Addition Of Hydrochlorothiazide Research Articles

Additive effect of isradipine in combination with captopril in hypertensive patients

The effects of combined treatment with the calcium antagonist isradipine and the angiotensin-converting enzyme inhibitor captopril were investigated in a randomized, placebo-controlled parallel-group trial comprising 28 patients with essential hypertension. The average age was 50 years (range, 31 to 65 years). After all patients were given captopril 50 mg twice daily plus placebo for four weeks, they were randomly assigned into groups receiving in addition either placebo or isradipine 1.25 mg twice daily in increasing doses at four-week intervals. During Weeks 20 to 24, the captopril plus placebo group was given hydrochlorothiazide 12.5 mg per day. Blood pressure was measured in the morning, 12 hours after tablet intake. Supine blood pressure was reduced in the captopril plus isradipine group by −8 −6 , −14 −9 , −16 −8 , and −11 −7 mm Hg compared with the placebo group. Changes in diastolic blood pressure were statistically significant at Week 8, whereas changes in systolic blood pressure were statistically significant at Weeks 12, 16, and 20. With the addition of hydrochlorothiazide (Weeks 20 to 24), only supine systolic blood pressure was significantly reduced. One patient was withdrawn from the trial due to a rash. The results indicate that combined treatment with a calcium antagonist and an angiotensin-converting enzyme inhibitor is effective in lowering blood pressure and that the combination is well tolerated during long-term therapy. The combination of captopril and isradipine was more effective than captopril given with a low dose of hydrochlorothiazide.

Comparison of Increase in the Enalapril Dose and Addition of Hydrochlorothiazide as Second-Step Treatment of Hypertensive Patients Not Controlled by Enalapril Alone

Forty-six patients were randomly allocated to two different groups of treatment if their diastolic blood pressure remained above 90 mm Hg after one month of treatment with 20 mg enalapril mg once daily. In the first group (ENA), 23 patients were given higher daily dosages of enalapril (40 mg and, when necessary, 60 mg). The second group of 23 patients (HCTZ) was given 20 mg/day enalapril and hydrochlorothiazide (25 mg/day and, when necessary, 50 mg). Blood pressure was measured by an automatic device and by the physician with a standard sphygmomanometer. Blood pressure was significantly lower in the HCTZ group, according to both the automatic device (130 +/- 9/80 +/- 8 vs. 141 +/- 5/86 +/- 8 mm Hg, p less than 0.01/p less than 0.05) and the sphygmomanometer (134 +/- 10/89 +/- 6 vs. 149 +/- 16/94 +/- 5 mm Hg, p less than 0.001/p less than 0.01). Plasma renin activity, increased by enalapril at the 20 mg dosage, rose in the HCTZ group but not in the ENA group (22.4 +/- 22 vs. 10.2 +/- 11 pmol/ml/h, p less than 0.05). Plasma aldosterone increased significantly in the HCTZ group (0.44 +/- 0.22 vs. 0.30 +/- 0.17 pmol/ml, p less than 0.05) but did not change in the ENA group (0.31 +/- 0.11 vs. 0.30 +/- 0.17 pmol/ml, NS). In the ENA group, converting enzyme activity was not reinforced (5.7 +/- 8 vs. 6.6 +/- 6 mU/ml, NS) despite an increase in plasma enalaprilat levels (172.4 +/- 108 vs. 72.1 +/- 42 ng/ml, p less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)

The Antihypertensive Response to Lisinopril: The Effect of Age in a Predominantly Black Population

After a 2-4 week no-treatment period, 24 patients (12 young, age 29-45 yr.; 12 elderly, age 65-81 yr.; 20 black, 4 white) with an untreated sitting diastolic blood pressure between 91-120 mm Hg received the nonsulfhydryl angiotensin converting enzyme inhibitor, lisinopril for three weeks in a singleblind, parallel group comparison. Patients who did not achieve goal blood pressure with the initial low-dose (10 mg/day) were treated with a high-dose regimen (40 mg/day) for three weeks. In those who remained incompletely responsive, hydrochlorothiazide 25 mg/day was added for four weeks in an attempt to normalize blood pressure (less than or equal to 90 mm Hg). Low-dose lisinopril monotherapy produced comparable reductions in the mean systolic and diastolic blood pressures (approximately -15/-8 mm Hg in both younger and older patients). Increasing the dose produced a slightly greater fall in mean blood pressures which normalized the blood pressure in five of six elderly patients unresponsive to the lower dose; addition of hydrochlorothiazide normalized three of the five remaining subjects from both groups who were unresponsive to high dose lisinopril. Lisinopril administration resulted in a rise in plasma renin activity and a fall in plasma aldosterone concentrations which were similar in both groups and which returned over time toward the baseline. The drug was well tolerated, producing one episode of symptomatic hypotension following the addition of hydrochlorothiazide to lisinopril monotherapy. Lisinopril alone or in combination with hydrochlorothiazide produces favorable antihypertensive effects in both younger and older predominantly black, low-renin patients with essential hypertension.

Hydrochlorothiazide Is Not Additive to Verapamil in Treating Essential Hypertension

Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170 +/- 17/109 +/- 6 mm Hg pretreatment to 150 +/- 25/95 +/- 8 mm Hg with verapamil; 170 +/- 5/109 +/- 2 mm Hg pretreatment to 164 +/- 25/103 +/- 10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150 +/- 25/95 +/- 8 mm Hg vs 150 +/- 20/95 +/- 6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2 +/- 0.25 mmol/L to 3.7 +/- 0.35 mmol/L) and stimulated plasma renin activity (1.5 +/- 1.3 ng/mL/h) pretreatment to 3.3 +/- 2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 +/- 1.3 ng/mL/h pretreatment to 2.7 +/- 2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted.

Hydrochlorothiazide is not additive to verapamil in treating essential hypertension

Calcium channel blockers, a newer class of antihypertensive medications, have gained considerable acceptance as monotherapeutic agents, particularly in low renin hypertension where diuretics are also most effective. To study whether thiazide diuretics exert an additional antihypertensive effect in the setting of calcium channel blockade, we gave verapamil hydrochloride (360 mg/d) or hydrochlorothiazide (25 mg/d) alone and in combination in an open study to 13 hypertensive patients with mild to moderate essential hypertension. Both verapamil and hydrochlorothiazide lowered blood pressure (170 +/- 17/109 +/- 6 mm Hg pretreatment to 150 +/- 25/95 +/- 8 mm Hg with verapamil; 170 +/- 5/109 +/- 2 mm Hg pretreatment to 164 +/- 25/103 +/- 10 mm Hg with hydrochlorothiazide), but addition of hydrochlorothiazide to verapamil resulted in no added benefit (150 +/- 25/95 +/- 8 mm Hg vs 150 +/- 20/95 +/- 6 mm Hg). Furthermore, while hydrochlorothiazide lowered serum potassium values (4.2 +/- 0.25 mmol/L to 3.7 +/- 0.35 mmol/L) and stimulated plasma renin activity (1.5 +/- 1.3 ng/mL/h) pretreatment to 3.3 +/- 2.7 ng/mL/h with verapamil), verapamil only modestly elevated renin activity (1.5 +/- 1.3 ng/mL/h pretreatment to 2.7 +/- 2.5 ng/mL/h with verapamil) and did not lower potassium values. Altogether, the data suggest that in essential hypertension, at least for verapamil, concurrent diuretic therapy may not be helpful or warranted.

Demography predicts blood pressure response to once-daily enalapril monotherapy of mild to moderate essential hypertensive patients.

Enalapril was given once daily in low dose (5 to 10 mg) and high dose (20 to 40 mg) in 25 (15 white and 10 black) mild-to-moderate essential hypertensive patients. The white patients had a significant (p less than 0.005) supine diastolic blood pressure (SDBP) lowering with all doses of enalapril (from 97.2 +/- 1.8 to 85 +/- 2.4 mm Hg lowest). The black patient's SDBP did not decrease significantly (100.8 +/- 2.4 to 96.2 +/- 3.7 mm Hg lowest) with enalapril but addition of hydrochlorothiazide achieved satisfactory SDBP control. It is concluded that hydrochlorothiazide should be added if greater than 10 mg/day of enalapril is needed in white patients and the initial therapy in black patients should be a combination of enalapril and hydrochlorothiazide.

Age and antihypertensive drugs (hydrochlorothiazide, bendroflumethiazide, nadolol and captopril)

Three double-blind Veterans Administration Cooperative Studies are reviewed to determine age-related changes in response to antihypertensive agents. In the first study 312 patients received hydrochlorothiazide titrated from 25 to 100 mg twice daily to lower diastolic blood pressure (BP) to <90 mm Hg. Of 121 patients aged 55 to 65 the decrease in BP averaged −21.8 −12.9 mm Hg, while in the 191 patients younger than 55 the reduction averaged −15.7 −11.5 mm Hg (p < 0.001; p = 0.048, respectively). Both systolic and diastolic BP reductions averaged significantly more in older whites; in older blacks it was systolic BP only. An additional 298 patients received titrated doses of propranolol alone, in this group there were no significant differences in BP response between younger patients and patients aged 55 to 65 except in the subgroup of white patients older than 60, in whom the systolic reduction was significantly less than in the younger patients. In a second study of bendroflumethiazide alone and with nadotol, systolic BP decreased more in older than in younger patients but there was no agerelated reduction with nadotol atone. In the third trial captopril was first given atone and later with hydrochlorothiazide. There were no age-related differences with captopril alone, but after the addition of hydrochlorothiazide there was a trend toward a greater antihypertensive response in the patients aged 55 to 69. Thus, responsiveness of older patients varies with the type of antihypertensive drug. Age appears to increase the antihypertensive response to thlazide diuretics but not to β-adrenergic blocking drugs or to captopril.

Prolonged Calcium Channel Blocker Therapy of Hypertension

The dihydropyridine calcium channel blocker nitrendipine was studied in 329 hypertensive patients at 12 separate centers for periods of 1 year or more. Patients with untreated supine diastolic blood pressures greater than 90 mm Hg were given nitrendipine 5 mg twice daily for 1 week; if the goal blood pressure was not achieved (supine diastolic blood pressure less than 90 mm Hg with a fall of at least 10 mm Hg), the dose was doubled, and if necessary it was doubled again after an additional week. By the end of titration, the goal blood pressure had been achieved in 138 patients (44%). During the subsequent 11 months of study, 155 patients continued to take nitrendipine alone; their posttitration supine diastolic blood pressure was 85 +/- 7 mm Hg, and at the end of the 1 year study it was 84 +/- 6 mm Hg. There were no significant changes in body weight or in heart rate. At their discretion, investigators could add other antihypertensive agents in patients not responding adequately to nitrendipine alone. In 41 patients with a supine diastolic blood pressure of 95 +/- 9 mm Hg after initial titration, propranolol was added to the nitrendipine and decreased the supine diastolic blood pressure to 88 +/- 8 mm Hg by the end of the study; and in another 76 patients with a posttitration supine diastolic blood pressure of 92 +/- 7 mm Hg, the addition of hydrochlorothiazide decreased the supine diastolic blood pressure to 86 +/- 7 mm Hg by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

The Antihypertensive Effect of Lisinopril Compared to Atenolol in Patients with Mild to Moderate Hypertension

In a multicenter, parallel, double-blind study, lisinopril was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to a once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased up to 80 mg or 200 mg, respectively, at 4-week intervals if sitting diastolic blood pressure (SDBP) was not well controlled. Hydrochlorothiazide (HCTZ) 12.5 or 25 mg was added after 12 weeks, if necessary, and titrated upward after 4 weeks to a maximum dose of 25 or 50 mg/day. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (less than 0.01). Lisinopril produced a significant (less than 0.01) greater reduction in sitting systolic blood pressure (SSBP) than atenolol. Addition of HCTZ caused further blood pressure reductions (p less than 0.01). Five patients (1.7%) on lisinopril and four (2.0%) on atenolol developed skin rashes during weeks 1-12. Two patients (0.7%) on lisinopril 80 mg developed proteinuria (greater than 1 g/day). Cough occurred more often with lisinopril (4.5%), and elevated triglycerides occurred more often with atenolol (2.0%).

Double-blind comparison of captopril and enalapril in mild to moderate hypertension

To compare the antihypertensive and humoral effects of the angiotensin-converting enzyme inhibitors captopril and enalapril, 20 patients with essential hypertension, not receiving treatment for 2 weeks and consuming a prescribed sodium ion intake, were randomly assigned to two parallel, double-blind treatment groups with stratification based on race and untreated seated diastolic blood pressure. These groups received a placebo (day -1) followed by either captopril, 200 mg every 12 hours (n = 9), or enalapril maleate, 20 mg every 12 hours (n = 11), alone (days 1 to 14) and then with hydrochlorothiazide, 25 mg every 12 hours (days 16 to 28). Captopril and enalapril were coadministered alone (day 15) and with hydrochlorothiazide (day 29) to assess whether further decreases in blood pressure would occur. Captopril and enalapril alone caused comparable decreases (p less than 0.05) in the mean 12 hour time-averaged seated diastolic blood pressure from values on day -1 (placebo), on day 1 (11 and 9 mm Hg, respectively) and day 14 (8 and 7 mm Hg, respectively). The addition of hydrochlorothiazide further decreased (p less than 0.05) blood pressure in each group (7 and 8 mm Hg, respectively) from values on day 14. Combined use of captopril and enalapril did not result in further reduction. Coupled with the comparable changes observed in each treatment group in serum angiotensin-converting enzyme activity, plasma renin activity and plasma aldosterone concentration, these data support the view that captopril and enalapril have similar antihypertensive effects and mechanisms.

Hypercalciuria associated with long-term administration of calcitriol (1,25-dihydroxyvitamin D3). Action of hydrochlorothiazide.

Urine calcium excretion was evaluated in 19 patients before and after calcitriol (1,25-dihydroxyvitamin D3) treatment that was followed up for a five- to seven-year period. The effects of increases of calcitriol dosage and modifications of calciuria with hydrochlorothiazide were systematically examined. The urine calcium excretion before calcitriol therapy was 2.3 +/- 0.8 mg/kg/day (mean- +/- SEM) and the urine calcium-creatinine concentration ratio was 0.12 +/- 0.04. With the dose of calcitriol at 23 ng/kg/day, these values increased to 3.2 +/- 0.8 mg/kg/day and 0.19 +/- 0.04, respectively. Following double dose of calcitriol (44 ng/kg/day), increments in calciuria and urinary calcium/creatinine concentration of 1.4 +/- 0.6 mg/kg/day and 0.10 +/- 0.03, respectively, were observed. With concomitant administration of hydrochlorothiazide (1 to 2 mg/kg/day) therapy at maintenance dose and calcitriol (31 ng/kg/day), the urine calcium excretion effectively decreased by 1.3 +/- 0.6 mg/kg/day and the urine calcium-creatinine concentration ratio by 0.05 +/- 0.02. The results suggest that children with calcium-phosphate disorders who require long-term treatment with calcitriol must be carefully monitored in terms of urine calcium excretion, especially when the dosages are increased to achieve maximal therapeutic efficacy. Calciuria induced by calcitriol administration is effectively reversed by addition of hydrochlorothiazide to the treatment regimen.

Effects of Hydrochlorothiazide and Amiloride in Renal Hypophosphatemic Rickets

The effects of thiazide diuretics on serum phosphate concentration, renal tubular threshold for phosphate, and urinary calcium excretion in children with renal hypophosphatemic rickets were studied. There were nine controlled acute studies conducted in five patients, and, in addition, seven long-term studies of up to 26 months were performed. During the acute studies, the children continued to receive the same doses of oral calcitriol and phosphate supplementation as at home. Hydrochlorothiazide, 1.50 to 2.25 mg/kg/d, was used alone in the first four studies; hydrochlorothiazide and amiloride at a dose of 1 mg for each 5 mg of hydrochlorothiazide were used in the other five studies. Administration of the diuretics for four days gave rise to a significant increase in serum phosphate concentration from 3.1 +/- 0.4 mg/dL to 3.7 +/- 0.9 mg/dL (P less than .01) and in tubular threshold for phosphate from 1.31 +/- 0.45 mg/dL to 1.74 +/- 0.60 mg/dL (P less than .01). These changes were accompanied by significant reductions in urinary sodium excretion from 135 +/- 39 mEq/24 h during the control period to 99 +/- 42 mEq/24 h on the fourth day of therapy (P less than .05), fractional sodium excretion from 0.99% +/- 0.42% to 0.81% +/- 0.42% (P less than .05), and urinary calcium excretion from 57.3 +/- 28.9 mg/24 h to 19.0 +/- 13.1 mg/24 h (P less than .01). Fractional excretion of phosphate divided by fractional excretion of sodium after the treatment with diuretics was not significantly different from that observed at the end of the control period. Increments in serum phosphate concentrations were correlated with elevations in serum albumin concentrations (r = .739; P less than .02). As an additional index of intravascular volume contraction, the elevations in serum phosphate concentrations were correlated with the increase in BUN, (r = .793; P less than .01). The addition of amiloride in the last five studies prevented the hypokalemia and alkalosis that had complicated the administration of hydrochlorothiazide. Long-term follow-up studies for a total of 119 therapy-months on six children and one adult, who continued to receive the diuretics concomitantly with calcitriol and phosphate supplementation, showed that they were free of complications except for a transient episode of hypercalcemia and hypercalciuria in one patient. In comparison with the previous period of treatment with calcitriol and phosphate without diuretics, linear growth velocity and healing of the rickets were not changed in two children and improved in the other four after the addition of hydrochlorothiazide and amiloride.(ABSTRACT TRUNCATED AT 400 WORDS)

The effect of captopril on renal hemodynamics in hypertensive patients.

The effects of captopril (50 or 100 mg t.i.d.) with and without hydrochlorothiazide (25 or 50 mg/day) on renal blood flow, glomerular filtration rate, and the renin-angiotensin system were determined in 20 patients with mild to moderate essential hypertension. Normalization of blood pressure (supine diastolic blood pressure less than 90 mm Hg) was achieved in 12 patients after four or six weeks of captopril alone (147 +/- 3/100 +/- 3 mm Hg after a two-week placebo lead-in vs. 135 +/- 4/83 +/- 1 mm Hg after captopril, P less than 0.01/P less than 0.001). In these 12 patients, no significant alterations in renal blood flow or glomerular filtration rate were observed. Plasma renin activity increased two- to threefold above baseline levels, whereas serum and urinary aldosterone decreased by 23 and 35 per cent, respectively. Eight other patients remained hypertensive after four weeks of captopril alone (165 +/- 6/110 +/- 3 vs. 156 +/- 8/102 +/- 4 mmHg, P greater than 0.05/P less than 0.05). With addition of hydrochlorothiazide, blood pressure fell (P less than 0.001) to 129 +/- 7/84 +/- 3 mm Hg. Captopril alone or in combination with diuretic had no significant effect on renal hemodynamics. In the eight patients requiring diuretic, plasma renin activity remained constant after captopril monotherapy, but rose threefold after hydrochlorothiazide was added. The combination of these two antihypertensive agents significantly lowered serum aldosterone levels and urinary aldosterone excretion by 53 and 50 per cent, respectively. In summary, captopril with and without a thiazide diuretic reduced blood pressure without altering renal hemodynamics.

Enalapril and Atenolol in Primary Hypertension–A Comparative Study of Blood Pressure Lowering and Hormonal Effects

The efficacy and tolerability of the new ACE-inhibitor enlalapril (MK 421) and the beta 1-selective adrenoceptor blocker atenolol for the treatment of primary hypertension were compared in a double blind parallel study. 12 patients were randomized to each drug. The doses of enalapril were 20 and 40 mg o.d and of atenolol 50 and 100 mg o.d. for 4 weeks each, whereafter hydrochlorothiazide (HCTZ) 25 or 50 mg o.d. was added if necessary to achieve a supine diastolic blood pressure (BP) <90 mm Hg 24 hours after drug intake. Supine BP was reduced from 160±7/111±4 mm Hg to 153±13/101±9 mm Hg (p<0.05/p<0.005) with enalapril and from 163±17/109±6 mm Hg to 145±11/95±7 mm Hg (p<0.005/p<0.001) with atenolol. The addition of HCTZ caused a profound additive BP reduction to 132±7/88±6 mm Hg with enalapril and to 130±10/88±7 mm Hg with atenolol. There was no significant difference between the efficacy of enalapril and atenolol alone or combined with HTCZ. The reduction in mean arterial pressure with enalapril tended to correlate with pre-treatment stimulated plasma renin activity and 24 hours urinary kallikrein excretion. Both drugs tended to reduce serum and urinary aldosterone and kallikrein excretion to the same extent. There was one drop-out in each group, one due to impotence on the combination of enalapril and HCTZ and one due to peripheral coldness during atenolol treatment. Other side effects were mild. No toxic adverse effects were registered.

The Calcium Channel Blocker Nitrendipine in Single- and Multiple-Agent Antihypertensive Regimens

The antihypertensive efficacy of the calcium channel blocker nitrendipine was evaluated in a 12-center collaborative study during 6 months of treatment. Following an initial placebo period, 318 patients with supine diastolic blood pressures greater than 90 mm Hg were given nitrendipine 5 mg twice daily for 1 week; if goal blood pressure was not reached (supine diastolic blood pressure less than 90 mm Hg with a fall of at least 10 mm Hg), the dose was doubled, and if necessary it was doubled again after an additional week. By the end of titration, goal blood pressure had been achieved in 132 patients (43%). During the subsequent 5 months of study, 155 patients continued to take nitrendipine alone; their post-titration supine diastolic blood pressure was 85 +/- 7 mm Hg, and at the end of the 6-month study it was 84 +/- 7 mm Hg. There were no changes in body weight or in heart rate. In 38 patients with a supine diastolic blood pressure of 95 +/- 9 mm Hg after titration, propranolol was added to the nitrendipine and decreased the supine diastolic blood pressure to 86 +/- 9 mm Hg by the end of the study; and in another 74 patients with a post-titration supine diastolic blood pressure of 93 +/- 7 mm Hg, addition of hydrochlorothiazide decreased the supine diastolic blood pressure to 86 +/- 7 mm Hg by the end of the study.(ABSTRACT TRUNCATED AT 250 WORDS)

Sodium balance and antidiuresis in thiazide-treated rats with diabetes insipidus

A sodium deficit was induced in Brattleboro rats by lowering the dietary sodium content. Urine volume was only slightly reduced. Addition of hydrochlorothiazide to the food caused a small, transient sodium deficit but led to a marked, sustained antidiuresis. The acute administration of a large dose of hydrochlorothiazide produced a larger, sustained sodium deficit but no lasting antidiuresis. These results indicate that sodium depletion cannot account for the antidiuresis of hydrochlorothiazide treatment in diabetes insipidus.

Treatment of Mild and Moderate Hypertension with Medroxalol, an α and β-Adrenergic Antagonist

Medroxalol, a new antihypertensive agent with alpha- and beta-adrenoreceptor blocking properties in both animals and humans, was administered in a single-blind study for 12 weeks to 29 patients with mild and moderate hypertension (standing blood pressure: 188-130/130-100 mm Hg). After 4 weeks of placebo administration, treatment with oral medroxalol was begun. Six weeks later, half the subjects added hydrochlorothiazide, 12.5 mg twice daily, to medroxalol for an additional 6 weeks, and the other half added placebo. During the final 4-week period medroxalol, but not hydrochlorothiazide, was discontinued and placebo substituted. Oral medroxalol doses of 100-400 mg twice daily reduced standing diastolic pressure to less than 100 mm Hg in 21 of the 26 subjects who completed the study. Compared to the last values on placebo, mean standing blood pressure was decreased by 15.6/12.0 mm Hg during the first 6 weeks of medroxalol at mean daily doses of 388-407 mg. Addition of hydrochlorothiazide permitted some decrease in medroxalol dosage. Upon medroxalol withdrawal, blood pressure and heart rate returned toward pretreatment values, with subjects continuing on diuretic showing lower blood pressures than the untreated individuals. Tolerance to medroxalol, with or without hydrochlorothiazide, was good. Mild orthostatic dizziness was the most frequent complaint associated with therapy, but postural hypotension was not found on physical examination. Medroxalol appears to be effective and well tolerated for reducing the blood pressure of most patients with mild to moderate hypertension and may be useful for chronic oral therapy of this disease.

Racial differences in response to low‐dose captopril are abolished by the addition of hydrochlorothiazide.

1 In a randomised study, 475 men with diastolic blood pressures of 92‐ 109 mm Hg received either placebo or captopril 37.5 mg, 75 mg or 150 mg/day for 7 weeks. 2 After 7 weeks patients taking placebo were given hydrochlorothiazide 25 mg twice daily, as were two‐thirds of each group taking captopril and they were observed for 7 additional weeks. 3 Captopril reduced blood pressure by 12.2 +/‐ 0.8/9.4 +/‐ 0.4 mm Hg at 7 weeks (n = 323) and captopril plus placebo reduced it by 10.3 +/‐ 1.9/10.2 +/‐ 0.9 mm Hg at 14 weeks (n = 83); placebo by 2.0 +/‐ 1.7/3.4 +/‐ 0.8 mm Hg (n = 76); and captopril plus hydrochlorothiazide by 24.4 +/‐ 1.1/16.2 +/‐ 0.6 mm Hg (n = 173). The effect of low‐dose captopril was similar to that of high doses. 4 White patients responded better than blacks, with a blood pressure reduction of 14.7 +/‐ 1.1/10.7 +/‐ 0.6 mm Hg (n = 170) v 9.1 +/‐ 1.2/8.0 +/‐ 0.7 mm Hg (n = 151). This difference was abolished by the addition of hydrochlorothiazide. 5 Only 15/384 (3.9%) of patients were dropped from the study because of adverse effects. 6 The prescription of low‐dose captopril might be extendable to patients with mild to moderate hypertension.

Long-term efficacy of angiotensin-converting-enzyme inhibition with captopril in mild-to-moderate essential hypertension.

1 Thirty-one patients with mild-to-moderate essential hypertension were treated with captopril for 30 months. 2 Captopril effectively lowered raised blood pressure in hypertensive patients with high, low, and normal renin concentrations. There was no significant change in heart rates. Captopril alone normalised blood pressure (diastolic pressure below 95 mm Hg) in 11 patients. In the other patients the addition of hydrochlorothiazide produced a further hypotensive effect. Blood pressure control could be maintained without any signs of tachyphylaxis. 3 Plasma concentrations of aldosterone and angiotensin II were significantly lower after 30 months of therapy than pretreatment values whether captopril was associated with diuretics or not. No relevant symptomatic or biochemical adverse reactions were observed. 4 These data establish the long-term potential of captopril for outpatient therapy in mild-to-moderate forms of essential hypertension.

Efficacy of an oral angiotensin-converting enzyme inhibitor (captopril) in severe hypertension

The antihypertensive effect of captopril was assessed during short- and long-term periods in ten patients with elevated blood pressure readings that were uncontrollable by standard therapy (supine diastolic blood pressure of greater than 100 mm Hg with a regimen of propranolol hydrochloride, hydralazine hydrochloride, and hydrochlorothiazide). When given alone, captopril therapy was unable to normalize the blood pressure in any patient. The addition of hydrochlorothiazide to the captopril therapy normalized the blood pressure in one patient and sharply improved the blood pressure in four others. The blood pressure in the remaining patients responded inadequately to this combination. The addition of propranolol to captopril and hydrochlorothiazide reduced the blood pressure further in most cases (seven on the ten patients had normal blood pressure readings while they received these three drugs). In four patients, the blood pressure response to the added propranolol was unrelated to changes in plasma angiotensin II concentration. Captopril was helpful in the management of refractory hypertension in most cases.