Tolerability and efficacy of fosinopril and hydrochlorothiazide compared with amiloride and hydrochlorothiazide in patients with mild to moderate hypertension

This 6-month multicentre, randomised, double-blind, parallel group clinical trial compared the tolerability and antihypertensive efficacy of a once-daily combination of fosinopril 20mg/hydrochlorothiazide 12.5mg (FOS/HCTZ) with a combination of amiloride 5mg/hydrochlorothiazide 50mg (AMI/HCTZ) in 217 patients with mild to moderate essential hypertension. Adverse events related to hypotension or to specifically targeted clinical laboratory values were observed infrequently with FOS/HCTZ compared with AMI/HCTZ: with FOS/HCTZ, only 4 of 104 patients (3.9%) experienced such events, compared with 16 of 113 (14.1%) in the AMI/HCTZ group (p < 0.001). While statistically significant differences were found between the two treatment groups for changes from baseline in serum potassium, cholesterol, triglyceride and glucose values, the metabolic profile was uniformly unfavourable towards the AMI/HCTZ group; for example, reductions in potassium and elevations in cholesterol, triglyceride and glucose were more pronounced with the AMI/HCTZ group than with the FOS/HCTZ group. Both antihypertensive regimens produced statistically significant reductions from baseline in seated diastolic blood pressure that were equivalent at most points of measurement during double-blind treatment. Therapeutic response rates were high (>/=95%) and were similar for both regimens throughout the study. Because the relative risk for adverse events was markedly less over the long term with FOS/HCTZ than with AMI/HCTZ, the combination of fosinopril and hydrochlorothiazide may offer significant tolerability advantages over amiloride plus hydrochlorothiazide for such patients.     

Efficacy and tolerability of valsartan in combination with hydrochlorothiazide in essential hypertension

OBJECTIVE: This study compared the efficacy and tolerability of two combination regimens of valsartan and hydrochlorothiazide (HCTZ) with valsartan monotherapy in patients with essential hypertension inadequately controlled with valsartan 80mg once daily. PATIENTS AND METHODS: A total of 708 patients with inadequately controlled blood pressure after 4 weeks' treatment with valsartan 80mg once daily participated in this double-blind comparative trial. Patients were randomly allocated once-daily treatment with valsartan 80mg, valsartan 160mg, valsartan 80mg + HCTZ 12.5mg or valsartan 80mg + HCTZ 25mg for 8 weeks. RESULTS: Statistically significant decreases in mean sitting diastolic blood pressure (SDBP) and mean sitting systolic blood pressure (SSBP) from baseline were seen in all treatment groups (least squares mean change from baseline SDBP: -5.1mm Hg, -6.2mm Hg, -8.2mm Hg, -10.8mm Hg; SSBP: -3.9mm Hg, -6.5mm Hg, -9.8mm Hg, -16.0mm Hg for valsartan 80mg, valsartan 160mg, HCTZ 12.5mg combination, HCTZ 25mg combination, respectively). A significant difference for mean SDBP, SSBP and responder rates in favour of the combination regimens was observed compared with either valsartan monotherapy. All treatments were well tolerated with the percentage of patients reporting treatment-related adverse experiences at any time ranging from 9.9% (valsartan 160mg) to 21.0% (HCTZ 25mg combination). CONCLUSION: The study demonstrated that a combination of valsartan 80mg and HCTZ 12.5mg or 25mg provides an effective and well tolerated treatment in patients who need additional blood pressure control beyond valsartan monotherapy.     

Tiapamil and hydrochlorothiazide: a double-blind comparison of two antihypertensive agents

Tiapamil is an investigational calcium-channel antagonist that is chemically related to verapamil. The antihypertensive efficacies of tiapamil and hydrochlorothiazide (HCTZ) were compared in a randomized double-blind trial. Thirty patients, age 44 to 80 years, with mild to moderate hypertension (World Health Organization stage I-II) entered and completed the study. Previous therapy, if any, was stopped for at least one week prior to study initiation, and patients received placebo tablets for two weeks. The participants were then given active medication, which was titrated for the next three weeks; HCTZ 25 to 50 mg bid or tiapamil 300 to 600 mg bid was given until supine diastolic blood pressure (BP) was no higher than 90 mm Hg or the ceiling dose was reached. Both drugs caused a significant reduction in systolic as well as in diastolic blood pressure (P less than .01). The reduction was seen in both the supine and erect position. The median decrease in supine systolic blood pressure from baseline to the end of treatment was 20 mm Hg in the tiapamil group and 27 mm Hg in the hydrochlorothiazide group, whereas the median decrease in supine diastolic blood pressure was 14 mm Hg and 18 mm Hg, respectively. The median difference in supine diastolic BP reduction after HCTZ and tiapamil administration was 3.8 mm Hg (not significant). There were no significant changes in heart rate. Dizziness occurred in one patient taking tiapamil and in three receiving HCTZ. One patient receiving HCTZ developed acute arthritis urica.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative evaluation of enalapril and hydrochlorothiazide in elderly patients with mild to moderate hypertension

Initial treatment of elderly hypertensive patients with an angiotensin-converting enzyme inhibitor is currently discouraged due to such patients' typical low-renin profile. To validate this principle, we studied 38 elderly males (aged greater than or equal to 65 years) with mild to moderate hypertension, comparing hemodynamic responses to and subjective impressions of enalapril or hydrochlorothiazide (HCTZ). After gradual withdrawal of existing antihypertensive therapy and a four-week, single-blind placebo period, each patient was randomized in a double-blind fashion to receive either enalapril 10-20 mg/d or HCTZ 12.5-25 mg/d for two to four weeks. Combination therapy with both agents was employed if either alone failed to reduce seated diastolic BP to less than or equal to 90 mm Hg. Equivalent proportions of patients receiving enalapril or HCTZ (8 of 19 and 10 of 19, respectively; p = ns) responded with significant reductions in systolic and diastolic BP in seated and standing positions. Combination therapy was most effective in patients receiving HCTZ prior to enalapril. In patients receiving enalapril before HCTZ, BP changes were minimal. No adverse effects were observed in the enalapril group but occurred in an equivalent fraction of patients in the other groups (4 of 10 HCTZ alone, 6 of 20 enalapril + HCTZ; p = ns). We conclude that enalapril may be considered a reasonable monotherapeutic antihypertensive agent in some elderly patients. Combination with HCTZ is beneficial in patients who fail to respond adequately to HCTZ alone.     

A comparison of felodipine and propranolol as additions to hydrochlorothiazide in the treatment of hypertension

Summary Eighty one patients with uncomplicated hypertension who required additional antihypertensive medication (diastolic Phase V [dBP]95 mm Hg) after 4 weeks treatment with hydrochlorothiazide (HCTZ) 25 mg o.m. were randomized to receive felodipine 5 mg b.i.d. (n=40) or propranolol (n=41) 80 mg b.i.d. in addition to HCTZ 25 mg o.m. If the dBP measured about 12 h post-dose was not 90 mm Hg after 4 weeks, the dose of felodipine or propranolol was doubled. The double blind trial period was 8 weeks for all patients.Over the 8 week period, felodipine reduced the seated dBP from 100 to 83 mm Hg and propranolol from 101 to 86 mm Hg. The attained seated dBPs were significantly different in the two groups. About one third of patients in each group received the high dose of second-line therapy. After 8 weeks 91% of patients receiving HCTZ+felodipine and 84% receiving HCTZ+propranolol had a dBP 90 mm Hg. Both regimens were well-tolerated with an equal incidence but different pattern of adverse events (felodipine: flushing, headache and peripheral oedema; propranolol: dyspepsia, fatigue and vasospasm).In this 8-week study, felodipine and propranolol were safe and effective second-line antihypertensive drugs when added to hydrochlorothiazide. At the doses selected, felodipine was at least as effective as propranolol.     

Treatment of essential hypertension in Asians: enalapril as monotherapy versus combination therapy with hydrochlorothiazide

This study compared enalapril maleate (Enaprin) as a single antihypertensive agent and enalapril plus hydrochlorothiazide in Korean patients to determine if one regimen is superior to the other in terms of efficacy and subjective adverse effects. After a 1-week washout period, 12 patients were randomized to receive enalapril 10 mg daily and 13 patients to receive enalapril 10 mg daily plus hydrochlorothiazide 25 mg daily. After 2 weeks, enalapril was increased to 20 mg daily if diastolic blood pressure was greater than 90 mm Hg. The study period was 12 weeks. The mean changes in diastolic blood pressure in mm Hg were enalapril alone -10.7 +/- 10.5 mm Hg and enalapril plus hydrochlorothiazide -25.1 +/- 12.1 mm Hg (difference between the two groups significant at p less than 0.01). Mean dose of enalapril required to achieve goal blood pressure was 18.8 mg for monotherapy and 13.0 mg for combination therapy (p less than 0.05). Adverse effects were comparable. We concluded that enalapril in combination with hydrochlorothiazide is more effective and safe, and allows for lower dosing of enalapril than the drug as monotherapy in Korean hypertensives.     

Telmisartan/hydrochlorothiazide: in the treatment of essential hypertension

Oral telmisartan/hydrochlorothiazide (HCTZ) combines two antihypertensive agents, a selective angiotensin II receptor antagonist with a long half-life and once-daily administration, and a thiazide diuretic. In two large, 8-week, double-blind trials, patients with hypertension unresponsive to monotherapy who received combined telmisartan/HCTZ 80/12.5 or 40/12.5 mg/day, achieved significantly larger reductions in diastolic and systolic blood pressure (BP), than recipients of continued telmisartan monotherapy (p < 0.05 for all). Compliance with telmisartan/HCTZ 80/12.5 mg/day was 98.9%. In patients with hypertension, telmisartan/HCTZ resulted in similar BP reductions to oral enalapril/HCTZ and atenolol/HCTZ in 26-week double-blind trials and greater reductions than oral losartan/HCTZ 50/12.5 mg/day in a 6-week randomised open-label trial (p < 0.001). Up to one-third of patients with hypertension initially responsive to telmisartan 40 or 80 mg/day in a 4-year study required the eventual addition of HCTZ 12.5 or 25 mg/day and/or another agent to maintain BP control. BP was controlled in about 75% of these by adding only HCTZ. In clinical trials of up to 4 years, including elderly patients, telmisartan/HCTZ had similar tolerability to placebo, with few reports of hypokalaemia. Most adverse events were mild to moderate.     

Efficacy and Safety of Olmesartan Medoxomil and Hydrochlorothiazide Compared with Benazepril and Amlodipine Besylate

BACKGROUND: Most patients with stage 2 hypertension require two or more antihypertensive agents in order to achieve the BP goals recommended in current treatment guidelines. Accordingly, combinations of two drugs with different mechanisms of antihypertensive action are widely used. OBJECTIVE: The aim of this randomized, double-blind, multicenter 12-week study was to compare the efficacy, safety, and tolerability of a combination of olmesartan medoxomil/hydrochlorothiazide (HCTZ) with that of benazepril plus amlodipine besylate in patients with stage 2 hypertension. METHODS: Patients were eligible for randomization following a 3- to 4-week placebo run-in period if they had either (i) mean seated DBP>or=90 mm Hg but<115 mm Hg and mean seated SBP>or=160 mm Hg but <200 mm Hg, or (ii) mean seated DBP>or=100 mm Hg but<115 mm Hg. The difference in mean seated SBP measured on two separate visits during the run-in period was required to beor=95 mm Hg and<115 mm Hg or SBP>145 mm Hg and相似文献   

Efficacy and tolerability of candesartan cilexetil/hydrochlorothiazide and amlodipine in patients with poorly controlled mild-to-moderate essential hypertension.

The antihypertensive efficacy and tolerability of combination therapy with candesartan cilexetil, 16 mg plus hydrochlorothiazide (CC/HCTZ), 12.5 mg was compared with that of amlodipine, in a multicentre, double-blind, randomised, parallel-group study in patients with mild-to-moderate essential hypertension inadequately controlled by monotherapy. After a two week run-in period on existing therapy, patients with a sitting diastolic blood pressure (DBP) of 90-110 mmHg and a sitting systolic blood pressure (SBP) 相似文献   

Concomitant therapy with labetalol and hydrochlorothiazide in moderate to moderately severe essential hypertension

Labetalol is a competitive, nonselective antagonist of both beta 1 and beta 2 adrenoceptors. It has been suggested that labetalol reduces blood pressure (BP) predominantly by decreasing peripheral vascular resistance while maintaining cardiac output. We conducted a double-blind, randomized study to assess the antihypertensive effect of labetalol in patients with a standing diastolic blood pressure (SDBP) between 105 and 119 mm Hg. The study consisted of three separate phases in succession. Phase I was a single-blind, placebo washout phase, two to four weeks in length. Those patients with a SDBP greater than or equal to 105 mm Hg at the end of phase I entered phase II, in which they were administered labetalol in a forced titration of 100 mg bid to 400 mg bid. Those with a SDBP less than or equal to 90 mm Hg on the 400 mg bid regimen for two weeks were maintained on labetalol alone (N = 8). Those patients whose BP was not controlled (SDBP greater than or equal to 99 mm Hg, N = 15) were randomized in a double-blind fashion to receive either hydrochlorothiazide (HCTZ) or placebo in addition to labetalol for the next five weeks. Eight of the 15 patients received HCTZ and seven received placebo. The BPs at baseline and at the end of phase II were similar in the two groups.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of once daily felodipine 10 mg ER and hydrochlorothiazide 25 mg in the treatment of mild to moderate hypertension

Summary The efficacy of extended release felodipine 10 mg (ER) o.d., a new dihydropyridine calcium antagonist, and 25 mg hydrochlorothiazide (HCTZ) o.d. have been compared in a randomized, double-blind, crossover trial in 28 mildly to moderately hypertensive subjects (supine diastolic blood pressure, BP, 95 mm Hg and 110 mm Hg on three separate occasions).Both drugs significantly reduced systolic and diastolic BP in the sitting position felodipine from 157.1/93.8 mm Hg at baseline to 133/78.9 mm Hg 2.5 h after medication and to 138/82.7 mm Hg after 2 weeks of treatment, and HCTZ from 156/95.6 mm Hg to 147/88.4 mm Hg 2.5 h after medication and to 149/89.5 mm Hg also after 2 weeks.A decrease of the same magnitude in standing systolic and diastolic BP was observed after both treatment regimens with the exception of diastolic BP 2.5 h after dosing with HCTZ, which was not significantly lower. At all times (2.5 h and 2 weeks), the reduction in systolic and diastolic BP was greater after felodipine compared to HCTZ. Heart rate was significantly increased after felodipine in both the sitting and standing positions, and both 2.5 h following medication and after 2 weeks of treatment. The difference between the regimens was significant only 2.5 h after dosing. Overall, felodipine 10 mg ER o.d. was superior to 25 mg HCTZ o.d. in lowering BP.Presented in part at the Vth Scientific Meeting of the American Society of Hypertension, 17–20 May 1990, New York     

Trough-to-peak ratio,smoothness index,and circadian blood pressure profile after treatment with once-daily fixed combination of losartan 100 and hydrochlorothiazide 25 in essential hypertension

The once-daily fixed combination of losartan 100 mg/hydrochlorothiazide 25 mg was evaluated for safety and efficacy in a multicenter open study by using 24-h ambulatory blood pressure monitoring in untreated patients with moderate-to-severe essential hypertension or patients with uncontrolled hypertension despite treatment with monotherapy or low-dose combination. After a 2-week washout period, 41 patients (22 men, 19 women) aged 34-74 years, showing a mean daytime blood pressure > 135/85 mm Hg, were treated with losartan 100 mg/hydrochlorothiazide 25 for 8 weeks. Ambulatory blood pressure was monitored at the end of the washout period and during the last week of treatment. A significant reduction in the average values of clinic blood pressure (from 169.9 +/- 13.5 mm Hg to 139.5 +/- 15.6 mm Hg, p < 0.001 for systolic blood pressure [SBP]; and from 102.2 +/- 7.1 mm Hg to 85.1 +/- 9.5 mm Hg, p < 0.001 for diastolic blood pressure [DBP]) was observed after treatment in the whole group of 41 patients. Likewise, average values of both 24-h SBP and 24-h DBP were significantly reduced (from 145.7 +/- 13.1 mm Hg to 128.3 +/- 14.6 mm Hg, p < 0.001 for 24-h SBP; and from 90.3 +/- 7.3 mm Hg to 79.2 +/- 8.6 mm Hg, p < 0.001 for 24-h DBP). The average lowering at peak was 20.2 +/- 11.8 mm Hg for 24-h SBP and 12.1 +/- 7.4 mm Hg for 24-h DBP, whereas the lowering at trough was 17.8 +/- 12.0 mm Hg and 10.4 +/- 8.1 mm Hg, respectively. The trough-to-peak ratio (T/P) was 0.88 for SBP and 0.86 for DBP, and the smoothness index was 7.36 for SBP and 6.37 for DBP. The response rate was 87.8% (blood pressure lowering > 5 mm Hg of either 24-h SBP or 24-h DBP average values). Among responders, T/P ratio was 0.89 for SBP and 0.87 for DBP, and the smoothness index was 8.09 for SBP and 7.15 for DBP. No side effects or changes in metabolic parameters were observed. The fixed combination of losartan 100 mg/hydrochlorothiazide 25 was very effective and well tolerated.     

Double-blind study of dilevalol and captopril, both in combination with hydrochlorothiazide, in patients with moderate to severe hypertension.

Sixty-one patients (41 men, 20 women) aged 29-73 years, with moderate to severe hypertension, were enrolled in a multicentre study to compare the efficacy, safety, and tolerability of dilevalol (D) and captopril (C). At the end of the baseline period, supine diastolic blood pressure (SuDBP) was 105-140 mm Hg on hydrochlorothiazide (HCTZ) 25 mg once daily and placebo t.i.d. Patients were randomly assigned to D + HCTZ (n = 29) or C + HCTZ (n = 32) and entered phase II titration of D (100-800 mg b.i.d.) or C (12.5 mg b.i.d. to 50 mg t.i.d.). If SuDBP was greater than 99 mm Hg, hydralazine was added (25 mg once daily to 50 mg b.i.d.). If SuDBP was less than or equal to 99 mm Hg, patients entered phase III, a 3-month maintenance period. Demographic profiles were not significantly different between the two groups. Baseline supine BP (mean +/- SEM) was similar in the two groups (D + HCTZ: 182 +/- 3/112 +/- 1; C + HCTZ: 179 +/- 4/113 +/- 1 mm Hg), as was baseline standing BP (D + HCTZ: 175 +/- 3/114 +/- 2; C +/- HCTZ: 173 +/- 4/113 +/- 1 mm Hg). At the end of phase II, there were no significant differences between treatments with respect to the changes in BP from baseline.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive treatment in elderly patients aged 75 years or over: a 24-week study of the tolerability of candesartan cilexetil in relation to hydrochlorothiazide

OBJECTIVE: To assess the safety and tolerability of the AT1-receptor blocker candesartan cilexetil in relation to the diuretic hydrochlorothiazide (HCTZ) in elderly patients. DESIGN AND SETTING: A multicentre, double-blind, randomised, parallel group study. 32 general practice centres and 3 hospital centres in Denmark and Finland participated in this study. Patients: 185 patients aged > or =75 years with mean sitting diastolic blood pressure (DBP) of 95 to 114mm Hg. INTERVENTIONS: After a placebo run-in period of 4 to 8 weeks, patients were randomised to once daily treatment with candesartan cilexetil 8mg or HCTZ 12.5mg for 24 weeks. In both treatment groups the dosage could be doubled after > or =2 weeks [according to blood pressure (BP) response] and, if necessary, subsequently decreased if the higher dosage was poorly tolerated. MAIN OUTCOME MEASURES: Proportion of patients with at least 1 adverse event; changes in laboratory values, electrocardiogram and BP during the double-blind treatment period. RESULTS: Once daily candesartan cilexetil 8 to 16mg was very well tolerated. The most common adverse events in both treatment groups were dizziness or vertigo and headache. Although the profile of adverse events was generally similar in the 2 treatment groups, it was notable that hypokalaemia and hyperuricaemia were not found in patients treated with candesartan cilexetil but occurred in 8.1 and 6.5%, respectively, of patients treated with HCTZ. At week 24, the adjusted mean changes in sitting DBP (24 hours postdose) from baseline were -12.0mm Hg [95% confidence interval (CI) -1 0.4 to -13.6] in patients treated with candesartan cilexetil and -11.4mm Hg (95% CI -9.3 to -13.6) in patients treated with HCTZ. The difference between treatments in favour of candesartan cilexetil was not statistically significant. CONCLUSIONS: This study shows that antihypertensive treatment with candesartan cilexetil in elderly patients (aged > or =75 years) is well tolerated with a good safety profile and avoids the metabolic adverse effects of diuretic therapy.     

A 52-week comparison of lisinopril, hydrochlorothiazide, and their combination in hypertension

Lisinopril is a long-acting converting-enzyme inhibitor. A 52-week study was undertaken to compare the antihypertensive efficacy and safety of lisinopril, hydrochlorothiazide (HCTZ), and a combination of the two drugs in 24 patients with a sitting diastolic blood pressure (DBP) of 90 to 120 mm Hg. After a four-week single-blind placebo-washout phase, ten patients received lisinopril, ten received HCTZ, and four received the combination in increasing doses in a double-blind fashion for the next 12 weeks. The target blood pressure was less than 90 mm Hg DBP and a decrease of at least 10 mm Hg. For the next 12 weeks, the responders continued to receive the same medications; however, the nonresponders from the two groups received the combination, increasing the number of patients receiving both to 13. The DBP was controlled in eight of the ten patients with lisinopril, three of the ten patients with HCTZ, and 11 of 13 (four original and nine nonresponders) with the combination. For the next 28 weeks, 17 patients agreed to continue into a single-blind phase, during which blood pressure was controlled in six of the seven patients who were treated with lisinopril alone and nine of ten who received the combination. The heart rate rose significantly in the HCTZ-treated patients during the short-term treatment and decreased significantly in those treated with lisinopril during the long-term phase. Side effects were more frequent in patients receiving the combination but were always mild and subsided spontaneously. Lisinopril appeared to be more effective than HCTZ as a step-1 drug, and the combination was superior to either agent alone.     

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.     

Olmesartan medoxomil/amlodipine/hydrochlorothiazide: fixed-dose combination in hypertension

The antihypertensive agents olmesartan medoxomil, amlodipine and hydrochlorothiazide (HCTZ) are now available as a fixed-dose combination tablet (olmesartan medoxomil/amlodipine/HCTZ). In a 12-week, randomized, double-blind, multicentre trial (TRINITY) in adults with moderate to severe hypertension, olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy produced significantly greater least squares mean reductions from baseline in seated diastolic blood pressure (BP) [primary endpoint] and seated systolic BP than olmesartan medoxomil/amlodipine, olmesartan medoxomil/HCTZ or amlodipine?+?HCTZ. Furthermore, significantly more patients achieved BP goals and targets with the triple combination regimen than with any of the dual combination regimens at week 12, with olmesartan medoxomil?+?amlodipine?+?HCTZ also demonstrating benefit over the dual regimens in terms of ambulatory BP control. According to subgroup analyses of the TRINITY trial, olmesartan medoxomil?+?amlodipine?+?HCTZ was more effective in reducing BP and achieving BP goals than each of the dual therapies, irrespective of hypertension severity, age, sex, race or diabetes mellitus status. Data from a number of smaller clinical studies indicated that olmesartan medoxomil?+?amlodipine?+?HCTZ triple combination therapy provides antihypertensive efficacy in patients whose BP is not adequately controlled with olmesartan medoxomil?+?amlodipine. Olmesartan medoxomil?+?amlodipine?+?HCTZ was generally well tolerated in the TRINITY study, with adverse events usually being mild or moderate in severity.     

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 and hydrochlorothiazide in hypertensive Africans

Summary The antihypertensive efficacy both of angiotensin converting enzyme (ACE) inhibitors and thiazide diuretics has been claimed to be influenced by plasma renin activity, which declines with age and is low in blacks. In a double-blind, placebo-controlled, double-dummy, randomized, parallel-group preliminary study, the antihypertensive efficacy and tolerability of the ACE inhibitor enalapril (20 mg day^–1) and hydrochlorothiazide (50 mg day^–1) were evaluated and compared for 4 weeks in 20 African patients with essential hypertension. The two groups had similar baseline clinical features and serum Na⁺ and K⁺ levels.Hydrochlorothiazide caused a significant and sustained fall in erect blood pressure with a reflex tachycardia. Enalapril exerted only a modest antihypertensive action, but significantly reduced erect heart rate.Direct comparison of hydrochlorothiazide — and enalapril — induced hypotension suggested a greater fall in subjects on the thiazide. The 95% confidence limits for the thiazide-enalapril difference in antihypertensive action at the end of the study was 39.5 to –7.5 mm Hg systolic and 22.0 to –6.6 mm Hg diastolic. The maximal blood pressure fall after hydrochlorothiazide was positively correlated with age (r=0.50;p<0.05), whilst that of enalapril was inversely related age to (r=–0.57,p<0.05).The results are compatible with the notion that ACE inhibitor monotherapy may be less effective than thiazide diuretic treatment in African and black patients with essential hypertension. The findings also support the concept that age and racial factors may influence the response to antihypertensive treatment.     

Long term effect of timolol and hydrochlorothiazide,or hydrochlorothiazide and amiloride,in essential hypertension

Summary Twenty-four patients with mild to moderate hypertension were treated for up to 60 weeks with hydrochlorothiazide and either placebo, timolol, or timolol and amiloride. The effect of adding timolol and amiloride to hydrochlorothiazide was evaluated in a double blind trial. In 22 of the 24 patients a supine diastolic blood pressure below or equal to 95 mm Hg was produced by hydrochlorothiazide and timolol. Replacing a potassium supplement with amiloride increased the antihypertensive effect.