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

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

Effects of atenolol and propranolol when added to long-term antihypertensive diuretic therapy.

The antihypertensive effects of atenolol and propranolol were compared in a double-blind crossover study of 19 patients with essential hypertension (World Health Organization, I and II) who were receiving long-term diuretic treatment (chlorthalidone, 50 mg daily) during the study. After a 3-wk placebo period, a beta-adrenergic antagonist was administered once daily (atenolol, 50 mg daily, or propranolol, 80 mg daily) for a week. If the MAP was more than 108 mm Hg at the end of the week, dosage of the beta-blocker was doubled the following week; when necessary, doubling was repeated to a maximum dose of 640 mg propranolol and 400 mg atenolol daily. Fifty milligrams atenolol had a greater effect than 80 mg propranolol and was as effective as 160 mg propranolol. The dose-response curve flattened off after 160 mg propranolol and 50 mg atenolol daily. The two highest doses of atenolol lowered MAP more than the highest doses of propranolo. Heart rate slowing was the same for both drugs and did not correlate with the fall in blood pressure. PRA was suppressed by all doses of propranolol, whereas atenolol suppressed PRA only at the 2 highest doses, (200 and 400 mg daily). With the lower propranolol doses, the percent MAP change correlated weakly with the percent PRA change (80 mg--r = 0.41, p less than 0.1; 160 mg--r = 0.64, p less than 0.05). Side effects were minimal, and were noted only with 640 mg propranolol; with this exception, the percentage of patients with no complaints rose when placebo was replaced by beta-blockers.     

Metoprolol with and without chlorthalidone in hypertension.

After a control period on a placebo, 45 patients with mild to moderate hypertension were treated with metoprolol, 100 mg twice daily alone and in free combination with chlorthalidone 50 mg daily using a double-blind crossover technique. The beta-blocker alone induced a significant fall in blood pressure; the diastolic pressure was reduced to 100 mg Hg or less in 37 of the 45 patients and to 95 mm Hg or less in 19 patients. The addition of chlorthalidone enhanced the antihypertensive effect so that in 33 patients diastolic pressure fell to 95 mm Hg or less. The drugs were well tolerated even by a small number of patients with chronic bronchitis and diabetes mellitus. None of the patients developed cardiac failure. Adding a diuretic caused a small reduction in serum potassium concentrations, and the relevance of this observation is discussed.     

Usefulness of moexipril and hydrochlorothiazide in moderately severe essential hypertension.

The purpose of this study was to assess the efficacy and tolerability of the angiotensin-converting enzyme inhibitor moexipril alone and in combination with hydrochlorothiazide versus hydrochlorothiazide monotherapy in patients with stage II and III essential hypertension. This was a double-blind, randomized, multicenter trial that evaluated moexipril (15 and 30 mg once daily), hydrochlorothiazide (25 and 50 mg once daily), and combinations of the drugs (15 mg moexipril/25 mg hydrochlorothiazide and 30 mg moexipril/50 mg hydrochlorothiazide) in 272 hypertensive patients whose seated diastolic blood pressure (BP) was 100 to 114 mm Hg. The primary efficacy variable was the mean change from baseline in seated diastolic BP at the end of the dosing period. Secondary efficacy measures included changes in systolic BP and standing BP. The lower doses of moexipril and hydrochlorothiazide reduced diastolic BP similarly (-8.0 +/- 1.4 versus -8.1 +/- 1.4 mm Hg; p = NS) as did higher doses of the monotherapeutic regimens (moexipril, -9.7 +/- 1.2 mm Hg versus hydrochlorothiazide, -11.0 +/- 1.2 mm Hg, p = NS). Combinations of moexipril and hydrochlorothiazide reduced diastolic BP significantly more than either monotherapy (lower doses, -16.0 +/- 1.4 mm Hg; p < 0.001; higher doses, -17.9 +/- 1.2 mm Hg; p < 0.001). Similar trends were observed for the systolic BP. Discontinuation rates due to adverse events were 0% for the moexipril monotherapy patients and 3% to 5% in patients on diuretic or combination treatment. These data demonstrate that 15 and 30 mg moexipril once daily lower BP similarly to hydrochlorothiazide in patients with stage II and III hypertension. There is also an additive effect when combining the two agents that lowers BP more significantly than either monotherapy.     

Antihypertensive and metabolic effects of a new converting enzyme inhibitor, enalapril

Thirty-one men with mild, uncomplicated essential hypertension were studied for 18 wk in a double-blind, placebo-controlled, randomized clinical trial. Those whose supine diastolic pressure was 90 to 104 mm Hg after 4 wk of placebo were randomly assigned to three groups. Group I (11 subjects) initially received one 10-mg enalapril capsule in the morning and one placebo capsule in the evening. Group II (10 subjects) received one 5-mg enalapril capsule twice daily. Group III (10 subjects) received one placebo capsule twice daily. Drug dosages were doubled and then quadrupled in all groups at wk 8 and 12. Metabolic, ophthalmologic, and audiometric studies were done on all subjects at wk 2, 4, 8, 12, and 16. Enalapril lowered diastolic pressure in the supine and upright positions in single and divided doses. Its antihypertensive effect was dose dependent, and it was greater in white patients than in black patients. The drug was well tolerated by all subjects and did not cause clinical or metabolic complications. It is concluded that enalapril is effective in lowering the arterial pressure in single and divided daily doses; its effect is dose dependent and is greater on the diastolic arterial pressure than on the systolic pressure; and it is well tolerated.     

Clonidine and prazosin effects in hypernoradrenergic vasodilator-treated and beta-blocker-treated patients

Our subjects were seven severely hypertensive patients with blood pressures (BPs) over 140/90 who were using minoxidil, propranolol, and diuretics. Clonidine followed by prazosin was added to their regimen on an outpatient basis to establish the dose-response for BP and catecholamines. Plasma renin activity (PRA), body weight, and renal function were measured. Clonidine was given in doses of 0.2, 0.4, 0.6, and 0.8 mg/day. Supine and standing systolic BP decreased at all dose levels of clonidine (P less than 0.01, P less than 0.05). Diastolic BP decreased in the standing position with doses of 0.4, 0.6, and 0.8 mg (P less than 0.01, P less than 0.05). Subjects were hypernoradrenergic initially with plasma norepinephrine (PNE) 895 +/- 122 pg/ml. PNE was suppressed by 0.2 to 0.8 mg clonidine (P less than 0.01) with near maximal suppression at 0.4 mg daily. Systolic BP correlated with PNE (r = 0.59, P less than 0.001). Supine and standing PRA decreased after 0.2 mg clonidine (P less than 0.05) but not after higher doses. Our findings suggest the antihypertensive action of clonidine is related to PNE suppression but not to that of PRA. Plasma epinephrine (PE), body weight, and renal function did not change. Prazosin was given after clonidine to the same patients in a dose range of 3 to 40 mg/day. With doses of 6 to 40 mg, systolic and diastolic and supine and standing BP fell (P less than 0.001, P less than 0.01). PNE remained elevated throughout all dose levels and did not correlate with BP. Weight rose with prazosin (P less than 0.02) but PE, PRA, and renal function did not change. Hence, clonidine and prazosin induced additional lowering of BP but had different effects of PNE and weight.     

Candesartan cilexetil: comparison of once-daily versus twice-daily administration for systemic hypertension. Candesartan Cilexetil Study Investigators.

This randomized, double-masked, placebo-controlled, forced-titration, parallel-arm study was designed to compare the blood pressure (BP)-lowering effect of candesartan cilexetil, a potent antagonist of the angiotensin II receptor subtype AT1, administered once daily with that of the same agent administered twice daily at the same total daily dose of 16 mg. After a 4- to 5-week placebo run-in period, 277 patients with a sitting diastolic BP of 95 to 109 mm Hg were randomly allocated to receive placebo (n = 92) or candesartan cilexetil 8 mg once daily for 4 weeks, followed by forced titration to either 16 mg once daily (n = 91) or 8 mg twice daily (n = 94) for 4 weeks. At 8 weeks, mean reductions in trough sitting diastolic BP were similar for the once- and twice-daily treatment groups (9.4 and 10.3 mm Hg, respectively). After 8 weeks of treatment, no statistically significant differences were observed in diastolic or systolic BP, peak or trough BP, or sitting or standing BP between the 2 active-treatment groups. The rates of positive responses (defined as a trough sitting diastolic BP of <90 mm Hg or a decrease in BP of > or =10 mm Hg) were also similar (approximately 60%) in the once- and twice-daily candesartan cilexetil groups. Furthermore, placebo-corrected trough-to-peak ratios for sitting diastolic BP exceeded 75% for both candesartan cilexetil regimens, indicating a persistent 24-hour duration of drug effect. Ambulatory BP monitoring performed in a subset of patients (n = 44) confirmed the consistent 24-hour BP-lowering effect and preservation of diurnal variation with once-daily dosing. No significant between-group differences were observed in the incidence or severity of clinical or laboratory adverse events. The results of this study suggest that identical daily doses of candesartan cilexetil administered once or twice daily have comparable efficacy and tolerability and that no additional clinical benefit is derived from twice-daily administration.     

Clinical experience with perindopril in patients nonresponsive to previous antihypertensive therapy: a large US community trial

A subgroup analysis of a large US community trial was conducted to evaluate the antihypertensive efficacy and safety of perindopril, an angiotensin-converting enzyme inhibitor (ACEI), in 3159 patients who lacked blood pressure (BP) control at entry with previous antihypertensive therapy. Patients received 4 mg perindopril daily for 6 weeks. Based on physicians' assessment of BP response, the patients were then either maintained on 4 mg daily (group 1) or the dose was increased to 8 mg daily (group 2) for an additional 6 weeks. The mean baseline sitting BP was 158.2/92.9 mm Hg. Perindopril monotherapy produced a significant BP decrease from baseline of 11.6/6.5 mm Hg and 14.9/8.4 mm Hg at weeks 6 and 12, respectively. In group 1 patients, the majority of BP decrease occurred at week 6 (17.3/9.5 mm Hg) and was maintained until the end of week 12 (18.2/10.1 mm Hg). In group 2 patients, the BP decrease on the 4-mg dose was modest at week 6 by 5.2/3.1 mm Hg. However, further dose up-titration of perindopril to 8 mg resulted in a clinically significant BP decrease of 11.9/6.8 mm Hg from baseline to week 12. Significant antihypertensive effects of perindopril were also demonstrated in the special patient populations of elderly (>or=65 years), black, isolated systolic hypertension, patients with concomitant cardiovascular diseases, and patients nonresponsive to other ACEI therapy. Overall, BP control (<140/<90 mm Hg) was achieved in 40.0% of patients at week 12. Perindopril was well tolerated with cough and angioedema reported in 8.5% and 0.4% patients, respectively. Physicians assessed therapeutic response to perindopril as satisfactory in 73.8% patients who were nonresponsive to previous antihypertensive therapy. These results suggest that, in a community-based practice, perindopril monotherapy (4-8 mg/d) is an effective and safe therapeutic option in patients nonresponsive to previous antihypertensive therapy.     

Efficacy of quadropril (spirapril) vs capropril in treatment of essential hypertension

AIM: To compare the efficacy of monotherapy with quadropril (spirapril) vs captopril in essential hypertension. MATERIAL AND METHODS: 20 female patients aged 55 +/- 2 years with moderate hypertension (WHO classification) were included in the study. 16 patients had congestive heart failure stage II NYHA and 4 patients stage III NYHA. ECG and echocardiography were performed in all the patients. Two patient groups of 10 patients were treated for 6 weeks. Group 1 received 6 mg quadropril once daily. Group 2 received 25 mg captopril 3 times daily. The therapy was considered to be efficient if diastolic pressure (BP) was reduced to 90 +/- 5 mm Hg and systolic BP to 140 +/- 10 mm Hg from baseline values in the range of 210/120-170/100 mm Hg. RESULTS: The hypotensive effect of quadropril resulted in stabilisation of BP during the second week of therapy. A significant BP decrease was achieved at the end of 6 week therapy. Systolic BP fell from 178.8 +/- 3.2 to 145 +/- 5.6 mm Hd and diastolic BP from 109.7 +/- 1.2 to 92.4 +/- 1.7 mm Hg. Central and cardiac hemodynamic parameters improved. In one patient the condition improved from CHF stage III to stage II NYHA. No adverse effects were observed. A hypotensive effect of captopril reduced significantly systolic blood pressure from 182.1 +/- 2.7 to 150 +/- 4.6 mm Hg and diastolic BP from 110.4 +/- 1.1 to 100.1 +/- 1.9 mm Hg. Two patients developed adverse effects: cough and chest dyscomfort. CONCLUSION: Quadropril monotherapy showed to be more effective in diastolic BP decrease compared with captopril monotherapy and had advantages in one daily dose regimen, absence of the first dose effect and side effects.     

Atenolol and chlorthalidone therapy for hypertension: a double-blind comparison

In a randomized, double-blind, parallel-group study of 31 patients with mild to moderate hypertension, we compared a placebo regimen with a regimen of atenolol and chlorthalidone (Tenoretic). The study, which lasted seven weeks, began with a single-blind two-week placebo lead-in period, followed by a four-week double-blind treatment phase, and concluded with a one-week single-blind placebo washout period. Of 24 patients included in the analysis of efficacy, seven received one Tenoretic 50 tablet per day (atenolol, 50 mg; chlorthalidone, 25 mg), nine received one Tenoretic 100 tablet per day (atenolol, 100 mg; chlorthalidone, 25 mg), and eight received placebo. Supine systolic/diastolic blood pressure (mean +/- SD) decreased from 154 +/- 15.2/102 +/- 4.6 mm Hg during the baseline period to 128 +/- 8.5/85 +/- 4.0 mm Hg during treatment in the group receiving Tenoretic 100, from 153 +/- 12.6/104 +/- 5.4 mm Hg to 137 +/- 4.5/91 +/- 4.4 mm Hg in the group receiving Tenoretic 50, and from 150 +/- 11.9/101 +/- 1.6 mm Hg to 145 +/- 11.6/93 +/- 5.1 mm Hg in the group receiving placebo. Reductions in systolic and diastolic blood pressures in the active treatment groups were significantly greater than the pressure reductions in the group receiving placebo (P less than .05 to .1). The combination of atenolol and chlorthalidone was well tolerated, and in no case was treatment discontinued because of side effects. This study showed that one tablet per day of either Tenoretic 50 or Tenoretic 100 is effective and well tolerated in the treatment of mild to moderate hypertension.     

Inhibition of prostaglandin synthesis by indomethacin interacts with the antihypertensive effect of atenolol

The interaction of inhibition of prostaglandin (PG) synthesis by indomethacin (75 mg/day) with the antihypertensive effect of atenolol (50 mg b.i.d.) was studied in 11 untreated otherwise healthy men 35 to 45 years old with essential hypertension. Atenolol for 3 weeks decreased supine blood pressure (BP) from 157/109 mm Hg during placebo to 148/97 mm Hg. Indomethacin alone for 1 week slightly increased BP and antagonized the antihypertensive action of atenolol. Atenolol reduced plasma renin activity (PRA) to 40% but did not modify either the urinary excretion of vasodilatory PGs (PGE2 and prostacyclin measured as 6-keto-PGF1 alpha) or plasma kininogen and urine kallikrein. Indomethacin suppressed PRA to 27% and PG excretion to approximately 70% but did not markedly change plasma kininogen and urine kallikrein excretion. The decreased excretion of 6-keto-PGF1 alpha, the metabolite of the main vasodilatory prostanoid prostacyclin, correlated with the increased BP measured in standing subjects. The effects of indomethacin were practically the same when given with atenolol as when given alone. We conclude that the slight increase in BP by indomethacin in essential hypertension is associated with the reduced production of vasodilatory PGs but not with alterations in activities of the renin-angiotensin or kallikrein-kinin systems.     

Blood pressure, plasma volume, and catecholamine levels during enalapril therapy in blacks with hypertension

The effect of enalapril, an antihypertensive inhibitor of angiotensin-converting enzyme, on plasma catecholamine levels and plasma volume (PV) has not been well established. In a randomized, double-blind study, 29 subjects (28 blacks and one white) received one of the following dosing regimens: hydrochlorothiazide (HCTZ), 25 mg twice a day (group 1; n = 12); enalapril, 10 mg twice a day (group 2; n = 12); or enalapril, 10 mg twice a day, with HCTZ, 25 mg twice a day (group 3; n = 5). Dosages were doubled after 4 wk if diastolic blood pressure was greater than or equal to 90 mm Hg. After 8 wk of therapy, supine blood pressure decreased by 24.1/16.0 mm Hg (systolic/diastolic) in group 1, by 10.8/4.0 mm Hg in group 2, and by 48.0/27.8 mm Hg in group 3. Mean values of supine plasma levels of norepinephrine, epinephrine, and dopamine did not change with therapy. PV fell 7.9% in group 1, 1.3% in group 2, and 5.0% in group 3. There were no correlations between changes in PV and blood pressure, but a decrease in PV correlated with an increase in plasma norepinephrine levels in the group treated with HCTZ alone (r = -0.65) and in all 29 subjects combined (r = -0.45). Enalapril alone was not very effective in lowering blood pressure in these subjects, but the combination of enalapril with HCTZ was very effective. There was no evidence of a direct effect of enalapril on the sympathetic nervous system or on PV.     

ACE Inhibitors as First-Line Treatment Agents: A Comparative Study of Trandolapril and Enalapril on Casual and Ambulatory Blood Pressures

This double-blind, randomized, parallel-ground study was designed to compare the efficacy of the angiotensin-converting enzyme inhibitors, trandolapril and enalapril, in 65 patients with mild to moderate primary hypertension. After a 4-week, single-blind, placebo run-in period, patients were randomized to receive either trandolapril 0.5 mg or enalapril 2.5 mg once daily. At 2-week intervals, trandolapril was titrated to 1, 2, or 4 mg and enalapril to 5, 10, or 20 mg in order to achieve a goal supine diastolic blood pressure (BP) of <90 mm Hg. In addition to casual BP measurement, 24-h ambulatory BP monitoring was performed at the end of the placebo period (baseline) and after 10 weeks of stable therapy at optimal and/or maximal dosage. Both drugs induced significant and comparable decreases in clinic systolic and diastolic BPs. The mean doses used were 3.2 mg for trandolapril and 16.6 mg of enalapril. The maximal effect was obtained at the highest dosage for both drugs in most patients with a mean decrease in supine diastolic BP of 8.6 mm Hg and 7.3 mm Hg for trandolapril 4 mg and enalapril 20 mg, respectively. Moreover, both agents significantly and similarly reduced mean 24-h as well as awake and sleep ambulatory BPs. Heart rates remained unchanged throughout the study. Our results demonstrate that both trandolapril and enalapril given at high dose exhibited significant decreases in clinic as well as in 24-h, awake, and sleep ambulatory BPs with no clear-up difference between the two treatment regimens. Moreover, our results emphasize the role of ambulatory BP monitoring when assessing the efficacy as well as the duration of action of new antihypertensive agents.     

Effects of felodipine on natriuresis, atrial natriuretic factor, the renin-angiotensin-aldosterone system, and blood pressure in essential hypertension

The aim of this study was to evaluate the short-term and long-term effects of felodipine, a new dihydropiridine calcium antagonist, on arterial blood pressure (BP), the renin-angiotensin-aldosterone system, diuresis, natriuresis, and the atrial natriuretic factor (ANF). In 15 essential hypertensives (WHO class II) BP, venous BP at the posterior tibial vein (VBPTV), diuresis, natriuresis, plasma renin activity (PRA), and both plasma aldosterone and ANF levels were evaluated at the end of a washout period and after two and 24 hours and 30, 90, and 180 days of follow-up with felodipine, 5 mg twice daily. The first dose of felodipine induced a significant decrease in BP, which was associated with increases in both heart rate and VBPTV. An acute diuretic and natriuretic effect, increases in ANF and PRA, and a transient decrease in plasma aldosterone levels were also observed. Throughout the follow-up period, the antihypertensive efficacy remained unchanged, whereas variations in electrolyte balance and hormonal parameters quickly disappeared, except for the increase in PRA, which lasted until the 30th day of therapy. In our study, felodipine showed a great antihypertensive activity during both short-term and long-term treatment. Moreover, the effect of the first dose was characterized by transient increases in circulating ANF and decreases in plasma aldosterone concentrations, which were associated with marked diuresis and natriuresis.     

Metabolic and antihypertensive effects of nebivolol and atenolol in normometabolic patients with mild-to-moderate hypertension.

This was a double-blind, randomized, two-center, active-controlled, prospective, parallel study designed to evaluate the effects of nebivolol at daily doses of 5 mg on lipid and carbohydrate metabolism and on blood pressure in comparison with atenolol at daily doses of 50 mg. Normometabolic subjects with mild-to-moderate essential hypertension were recruited for this study, which included a 4-week, single-blind placebo washout phase and a 12-week double-blind treatment phase. After 12 weeks of treatment, both drugs demonstrated a significant decrease from baseline in high-density lipoprotein (HDL) apolipoprotein A-I (HDL-apoA-I) (nebivolol, P <.02; atenolol, P <.05). A significant reduction in HDL cholesterol (HDL-C) from baseline was also observed with nebivolol (P <.05). There were no significant differences between the drugs for these parameters, and the ratio low-density lipoprotein cholesterol (LDL-C)-to-HDL-C did not change significantly after 12 weeks of active treatment with nebivolol or atenolol. There were no significant changes in total cholesterol, HDL (2) -C, HDL (3) -C, LDL-C, very-low-density lipoprotein cholesterol (VLDL-C), total triglycerides, HDL-triglycerides (TG), LDL-TG, VLDL-TG, total apoB, LDL-B, VLDL-B (including the ratio LDL-C-to-LDL-apoB), or Lp(a) during treatment with both drugs. No significant differences in plasma apoA-I and apoC-III as well as in apoA-I-, C-III-containing lipoprotein particles (including the apoC-III ratio) were observed between the drugs, neither before nor after each active treatment. There were no significant differences between the drugs or within each treatment group in plasma glucose, insulin, or C-peptide concentrations after a 2-hour oral glucose tolerance test. Mean clinic trough sitting systolic blood pressure (SBP)/diastolic blood pressure (DBP) significantly decreased from 150/98 mm Hg at baseline to 141/90 mm Hg at termination for nebivolol and from 160/99 mm Hg at baseline to 145/88 mm Hg at termination for atenolol. No significant between-treatment differences were observed for the mean clinic trough sitting SBP/DBP. Both drugs significantly increased the atrial natriuretic factor (ANF) N-terminal plasma levels, whereas no changes were observed in ANF C-terminal plasma concentrations. A significant decrease (P <. 05) in the plasma adrenocorticotropic hormone levels was observed after administration of both drugs. A significant decrease (P <.05) in plasma cortisol levels was observed only after atenolol treatment. The incidence of adverse events reported during nebivolol treatment was comparable to that observed during atenolol treatment. Heart rate was significantly reduced by both drugs. There were no significant changes in hematology, biochemistry, or urinalysis studies. Neither nebivolol nor atenolol adversely affected lipid or carbohydrate metabolism in normometabolic hypertensive patients. Both treatments demonstrated adequate and similar antihypertensive effects and were well tolerated.     

Assessment of the antihypertensive efficacy of various doses of delapril by office and ambulatory blood pressure measurement: The DEFIND study

This study was undertaken to compare and verify the antihypertensive effects of various delapril doses versus placebo on office and ambulatory blood pressure (BP). After a 2-wk placebo period, 303 patients with mild to moderate essential hypertension were randomized in a double-blind study to 8 wk of treatment with placebo, or delapril 7.5 mg twice daily, delapril 15 mg twice daily, delapril 30 mg twice daily, or delapril 30 mg once daily. BP changes versus baseline and rates of normalized office systolic blood pressure (SBP) > 140 mm Hg and diastolic blood pressure (DBP) > 90 mm Hg, as well as responder office SBP > 140 mm Hg or reduction ≥20 mm Hg and office DBP > 90 mm Hg or reduction ≥10 mm Hg, were calculated. In the intention-to-treat population (n=296), office SBP and DBP reductions were more notable with 30 mg twice daily (15.6/11.5 mm Hg) and 15 mg twice daily (14.8/12.5 mm Hg) than with other delapril regimens (30 mg once daily: 11.8/10.5 mm Hg; 7.5 mg twice daily: 12.9/10.1 mm Hg) and placebo (P< .05 for DBP;P< .01 for SBP). The same was true for frequency of responders (63.8% and 60.3%; P≤.05 vs placebo) and normalized patients (58.6% and 53.4%;P< .05 vs placebo). Analysis of ambulatory BPs confirmed the accuracy of office BPs. Drug-related adverse events occurred in 3.4% to 6.7% of patients given delapril and in 6.5% of those given placebo. The lowest effective dose of delapril, 15 mg twice daily, may be recommended as the initial dose for patients who begin treatment with this agent.     

Treatment of hypertension in the elderly

We have evaluated the effectiveness of antihypertensive therapy for predominant systolic hypertension in 55 patients, aged 61 to 76 years, with untreated systolic blood pressures of at least 160 mm Hg and diastolic blood pressures less than 100 mm Hg. In this retrospective analysis, 41 of the patients had been treated with the centrally acting agent guanabenz (average dose 24 +/- 14 [SD] mg daily) given alone, and 14 had received a combination of guanabenz (17 +/- 10 mg daily) and hydrochlorothiazide (60 +/- 30 mg daily). After six months of therapy, each regimen significantly decreased both systolic and diastolic blood pressures. Moreover, there were no differences between the two treatment regimens in their antihypertensive efficacy, and there was no evidence of orthostatic effects. In both treatment groups, approximately 50% of the patients had excellent therapeutic responses (decrease in supine systolic blood pressure of at least 20 mm Hg). The main side effects of treatment were drowsiness and dry mouth, though these tended to be mild and of short duration. Thus, in predominant systolic hypertension in elderly patients, guanabenz, either alone or in combination with a diuretic, appears to be an effective and well tolerated form of treatment.     

Comparative study of spirapril (quadropril) and amlodipine efficacy. Results of randomized trial in patients with mild to moderate arterial hypertension

AIM: To compare in the non-blind randomised parallel study the efficiency of quadropril and amlodipine in the treatment of mild to moderate arterial hypertension. MATERIAL AND METHODS: A total of 80 patients (57.6 +/- 1.0 years) were included in this study. The patients were randomised in two groups, 40 patients each. Patients of group 1 received monotherapy with quadropril, while those of group 2 were treated with amlodipine. The treatment duration was 8 weeks in both groups. Quadropril was given in a fixed dose of 6 mg once daily. The initial dose of amlodipine was 5 mg/day. In case of insufficient effect the dose was elevated to 10 mg/day. The efficacy was evaluated by changes in blood pressure (BP) measured at rest. Moreover, in 50 randomly chosen patients 24-h monitoring of BP was performed at the start and end of the treatment. RESULTS: In the quadropril group baseline systolic BP reached 158.6 +/- 2.1 mm Hg, diastolic BP--101.8 +/- 0.8 mm Hg, heart rate was 74.3 +/- 1.6 beats/min. In the amlodipine group baseline systolic BP was 159.9 +/- 2.4 mm Hg, diastolic BP--101.8 +/- 1.0 mm Hg, heart rate was 71.3 +/- 1.0 beats/min. Systolic BP decreased at the end of quadropril therapy to 138.5 +/- 2.2 mm Hg, diastolic BP to 88.1 +/- 1.4 mm Hg. No significant change of the heart rate was observed. Under 5 mg of amlodipine systolic BP decreased to 137.9 +/- 2.5 mm Hg and diastolic BP to 87.1 +/- 1.6 mm Hg. Heart rate increased to 73.3 +/- 2.2 beats/min. Under therapy with 10 mg amlodipine systolic BP decreased to 145.9 +/- 3.8 mm Hg, diastolic BP to 89.7 +/- 3.4 mm Hg. Heart rate increased to 77.3 +/- 4.0 beats/min (p < 0.01). The hypotensive effect of quadropril remained stable while the effect of amlodipine decreased by the 8th week of therapy (p < 0.01). Side effects were observed significantly more often in the amlodipine group, then in the quadropril group. The main quadropril side effect was cough. Side effects observed in the amlodipine group were edemas, tachycardia, weakness. CONCLUSION: Both quadropril and amlodipine demonstrated a comparable antihypertensive effect although in 11 of 40 patients in the amlodipine group a dose increase was necessary and tolerability of quadropril was better.     

Irbesartan monotherapy in systemic hypertension: An open-label, uncontrolled trial

Background: Irbesartan is an orally active, specific blocker of the AT₁ receptor of angiotensin II that produces insurmountable antagonism. Irbesartan's plasma half-life of 11 to 15 hours and higher affinity for the AT₁ receptor versus other angiotensin II receptor subtypes may make it a suitable choice for once-daily treatment of hypertension. Few studies have examined the efficacy of this agent in Asian patients.Objective: The purpose of this open-label, uncontrolled study was to assess the 24-hour efficacy of irbesartan once-daily monotherapy in Chinese outpatients with mild to moderate hypertension.Methods: Patients with stage I or stage II hypertension (as defined by the Sixth Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure) were treated with irbesartan once daily for 6 to 8 weeks. The dose of irbesartan was titrated from an initial dose of 150 mg to 275 mg or 300 mg if adequate blood pressure (BP) control was not achieved by week 3 or 4; doses were taken once daily between 8 am and 9 am. For each patient, 24-hour ambulatory BP monitoring was performed twice, once before and once after 6 to 8 weeks of treatment.Results: A total of 25 patients (mean age, 54 years) were enrolled; 24 completed the study. Mean 24-hour systolic/diastolic BP after irbesartan treatment was significantly decreased compared with baseline values (128 ± 14 mm Hg/82 ± 8 mm Hg vs 143 ± 12 mm Hg/91 ± 7 mm Hg, P < 0.05 for both). The mean final dose of irbesartan was 243.8 ± 63.5 mg daily after a 7-week titration period. Mean daytime (6 am to 6 pm) BP decreased from 146 ± 11 mm Hg/94 ± 7 mm Hg to 130 ± 14 mm Hg/84 ± 8 mm Hg (P < 0.05), and nighttime (6 pm to 6 am) BP decreased from 139 ± 14 mm Hg/88 ± 7 mm Hg to 127 ± 15 mm Hg/81 ± 9 mm Hg (P < 0.05). The BP decrease was more pronounced during the day. Before treatment, the circadian variation showed a peak BP at 11 am and a nadir at 4 am. After treatment, significant BP reductions versus baseline (P < 0.05 for both diastolic and systolic BP) were observed for 23 of the 24 hourly mean points. The circadian rhythm of BP cycles was preserved. Mean heart rate did not change after treatment. Two patients reported dizziness and 1 reported heartburn.Conclusions: Irbesartan administered as once-daily monotherapy provided effective BP control during 23 of the 24 hourly mean points while preserving the circadian rhythm of BP cycles, and was well tolerated.     

The effects of single-dose atenolol, labetalol, and propranolol on cardiac and vascular function

The pharmacodynamic effects of single oral doses of atenolol (100 mg), labetalol (300 mg), and propranolol (80 mg) were compared with those of placebo in a randomized, double-blind, Latin square design in 12 patients with hypertension. Atenolol and propranolol both significantly reduced cardiac output (-0.55 vs. -0.31 L/min) and heart rate (-8.0 vs. -6.6 bpm), whereas labetalol had no effect on either parameter (-0.08 L/min; + 1.0 bpm). Labetalol significantly reduced vascular resistance (-339 dynes X cm/sec5), but atenolol and propranolol did not (147 vs. 62 dynes X cm/sec5). Only labetalol significantly reduced the systolic (-15.3 mm Hg), diastolic (-11.5 mm Hg), and mean blood pressures (-12.8 mm Hg). Atenolol significantly reduced only diastolic blood pressure (-5.20 mm Hg), whereas propranolol failed to lower these parameters significantly. These data indicate that the hemodynamic profile of labetalol differs from that of selective and nonselective beta-blockers. Labetalol lowered blood pressure primarily by reducing vascular resistance, whereas reductions in heart rate and cardiac output were the predominant effects of atenolol and propranolol.