4-week placebo washout period, a 10-week titration period with doxazosin, 1 to 16 mg, or enalapril, 10 to 40 mg once daily followed by a 4-week maintenance period. The target response was a standing diastolic blood pressure ≤90 mm Hg. In the 62 efficacy evaluable patients the mean final daily dose of doxazosin was 5.6 mg and 25.5 mg for enalapril. The percentages of therapeutic successes were 74% in the doxazosin- and 81% in the enalapril-treated groups; the proportions in whom standing diastolic blood pressure ≤90 mm Hg were 55% and 61%, respectively. Both sitting and standing blood pressures were significantly reduced at all visits during the 14-week treatment period in both groups. Twelve patients receiving doxazosin reported 14 adverse events and nine patients administered enalapril reported 19 adverse events; therapy was stopped in three patients in each group because of side effects. The overall assessment of efficacy was excellent or good for 71% of the doxazosin-treated and 67% of the enalapril-treated patients, respectively. Toleration of therapy was excellent or good for 91% of the doxazosin-treated and 88% of the enalapril-treated patients, raspectively. No clinically significant changes were observed in the serum lipids, plasma blochemistry, or hematologic profiles. The results of this study indicate that doxazosin and enalapril have comparable antihypertensive efficacy and possess similar primary prevention potential.     

Comparison of the effects of doxazosin and atenolol on blood pressure and blood lipids: A one-year,double-blind study in 228 hypertensive patients

The efficacy and toleration of doxazosin and atenolol were compared over a 52-week period in a double-blind, multicenter study of 228 patients with mild-to-moderate hypertension. Over the treatment period, both drugs significantly reduced blood pressure, and there were no clinically or statistically significant differences between treatment groups for reductions in standing systolic and diastolic blood pressures or in sitting diastolic blood pressure. However, atenolol treatment caused significantly greater reductions in sitting systolic blood pressure and heart rate. Neither drug significantly affected total serum cholesterol concentrations. Doxazosin treatment lowered serum triglycerides, whereas atenolol treatment produced an increase in serum triglycerides (p < 0.001, week 30; p < 0.01, week 50, between treatment groups). Increases in high-density lipoprotein cholesterol and high-density lipoprotein to total cholesterol ratio were obtained with doxazosin treatment, whereas atenolol treatment decreased these lipid fractions (p < 0.0001, weeks 30 and 50, between treatment groups). Using the Framingham equation, it was calculated that at week 50 the risk of developing coronary heart disease was reduced by 22% for the group taking doxazosin (p < 0.001 vs baseline) and by 4% (not significant) for patients taking atenolol (p = 0.01, between treatment groups). It is concluded that doxazosin is a well-tolerated and effective antihypertensive drug with a favorable effect on blood lipids. Doxazosin provides an attractive, new alternative first-line drug for the treatment of mild-to-moderate hypertension.     

Doxazosin GITS versus standard doxazosin in mild to moderate hypertension

BACKGROUND: The selective alpha 1-adrenoceptor antagonist doxazosin in both standard formulation and gastrointestinal therapeutic system (GITS) controlled-release formulation is effective for hypertension without having a negative impact on serum lipids. This study was designed to compare the relative efficacy of these two formulations of doxazosin on clinic and ambulatory blood pressure and serum lipids in patients with mild to moderate hypertension. METHODS: Hypertensive patients aged 18-70 years (n = 335) were evaluated in a multi-center prospective randomized study. Following a 2-week placebo run-in phase, patients were randomized to receive doxazosin 2 or 4 mg, with dose titration, or doxazosin GITS 4 mg, no dose titration, for 9 weeks. RESULTS: Both doxazosin formulations reduced clinic diastolic and systolic blood pressure from baseline (P < 0.0001). Doxazosin GITS and doxazosin 4 mg had similar blood pressure-lowering effects. Doxazosin GITS reduced sitting diastolic and systolic blood pressure compared with doxazosin 2 mg (P < 0.01 for both). A greater proportion of the doxazosin GITS group reached goal blood pressure (< or = 140/90 mm Hg) after 9 weeks compared with the doxazosin 2-mg group. All doses of doxazosin reduced 24-h and daytime (7:00 am to 10:00 pm) ambulatory blood pressure from baseline (all P < 0.01). Doxazosin GITS significantly reduced nighttime (10:00 pm to 7:00 am) ambulatory blood pressure from baseline. A neutral effect on serum lipids was observed with doxazosin. CONCLUSIONS: Doxazosin GITS and doxazosin were effective in reducing clinic and ambulatory blood pressure. The GITS formulation reduced the need for dose titration. Both doxazosin formulations were well tolerated.     

A multicenter trial of doxazosin in West Germany

The antihypertensive efficacy and safety of the new long-acting selective alpha 1 inhibitor doxazosin were assessed in patients seen in clinical practice. A total of 232 mild to moderate hypertensive patients were treated by 35 physicians. After an initial 2-week period (phase 1) during which eligibility to enter the study was determined (diastolic blood pressure [BP] of 95 to 114 mm Hg), all patients received doxazosin 1 to 8 mg once daily for 8 weeks (phase 2). Patients were then maintained for another 4 weeks on the dosage necessary to control diastolic BP to less than or equal to 90 mm Hg (phase 3). Efficacy and toleration of doxazosin therapy during the study period were good; 81% of evaluable patients (n = 180) achieved BP control with a once-daily mean dosage of 3.3 mg. At the end of phase 2 BPs were reduced by (systolic/diastolic) 23.8/17.3 (sitting) and 23.7/17.1 mm Hg (standing). Side effects were generally mild to moderate and either were tolerated or disappeared with continued therapy; 7 patients withdrew from the study because of intolerable side effects. Overall results demonstrated that doxazosin is suitable for treatment of mild to moderate hypertension and can be administered on a once-daily basis, which enhances compliance.     

The addition of doxazosin to the therapeutic regimen of hypertensive patients inadequately controlled with other antihypertensive medications: a randomized,placebo-controlled study

This randomized, double-blind, placebo-controlled study evaluated the use of doxazosin as an add-on therapy for inadequately controlled hypertension. Patients with a sitting diastolic blood pressure (BP) of 95 to 115 mm Hg received either doxazosin (n = 38) or placebo (n = 32) in addition to one or two baseline antihypertensive medications. After an upward titration period, patients were maintained on a fixed dosage of doxazosin (1 to 16 mg/day) or matching placebo for 4 weeks. Doxazosin add-on therapy led to improvements, compared with placebo, in sitting systolic BP (adjusted mean change = −20.9 v −8.5 mm Hg, P = .001), sitting diastolic BP (−13.0 v −8.1 mm Hg, P = .026), and standing systolic BP (−22.0 v −11.5 mm Hg, P = .011). Baseline antihypertensive therapy was gradually tapered or discontinued in patients who achieved a target reduction in BP (sitting diastolic BP of < 90 mm Hg in addition to a minimum improvement of 10 mm Hg in sitting diastolic BP over baseline) with add-on therapy (55% [n = 21] with doxazosin, 31% [n = 10] with placebo). Twelve patients in the doxazosin group maintained the target reduction in BP after complete withdrawal of their baseline antihypertensive therapy, compared with none in the placebo group. A small but statistically significant positive effect on the lipid profile was seen in the doxazosin group during add-on therapy. Doxazosin treatment was well tolerated, with an adverse event profile similar to that of placebo. These findings demonstrate that doxazosin add-on therapy is an effective, well-tolerated treatment strategy for patients with inadequately controlled hypertension.     

Doxazosin GITS compared with doxazosin standard and placebo in patients with mild hypertension

Doxazosin, an effective treatment for mild-to-moderate hypertension and benign prostatic hyperplasia, in its standard formulation requires a multiple-step titration regimen to minimize the potential for first-dose effects. A new controlled-release gastrointestinal therapeutic system (GITS) formulation of doxazosin was developed to enhance the pharmacokinetic profile, significantly reducing serum peak-to-trough ratios, thereby minimizing the need for titration. We assessed the efficacy and tolerability of doxazosin GITS compared with doxazosin standard and placebo in a prospective, randomized, double-blind, parallel-group, dose-titration, multicenter study of 392 patients with mild hypertension (blood pressure [BP] < or = 180/95-105 mmHg). Patients were randomized to doxazosin GITS, doxazosin standard, or placebo in 2:2:1 manner. The primary outcome measure was the proportion of patients in the per-protocol analysis (PPA) who achieved goal BP response (sitting BP < or = 90 mmg or 10 mmHg decrease from baseline at 24 h postdose at the final evaluable visit). Goal BP response in the intention-to-treat (ITT) population and prespecified BP and/or heart rate changes in the PPA and/or ITT population were also analyzed. Tolerability was assessed throughout the study. Doxazosin GITS and doxazosin standard produced comparable goal BP responses superior to that of placebo, with 92 of 156 patients (59.0%) on doxazosin GITS and 86 of 152 patients (56.6%) on doxazosin standard in the PPA population achieving goal BP response 24 hours postdose on the final visit, compared with 25 of 70 patients (35.7%) on placebo. Both active treatments produced mean significant BP reductions compared with baseline and placebo (p < 0.001). The most commonly reported side effects were headache, dizziness, and asthenia. No syncope was reported in the doxazosin GITS group; two cases were observed in the doxazosin standard group and one case in the placebo group. Doxazosin GITS was well tolerated and as effective as doxazosin standard in patients with mild hypertension, producing well-tolerated, comparable BP reductions with minimal need for titration. Both active treatments were clinically and statistically superior to placebo.     

Prediction of sustained antihypertensive efficacy of chronic captopril therapy: Relationships to immediate blood pressure response and control plasma renin activity

The blood pressure (BP) lowering effect of the orally active angiotensin converting enzyme inhibitor, captopril (SQ 14225), was studied in 59 hypertensive patients maintained on a constant sodium intake. Within 2 hours of the first dose of captopril BP fell from $\text{171}\text{107}$ to a maximum low of $\text{142}\text{92}\text{mm Hg}$ (p < 0.001), and after 4 to 8 days of treatment BP averaged $\text{145}\text{94}\text{mm Hg}$ (p < 0.001). The magnitude of BP drop induced by captopril was significantly correlated to baseline plasma renin activity (PRA) both during the acute phase (r = ?0.38, p < 0.01) and after the 4 to 8-day interval (r = ?0.33, p < 0.01). Because of considerable scatter in individual data, renin profiling was not precisely predictive of the immediate or delayed BP response of separate patients. However, the BP levels achieved following the initial dose of captopril were closely correlated to BP measured after 4 to 8 days of therapy, and appeared to have greater predictive value than control PRA of the long-term efficacy of chronic captopril therapy despite marked BP changes occurring in some patients during the intermediate period. Because of these intermediate BP changes, addition of a diuretic to enhance antihypertensive effectiveness of angiotensin blockade should be restrained for several days after initiation of captopril therapy.     

Controlled-release doxazosin as combination therapy in hypertension: the GATES study

Doxazosin gastrointestinal therapeutic system (GITS) or placebo was added to the antihypertensive therapy of uncontrolled hypertensive patients in a prospective, randomized, double-blind trial. Patients received doxazosin GITS 4 mg/d (n=89) or placebo (n=86) for 6 weeks in addition to entry antihypertensive medication. Doxazosin GITS was increased to 8 mg/d after 2 or 4 weeks if patients did not respond (sitting blood pressure <140/90 mm Hg and 10/10-mm Hg decrease from baseline). Reductions from baseline in sitting and standing blood pressures were greater with doxazosin GITS than placebo at all time points (p相似文献   

Effects of diltiazem-induced calcium blockade upon exercise capacity in effort angina due to chronic coronary artery disease

Few data are available regarding the effects of calcium blockade upon exercise tolerance in patients with stable effort angina due to coronary artery disease (CAD). Therefore we compared the effects of the calcium blocking agent, diltiazem (D), to placebo (P) in 12 patients with chronic effort angina and catheterization documented fixed CAD. The 8-week total protocol consisted of a 1-week baseline period followed by the double-blind randomized crossover alternate 1-week administration of P and D in doses of 120, 180, and 240 mg. Maximal exercise tests (MET) were performed at the end of each 1-week period, while rest radionuclide ventriculography (RVG) was obtained during 240 mg D and corresponding crossover P. Resting heart rate decreased from baseline and initial P at D doses of 60 and 240 mg, but not from P during crossover period. No changes were observed at any dose of D either at rest or during MET in systolic blood pressure or rate · pressure double product. D at 240 mg, but not lower doses, increased MET duration (437 vs 490 seconds, p < 0.01) and time to angina (383 vs 441 seconds, p < 0.01). Ejection fraction by RVG was greater with D than P (0.54 vs 0.50, p < 0.05). Thus these data indicate that calcium blockade with diltiazem provides antianginal efficacy by reducing myocardial oxygen demand, and increases exercise tolerance without depression of myocardial performance in effort angina patients with fixed chronic CAD.     

Efficacy and tolerability of tasosartan,a novel angiotensin II receptor blocker: Results from a 10-week,double-blind,placebo-controlled,dose-titration study

Background Angiotensin II receptor antagonists are selective blockers of the renin-angiotensin system and represent an alternative to angiotensin-converting enzyme inhibitors in the treatment of hypertension. Tasosartan is a newly developed nonpeptide AT₁ receptor blocker. Methods and Results In this double-blind, randomized, dose-titration, multicenter trial, tasosartan and placebo were compared in patients with stage I and stage II hypertension. A prequalification washout period (antihypertensive medications withdrawn) and a 2-week qualification period (patients received single-blind placebo) preceded a 10-week, double-blind treatment period. The patients received either 50 mg tasosartan (n = 132) or placebo (n = 130) once per day and were evaluated once per week. The dose of tasosartan was increased at 3-week intervals to 100 mg and then to 200 mg if the mean sitting diastolic blood pressure (SiDBP) exceeded 90 mm Hg. Compared with placebo, tasosartan produced significantly (P < .05) greater reductions in both SiDBP (–9.4 ± 0.7 vs –2.0 ± 0.7 mm Hg) and sitting systolic blood pressure (SBP) (–12.2 ± 1.2 vs +0.4 ± 1.2 mm Hg). The rate of response (SiDBP ≤90 mm Hg or a decrease from baseline of ≥10 mm Hg) was significantly (P < .05) greater in the tasosartan group than in the placebo group (55% vs 19%). The mean 24-hour blood pressure reduction with tasosartan was –12.6 ± 0.9/–8.1 ± 0.6, significantly greater (P < .05) than the reduction with placebo (+0.6 ± 0.9/+0.5 ± 0.6 mm Hg). The trough-to-peak ratio (determined from the ambulatory data) was 0.66 for DBP and 0.72 for SBP for the tasosartan treatment group, demonstrating 24-hour efficacy with once-a-day administration. The safety profile of tasosartan was similar to placebo. Conclusions These results demonstrate that tasosartan at 50 to 200 mg given once a day over a titration period of 10 weeks was effective and safe in the treatment of essential hypertension. (Am Heart J 1999;137:118-25.)     

Exercise-induced increase in diastolic pressure: indicator of severe coronary artery disease.

The diastolic blood pressure response to treadmill exercise testing was analyzed in 281 patients. Diastolic blood pressure was measured at rest, during each stage of exercise, immediately on recovery, and 1, 3 and 5 minutes into the recovery period. No change or a decrease in diastolic blood pressure was considered a normal response. An increase in diastolic blood pressure of more than 15 mm Hg on at least two determinations, comparing values at rest with those on exercise, was considered an abnormal response. Only patients showing a normal increase in systolic blood pressure during exercise were included. Two hundred and nine patients had a normal and 72 patients an abnormal diastolic blood pressure response. In a subgroup of 41 patients who underwent coronary arteriography, 50 percent of patients with a normal diastolic pressure response had normal coronary arteries, compared with 17 percent of those with an abnormal response (P < 0.03). Only 11 percent of patients with a normal diastolic pressure response had triple vessel or left main coronary artery disease, compared with 44 percent of patients with an abnormal response (P < 0.03). Blood pressure at rest ($\text{132}\text{84}\text{mm Hg}$) and peak heart rate (mean 155 beats/min) were similar in each group. There was no significant difference between exercise-induced ischemic S-T segment changes in the two groups (13 percent for patients with a normal diastolic pressure response versus 15 percent for those with an abnormal diastolic pressure response). In conclusion, an abnormal diastolic pressure response to treadmill testing may be a good indicator of coronary artery disease even in the absence of S-T segment changes.     

Comparison of the Combination of Enalapril and a Very Low Dose of Hydrochlorothiazide with Atenolol in Patients With Mild-to- Moderate Hypertension

The blood pressure lowering effect and tolerability of the angiotensin-converting enzyme inhibitor enalapril combined with a very low dose of hydrochlorothiazide (HCTZ) were compared with the selective betareceptor blocker atenolol in patients with mild-to-moderate hypertension. Three hundred seventy-four patients were randomized into a triple-blind, parallel, active-controlled 12-week study period comparing enalapril/HCTZ (20/6 mg) with atenolol (50 mg) after a 4-week placebo baseline period. Blood pressure (BP), clinical and laboratory safety, and metabolic laboratory variables were assessed. Enalapril/HCTZ as well as atenolol reduced both sitting and standing diastolic and systolic BP (P < .001), but enalapril/HCTZ had a more pronounced effect than atenolol on sitting systolic BP (P = .019); there was a trend toward more patients achieving target diastolic BP (<90 mm Hg, P = .053). No clinically important differences in safety and tolerability were observed.     

Barnidipine, a Novel Calcium Antagonist for Once-Daily Treatment of Hypertension: A Multicenter, Double-Blind, Placebo-Controlled, Dose-Ranging Study

The antihypertensive effects and tolerance of once-daily barnidipine, a novel dihydropyridine calcium antagonist, were evaluated. A total of 190 patients with a sitting diastolic blood pressure (DBP) of 95–114 mmHg were investigated in this multicenter, double-blind, placebo-controlled, dose-ranging study. After a 4-week single-blind placeborun-in period, patients were randomized to placebo or barnidipine (10 mg, 20 mg, or 30 mg modified release capsules) once daily for 6 weeks. Nonresponders (sitting DBP ≥90 mmHg and a decrease of <10 mmHg) were treated for an additional 6 weeks with a dose increase of 10 mg. At each clinic visit, sitting and standing blood pressure and heart rate were measured approximately 24 hours after the last dose of study drug was taken. Compared with placebo, barnidipine lowered blood pressure, with a trend toward a dose–response relationship over the dose range 10–30 mg. A dose increment of 10 mg in nonresponders resulted in additional reductions in blood pressure. At the end of the active treatment period, the responder rates were 41% and 57% for 10 mg and 20 mg barnidipine, respectively. Heart rate in both sitting and standing positions was not affected by barnidipine. Treatment with barnidipine was well tolerated, and the incidence of adverse events was dose related and consistent with vasodilatation. In conclusion, barnidipine (10–30 mg) administered once daily is well tolerated and reduces blood pressure inpatients with mild to moderate hypertension. On behalf of the Dutch Barnidipine Multicenter Study Group On behalf of the Dutch Barnidipine Multicenter Study Group This revised version was published online in July 2006 with corrections to the Cover Date.