Comparison of hydrochlorothiazide and sustained-release diltiazem for mild-to-moderate systemic hypertension

The safety and efficacy of sustained-release diltiazem, 120 to 180 mg twice daily, was compared with those of hydrochlorothiazide, 25 to 50 mg twice daily, in 207 patients with mild-to-moderate hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg) using a baseline, placebo, parallel-design study protocol. All patients received placebo for 2 to 4 weeks, followed by either study drug during the double-blind phase, titrated over 8 weeks to achieve a goal of supine diastolic BP reduction of at least 10 mm Hg and/or a diastolic BP of less than 90 mm Hg. Patients not achieving the treatment goal with either drug alone received the other drug in combination. Both drugs produced significant decreases in supine and upright BP throughout the 26-week study. The magnitude of decrease in mean supine diastolic BP was similar for both drugs as monotherapy at week 14 (-11.4 and -12.1 mm Hg, respectively). Hydrochlorothiazide produced significantly greater reductions at week 14 in mean supine systolic BP than sustained-release diltiazem (-19.5 and -12.7 mm Hg, respectively). The difference in mean supine diastolic BP reduction with the 2 drugs diminished when hydrochlorothiazide (50 mg/day) was compared with sustained-release diltiazem. The BP effects were sustained for 6 months with both drugs. The 2 drugs appeared to lower BP more in patients older than 60 years and more in black than in white patients. The combination of the 2 drugs decreased supine diastolic BP to goal levels in about 56% of the patients not achieving goal with either drug alone. Adverse effects were minimal with either drug alone and in combination, except for hypokalemia, which increased with thiazide alone and in combination.     

Comparison of diltiazem and hydrochlorothiazide for treatment of patients 60 years of age or older with systemic hypertension

This randomized, double-blind, parallel design trial compared the efficacy and safety of monotherapy with either sustained-release diltiazem or hydrochlorothiazide in 61 men greater than or equal to 60 years of age with a diastolic blood pressure (BP) between 94 and 104 mm Hg. BP, heart rate, laboratory blood and urine tests, left ventricular wall thickness and mass index (as estimated by M-mode echocardiography) and rate and type of ventricular premature complexes (via ambulatory electrocardiographic monitoring) were determined before, during and after drug treatment. Both drugs produced highly significant (p less than 0.001) decreases in supine and upright systolic and diastolic BP. The mean dosages of diltiazem and hydrochlorothiazide used were 260 and 52 mg/day, respectively; at these dosages, 80% of diltiazem-treated versus 71% of hydrochlorothiazide-treated patients achieved goal reduction in BP (supine diastolic BP reduction of greater than 10 mm Hg and to less than 90 mm Hg). Both drugs were well tolerated, although hydrochlorothiazide therapy was associated with multiple biochemical abnormalities not seen with diltiazem. Neither drug affected left ventricular mass index or the rate of ventricular ectopic activity. Diltiazem and hydrochlorothiazide are both effective and safe agents when used as monotherapy in older patients with systemic hypertension unaccompanied by other clinically significant cardiovascular disease.     

Diltiazem and captopril alone or in combination for treatment of mild to moderate systemic hypertension

The efficacy and safety of sustained-release diltiazem, 60 to 180 mg twice daily, was compared with that of captopril, 25 to 75 mg twice daily, alone and in combination, in 132 patients with mild to moderate essential hypertension (supine diastolic blood pressure [BP] 95 to 114 mm Hg). All patients received placebo for 4 to 6 weeks, followed by randomization to diltiazem or captopril during the double-blind monotherapy phase. Either study drug was titrated over 6 weeks to achieve a goal supine diastolic BP reduction of at least 10 mm Hg and a diastolic BP of less than 90 mm Hg. Patients achieving the goal BP reduction were maintained on monotherapy for an additional 8 weeks. Patients not achieving the treatment goal after 8 weeks with either drug alone received the other drug in combination, titrated to achieve goal BP response. Both drugs lowered BP significantly and, at the doses used, diltiazem had a greater effect on diastolic BP than did captopril. The mean changes from baseline at week 8 were -10.6 and -7.3 mm Hg, respectively, (p = 0.01). Goal BP was achieved in 38% of patients taking diltiazem monotherapy and in 34% of patients taking captopril monotherapy. There were no significant differences between diltiazem and captopril in diastolic or systolic BP reductions by race or age. The addition of alternate therapy for non-goal achievers at week 8 resulted in significant reductions in diastolic and systolic BP by week 16.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of hydrochlorothiazide and diltiazem on reflex vasoconstriction in hypertension

The purpose of our study was to determine the effects of treatment with hydrochlorothiazide (n = 10) or diltiazem (n = 8) on reflex humoral, hemodynamic, and vascular responses to graded lower body negative pressure in subjects with mild to moderate hypertension (supine diastolic pressure, 95-114 mm Hg). All subjects received placebo for 2 to 4 weeks followed by either hydrochlorothiazide (25-50 mg b.i.d.) or diltiazem (120-180 mg b.i.d.) to achieve a reduction in supine diastolic pressure of 10 mm Hg or more and a final pressure below 90 mm Hg. Mean arterial pressure, forearm vascular resistance, plasma norepinephrine, and renin responses to graded lower body negative pressure (-10, -20, -40 mm Hg) and head-up tilt were examined before and after 12 weeks of treatment with either drug. Pretreatment basal values of mean arterial pressure (114 +/- 2 vs 117 +/- 2 mm Hg), forearm vascular resistance (29 +/- 3 vs 35 +/- 7 units), and plasma renin activity (0.7 +/- 0.2 vs 0.6 +/- 0.2 ng angiotensin I/ml/hr) were not significantly different between groups. There were no significant differences in basal plasma norepinephrine or in the increases of norepinephrine in response to lower body negative pressure before and after treatment in either group. Forearm vascular resistance responses to lower body negative pressure were virtually abolished in the diltiazem-treated group but not in the hydrochlorothiazide-treated group despite similar levels of mean arterial pressure and basal forearm vascular resistance.(ABSTRACT TRUNCATED AT 250 WORDS)     

Isradipine vs propranolol in hydrochlorothiazide-treated hypertensives. A multicenter evaluation

A randomized, parallel, controlled study was conducted to evaluate the safety and efficacy of isradipine, 2.5 to 10 mg orally twice a day, compared with propranolol hydrochloride, 60 to 240 mg orally twice a day, in 78 hypertensives whose supine diastolic blood pressure was greater than 95 mm Hg while receiving 50 mg/d or more of hydrochlorothiazide. Isradipine or propranolol was titrated during a 10-week double-blind phase to achieve a supine diastolic blood pressure below 90 mm Hg while a fixed dose of hydrochlorothiazide was maintained. Supine diastolic blood pressure was reduced by 10 mm Hg in 88% of the isradipine/hydrochlorothiazide-treated and 83% of the propranolol/hydrochlorothiazide-treated groups and to less than 90 mm Hg in 55% of the isradipine/hydrochlorothiazide-treated and 69% of the propranolol/hydrochlorothiazide-treated patients. There was no significant difference in supine blood pressure reduction between either group, but there was a 3-to 4-beats per minute increase in supine heart rate in isradipine-treated patients and an expected 15- to 20-beats per minute decrease in heart rate in propranolol-treated patients. Five of 7 patients in the isradipine-treated group and 8 of 9 patients in the propranolol-treated group discontinued the therapy because of adverse reactions or treatment failure. Using Fisher's Exact Test, we found no significant difference in the relative frequency of individual adverse reactions between groups, although the absolute adverse reaction frequency was significantly higher with isradipine. This study demonstrates the effectiveness and safety of supplemental isradipine in the treatment of hypertension not controlled by hydrochlorothiazide alone.     

Diltiazem and propranolol in mild to moderate essential hypertension as monotherapy or with hydrochlorothiazide

We compared the safety and efficacy of diltiazem and propranolol, and examined demographic factors influencing responses to these agents. One hundred ninety-six patients with supine diastolic blood pressures of 95 to 114 mm Hg were treated with propranolol (80 to 240 mg twice a day) or a sustained-release preparation of diltiazem (60 to 180 mg twice a day) in a double-blind, randomized, parallel group protocol for 6 months. Hydrochlorothiazide was added for patients not achieving the treatment goal. Both agents produced nearly identical and highly significant (p less than 0.001) reductions in supine blood pressure. There were no significant differences at the end of the optional combination therapy phase, although additional reduction with hydrochlorothiazide was slightly greater in the propranolol group. Blood pressure responses in relation to age, gender, race, and smoking history showed that diltiazem produced greater changes in older subjects and women, whereas propranolol was less effective in blacks. However, these differences were not critical.     

Comparison of diltiazem and nifedipine for both angina pectoris and systemic hypertension

In a randomized, double-blind, placebo-controlled crossover trial, diltiazem and nifedipine were compared in 10 patients with stable angina pectoris and mild to moderate hypertension (supine diastolic blood pressure greater than or equal to 90 mm Hg). Patients received placebo for 2 weeks, then increasing doses of diltiazem (90 to 360 mg/day) or nifedipine (30 to 120 mg/day) in 3 daily divided doses over 2 weeks, followed by 1 week of therapy at the maximal dose, a 1-week placebo "washout," then crossover to the other drug. Heart rate and blood pressure at rest and during exercise, anginal frequency, nitroglycerin consumption and treadmill exercise tolerance were assessed. Compared with placebo, anginal frequency and nitroglycerin consumption were reduced with both diltiazem and nifedipine (p less than 0.01) and exercise tolerance was increased with both drugs (p less than 0.01). Standing blood pressure at rest was reduced by diltiazem and nifedipine (146.6 +/- 11.4/97.7 +/- 5.3 mm Hg at placebo, baseline reduced to 129.6 +/- 15.2/79.5 +/- 13.7 mm Hg with diltiazem, and to 122.2 +/- 9.9/82.0 +/- 7.1 with nifedipine, p less than 0.01 for both). Compared with placebo, diltiazem and nifedipine also reduced exercise diastolic blood pressure (p less than 0.01), but not systolic blood pressure. Diltiazem lowered the heart rate at rest from 88.5 +/- 14.4 beats/min at placebo baseline to 79.7 +/- 17.9 beats/min (p less than 0.01); the heart rate with diltiazem was 11 beats/min lower than that with nifedipine (p less than 0.05). Both diltiazem and nifedipine had similar effects on the heart rate-blood pressure product at rest and during exercise.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive therapy with diltiazem and comparison with hydrochlorothiazide

Fourteen hypertensive patients with a mean sitting systolic and diastolic blood pressure (BP) of 153 +/- 16/100 +/- 4 mm Hg were treated successively with hydrochlorothiazide and diltiazem for 8 weeks each. The BP response and changes in heart rate, left ventricular size and function, and plasma catecholamine concentrations and renin activity were monitored. The 2 drugs had comparable antihypertensive effects, with mean decreases of 14, 9 and 11 mm Hg for the sitting, standing and supine diastolic BP, respectively, during hydrochlorothiazide treatment and mean decreases of 16, 18 and 12 mm Hg during diltiazem treatment. Heart rate was unchanged, although plasma norepinephrine concentrations increased significantly during diltiazem treatment. Plasma renin activity increased slightly, from 0.6 to 0.9 ng/ml/hour during diltiazem treatment, but the change was not significant (p less than 0.10). Left ventricular ejection fraction and end-diastolic volume were not affected by either agent. In conclusion, diltiazem is an effective antihypertensive agent, which because of its benign side effect profile, may be useful as a step 1 agent.     

Comparison of acebutolol with and without hydrochlorothiazide versus carvedilol with and without hydrochlorothiazide in black patients with mild to moderate systemic hypertension.

In the present study, we assessed the antihypertensive efficacy of acebutolol 200 mg versus carvedilol 25 mg once daily, given as monotherapy for 3 months to 40 black patients (20 patients in each group, mean age 53+/-10 years, 24 women) with mean blood pressure (BP) during the day >90 and <110 mm Hg. Patients in whom blood pressure could not be controlled took medication, which was increased at 3-month intervals as follows: step 2, acebutolol 200 mg or carvedilol 25 mg plus hydrochlorothiazide 12.5 mg once daily; step 3, acebutolol 400 mg or carvedilol 50 mg plus hydrochlorothiazide 25 mg once daily. Overall, significant but modest BP reduction was achieved with both beta blockers at 3 months. In the acebutolol group, 24-hour BP decreased from 142+/-15/94+/-7 mm Hg to 138+/-16/89+/-8 mm Hg (p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 145+/-15/98+/-5 mm Hg to 140+/-14/93+/-7 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs. baseline). In the carvedilol group, 24-hour BP decreased from 145+/-11/93+/-6 to 138+/-16/87+/-9 mm Hg (p<0.05 for systolic BP and p<0.005 for diastolic BP at 3 months vs baseline). Mean day BP decreased from 149+/-10/99+/-5 to 141+/-16/91+/-87 mm Hg (p<0.05 for systolic BP and p<0.0005 for diastolic BP at 3 months vs baseline). At 12 months, most patients required combination therapy to achieve BP control. The control (mean day diastolic BP <90 mm Hg) and response (mean day diastolic BP decrease > or =10 mm Hg) rates at 12 months were 59% and 82% in the acebutolol and 78% and 78% in the carvedilol groups, respectively. In conclusion, acebutolol or carvedilol in combination with hydrochlorothiazide, rather than acebutolol or carvedilol alone, should be considered as first-line antihypertensive therapy in black patients with mild to moderate hypertension.     

Antihypertensive effect of diltiazem in a slow-release formulation for mild to moderate essential hypertension

The antihypertensive efficacy and frequency of adverse reactions following administration of diltiazem in a new slow-release formulation were compared with placebo in 34 patients with mild to moderate essential hypertension in a randomized, double-blind, crossover study. After 6 weeks of treatment with diltiazem (240 or 360 mg/day), average supine blood pressure (BP) decreased from 165 +/- 21/101 +/- 5 mm Hg at baseline to 152 +/- 16/93 +/- 4 mm Hg compared with 160 +/- 19/100 +/- 7 mm Hg with placebo (p less than 0.01/p less than 0.001). Standing BP decreased from 162 +/- 20/107 +/- 6 mm Hg at baseline to 150 +/- 14/101 +/- 5 mm Hg compared to 159 +/- 18/107 +/- 8 mm Hg with placebo (p less than 0.01/p less than 0.001). The supine heart rate after diltiazem was 65 +/- 7 beats/min and after placebo 69 +/- 9 beats/min (p less than 0.01). There were no hematologic side effects. Only minor differences between diltiazem and placebo were observed in some of the biochemical laboratory values. Four patients were withdrawn due to side effects during treatment with diltiazem and 2 with placebo. Diltiazem in a slow-release formulation given twice a day lowered blood pressure significantly as monotherapy in patients with mild to moderate hypertension and was well tolerated.     

Pulse pressure changes with six classes of antihypertensive agents in a randomized, controlled trial

Pulse pressure has been more strongly associated with cardiovascular outcomes, especially myocardial infarction and heart failure, than has systolic, diastolic, or mean arterial pressure in a variety of populations. Little is known, however, of the comparative effects of various classes of antihypertensive agents on pulse pressure. In retrospective analyses of the Veterans Affairs Single-Drug Therapy for Hypertension Study, we compared changes in pulse pressure with 6 classes of antihypertensive agents: 1292 men with diastolic blood pressure of 95 to 109 mm Hg on placebo were randomized to receive hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem, prazosin, or placebo. Drug doses were titrated to achieve a goal diastolic blood pressure of <90 mm Hg during a 4- to 8-week medication titration phase. Pulse pressure change (placebo subtracted) was assessed from baseline to the end of the 3-month titration and 1-year maintenance. Mean baseline systolic, diastolic, and pulse pressures were 152, 99, and 53 mm Hg, respectively. Reductions in pulse pressure during titration were greater (P<0.001) with clonidine (6.7 mm Hg) and hydrochlorothiazide (6.2 mm Hg) than with captopril (2.5 mm Hg), diltiazem (1.6 mm Hg), and atenolol (1.4 mm Hg); reduction with prazosin (3.9 mm Hg) was similar to all but clonidine. After 1 year, pulse pressure was reduced significantly more (P<0.001) with hydrochlorothiazide (8.6 mm Hg) than with captopril and atenolol (4.1 mm Hg with both); clonidine (6.3 mm Hg), diltiazem (5.5 mm Hg), and prazosin (5.0 mm Hg) were intermediate. These data show that classes of antihypertensive agents differ in their ability to reduce pulse pressure. Whether these differences affect rates of cardiovascular events remains to be determined.     

Acute and chronic studies of diltiazem in elderly versus young hypertensive patients

The pharmacodynamics, disposition and hormonal responses to acute intravenous and chronic oral diltiazem treatment were compared in young and elderly hypertensive patients. In elderly patients, supine diastolic blood pressure decreased significantly during the first week of treatment (baseline mean +/- standard error of the mean, 100 +/- 1 to 93 +/- 2 mm Hg) and decreased further during the study to 86 +/- 2 mm Hg at the end of the study. Diastolic blood pressure of the young patients decreased significantly by the third week of treatment (from 104 +/- 2 to 97 +/- 3 mm Hg) and decreased further during the study to 94 +/- 2 mm Hg at the end of the study. Baseline supine systolic blood pressure was greater in elderly than in young patients (167 +/- 5 vs 144 +/- 3 mm Hg; p less than 0.01) and was significantly reduced in the elderly by the fourth week (167 +/- 5 to 154 +/- 3 mm Hg; p less than 0.003), with a significantly reduction sustained throughout the 14-week period. Young patients had little change in systolic blood pressure. Supine heart rate tended to decrease in both groups during the 14-week period. Acute intravenous diltiazem pharmacokinetics determined at the beginning of the study showed that total diltiazem clearance was similar in elderly (13.3 +/- 1.0 ml/min/kg) and young (13.7 +/- 1.9 ml/min/kg) patients as was volume of distribution (4.2 +/- 0.3 vs 4.3 +/- 0.6 liters/kg) and elimination half-life (3.78 +/- 0.19 vs 3.69 +/- 0.23 hours).(ABSTRACT TRUNCATED AT 250 WORDS)     

Calcium entry blockers for systemic hypertension

Calcium entry blockers appear to be effective antihypertensive agents in both young and older patients. Studies comparing diltiazem and placebo, diltiazem and propranolol, and diltiazem and hydrochlorothiazide indicate that this calcium entry blocker is more effective than placebo, equally effective as the beta-adrenergic inhibitors at least in short-term studies, but not as effective in lowering systolic blood pressure (BP) when compared with hydrochlorothiazide (diastolic BP -11.5 mm Hg with diltiazem vs -12.2 mm Hg with hydrochlorothiazide; systolic BP -12.2 mm Hg with diltiazem vs -20.0 mm Hg with hydrochlorothiazide). Combination therapy with diltiazem and hydrochlorothiazide proved effective in a high percentage of mono-therapy nonresponders. The most common adverse reactions to diltiazem included headaches, dizziness and edema. The exact place of calcium entry blockers in therapy as initial or step-2 therapy with a diuretic in hypertension must be determined by additional long-term experience in large numbers of patients.     

Effects of hydrochlorothiazide, diltiazem and enalapril on mononuclear cell sodium and magnesium levels in systemic hypertension

Sixteen patients (mean age 68 years) with mild to moderate hypertension were treated with either diltiazem or hydrochlorothiazide for 6 weeks, followed by enalapril for a further 6 weeks. A second group of 40 patients (mean age 71 years) was treated with either hydrochlorothiazide or enalapril for 12 weeks; nonresponders received both drugs for 8 weeks. Treatment with hydrochlorothiazide or enalapril resulted in a lowering of systolic and diastolic blood pressures, but diastolic pressure was lower in patients treated with enalapril (89 +/- 2 and 82 +/- 2 mm Hg, respectively; p less than 0.05). Treatment with diltiazem resulted in a decrease in diastolic pressure only. Treatment with hydrochlorothiazide resulted in a 17% decrease in serum potassium (p less than 0.05), which returned to normal when enalapril was substituted. Hydrochlorothiazide also produced a 23% decrease in mononuclear cell sodium content at 4 weeks (p less than 0.01), with a further 15% decrease at 12 weeks (p less than 0.05). Mononuclear cell potassium and magnesium also decreased at 12 weeks by 18 and 16%, respectively (p less than 0.05). All these effects were reversed when enalapril was substituted. A similar pattern of events was seen with diltiazem, which was again reversed with enalapril. Finally, there was no relation between changes in mononuclear cell sodium or other cation content and changes in blood pressure.     

A parallel group randomised comparative study of felodipine and nifedipine in hypertension.

We compared the antihypertensive effects and tolerability of a new calcium channel antagonist felodipine with nifedipine in an open randomised parallel group study in 49 patients with moderate hypertension (diastolic blood pressure 105-120 mm Hg). After two weeks run in period felodipine 5 mg and 10 mg once daily was compared with nifedipine 10 mg tid for an active treatment period of 4 weeks. Twenty three patients (mean age 42 +/- 10 years) received felodipine 5 mg once daily for first 2 weeks and 10 mg once daily for subsequent 2 weeks. Twenty six patients (mean age 45 +/- 9 years) received nifedipine 10 mg tid for 4 weeks. The mean reduction in supine diastolic blood pressure in two groups was 17 +/- 6 mm Hg (nifedipine) and 19 +/- 8 mm Hg (felodipine) (p = NS). The goal diastolic blood pressure of less than or equal to 90 mm Hg was achieved in 31 percent (nifedipine group) and 43.5 percent (felodipine group) of patients (p = NS). Side effects were common with both drugs; however, the tolerability was better with felodipine than with nifedipine. In conclusion felodipine was as effective as nifedipine and had the advantage of once a day dosage.     

Efficacy and safety of sustained-release diltiazem as replacement therapy for beta blockers and diuretics for stable angina pectoris and coexisting essential hypertension: a multicenter trial

To determine if a sustained-release form of the calcium entry blocker diltiazem would be a satisfactory substitute for the combination of beta-adrenergic blocking agent and thiazide diuretic in the treatment of systemic hypertension and angina pectoris, 38 patients were studied in a 4-center trial. Blood pressure and heart rate were measured in the supine position, immediately after and 5 minutes after standing. Modified Bruce protocol treadmill tests were performed to determine the time to onset of 1 mm ST-segment depression, time to onset of chest pain and time to termination of exercise. Diltiazem monotherapy resulted in equivalent blood pressure control in 28 of 38 patients (74%). In the remaining patients, blood pressure control was achieved with resumption of the diuretic. Blood pressure with beta blocker plus diuretic compared with diltiazem were, in the supine position 137 +/- 22/82 +/- 7 (+/- 1 standard deviation) versus 139 +/- 22/82 +/- 8 mm Hg, immediately after standing 131 +/- 20/84 +/- 9 versus 133 +/- 21/82 +/- 10 mm Hg and after standing for 5 minutes 134 +/- 19/85 +/- 8 versus 137 +/- 18/85 +/- 9 mm Hg (difference not significant for each). The heart rate with diltiazem was higher supine (67 +/- 11 versus 60 +/- 11 beats/min), standing (73 +/- 13 versus 64 +/- 14 beats/min) and 5 minutes after standing (73 +/- 14 versus 63 +/- 14 beats/min, p less than 0.01 for each).(ABSTRACT TRUNCATED AT 250 WORDS)     

Treatment of hypertension in the elderly: I. Blood pressure and clinical changes. Results of a Department of Veterans Affairs Cooperative Study

We compared the efficacy and adverse effects of antihypertensive drug regimens in 690 men past age 60 with diastolic blood pressure 90-114 mm Hg and systolic blood pressure less than 240 mm Hg. They received either a low (25-50 mg) or high (50-100 mg) dose of hydrochlorothiazide daily. Of 644 patients who completed the hydrochlorothiazide titration, 375 (58.2%) were responders (diastolic blood pressure less than 90 and less than or equal to 5 mm Hg below baseline) and 92.8% of these completed a 6-month maintenance period. Blood pressure was reduced from 157.6/98.5 mm Hg by 18.3/9.5 mm Hg with low dose hydrochlorothiazide and by 20.4/9.6 mm Hg with high dose hydrochlorothiazide; more patients achieved goal blood pressure with the high dose. Whites and blacks responded equally. Serum potassium less than 3.5 mmol/l occurred in 104 of 321 (32.3%) of the high dose versus 62 of 333 (18.6%) of the low dose hydrochlorothiazide patients. The 269 nonresponders to hydrochlorothiazide were randomly assigned in a double-blind study to receive hydralazine, methyldopa, metoprolol, or reserpine in addition to hydrochlorothiazide; 79.2% responded to the addition of the second drug and 87.3% of these completed a 6-month maintenance phase. Overall, there were no significant efficacy differences among the step 2 regimens. We conclude that the lower dose of hydrochlorothiazide was nearly as effective as the higher dose, and the addition of a second drug was effective and generally well tolerated in elderly patients.     

Effects of diltiazem on hormonal and hemodynamic responses to lower body negative pressure and tilt in patients with mild to moderate systemic hypertension

Mean arterial blood pressure, forearm vascular resistance, plasma norepinephrine, plasma renin activity and aldosterone responses to graded lower body negative pressure and tilt at 80 degrees were examined in 10 men with mild to moderate essential hypertension before and after 12 weeks of diltiazem (240 to 360 mg/day) therapy. Diltiazem therapy lowered basal supine systolic and diastolic blood pressures without affecting basal heart rate. Mean arterial blood pressure and forearm vascular resistance were decreased from 114 +/- 1.5 to 105 +/- 1 mm Hg, p less than 0.01 and from 29.3 +/- 3.5 to 18.9 +/- 2.1 units, p less than 0.01, respectively. Diltiazem therapy had no effect on basal supine levels of norepinephrine, plasma renin activity or aldosterone, nor on the responses of these hormones to lower body negative pressure. Diltiazem did decrease the forearm vascular resistance responses to lower body negative pressure and tilt. Diltiazem abolished an orthostatic increase (10 +/- 0.3 mm Hg) in mean arterial blood pressure and this was associated with a greater plasma norepinephrine response to tilt. These results suggest that diltiazem decreases vascular resistance through a reduction in the postjunctional effects of norepinephrine on vascular smooth muscle.     

Intravenous nicardipine for the treatment of severe hypertension

PURPOSE: Severe hypertension responds to treatment with nifedipine given orally or sublingually. Nicardipine hydrochloride, a water soluble dihydropyridine analogue similar to nifedipine, has less of a negative ionotropic effect and produces less reflex tachycardia than nifedipine. Our purpose was to assess the antihypertensive efficacy and safety of intravenous nicardipine in a group of patients with severe hypertension (defined as a supine diastolic blood pressure of more than 120 mm Hg). PATIENTS AND METHODS: Eighteen patients with severe hypertension received treatment with intravenous nicardipine. Nicardipine titration was performed using doses of 4 to 15 mg/hour to achieve therapeutic goal (diastolic blood pressure 95 mm Hg or less or decrease in diastolic blood pressure of more than 25 mm Hg). After this therapeutic end-point was reached, patients received maintainance therapy with nicardipine for varying lengths of time: one hour (Group I), six hours (Group II), or 24 hours. When blood pressure control was lost, patients in Groups I and II entered a second maintenance period lasting a maximum of 24 hours. Onset and offset of action of nicardipine at various infusion rates and times of infusion were measured. RESULTS: Onset time to achieve therapeutic response was rapid at 15 mg/hour (0.31 +/- 0.13 hours) when compared with lower doses (1.11 +/- 0.36 hours at 4 mg/hour; 0.54 +/- 0.09 hours at 5 mg/hour; 0.52 +/- 0.09 hours at 7 to 7.5 mg/hour). Those who showed a therapeutic response received maintenance infusions with nicardipine for one (n = 7), six (n = 6), or 24 (n = 5) hours. Sustained blood pressure control at a constant rate of nicardipine infusion was seen in all patients during the maintenance period. After discontinuation of nicardipine, the time for offset of action (increase in diastolic blood pressure of 10 mm Hg or more) was independent of duration of infusion. Decreases in both systolic and diastolic pressures correlated well with plasma nicardipine levels. Heart rate increased by about 10 beats/minute, but this increase did not correlate with plasma nicardipine levels. Side effects were minimal, consisting of headache and flushing. In seven patients, local phlebitis developed at the site of infusion. This occurred after at least 14 hours of infusion at a single site, and the incidence can probably be reduced by shortening the infusion time at a single site. CONCLUSION: Nicardipine appears to be a safe and effective drug for intravenous use in the treatment of severe hypertension.     

Concomitant administration of terazosin and atenolol for the treatment of essential hypertension

The safety and efficacy of once-daily terazosin hydrochloride administered concomitantly with once-daily atenolol for the treatment of essential hypertension were evaluated in this double-blind, multiclinic, placebo-controlled study. After each patient received 50 mg of atenolol daily for eight weeks, patients with a supine diastolic blood pressure (DBP) of 95 to 110 mm Hg and whose supine DBP had decreased at least 5 mm Hg were randomized to receive either terazosin (plus atenolol) or placebo (plus atenolol) for ten weeks. Patients assigned to the terazosin hydrochloride treatment group received increasing dosages (1,2,5, and 10 mg daily) [corrected] of terazosin at two-week intervals until the maximum dose was reached or until the supine DBP was decreased to less than 90 mm Hg. Terazosin-treated patients (n = 43) had significant mean decreases from the baseline in supine BP (systolic/diastolic = -8.8/-8.5 mm Hg) and standing BP (-10.9/-9.5 mm Hg), whereas the decreases in BP in the placebo-treated patients (n = 49; supine, -2.3/-2.6 mm Hg; standing, -1.4/-1.3 mm Hg) were not significant. When terazosin and placebo were compared, the differences in BP were significant. Terazosin-treated patients had significantly greater decreases in mean percent change of total cholesterol (-4.8%) and low-density lipoprotein plus very-low-density lipoprotein cholesterol (-6.3%) levels, compared with the placebo-treated patients (+0.6% and +1.1%, respectively). Concomitant administration of terazosin and atenolol to patients with essential hypertension was found to be safe and efficacious.