Once vs twice daily administration of a fixed combination of captopril plus hydrochlorothiazide in essential hypertension: a double-blind crossover study in known responders to a standard combination.

The purpose of this randomized, double-blind, crossover trial was to compare the hypotensive effects of a fixed combination of captopril (C) 50 mg and hydrochlorothiazide (HCTZ) 25 mg (C 50/HCTZ 25) once daily with those of a fixed combination of C 25 mg and HCTZ 12.5 mg (C 25/HCTZ 12.5) twice daily. We studied 199 patients (108 M, 91 F) with mild to moderate essential hypertension whose BP was already controlled by the co-administration of C 25 mg and HCTZ 12.5 mg twice daily. They were randomly assigned to either C 25/HCTZ 12.5 twice daily during the first 6 weeks and C 50/HCTZ 25 once daily during the second 6 weeks or C 50/HCTZ 25 once daily followed by C 25/HCTZ 12.5 twice daily. Both regimens showed comparable efficacy on office diastolic BP (91.6 vs 91.3 mm Hg). Systolic BP was slightly but significantly higher (P = 0.02) with the once daily formulation (141.2 vs 139.1 mm Hg). Fixed combinations once daily and twice daily resulted in identical working ambulatory BP (133.7 +/- 13/83.6 +/- 8 mm Hg vs 132.4 +/- 11/83.3 +/- 7 mm Hg) without affecting heart rate. Adverse events were reported by 16% of patients and cough was the most common occurring in 7%. In conclusion, these results indicate that the fixed combination of C 50/HCTZ 25 given once daily controls office and working BP as well as the fixed combination C 25/HCTZ 12.5 given twice daily in patients with mild to moderate hypertension.     

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)     

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     

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.     

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)     

A double-blind, randomized, placebo-controlled comparison of the metabolic effects of low-dose hydrochlorothiazide and indapamide

To compare the metabolic effects of indapamide (I) and hydrochlorothiazide (HCTZ) at equivalent hypotensive doses, 11 hypertensive patients (5 male, 8 black, aged 56 +/- 8 yr--mean +/- SEM) having serum uric acid concentrations greater than 8.0 mg/dL while receiving previous therapy with thiazides, received 28-day courses of placebo, indapamide (2.5 mg/d), and HCTZ (25 mg/d) in randomized, double-blind, double-crossover design. Supine and standing blood pressures, weight, pulse rates and sera were obtained after each 28 day period. Blood pressures and weights were lowered (P less than .001 and 0.01, respectively) equally by the diuretics: supine blood pressures fell from 168 +/- 4/104 +/- 2 (placebo) to 153 +/- 4/93 +/- 2 (HCTZ) and 155 +/- 4/94 +/- 2 mm Hg (I); standing blood pressures (after 2 minutes upright) also decreased: 171 +/- 5/104 +/- 2 (placebo) to 156 +/- 5/93 +/- 2 (HCTZ) and 157 +/- 4/94 +/- 2 mm Hg (I). There was a statistically significant difference (P less than .05) across treatments by analysis of variance in both uric acid and potassium concentrations: serum urate (in mg/dL) was lowest with placebo (7.1 +/- 0.3), and rose to 8.3 +/- 0.2 with HCTZ (P less than .001 compared with placebo by paired t test), and 8.1 +/- 0.2 with I (P less than .005 vs. placebo). The urate concentration with I was significantly lower than that with HCTZ (P less than .02), but the magnitude of the difference was small (0.2 mg/dL).(ABSTRACT TRUNCATED AT 250 WORDS)     

Endocrine and vascular responses in hypertensive patients to long-term treatment with diltiazem

Forty patients (aged 28-66 years) with essential hypertension were randomized to 14 weeks of treatment with diltiazem or hydrochlorothiazide (HCTZ) in a double-blind, parallel study design. A significant reduction in supine body weight (-6.0 +/- 1.5 lb; p less than 0.001) and increase in pulse (+6 +/- 2 beats/min; p less than 0.001) occurred in HCTZ-treated patients. Patients receiving diltiazem had no change in weight, but did have a significant fall in pulse (-5 +/- 2 beats/min; p less than 0.05). The average reduction in supine systolic and diastolic blood pressures was comparable in both patient groups (-16 +/- 4/-11 +/- 2 mm Hg for HCTZ; -17 +/- 3/-12 +/- 1 for diltiazem). The reduction in blood pressure in HCTZ- and diltiazem-treated patients was not dependent on baseline plasma renin activity (PRA), but did not correlate significantly with changes in PRA and prostaglandin E2-metabolite (PGE2-M) (r = 0.51, p = 0.016). PRA increased +2.8 +/- 0.6 ng/ml/h (p less than 0.001) with HCTZ and +0.8 +/- 0.3 ng/ml/h (p less than 0.05) with diltiazem. PGE2-M also rose with both drugs (52 +/- 22 pg/ml for HCTZ; 63 +/- 36 pg/ml for diltiazem). Thus, diltiazem and HCTZ were similar in that the depressor response to each drug activated the renin-angiotensin system, which in turn was accompanied by increased production of PGE2-M.     

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   

Effect of eprosartan and enalapril in the treatment of black hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the 40 black patients recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final six weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). This trend was reflected in the black subgroup but the numbers were too small to confirm significance. At study endpoint the mean change in SitDBP was -10.5 +/- 1.9 mmHg and -9.6 +/- 2.4 mmHg for eprosartan-treated and enalapril-treated patients, respectively. The mean change in SitSBP for eprosartan-treated black patients was -18.8 +/- 3.5 mmHg and for enalapril-treated patients was -10.5 +/- 3.7 mmHg. The black subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and appears to be safe in black hypertensive patients. The combination of eprosartan and HCTZ was also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. The incidence of treatment-associated cough in the black subgroup was low, but there were no apparent differences between treatment groups.     

Arterial and endocrine effects of a combination of an angiotensin converting enzyme inhibitor and a vasodilator in normotensive healthy volunteers.

The aim of the present study was to look for possible additive or synergistic effects of the combined oral administration of a single dose of an angiotensin converting enzyme (ACE) inhibitor, benazepril (10 mg) (B), and a long-acting vasodilator, cadralazine (5 mg) (C), on blood pressure, arterial parameters, and active plasma renin. The study was carried out in eight normotensive subjects according to a double-blind, randomized, placebo-controlled, crossover design. Blood pressure (BP), heart rate, humeral artery diameter (D), carotid-femoral pulse-wave velocity (PWV), finger-pulse ratio (FPR), and plasma active renin (PAR) were measured at baseline and every 2 h over 8 h. A significant treatment effect was observed for supine and tilted BP, FPR, PWV, and PAR. The largest decrease in supine systolic and diastolic BP was observed with the combination (10.0 +/- 6.9/7.2 +/- 3.7 mm Hg). Six hours after drug intake, the mean changes in FPR were 0.05 +/- 0.24 (P), -0.06 +/- 0.30 (C), 0.13 +/- 0.32 (B), and 0.28 +/- 0.34 (B + C), and the mean changes in PWV were 0.14 +/- 0.66 m/s (P), 0.09 +/- 0.54 m/s (C), -0.29 +/- 0.50 m/s (B), and -0.55 +/- 0.48 m/s (B + C). PAR was more markedly augmented with the combination of the two drugs (142 +/- 40 pg/ml) than with benazepril alone (90 +/- 62 pg/ml). It was concluded that a single noneffective dose of a vasodilator administered together with an ACE inhibitor in normotensives can lower blood pressure and increase arterial compliance and plasma active renin.     

Comparison of equal-weight oral dosages of verapamil hydrochloride and diltiazem hydrochloride in patients with mild to moderate hypertension

The clinical efficacy, safety, and tolerability of oral verapamil and diltiazem, at total daily dosages of equal weight, were evaluated in a placebo-controlled, double-blind crossover study. Thirty-six ambulatory patients with chronic, stable, mild to moderate hypertension (supine diastolic blood pressure of 94-116 mm Hg) received a dosage of either verapamil or diltiazem 80 mg t.i.d. as the hydrochloride salt for one week after an antihypertensive-drug washout period. Each then received 120 mg of the same drug t.i.d. for one week. After another two-week washout period, the patients were crossed over to the other drug. Each patient had a 12-lead electrocardiogram and measurement of supine and standing blood pressure weekly. In the 32 patients completing the study, low-dose verapamil reduced supine diastolic blood pressure (DBP) from a mean of 101.5 +/- 5.2 to 95.3 +/- 9.5 mm Hg; high dose verapamil reduced DBP to 90.9 +/- 7.4 mm Hg. Standing DBP was reduced to a similar degree. Diltiazem showed an almost identical effect: Supine DBP was reduced from a mean of 101.7 +/- 5.3 to 94.0 +/- 10.1 mm Hg with the low dose and to 91.0 +/- 8.6 mm Hg with the high dose, with similar effects on standing DBP. The high dose of both drugs significantly increased the QTc interval, and both doses of diltiazem significantly increased the PR interval compared with baseline. Both drugs exhibited consistent efficacy with minimal adverse effects. The electrophysiologic safety profile of verapamil was superior to that of diltiazem.     

Antihypertensive therapy with once-daily administration of terazosin, a new alpha 1-adrenergic-receptor blocker

The antihypertensive activity of terazosin, an investigational alpha 1-adrenergic-receptor blocker, and its effect on blood lipids were compared with placebo in a double-blind study. After a 3-week placebo baseline period, patients were randomized to receive terazosin (n = 22) or placebo (n = 16). The dose of terazosin was titrated over 2 weeks to a maintenance dosage of 10 mg once daily for 4 weeks. Antihypertensive efficacy was assessed: (1) at the end of the 24-hour dosing interval by comparing the average blood pressure (BP) after 3 and 4 weeks of maintenance therapy to the average BP after 2 and 3 weeks of placebo therapy, and (2) for 3 hours after drug ingestion at the final visit in comparison to the predose BP at that visit. At the end of the 24-hour dosing interval, 10 mg of terazosin reduced the mean supine systolic BP from 155.6 to 152.2 mm Hg and mean supine diastolic BP from 101.9 to 99.0 mm Hg (p less than 0.05). During the 3 hours after drug ingestion, mean supine systolic and diastolic pressures decreased maximally from 151.8 to 142.7 mm Hg (p less than 0.05) and from 99.5 to 91.0 mm Hg (p less than 0.05) respectively. No supine BP reduction differed significantly from the placebo response. During terazosin therapy there was a nonsignificant increase in mean body weight of 1.4 +/- 2.9 kg and no change in blood lipids. Thus the drug demonstrated greater antihypertensive activity 1-3 hours after ingestion than at the end of the 24-hour dosing interval.(ABSTRACT TRUNCATED AT 250 WORDS)     

Antihypertensive effect of trimepranol, a new beta-blocking agent.

Trimepranol (TMP) is a new propranolol-like, non-selective beta-adrenoreceptor blocking drug. Its antihypertensive effect versus placebo was evaluated in a double-blind corss-over study in 25 ambulatory patients, whose supine diastolic blood pressure (BP) was at least 95 mm Hg. After four weeks treatment with placebo, the dose of TMP was titrated weekly until the supine diastolic BP was below 95 mm Hg or intolerable side effects occurred. The trimepranol dose thus determined was 10 mg bid for three patients, 20 mg bid for twelve patients and 40 mg bid for ten patients. The subsequent double-blind cross-over study consisted of two six weeks treatment periods, either with trimepranol followed by placebo (Group I) or in reverse order (Group II). BP and heart rate at the end of these periods were compared. Supine BP fell from 156 +/- 3/105 +/- 2 mm Hg at the end of placebo periods to 140 +/- 2/93 +/- 1 mm Hg (p less than 0.001) for systolic and diastolic BP at the end of trimepranol periods, when the data of Groups I and II are pooled. In 19 out of 25 patients, supine diastolic BP declined below 95 mmHg during the trimepranol period. A statistically significant correlation was found between the antihypertensive and bradycardic effects of trimepranol. Mild side effects occurred in the heart volumes of the patients. We conclude that bid trimepranol is an effective antihypertensive agent.     

A Randomized,Controlled Trial Comparing Diltiazem,Hydrochlorothiazide, and Their Combination in the Therapy of Essential Hypertension

Study Objectives . To compare the efficacy of combination therapy with sustained-release diltiazem and hydrochlorothiazide (DTZ SR-HCTZ) with that of monotherapy with DTZ SR, HCTZ, or placebo in the treatment of essential hypertension; and to determine whether the addition of a diuretic to diltiazem at apparent optimum doses of each agent significantly enhances their antihypertensive effects. Design . Multicenter, randomized, double-blind, placebo-controlled, parallel-group trial with a 6-week treatment phase. Setting . Private and university-based clinics. Patients and Participants . Subjects of either sex, ranging in age from 18–70 years, with a diagnosis of stable essential hypertension made from two consecutive weekly mean supine diastolic blood pressure (DBP) readings of 95 mm Hg or above to 110 mm Hg or less that varied 7 mm Hg or less after 4–6 weeks in the baseline phase. Of the patients enrolled, 298 met the inclusion criteria. Interventions . Combination therapy with DTZ SR-HCTZ 120 mg-12.5 mg, or monotherapy with DTZ SR 120 mg or HCTZ 12.5 mg, or placebo was administered twice daily. Measurements and Main Results . Combination therapy with DTZ SR-HCTZ lowered both supine DBP and SBP significantly (p<0.005) more than either single agent. The combination also lowered DBP and SBP significantly more than either monotherapy. During a 12-hour in-clinic monitoring period spanning a dosing interval, both the combination and DTZ SR therapies maintained efficacy, whereas the antihypertensive effects of HCTZ dissipated after 8 hours. Treatment-related adverse events for the combination and HCTZ were similar but slightly greater than those for DTZ SR and placebo. Conclusions . The addition of a diuretic to sustained-release diltiazem produced an enhanced antihypertensive effect compared with monotherapy with either individual agent.     

Influence of two doses of irbesartan on non-dipper circadian blood pressure rhythm in salt-sensitive black hypertensives under high salt diet

The authors examined whether the blockage of angiotensin II receptors by irbesartan (IRB) can reverse the "non-dipper" circadian rhythm of blood pressure (BP) to a "dipper" pattern in black salt-sensitive hypertensive patients submitted to a high-sodium loading. Twelve black salt-sensitive hypertensive patients (seven men; age, 35-58 years) on a high-sodium diet (300 mmol Na+ per day) were followed for 8 weeks. A placebo was given during the first 2 weeks, followed by 2 weeks on IRB 150 mg/d, 2 weeks on placebo, and 2 weeks on IRB 300 mg/d. On the last day of placebo, IRB 150 mg/d, and IRB 300 mg/d treatments, 24-hour BP and urinary 24-hour excretion of Na+ and potassium were measured. On placebo, ambulatory mean arterial pressure (MAP) was 112 mm Hg+/-2 (24 h), 112 mm Hg+/-2 (daytime), and 111 mm Hg+/-2 (nighttime), showing a clear circadian non-dipper profile. Versus placebo, IRB 150 mg/d reduced MAP by 4.2 mm Hg+/-1.1 (24 h), 2.6 mm Hg+/-0.8 (daytime) and 6.0 mm Hg+/-1.3 (nighttime; P<0.05 vs. placebo) and IRB 300 mg/d reduced MAP by 7.8 mm Hg+/-1.4 (24 h), 3.9 mm Hg+/-1.1 (daytime), and 11.8 mm Hg+/-2.1 mm Hg (all P<0.02 vs. placebo); nighttime/daytime MAP decrease was 0.7+/-0.8% on placebo, 3.5+/-2.1% on IRB 150 mg/d, and 7.0+/-1.2% on IRB 300 mg/d (P<0.02 for trend). Compared with placebo, IRB significantly increased serum potassium and plasma renin activity and reduced fractional excretion of potassium and plasma aldosterone levels in a dose-dependent manner. Body weight and urinary sodium excretion did not change throughout the study. It was concluded that the angiotensin receptor blocker IRB can reverse the BP non-dipper profile in salt-sensitive hypertensive patients on a high-salt diet, restoring nocturnal BP decline by a predominantly dose-dependent reduction of nighttime BP. Although the increment of potassium balance and reduction of aldosterone may account for this effect, it occurs independently of increased natriuresis. It is speculated that blunting of nighttime BP decrease in black salt-sensitive hypertensive patients may be related to a deficient suppression of the renin-angiotensin system during the night.     

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.     

Effect of eprosartan and enalapril in the treatment of elderly hypertensive patients: subgroup analysis of a 26-week, double-blind, multicentre study. Eprosartan Multinational Study Group

A double-blind comparator study was performed in 528 hypertensive patients [baseline sitting diastolic blood pressure (SitDBP) 95-114 mmHg]. The primary objective was to compare the incidence of drug-related cough in patients treated with enalapril and eprosartan. The secondary objective was to compare antihypertensive efficacy between treatments. This paper reports the results of a prespecified subgroup analysis performed in the patients under and over 65 years of age recruited into the study. Eprosartan was titrated from 200 mg b.i.d. to 300 mg b.i.d. and enalapril from 5 mg o.d. to 20 mg o.d. over 12 weeks. Hydrochlorothiazide (HCTZ) 12.5-25 mg o.d. could be added where required to the treatment for the final 6 weeks of the titration phase if SitDBP > or = 90 mmHg. Patients received the maximum titrated dosage during the maintenance phase. In the study overall, the incidence of cough at monotherapy endpoint was significantly higher in the enalapril-treated group than in the eprosartan-treated group (p = 0.018). Similar mean changes in blood pressure from baseline were evident with each treatment. The elderly subpopulation mirrored the response of the study as a whole. Both treatments lowered BP with a further reduction evident following the addition of HCTZ at week 18. In conclusion, eprosartan is effective and safe in elderly hypertensive patients. The combination of eprosartan and HCTZ is also well tolerated and provided additional efficacy in those patients not responding to eprosartan alone. Compared with eprosartan enalapril was associated with an increased risk of cough. These results suggest that, irrespective of age, patients may be less likely to discontinue treatment with eprosartan than with an ACE inhibitor.     

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.     

A comparison of fosinopril and hydrochlorothiazide with hydrochlorothiazide in non-insulin-dependent diabetes mellitus patients with mild to moderate hypertension

A multicentre, randomised, double-blind, parallel-group study of the tolerability and antihypertensive efficacy of once-daily fosinopril 20 mg/hydrochlorothiazide 12.5mg (FOS/HCTZ) compared with once-daily hydrochlorothiazide 25mg (HCTZ) was conducted in 142 patients with non-insulin-dependent diabetes mellitus (NIDDM) and mild to moderate essential hypertension. After 12 weeks of treatment, both groups had statistically significant mean changes from baseline in seated diastolic and systolic blood pressures (FOS/HCTZ, -15.0mm Hg; HCTZ, -11.9mm Hg for seated diastolic blood pressure). The difference between treatment groups was statistically significant (p < 0.001). In addition, normalisation of seated diastolic blood pressure was achieved in 85% of FOS/HCTZ patients compared with 71% of HCTZ patients. A statistically significant difference (p < 0.05) in favour of FOS/HCTZ was observed for the total number of favourable responses (normalisation or >/=10mm Hg reduction in seated diastolic blood pressure) at week 12 and for the end-point analysis. One FOS/HCTZ patient and 5 HCTZ patients discontinued treatment because of adverse events. No clinically significant changes in serum glucose, potassium or cholesterol were observed. A slight but statistically significant increase in fasting triglycerides occurred with FOS/HCTZ compared with HCTZ (+26.1 vs +13.5 mg/dl, respectively; p < 0.05). These results show that the combination of fosinopril and hydrochlorothiazide has considerable potential as an effective antihypertensive regimen that does not significantly alter glucose or lipid metabolism in patients with NIDDM.     

Felodipine vs hydralazine: a controlled trial as third line therapy in hypertension. Cooperative Study Group.

In a placebo-controlled, double-blind, randomized, parallel group study one hundred and one patients with supine diastolic blood pressure greater than or equal to 100 mm Hg phase V, despite treatment with atenolol 100 mg plus chlorthalidone 25 mg once daily also received either felodipine 5-20 mg twice daily or hydralazine 25-100 mg twice daily for 6 weeks. Felodipine achieved a lower supine blood pressure (mean +/- s.d. 177/108 +/- 29/8-138/82 +/- 19/8 mm Hg) than hydralazine (174/109 +/- 25/8-149/92 +/- 26/11 mm Hg), (P less than 0.05/P less than 0.001). Felodipine also lowered supine diastolic blood pressure to less than 90 mm Hg more often than hydralazine (42 vs 22 patients, P less than 0.001). The incidence of unwanted effects was similar in both groups. The felodipine treated patients experienced more ankle swelling and flushing than those in the hydralazine group who experienced more headache and minor gastro-intestinal upset.