An appraisal of antihypertensive efficacy and adverse reactions with two drug regimens: enalapril maleate as part of triple therapy compared to conventional triple therapy in moderate to severe hypertension.
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Abstract:
A randomized, double-blind, parallel treatment trial was carried out in 24 patients with moderate to severe hypertension to compare the effectiveness and tolerance of two treatment regimens in reducing and maintaining supine diastolic blood pressure below 90 mmHg. Patients in Group I received 10 to 40 mg enalapril maleate per day with the addition of 50 mg hydrochlorothiazide per day and then 250 to 1000 mg alpha-methyldopa per day, if necessary. Patients in Group II received 50 mg hydrochlorothiazide per day with the addition of 80 to 240 mg propranolol and then 100 to 200 mg hydralazine per day, if necessary. Apart from the hydrochlorothiazide dosage which was fixed, the dosage of the other active drugs was titrated incrementally until the target blood pressure level was achieved. Blood pressures, heart rate and body weight were monitored at 2-weekly intervals during 26 weeks of active therapy. In Group I, blood pressure control was achieved and maintained with enalapril alone in 9 patients, 2 patients required double therapy and 1 patient triple therapy. In Group II, 9 patients required double therapy, 2 triple therapy, and only 1 patient received monotherapy. Supine and erect blood pressure control was comparable in both groups. There was, however, a significant decrease in supine heart rate in patients in Group II. More importantly, 8 of the 12 patients in Group II experienced non-life threatening adverse reactions (4 were hypokalaemic and required supplementary potassium, 2 had cold hands and feet, 1 man had sexual dysfunction and 1 acute gout) and no adverse reactions were reported by Group I patients.Keywords:
Methyldopa
Supine position
Hydralazine
Thiazide
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A randomized, double-blind, parallel treatment trial was carried out in 24 patients with moderate to severe hypertension to compare the effectiveness and tolerance of two treatment regimens in reducing and maintaining supine diastolic blood pressure below 90 mmHg. Patients in Group I received 10 to 40 mg enalapril maleate per day with the addition of 50 mg hydrochlorothiazide per day and then 250 to 1000 mg alpha-methyldopa per day, if necessary. Patients in Group II received 50 mg hydrochlorothiazide per day with the addition of 80 to 240 mg propranolol and then 100 to 200 mg hydralazine per day, if necessary. Apart from the hydrochlorothiazide dosage which was fixed, the dosage of the other active drugs was titrated incrementally until the target blood pressure level was achieved. Blood pressures, heart rate and body weight were monitored at 2-weekly intervals during 26 weeks of active therapy. In Group I, blood pressure control was achieved and maintained with enalapril alone in 9 patients, 2 patients required double therapy and 1 patient triple therapy. In Group II, 9 patients required double therapy, 2 triple therapy, and only 1 patient received monotherapy. Supine and erect blood pressure control was comparable in both groups. There was, however, a significant decrease in supine heart rate in patients in Group II. More importantly, 8 of the 12 patients in Group II experienced non-life threatening adverse reactions (4 were hypokalaemic and required supplementary potassium, 2 had cold hands and feet, 1 man had sexual dysfunction and 1 acute gout) and no adverse reactions were reported by Group I patients.
Methyldopa
Supine position
Hydralazine
Thiazide
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A combination of low-dose oral enalapril, methyldopa and hydrochlorothiazide was evaluated in the acute treatment of severe hypertension. Blood pressure moved from an average 210/120 mmHg at the onset to an average 135/79 mmHg within 24 hours, without any significant side effects and at about half the cost of commonly used parenteral hydralazine.
Methyldopa
Hydralazine
Nigerians
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Essential hypertension
Supine position
Combination therapy
Thiazide
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Using a placebo baseline, positive controlled, double-blind, randomized titration to effect our study protocol, we assessed the antihypertensive actions of enalapril, hydrochlorothiazide, and their combination in 37 patients with moderate essential hypertension. Patients were maintained on their regular diets and received a placebo for 4 weeks. Patients with moderate systemic hypertension were randomized to receive enalapril monotherapy at a dose of 10 mg twice daily (n = 16), hydrochlorothiazide monotherapy at a dose of 25 mg twice daily (n = 15), or combination therapy consisting of 10 mg enalapril and 25 mg hydrochlorothiazide twice daily (n = 6). Therapy could be titrated to twice the starting dose. All treatment regimens reduced blood pressure, but only one patient had blood pressure normalized (diastolic blood pressure less than or equal to 90 mmHg) with enalapril (7%), two patients with hydrochlorothiazide (15%), and 80% of patients with combination therapy. The patients who had not achieved normal blood pressure received combination treatment, and after 8 additional weeks, more than 70% showed normal blood pressure. After one year of combination therapy, 92% of the patients continue to have normal blood pressure. Both the monotherapy and combination regimens were very well tolerated in this study. In conclusion, enalapril, hydrochlorothiazide, and their combination are effective in reducing blood pressure in patients with moderate hypertension. However, monotherapy is successful in normalizing blood pressure only in a small percentage of patients. Combination therapy achieved normalization of blood pressure in almost all patients, suggesting that most patients on regular diets with moderate hypertension may require a diuretic-ACE inhibitor combination rather than monotherapy to achieve effective blood pressure control.
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Forty-five hypertensive patients were given hydrochlorothiazide for 1 month and were then allocated at random to one of three treatment groups: methyldopa and hydrochlorothiazide, methyldopa alone, or hydrochlorothiazide alone. Combination of hypotensive drugs reduced supine mean arterial pressure more effectively than methyldopa alone. Methyldopa and hydrochlorothiazide may have a slightly greater depressor effect on supine blood pressure than a thiazide alone, but the difference was not statistically significant in this study. Combination produced a significantly greater decrease in standing mean arterial pressure than did either drug alone. Pulse rate was modestly reduced in patients who received methyldopa. The mild increase in body weight after methyldopa alone was not seen in the other two groups. Serious toxicity was not observed in this short-term trial.
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Supine position
Thiazide
Essential hypertension
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Background. Nonsteroidal antiinflammatory drugs (NSAIDs) may alter blood pressure through their inhibitory effects on prostaglandin biosynthesis. Such potential hypertensive effects of NSAIDs have not been adequately examined in the elderly, who are the largest group of NSAID users. Methods. We performed a randomized, double-blind, two-period crossover trial of ibuprofen (1800 mg per day) vs placebo treatment in patients older than 60 years of age with hypertension controlled with hydrochlorothiazide. While continuing their usual thiazide dosage, subjects were randomized to a 4-week treatment period (ibuprofen or placebo) followed by a 2-week placebo wash-out period and a second 4-week treatment period with the alternative therapy. Supine and standing systolic and diastolic blood pressures were measured weekly. Results. Of 25 randomized subjects, 22 completed the study protocol (mean age = 73 ± 6.7 years). Supine systolic blood pressure and standing systolic blood pressure were increased significantly with ibuprofen treatment, compared with placebo. Mean supine systolic blood pressures were 143.8 ± 21.0 and 139.6 ± 15.9 mmHg on ibuprofen and placebo, respectively (p = .004). Mean standing systolic blood pressures were 148.1 ± 19.9 and 143.4 ± 17.9 mmHg on ibuprofen and placebo, respectively (p = .002). Conclusion. We conclude that 1800 mg per day of ibuprofen does induce a significant increase in systolic blood pressure in older hypertensive patients treated with hydrochlorothiazide. NSAID therapy may negatively impact the control of hypertension in elderly patients.
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Ibuprofen
Thiazide
Crossover study
Chlorthalidone
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Hydralazine
Methyldopa
Supine position
Thiazide
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SummaryA randomized double-blind trial was carried out to determine the relationship of the changes in blood pressure and heart rate with changes in echocardiographic left ventricular indices in moderate to severe hypertensive patients with established left ventricular hypertrophy who were being treated chronically with enalapril or hydrochlorothiazide plus propranolol for 26 weeks. After a 2-week period on placebo, drug dosages in the two groups were adjusted to individual needs until blood pressure was normalized (diastolic <90 mmHg). Patients in Group I received 10 to 40 mg enalapril/day; those in Group II received 50 mg hydrochlorothiazide plus 80 to 240 mg propranolol/day. Echocardiographic measurements were made at the end of the placebo and 26-week active treatment periods. Significant correlations were observed between the changes in four pairs of variables in each group. In the 8 patients receiving enalapril, there were negative correlations between interventricular septal thickness and supine systolic blood pressure, erect and supine heart rates, and a positive correlation between relative wall thickness and erect diastolic blood pressure. In the 7 patients on hydrochlorothiazide plus propranolol, there were negative correlations between relative wall thickness and erect and supine heart rate, and positive correlations between left ventricular mass and erect diastolic blood pressure, and the percentage change in internal diameter of the left ventricle and supine systolic blood pressure. Possible explanations for and implications of these regional changes are discussed.
Supine position
Interventricular septum
Essential hypertension
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Hydralazine
Methyldopa
Regimen
Essential hypertension
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