Comparison of hydrochlorothiazide and atenolol as initial treatment in uncomplicated hypertension

Summary After screening a local population in the northern part of The Netherlands for hypertension, 119 patients with a diastolic pressure (DP) between 95 and 120 mmHg were randomised and treated either with 50 mg hydrochlorothiazide (n=59) or 100 mg atenolol (n=60). After 1 month of treatment 6 patients in the hydrochlorothiazide group and 24 patients in the atenolol group had reached a DP90 mmHg (p<0.001). 43 of the 50 non-responders to hydrochlorothiazide were switched to atenolol and 30 of the 35 non-responders to atenolol were changed to hydrochlorothiazide. One month after the switch 19 patients in the atenolol group and 2 patients in the hydrochlorothiazide group had reached a DP90 mmHg (p<0.001). After 6 months of treatment 32 of the 43 atenolol responders and 7 of the 8 hydrochlorothiazide responders were still receiving the same medication, as their DP was still90 mmHg. Non-responders to either medication were given the combination (n=46). 21 patients now became normotensive as did a further 10 after increasing the dose of atenolol to 200 mg. Thus, in all 70 patients had a blood pressure 90 mmHg after treatment for 4 months. Both drugs induced a significant reduction in the total of number of complaints after 1 month of treatment. They did not differ from each other. The reduction was seen both in responders and non-responders and persisted during treatment for 6 months. It is concluded that in terms of short-term efficacy the cardioselective, hydrophilic beta adrenoceptor-blocking drug atenolol is preferable to hydrochlorothiazide in the treatment of uncomplicated hypertension.     

A dose-response study of atenolol in mild to moderate hypertension in general practice.

A double-blind, crossover, multicentre study of 98 previously untreated patients with mild to moderate essential hypertension was carried out in general practice to assess the effect of 50 mg, 100 mg, and 200 mg atenolol, given once daily, compared with that of placebo over a period of 4 weeks each. At the end of the double-blind phase, all patients took 100 mg atenolol daily for a further 8 weeks. All three doses of atenolol produced statistically significant falls in systolic and diastolic pressure and pulse rate (p less than 0.001). The lowest pressures were achieved with 100 mg daily; a difference of 22/15 mmHg at the end of the double-bling phase, and a difference of 25/16 mmHg at the final observation. Body weight, blood urea, blood uric acid, and serum electrolytes remained within normal limits throughout the study. The incidence of side-effects with 50 mg and 100 mg atenolol was not significantly different from that caused by placebo, but the incidence of tiredness at the 200 mg dose level was greater than that caused by placebo and by the lower doses. The incidence of possible side-effects elicited by a questionnaire was low, the greatest number being volunteered by patients taking placebo. It is concluded that the optimal dose of atenolol for treating patients with mild to moderate hypertension in general practice is 100 mg daily.     

Effects of hydrochlorothiazide combined with amiloride in atenolol-resistant hypertensive patients

Twenty hypertensive outpatients WHO stage I or II, with supine diastolic blood pressure greater than or equal to 95 mmHg at the end of a 4-week treatment period with atenolol (Tenormin) 100 mg daily, continued atenolol in free association with half a tablet of Moduretic (i.e., hydrochlorothiazide 25 mg + amiloride 2.5 mg) for a further 4 weeks. Atenolol monotherapy induced a drop of systolic blood pressure from 175.0 +/- 11 (mean +/- s.d.) mmHg to 158.7 +/- 6 mmHg (p less than 0.01), and of diastolic blood pressure from 113.5 +/- 8 mmHg to 102.7 +/- 5 mmHg (p less than 0.01). After 4 weeks with atenolol in association with half a tablet of Moduretic, systolic blood pressure further decreased to 145.7 +/- 8 mmHg (p less than 0.01), and diastolic blood pressure to 90.2 +/- 10 mmHg (p less than 0.01). Seven out of 20 patients remained with diastolic blood pressure greater than or equal to 95 mmHg despite the above combination therapy. In these patients, the doubling of diuretic dose (hydrochlorothiazide 50 mg + amiloride 5 mg) in combination with atenolol resulted in a further drop in systolic pressure (to 142.1 +/- 9 mmHg) and diastolic (to 92.1 +/- 6 mmHg) (both p less than 0.01). Plasma potassium concentration showed a slight and non-significant increase during atenolol monotherapy (from 4.4 +/- 0.5 mEq/l to 4.6 +/- 0.7 mEq/l; n.s.).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of atenolol 50 mg and 100 mg as initial treatment in uncomplicated mild to moderate hypertension

Summary After screening a local population in the northern part of The Netherlands for hypertension, 59 patients with a diastolic pressure (DP) between 95 and 130 mmHg were randomized and treated either with 50 mg atenolol (n=29) or 100 mg atenolol (n=30) for 1 month. There was no significant difference between the two treatments, neither in the fall in systolic and diastolic pressures nor in the number of complaints reported. It is concluded that in the initial treatment of uncomplicated mild to moderate hypertension, 100 mg atenolol has no advantage over a 50 mg dose.     

Safety and antihypertensive efficacy of carvedilol and atenolol alone and in combination with hydrochlorothiazide

Carvedilol has been shown to be effective and safe in patients with essential hypertension when given as monotherapy. In this double-blind, randomized, group-comparative study, 2 groups of 59 patients with mild to moderate essential hypertension [median supine systolic/diastolic blood pressure at baseline (SBP/DBP), 168/105 mm Hg] were treated with either 25 mg carvedilol once daily (o. d.) or 50 mg atenolol o. d. for 4 weeks. Responders at 4 weeks (DBP, < 90=" mmhg)=" terminated=" the=" study.=" nonresponders=" continued=" the=" study.=" hydrochlorothiazide=" (hctz)=" was=" added=" at=" 25=" mg=" o.=" d.=" for=" a=" further=" 6=" weeks.=" the=" median=" blood=" pressure=" decreased=" under=" monotherapy=" with=" carvedilol=">n = 59) from 167/105 at baseline to 155/94 mmHg after 4 weeks, and in the atenolol group (n=59) it decreased from 168/105 to 162/97 mmHg. The patients who received carvedilol in combination with HCTZ and were evaluated for efficacy (n = 38) showed a decrease in SBP/DBP from 156/97 at the end of monotherapy to 145/88 mmHg after 10 weeks; the combination of atenolol with HCTZ (n = 44) reduced BP from 162/97 to 147/88. Both carvedilol and atenolol were safe when given either alone or in combination with HCTZ. In conclusion, after long-term administration, 25 mg carvedilol o. d. and 50 mg atenolol o. d. significantly reduced both SBP and DBP over 24 h. The addition of HCTZ led to a further increase in antihypertensive efficacy. Combined treatment with carvedilol or atenolol and HCTZ was very well tolerated, without hypotensive events or relevant changes in objective safety parameters.     

Enalapril in moderate to severe hypertension: A comparison with atenolol

Patients with moderate to severe essential hypertension (mean untreated supine blood pressure 190/112 mm Hg) received once daily enalapril 20-40 mg or atenolol 50-100 mg, supplemented if required by hydrochlorothiazide 25-100 mg, in a randomized observer-blind trial. Both regimens produced a highly significant reduction in supine and standing blood pressure. There was no significant difference in the antihypertensive effects of enalapril and atenolol when they were used as monotherapy. After hydrochlorothiazide was added to patients not achieving 'target' blood pressure, the fall in systolic pressure was significantly greater in the enalapril group than in the atenolol group, despite similar dosage of hydrochlorothiazide in the two groups. At the end of 6 months' treatment, a supine diastolic blood pressure of 90 mm Hg or below was achieved in 74% of patients on enalapril plus hydrochlorothiazide and 56% of patients on atenolol plus hydrochlorothiazide. This difference was not statistically significant. A small rise in plasma urea and creatinine was observed in the enalapril group and a small rise of urea only in the atenolol group. These changes were statistically significant but of uncertain clinical importance. This study confirms that once daily enalapril and atenolol, both alone and in combination with hydrochlorothiazide, are effective drugs in the management of moderate to severe hypertension.     

Comparison of labetalol,propranolol and hydralazine in hypertensive out-patients

Summary In a randomised cross-over trial the combination labetalol/hydrochlorothiazide was compared with the combination of propranolol/hydralazine/hydrochlorothiazide in 34 uncomplicated hypertensive patients, who were not satisfactorily controlled with hydrochlorothiazide 50 mg alone. The elevated diastolic pressure (D.P.) in 27 patients responded satisfactorily to the labetalol schedule and in 28 patients to the propranolol/hydralazine schedule. No difference was found in the rate of decrease of D.P., nor in the disappearance of hypertension — related complaints. Although the duration of the washout between treatments was at least one month, treatment was significantly more efficacious during the second period. Labetalol pre-treatment especially seemed to enhance the effect of subsequent propranolol/hydralazine administration. Side effects due to therapy were rare and were not related to any particular treatment. The median daily dose of labetalol in responders was 600 mg and that of propranolol/hydralazine 120/60 mg (in both therapies hydrochlorothiazide 50 mg was given in addition). Patients showed a slight preference for the labetaol medication. It is concluded that labetalol/hydrochlorothiazide and propranolol/hydralazine/hydrochlorothiazide are equally satisfactory in the treatment of uncomplicated hypertension.     

Antihypertensive effect of doxazosin and atenolol in short- and long-term double-blind comparison

The antihypertensive effect and safety of doxazosin once daily as well as the effect on serum lipids was compared with that of atenolol once daily in 40 patients with mild to moderate hypertension. During the first 4 weeks, all patients received placebo therapy. During the subsequent 46 weeks, patients were randomized to doxazosin or atenolol treatment. Treatment was initiated with 1 mg doxazosin or 50 mg atenolol once daily. The dose could be doubled biweekly for 10 weeks until a final dose of 16 mg doxazosin or 100 mg atenolol was reached. The patients then entered the maintenance phase for 36 weeks. The average final dose of doxazosin was 9.2 +/- 1.3 (SEM) mg and that of atenolol was 76.5 +/- 6.2 mg. During the 46 weeks of active treatment, the recumbent diastolic blood pressure (DBP) tended to be lower (p less than 0.05) in patients receiving atenolol at 10, 12, and 22 weeks of treatment. Recumbent systolic BP (SBP) and standing SBP and DBP were not different, however, between patients receiving doxazosin and those receiving atenolol. Recumbent and standing heart rate (HR) were lower (p less than 0.01) during atenolol. The decrease in serum total triglycerides, total cholesterol, and low-density lipoprotein (LDL)-cholesterol after 46 weeks of doxazosin was different (p less than 0.05) from the changes observed during atenolol therapy. Our data indicate that the antihypertensive action of doxazosin is accompanied by favorable effects on serum lipids.     

Enalapril versus atenolol in the treatment of hypertensive smokers

Summary A randomised crossover study has been done to compare the antihypertensive efficacy of enalapril and atenolol in 45 smoking, hypertensive men. Treatment was started with enalapril 20 mg/d or atenolol 50 mg/d and, if necessary, the doses were doubled after 4 weeks to achieve a sitting diastolic blood pressure 95 mm Hg, after which hydrochlorothiazide was added, if necessary.Both drugs lowered blood pressure significantly. However, enalapril was more efficient in lowering both systolic and diastolic blood pressure; the mean difference was significant after both 4 and 8 weeks in the sitting systolic (11.6 mm Hg and 7.9 mm Hg) and diastolic (3.3 mm Hg and 3.0 mm Hg) pressures and in the erect systolic pressures (8.2 mm Hg and 7.2 mm Hg), and after 8 weeks in the supine systolic pressure, too (8.9 mm Hg). The effect on enalapril was especially marked in moderate (<20 cigarettes/day) smokers. The need for diuretics was also significantly less in the enalapril group.It appears that angiotensin-converting enzyme inhibitors may be superior to -adrenoceptor blockers in the treatment of hypertensive smoking patients.     

Effect of antihypertensive treatment with valsartan or atenolol on sexual activity and plasma testosterone in hypertensive men

OBJECTIVE: To compare the effects of valsartan and atenolol on sexual activity and plasma testosterone in newly diagnosed, previously untreated, essential hypertensive male subjects. METHODS: One hundred and ten hypertensive men, aged 40-49 years, homogeneous for marital status and without any previous sexual dysfunction were randomly treated with valsartan 80 mg daily (o.d.) or atenolol 50 mg o.d. for 16 weeks according to a double-blind, parallel-arm study design. After 8 weeks the dose was doubled in the non-responders (diastolic blood pressure > 90 mmHg). Clinical evaluation was performed after 8 weeks and 16 weeks of treatment and included blood pressure and plasma testosterone measurements and the compilation of a questionnaire about sexual activity (sexual intercourse episodes/month). RESULTS: Despite similar blood pressure lowering, atenolol significantly reduced sexual activity (from 6.0 sexual intercourse episodes/month to 4.2 sexual intercourse episodes/month, P < 0.01 vs placebo), whereas valsartan increased it, although not significantly (from 5.8 sexual intercourse episodes/month to 7.4 sexual intercourse episodes/month, P = 0.058), compared with placebo, but significantly compared with the atenolol group ( P < 0.05). Testosterone was reduced by atenolol (from 18.2 nmol/l to 13.8 nmol/l, P < 0.01 vs baseline) but was not affected by valsartan (from 17.6 nmol/l to 18.3 nmol/l). CONCLUSIONS: These results suggest that atenolol induces a worsening of sexual activity and a reduction of testosterone, whereas valsartan does not worsen sexual activity and does not change testosterone levels.     

Atenolol-nifedipine combinations compared to atenolol alone in hypertension: efficacy and tolerability.

1. In a double-blind, randomised, three-way-crossover study, 25 patients with sitting diastolic blood pressure between 95 and 120 mm Hg (Phase V) after 4 weeks' run-in on atenolol 50 mg twice daily, received atenolol 50 mg twice daily alone, atenolol 50 mg plus nifedipine 20 mg each twice daily and atenolol 50 mg plus nifedipine 40 mg each twice daily in three treatment periods each lasting 4 weeks. 'Washout' periods were not included. 2. The two combination treatment regimes lowered the 12 h post-dose blood pressure more effectively than did atenolol alone, but the high dose nifedipine combination was no more effective than the low dose nifedipine combination. Sitting systolic BP (+/- s.e. mean) at the end of each period was 174 +/- 5 mm Hg after the atenolol run-in, 170 +/- 5 mm Hg with atenolol alone, 156 +/- 5 mm Hg with the low dose combination and 158 +/- 4 mm Hg with the high dose combination. Corresponding diastolic BP readings were 106 +/- 2 mm Hg, 106 +/- 2 mm Hg, 97 +/- 2 mm Hg and 99 +/- 2 mm Hg respectively. 3. Side-effects tended to occur less commonly with the low dose of the fixed combination than with atenolol alone. An increased number of side-effects occurred with the 40 mg twice daily doses of nifedipine, particularly flushing/erythema, oedema of the ankles/feet, and a hot feeling in the legs. These differences did not reach significance. 4. Overall compliance was good (98 +/- 0.7 s.e. mean %) and was similar within the different treatment regimes.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cadralazine and chlorthalidone as a second-step drug with atenolol in hypertensive patients: Differences in blood pressure control during exercise

Summary The long-term efficacy of a new vasodilator, cadralazine (ISF 2469), and chlorthalidone have been compared in 20 hypertensive patients not adequately controlled by atenolol. After 4 weeks of treatment with atenolol 100 mg once daily, patients whose diastolic blood pressure was >95 mmHg were randomly divided into two groups to receive in addition to atenolol, either cadralazine 15 mg once daily or chlorthalidone 25 mg once daily. Both treatments were administered for 6 months. At the end of treatment with atenolol and after 3 and 6 months of combination therapy, blood pressure and heart rate were measured at rest and during bicycle exercise 24 h after the last dose. Compared to atenolol alone, both cadralazine and chlorthalidone caused a significant and similar reduction in resting blood pressure. Both groups showed an increase in diastolic blood pressure during exercise while receiving atenolol alone. The addition of chlorthalidone did not modify the pressor response to exercise, whereas patients taking cadralazine had a decrease in exercise diastolic blood pressure, which was fully evident after 6 months of therapy. The reduction in exercise diastolic blood pressure induced by cadralazine was proportional to the increase in exercise heart rate, suggesting a fall in peripheral vascular resistance. Chlorthalidone caused a significant increase in serum glucose and uric acid and a decrease in K⁺, whereas no change was observed during cadralazine It is concluded that cadralazine given once a day with atenolol has the same efficacy in controlling blood pressure at rest as the combination of atenolol and chlorthalidone, and in addition it improves the pressor response to dynamic exercise and does not cause unwanted metabolic effects.     

Comparison of quinapril and atenolol as single drugs or in combination with hydrochlorothiazide in moderate to severe hypertensives, using automated ambulatory monitoring.

1. Forty patients with moderate to severe hypertension and daytime ambulatory diastolic blood pressure > or = 90 mm Hg were randomized double-blind to once-daily treatment with either quinapril up to 20 mg (n = 20) or atenolol up to 100 mg (n = 20) as single drugs or in combination with hydrochlorothiazide 25 mg over a period of 12 weeks. 2. Conventional and ambulatory blood pressure, heart rate, side effects and metabolic changes were compared at the end of the run-in period on placebo, after 4 weeks on monotherapy and at the end of the 12-week period of active treatment. 3. Quinapril and atenolol reduced conventional blood pressure equally with substantial additional effect seen on combination therapy. The two regimens induced a significant decrease in ambulatory BP. However, the atenolol treated ambulatory hypertensive group experienced significantly greater decreases in diastolic blood pressure during 24 h, awake and sleep periods than did the quinapril group. 4. Adverse reactions were mild with both drugs except for severe Raynaud phenomenon in one patient in the atenolol group. Triglyceride levels were significantly increased with atenolol alone and in combination with hydrochlorothiazide. 5. Thus, within the limits of the dose ranges tested, quinapril and atenolol as single drugs or in combination with hydrochlorothiazide reduce significantly conventional and ambulatory blood pressure in moderate to severe hypertensives, but atenolol is more effective in reducing ambulatory diastolic blood pressure.     

Sustained release verapamil in hypertension. Results from a noninvasive ambulatory blood pressure monitoring and a clinical study

Summary The antihypertensive effect of a new sustained-release matrix formulation of verapamil 200 mg was investigated in a dose-response study in patients with mild to moderate essential hypertension. Noninvasive ambulatory blood pressure measurements were recorded over 24 h in 6 patients with diastolic blood pressure 100 mmHg. The patients received sustained-release verapamil 200 mg once daily and twice daily in a randomized order. Each medication period lasted 2 weeks. Verapamil 200 mg twice daily had a better antihypertensive effect than the same dose once daily. After a 6-week placebo period 27 patients with a diastolic blood pressure 100 mmHg were included in a double-blind clinical trial. The patients received sustained release verapamil 200 mg once daily and twice daily in a randomized crossover manner. Each medication period lasted 6 weeks, with an intervening 6-week placebo period. A diastolic blood pressure of 95 mmHg was achieved in 6 patients with the once-daily regimen and in 14 with the twice-daily regimen. The mean fall in diastolic blood pressure was 4 and 9 mmHg, respectively (p<0.05). We conclude that sustained-release verapamil 200 mg once daily gives a satisfactory blood pressure response only in a minority of patients, while 200 mg twice daily has a significantly better antihypertensive effect. Both doses were well tolerated.     

Treatment with atenolol prevents progression of microalbuminuria in type I diabetic patients.

Nine patients with Type I diabetes mellitus, diastolic blood pressure of 90 to 100 mmHg and persistent microalbuminuria of greater than or equal to 30 micrograms/min were treated with 50 to 100 mg atenolol daily for 3 years in an uncontrolled pilot study to assess the effect of long-term reduction of blood pressure on microalbuminuria. Treatment with atenolol prevented progression of microalbuminuria with a median (range) urinary albumin excretion rate before treatment of 74 (33 to 196) micrograms/min and 50 (5 to 123) micrograms/min after 3 years of therapy (p less than 0.05). Blood pressure was significantly reduced from 156 (121 to 187) mmHg systolic and 95 (90 to 100) mmHg diastolic before treatment to 143 (112 to 168) mmHg systolic (p less than 0.04) and 82 (66 to 84) mmHg diastolic (p less than 0.0003) at 3 years. Measurements of renal function and diabetic control remained unchanged throughout the study period. These results suggest that early and prolonged use of antihypertensive therapy is beneficial in slowing down progression of microalbuminuria.     

Rapid onset of action of oral labetalol in severe hypertension.

Nine patients with persistently elevated diastolic blood pressure, exceeding 130 mmHg, received an oral dose of labetalol ranging from 200 mg to 400 mg. In all patients, this produced a significant and gradual decline in recumbent systolic and diastolic blood pressure, unaccompanied by symptoms or complications, with only minor changes in heart rate. Individual variation in the rate of blood pressure fall suggested differences in absorption and first-pass metabolism. It is suggested that the efficacy of oral labetalol merits further investigation in the rapid control of severe hypertension.     

ANGIOTENSIN-CONVERTING ENZYME INHIBITION AS FIRST-LINE TREATMENT FOR HYPERTENSION

1. Perindopril (4 mg) was compared with atenolol (50 mg), captopril (25 mg b. d.) or a diuretic (hydrochlorothiazide 50 mg and amiloride 5 mg) in three studies involving a total of 503 hypertensive patients with a diastolic blood pressure (DBP) of 95–125 mmHg.
2. A 4 week single-blind placebo period preceded 12 weeks of active treatment. Dose titration was at weeks 4 and 8 if supine DBP >90 mmHg. The dose was doubled and if necessary a diuretic was added in the atenolol or captopril comparisons, and atenolol was added in the diuretic study.
3. The fall in supine blood pressure (BP) was 27/17 mmHg with perindopril and 21/16 mmHg for atenolol. Monotherapy controlled 55% of patients on perindopril and 48% on atenolol, increasing to 78% and 58% with the addition of hydrochlorothiazide, respectively. Captopril caused a BP fall of 19/12 mmHg compared with 27/18 mmHg for perindopril, with 49% of both groups being controlled on monotherapy.
4. Diuretic addition produced a greater antihypertensive effect with perindopril (75%) compared with 57% for captopril in achieving control. Perindopril caused a comparable fall in supine BP to the diuretic combination 27/19 mmHg and 31/18 mmHg, but the fall in erect systolic BP was significantly greater for the diuretic. At 3 months, 85% of the diuretic group and 78% of the perindopril group achieved the target BP.
5. A multicentre trial of 856 patients treated with perindopril (690 patients treated for 1 year or more) has shown that BP control is maintained in the long term with a low incidence of side-effects (7.9%) causing withdrawal from treatment. These studies demonstrate that perindopril compares favourably with standard first-line therapy for mild to moderate hypertension.     

A pharmacokinetic and pharmacodynamic study of the potential drug interaction between tasosartan and atenolol in patients with stage 1 and 2 essential hypertension

The primary objective of this study was to evaluate the pharmacokinetics (PK) and pharmacodynamics (PD) of tasosartan and atenolol administered alone and concomitantly under steady-state conditions in 17 patients ages 18 to 65 years diagnosed with stage 1 to 2 essential hypertension. After a 3- to 14-day qualification period, all patients received placebo tasosartan on days--1 through 5 and 25 through 34, atenolol alone (50 mg) on days 1 through 5, atenolol (50 mg) + tasosartan (50 mg) on days 6 through 19, and tasosartan (50 mg) alone on days 20 through 24. A PK and PD evaluation of atenolol alone was performed on study day 5. On study day 19, PK and PD of both tasosartan and atenolol were assessed. PK and PD evaluation for tasosartan alone was assessed on study day 24. The coadministration of atenolol + tasosartan did not affect the pharmacokinetics of tasosartan, its major metabolite (enoltasosartan), or atenolol when compared with tasosartan or atenolol administered separately. For area under the change in diastolic blood pressure curve, the reduction was significantly greater after tasosartan + atenolol compared with that after atenolol alone (336 +/- 85 and 190 +/- 71 mmHg.24 h; p < 0.05 for combination and atenolol alone, respectively; mean +/- SEM). Combination therapy also caused a maximal reduction in diastolic blood pressure that is significantly more than with monotherapy with atenolol (-27 +/- 2 mmHg and -20 +/- 2 mmHg, respectively, p < 0.05). The additive effects of tasosartan and atenolol in decreasing diastolic blood pressure may provide a rationale for combination antihypertensive therapy.     

A double-blind comparison of felodipine and hydrochlorothiazide added to metoprolol to control hypertension

Summary Seventy-six uncomplicated hypertensive patients treated in General Practice, whose seated diastolic blood pressure (Phase V) (dBP) remained 95 mmHg after a minimum of 4 weeks treatment with metoprolol 50 mg b.i.d. as antihypertensive monotherapy, were randomized to receive the selective calcium antagonist felodipine 5 mg b.i.d. or hydrochlorothiazide 12.5 mg b.i.d. in addition to metroprolol 50 mg b.i.d. The trial duration was 8 weeks, the dose of the felodipine or hydrochlorothiazide being doubled after 4 weeks if control of BP (dBP <90 mmHg) was not achieved on the initial doses.Over the trial period of 8 weeks, felodipine reduced dBP from 102 to 85 mmHg and hydrochlorothiazide from 101 to 91 mmHg; the dBP reduction in the felodipine group was greater than that in the hydrochlorothiazide group (17 vs 9 mmHg) and the attained dBP lower in the felodipine group. About half of the patients in each group required the higher dose.Both regimes were effective and well tolerated. In the dosages used, felodipine was a slightly more effective antihypertensive drug than hydrochlorothiazide when added to metoprolol. There was no apparent difference in the tolerability of the two regimes.     

The pharmacokinetics and pharmacodynamics of doxazosin compared with atenolol during long-term double-blind treatment

Summary The pharmacodynamics of doxazosin and atenolol were compared on single study days in 39 patients with mild to moderate hypertension receiving long-term double-blind treatment. The pharmacokinetics of doxazosin were investigated in the 20 patients receiving doxazosin. Individually titrated once daily doses of doxazosin were 1, 2, 4, 8 or 16 mg and of atenolol 50 or 100 mg. Patients were first investigated after at least one month on constant dose and then again after at least a further three months. Mean plasma concentrations of doxazosin were proportional to dose and the plasma half-life was 11.5 h and independent of dose. There was low variability of doxazosin plasma concentrations between patients receiving the same dose. Concentrations and half-life were unchanged during the period between investigations. Mean reductions of AUC (0–12 h) blood pressure during the 12-h period post-dose and of blood pressure at 24 h post-dose were not statistically different between doxazosin and atenolol. There was effective control of blood pressure by both drugs at all time points of the day. The pharmacokinetic and pharmacodynamic results obtained in this study are compatible with the use of doxazosin in a once daily dose regimen for the treatment of essential hypertension.