Antihypertensive Therapy in Elderly Patients with Isolated Systolic Hypertension: Third Progress Report of the Syst-Eur Trial

The Syst-Eur trial is a randomised, double-blind, placebo-controlled trial that examines the hypothesis that antihyper-tensive treatment can prevent or delay cardiovascular complications in elderly patients (> 60 years) with isolated systolic hypertension. On March, 1st 1993 a total of 1395 patients with a sitting systolic blood pressure on placebo averaging 160–219 mmHg and a diastolic blood pressure < 95 mmHg were randomised into this trial. The placebo and active treatment groups were similar at randomisation with respect to age (7 2 ±7 years, mean ± SD), percentage of women (68%), percentage of patients with cardiovascular complications (30%) and sitting blood pressures (175±12/85±6 mmHg). The fall in sitting systolic and diastolic blood pressures from baseline to 2 years was significantly more pronounced (p<0.001) in the actively treated (-22±18/-6±9 mmHg) as compared with the placebo treated Syst-Eur patients (-10±20/- 1±9 mmHg). Active treatment consists of nitrendipine if necessary associated with a converting-enzyme inhibitor and a thiazide. Whether treatment with these antihypertensive agents results in a clinically meaningful reduction of cardiovascular morbidity and mortality is the subject of investigation in this trial.     

A screening programme for hypertension in general practice

It is recommended that hypertensive patients with a diastolic blood pressure of 100 mmHg be treated. However, it has been proposed that only 50% of hypertensives are diagnosed, and of these, 50% are not treated. We therefore set out to identify hypertensive patients in our practice, who were then actively treated, some in a clinical trial of ketanserin. Of the 3,384 patients (1,667 males and 2,707 females) who were invited to our surgery for a blood pressure measurement, 2,606 patients (77%) attended. The overall prevalence of hypertension in the patients, aged 35-65 years was 2.9%. This prevalence increased with age: from 1.0% in the 35-44 year age group to 3.5% at 45-54 years, and 4.4% at 55-64 years. The mean systolic but not diastolic blood pressure increased with age. There were more male hypertensives than females, except over 55 years of age. Of the 84 hypertensives identified after one visit, the majority remained hypertensive after an additional visit, and 31 agreed to participate in a clinical trial. After a four-week placebo run-in, 22 patients had a diastolic blood pressure above 95 mmHg and were randomly allocated to receive ketanserin 40 mg twice daily or metoprolol 100 mg twice daily. Treatment continued double-blind for three months. There were no significant differences in blood pressure reduction between the treatment groups. The heart rate was reduced more by metoprolol. There were no withdrawals for side effects and no major differences in subjective complaints between the two treatment groups.     

Treatment of hypertension in the elderly. III. Response of isolated systolic hypertension to various doses of hydrochlorothiazide: results of a Department of Veterans Affairs cooperative study. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

In a double-blind randomized study, we evaluated the effects of 25 mg vs 50 mg of hydrochlorothiazide in 51 elderly patients (aged 68.9 +/- 7.0 years) with isolated systolic hypertension (blood pressure, 160 to 239 mm Hg systolic and less than 90 mm Hg diastolic). Dose levels could be increased to twice daily to control blood pressure. The reductions in blood pressure (25.4/6.8 mm Hg and 28.9/7.4 mm Hg) and proportion of patients in whom blood pressure was controlled (78% and 89%) were similar in the lower- and higher-dose groups during the titration phase. However, serum potassium level was reduced more in the higher-dosage (0.57 mmol/L) than the lower-dosage (0.17 mmol/L) group. There were no significant changes in blood pressure during a 24-week maintenance phase. No patient required withdrawal from the study because of adverse effects, and cognitive-behavioral function was well preserved. We conclude that hydrochlorothiazide is effective and well tolerated in older patients with isolated systolic hypertension, many of whom may be effectively treated with 25 mg of hydrochlorothiazide once daily.     

Initial antihypertensive drug therapy. Final report of a randomized, controlled trial comparing alpha-blocker and diuretic

We compared the effect on serum lipids of an alpha-blocker (prazosin) and a diuretic (hydrochlorothiazide) used as initial antihypertensive drug treatment for 102 men and women with less severe hypertension (average entry blood pressure, 148/97 mm Hg, with no major organ system damage). A two-center trial randomized patients to treatment with either prazosin or hydrochlorothiazide; the alternate drug was added if adequate blood pressure control was not achieved with the originally assigned drug, and patients were removed from any drug they were not able to tolerate. After an average of 40 weeks on the assigned drug regimen, a decline was observed in prazosin-treated patients in both serum total cholesterol (-9.3 mg/dl) and serum triglycerides (-33.9 mg/dl). In contrast, an increase in both these lipids was seen in hydrochlorothiazide-treated patients (+5.0 mg/dl for serum total cholesterol and +18.6 mg/dl for serum triglycerides). The net trial differences between the groups were 14.3 mg/dl for total cholesterol and 52.5 mg/dl for triglycerides, in favor of prazosin (p less than 0.001 for both comparisons). These differences in lipids between the two groups persisted into the second year of the trial (p less than 0.05). There were no significant differences between the drug groups in regard to the level of high density lipoprotein cholesterol or its subfractions or low density lipoprotein cholesterol. In patients who required a combination of the two drugs to achieve blood pressure control, the alpha-blocker diminished or eliminated the lipid-raising effects of the diuretic. Both drugs were similar in their ability to control the elevation of diastolic pressure.(ABSTRACT TRUNCATED AT 250 WORDS)     

Combination therapy with felodipine and metoprolol compared with captopril and hydrochlorothiazide. German MC Study Group.

This study compared the antihypertensive efficacy and tolerability of a combination tablet containing the vascular-selective calcium antagonist felodipine and the beta1-selective adrenergic antagonist metoprolol, with a combination tablet of captopril-hydrochlorothiazide in a randomized, double-blind trial involving 109 patients with mild to moderate hypertension. After 2 weeks on placebo, patients with a supine diastolic blood pressure of 95-115 mm Hg were randomized to felodipine-metoprolol, 5/50 mg o.d. (Logimax) or captopril-hydrochlorothiazide, 25/25 mg o.d. (Capozide). After a further 4 weeks, there was a mandatory dose increase to felodipine-metoprolol 10/100 mg o.d., and captopril-hydrochlorothiazide, 50/25 mg o.d., and treatment then continued for a another 4 weeks. At the end of the study, felodipine-metoprolol reduced supine blood pressure significantly more than captopril-hydrochlorothiazide. The mean differences in change in supine systolic and diastolic blood pressure between treatments after 8 weeks were 5.2 and 3.4 mm Hg, respectively, in favour of felodipine-metoprolol (p<0.05). Standing blood pressure also showed trends in favour of felodipine-metoprolol. The proportion of responders was similar in both groups. Both treatments were well tolerated. Two patients treated with felodipine-metoprolol and 5 with captopril-hydrochlorothiazide discontinued treatment due to adverse events. Felodipine-metoprolol combination reduced supine blood pressure significantly more than captopril-hydrochlorothiazide with maintained tolerability.     

Safety and effectiveness of terbutaline in children with chronic asthma.

The bronchodilator and cardiovascular effects of orally administered tablets containing 2.5 mg of terbutaline and 25 mg of ephedrine were compared in a double-blind parallel manner in children (ages, 7 to 14 years) weighing 25 to 50 kg (44 to 110 lb). Both drugs produced bronchodilation within one-half hour, and this effect was maintained up to six hours, with a peak between two and three hours. Small increases in the pulse rate were measured within an hour following administration of both drugs. No significant variation was noted in blood pressure. No adverse effects (including tachyphylaxis and tremor) were observed for either drug during a three-month period. Both bronchodilator agents were shown to be equally effective in the dosages used. Terbutaline is a safe bronchodilator drug when administered orally in 2.5-mg doses for children with chronic asthma in this range of ages and weights, with minimal cardiovascular side effects and effective bronchodilation.     

Quality of life in hypertensives treated with atenolol or captopril: a double-blind crossover trial.

AIM: To compare the effects of captopril and atenolol on quality of life of hypertensive patients. METHODS: In a randomly allocated double-blind crossover trial with two 6-week treatment periods captopril at 25 mg twice a day or atenolol at 50 mg once a day were administered to 265 hypertensive patients (mean age 56 years; 55% men). Of these, 65% were newly treated hypertensives and 35% were previously uncontrolled on a diuretic alone. A seated diastolic blood pressure of 95-115 mmHg was required after a 3-week placebo run-in period. Any previous diuretic therapy was changed to hydrochlorothiazide (25 mg once a day) and the dose was kept constant throughout the trial. Newly diagnosed patients did not take a diuretic at any time. Quality of life was assessed from self-completed questionnaires measuring psychological well-being, symptomatic side effects of treatment, and activity and perceived well-being (a health index). A relative's perception of the patients' mood was also obtained where possible. RESULTS: Twelve patients withdrew on atenolol and 10 on captopril. No differences between the drugs were observed in quality of life measures, and 95% confidence intervals suggested that important differences were excluded. CONCLUSION: We conclude that at the doses used in this trial there were no important differences between captopril and atenolol in their effects on quality of life.     

Treatment of alcoholic hepatitis with silymarin. A double-blind comparative study in 116 patients

A randomized double-blind trial of silymarin versus placebo was carried out in 116 patients with histologically proven alcoholic hepatitis, 58 of them with cirrhosis. Patients were not included in case of hepatic encephalopathy, contraindication to percutaneous liver biopsy, hepatocellular carcinoma, evident lack of discipline or refusal to enter the trial. Fifty-seven patients received silymarin orally 420 mg/day and 59 received placebo during 3 months. Biologic parameters were assessed in the serum, and a percutaneous liver biopsy was obtained at the start of the trial and 3 months later. Histologic scores of alcoholic hepatitis and fibrosis were established on each biopsy specimen by two independent pathologists. The 2 groups were comparable at inclusion; 26 p. 100 of patients were lost to follow-up at 3 months, abstinence was obtained in 46 p. 100 of patients at the end of the trial. These percentages were similar in the two groups. Four patients died of hepatic failure during the trial, 3 in the placebo group. Significant improvement in the score of alcoholic hepatitis and serum amino transferase activity, was noted in both groups during the trial, irrespective of treatment with silymarin or placebo. No side-effects were noted. Our results suggest that silymarin 420 mg/d is not clinically relevant in the treatment of moderate alcoholic hepatitis.     

Nicardipine in elderly patients with hypertension: a review of experience in France

A double-blind, placebo-controlled clinical trial in France has studied the efficacy and safety of nicardipine in 31 elderly patients, aged 57 to 95 years (mean age 84 years), 16 of whom were actively treated with nicardipine, 10 to 30 mg three times a day (mean dose 69.4 mg/day). After 4 weeks, nicardipine lowered mean blood pressure (186/99 to 150/83 mm Hg; p less than 0.001), and the changes in systolic and diastolic blood pressure were significantly greater in the nicardipine group than in the placebo group. Nicardipine was well tolerated; orthostatic hypotension was not observed and there was no change in heart rate. Plasma renin activity (PRA) was measured in eight patients, but there was no correlation between PRA and the antihypertensive effect of nicardipine. Results of a pharmacokinetic study performed in 15 elderly patients showed a rapid rate of absorption and higher plasma levels than those observed in younger patients with hypertension (mean age 54 years). The results support those of the major French multicenter open study of 29, 104 elderly patients with hypertension (mean age 64 +/- 12 years) treated with nicardipine. The findings of this trial are reviewed and discussed, and recommendations made on the directions for future research in cardiovascular medicine with calcium channel blockers. Results of the trials discussed in this article show that nicardipine is an effective and well-tolerated drug in elderly patients and has wide-ranging effects on the cardiovascular system.     

Cilnidipine is as effective as benazepril for control of blood pressure and proteinuria in hypertensive patients with benign nephrosclerosis.

To investigate the beneficial effects of cilnidipine, a calcium channel blocker that shows high selectivity for N-type receptors, on the progression of chronic renal insufficiency, we compared the efficacy of cilnidipine to that of benazepril, an angiotensin-converting enzyme (ACE) inhibitor with known renal protective effects, in a one-year trial evaluating hypertensive control, serum creatinine, and albuminuria in a cohort of patients. Given the seeming importance of the etiology of chronic renal insufficiency in determining drug efficacy, we limited our study to 20 patients with a single common condition, benign nephrosclerosis. The average age of the patients was 62+/-4 years old. The changes in systolic and diastolic blood pressure over the course of the study year revealed a similar reduction with cilnidipine and benazepril. Both cilnidipine and benazepril induced similar reductions in systolic and diastolic blood pressure over the course of the study year. The baseline levels of serum creatinine were 1.40+/-0.2 mg/dl and urinary excretion of albumin was 168+/-10 mg daily. The levels of serum creatinine were not significantly changed throughout the study in either group, although the levels of urinary excretion of albumin were significantly decreased in both groups. There were no significant differences in either of these values between the two groups. In conclusion, both cilnidipine and benazepril equally and effectively reduced blood pressure and albuminuria in hypertensive patients with benign nephrosclerosis in a one-year trial.     

Effects of amlodipine and lisinopril on intima-media thickness in previously untreated, elderly hypertensive patients (the ELVERA trial)

OBJECTIVE: To compare the effects of the calcium channel blocker amlodipine and the angiotensin-converting enzyme inhibitor lisinopril on intima-media thickness (IMT) in elderly, previously untreated hypertensive individuals. DESIGN: A double-blind randomized parallel-group trial (the ELVERA trial). PATIENTS: The study population comprised 166 newly diagnosed hypertensive individuals (aged 60-75 years) with diastolic blood pressure between 95 and 115 mmHg or systolic blood pressure between 160 and 220 mmHg, or both. INTERVENTION: Patients were allocated randomly to groups to receive amlodipine 5-10 mg or lisinopril 10-20 mg for 2 years. MAIN OUTCOME MEASURES: Before and after 1 and 2 years of treatment, IMT was measured in three carotid and two femoral arterial sites by B-mode ultrasound. The primary endpoint was the change from baseline of the combined mean maximum far wall IMT of carotid and femoral arteries, evaluated by repeated measurement analysis of the treatment effect in an intention-to-treat analysis. RESULTS: After 2 years of treatment, amlodipine decreased IMT by 0.089 mm [95% confidence interval (CI) 0.144 to 0.037]. Lisinopril decreased IMT by 0.065 mm (95% CI 0.124 to 0.010). No differences between the two drugs were found (P = 0.18). Both treatment regimens achieved the greatest reduction of IMT after 1 year, with a slight increase after the second year, whereas the reduction in blood pressure was maintained. Comparing the carotid and femoral arteries, a significant treatment difference in the change from baseline in favour of amlodipine was observed in the IMT of the elastic common carotid artery (P < 0.05). The effects of the two drugs on the muscular common femoral artery were not different. CONCLUSION: In a long-term study, amlodipine and lisinopril reduce IMT to a similar extent in newly diagnosed elderly hypertensive patients. It is suggested that the two drugs have different effects on arteries that are not prone to atherosclerosis.     

Effect of acute administration of acamprosate on the risk of encephalopathy and on arterial pressure in patients with alcoholic cirrhosis]

To evaluate the risk of hepatic encephalopathy and arterial hypotension in cirrhotic patients after acute administration of acamprosate, a GABA mimetic drug used in the weaned alcoholic, a randomized double-blind trial was conducted in 24 cirrhotic patients with low or moderate hepatic insufficiency (Pugh grade A or B). Twelve patients received 666 mg (2 tablets) of acamprosate and 12 received placebo. The 2 groups were similar before treatment, except for a male predominance in the acamprosate group. Tested parameters were the P100 latency of visual evoked potentials using a checkerboard pattern reversal as stimulus, the number connection test and the arterial blood pressure in upright and recumbent positions. The two first parameters were studied before and 2 hours after treatment. Blood pressure was recorded every half hour during 6 hours. No significant effect on the development of subclinical hepatic encephalopathy was noted. Nevertheless, even if some authors disagree with the GABA hypothesis of hepatic encephalopathy, it is possible that the dose was too low to induce subclinical hepatic encephalopathy. A study with more prolonged treatment could be necessary to be sure of the drug's safety in these patients. On the other hand, a transient decrease of diastolic arterial blood pressure was observed without significant systolic blood pressure modification. These results suggest that a moderate dose of acamprosate does not induce subclinical encephalopathy, but transient diastolic hypotension.     

Relation Between Low Dose of Hydrochlorothiazide, Antihypertensive Effect and Adverse Effects

Thiazide diuretics are widely used in the drug treatment of hypertension but their dose-response curves for the antihypertensive and adverse metabolic effects differ. To characterize the lower end of the dose-response curve a double-blind, parallel group trial was performed as multicentre study in Scandinavia. One hundred and eleven patients with newly diagnosed or previously treated mild to moderate hypertension (untreated diastolic blood pressure of 95-115 mmHg after 4 weeks placebo) were randomly allocated to various doses of hydrochlorothiazide (3, 6, 12.5 or 25 mg) or placebo for 6 weeks. Blood pressure and biochemical variables (plasma renin activity, serum potassium, magnesium, urate, fasting glucose, total cholesterol, HDL-cholesterol, triglycerides and apolipoproteins A1 and B were measured. 12.5 mg hydrochlorothiazide had a borderline effect on blood pressure whilst 25 mg had a definite antihypertensive effect. Biochemical changes were seen in plasma renin activity, serum potassium and urate after the 12.5 and 25 mg dose. Three and 6 mg had no effect on blood pressure or metabolic parameters.     

卡托普利与小剂量氢氯噻嗪合用治疗高血压疗效观察

目的：研究卡托普利与小剂量氢氯噻嗪合用对高血压患者的疗效及对代谢的影响。方法：５０例原发性高血压患者随机分为两组,第１组：单用卡手早１２．５ｍｇ～７５ｍｇ,每日２～３次。第２组,卡手早１２．５ｍｇ,每日２次,加服氢氯噻嗪１２．５ｍｇ,每日１次,两组治疗时间均为８周,测定治疗前后的基础血压,空腹血糖、血脂、血、血 到、 纱氮、肌酐以及有后的２４小时动态血压。 托普利加小剂量氢氯噻嗪组的总有效率及２４     

Results of the surgical treatment of Conn's adenomas

During the last 10 years we operated on 69 Conn's adenomas of which 59 were followed up for a mean period of 16 months (range: 3-96 months). Surgery cured the hypertension (blood pressure less than 140/90) in 47 p. 100 of the patients. Improved blood pressure (systolic: mean = 46 mmHg; range 0-135 mmHg and diastolic: mean = 25 mmHg; range 0-66 mmHg) was noted in another 47 p. 100 of patients whereas no blood pressure change was noted in 3 patients. Biological primary aldosteronism was found post-operatively in 2 of these 3 patients and also in one whose hypertension was improved. In this last patient plus the three unimproved by surgery, small tumours (less than 10 mm) were found and co-existnt multifocal hyperplasia was found in the 2 patients who had had an adrenalectomy. Fifty-one patients were treated pre-operatively by spironolactone (SP) alone (3.2 +/- 1.3 mg/kg) for a mean period of 6.8 weeks (range: 3 to 20 weeks). Only 2 of the 24 patients controlled by SP were not cured by surgery and one of them had persistnt primary aldosteronism. Conversely, 3 of the 27 uncontrolled by SP were cured post-operatively, and these exceptions could be due to the weak dose of SP (n = 2) and an observance problem (n = 1). Patients cured by surgery had shorter duration of hypertension (4.3 +/- 3.0 years vs 10.1 +/- 8.1; p less than 0.01) and lower diastolic pressure (111 +/- 14 mmHg vs 121 +/- 12; p less than 0.01) than uncured patients. No significant difference between these two groups was observed with respect to systolic pressure, age, sex, plasma potassium, plasma renin activity and plasma aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)     

A study of the use of captopril in elderly hypertensive patients

Captopril (12.5-25 mg b.d.) was compared with placebo in a double-blind, cross-over study in elderly, hypertensive subjects. Sixteen patients, aged between 65 and 80 years, were studied. The mean baseline blood pressure off treatment was 204.7 +/- 24.5/111.8 +/- 11.1 mmHg. In the 14 patients who completed the study, captopril significantly reduced the systolic and diastolic pressures compared with baseline (P less than 0.001) and compared with placebo (P less than 0.01). The fall in blood pressures was significantly greater at 4 weeks than at 2 weeks (P less than 0.001). No significant change in blood pressure was noted from baseline whilst on placebo. No significant serious side-effects were encountered during the study. We conclude that captopril would appear to be an effective antihypertensive agent which can be safely used in the elderly.     

Furosemide-induced natriuresis is augmented by ultra-low-dose captopril but not by standard doses of captopril in chronic heart failure.

BACKGROUND. Ten chronic heart failure patients were studied on three occasions in randomized double-blind fashion to compare the acute hemodynamic, neurohormonal, and renal sodium-handling responses to 1 mg captopril versus 25 mg captopril, both in the absence of loop diuretic therapy and during furosemide-stimulated natriuresis. METHODS AND RESULTS. Compared with placebo, 1 mg captopril caused nonsignificant decreases in mean arterial pressure and circulating angiotensin II level and had no effect on glomerular filtration rate as determined by 51Cr-EDTA elimination. Captopril (25 mg) produced marked suppression of serum angiotensin II with or without oral furosemide (both p less than 0.002), a marked decrease in mean arterial pressure (p less than 0.001) that was accentuated by furosemide (p less than 0.00001), and a decrease in glomerular filtration rate (p = 0.0007). No difference from placebo in renal sodium excretion was noted with either 1 or 25 mg captopril in the absence of furosemide. In contrast, while 25 mg captopril caused slight attenuation of the natriuretic response to furosemide, 1 mg captopril significantly enhanced furosemide-induced natriuresis (p less than 0.05). No correlation was found in our patients between the natriuretic effect of furosemide and either absolute mean arterial pressure or change in mean arterial pressure during the furosemide phase of each study session. This suggests that blood pressure is not the important factor mediating the divergent renal responses to furosemide of the two captopril dosage regimens. CONCLUSIONS. We propose that in the face of furosemide-induced postglomerular vasodilatation in chronic heart failure, captopril at a starting dose of 1 mg (but not 25 mg) preserves enough circulating angiotensin II to maintain efferent arteriolar tone and thus glomerular filtration, while offsetting the antinatriuretic renal tubular effects of angiotensin II.     

Failure of colchicine to improve short-term survival in patients with alcoholic hepatitis

Colchicine treatment was used in this randomized placebo-controlled trial in patients with severe acute alcoholic hepatitis [serum bilirubin greater than or equal to 5 mg/dL (85.5 mumol/L) mean, 17.5 +/- 7.5 mg/dL (299.25 +/- 128.25 mumol/L)]. Hospitalization mortality and morbidity and the effect on biochemical test results were the end points of the treatment. Patients in the two groups were evenly matched by demographics and laboratory test results. Mean time to study entry was less than 7 days from admission. The duration of the trial was 30 days. Thirty-six patients (24 men, 12 women) received colchicine (1 mg orally every morning) and 36 (25 men, 11 women) received an identical placebo. Seven (19%) colchicine-treated and six (17%) control patients died during the index hospitalization after a mean of 17.4 +/- 10.8 and 17.8 +/- 5.3 days, respectively (NS). During a 4-month follow-up period from entry into the trial, there were two additional deaths in each group. No differences between placebo- and colchicine-treated patients were observed in any of the laboratory parameters (serum bilirubin, aspartate transaminase, alanine transaminase, prothrombin activity, albumin, white blood cell count, hemoglobin, and creatinine) that were followed up over the 30-day treatment period. The frequency of complications did not differ statistically between the two groups. This study showed no effect of colchicine treatment on mortality and morbidity of severe alcoholic hepatitis. Colchicine cannot be recommended for the treatment of patients with alcoholic hepatitis.     

A comparison of the efficacy and safety of irbesartan/HCTZ combination therapy with irbesartan and HCTZ monotherapy in the treatment of moderate hypertension

This prospective, double-blind, parallel-group study randomized patients with moderate hypertension (seated systolic blood pressure (SeSBP) 160-179 mm Hg when seated diastolic blood pressure (SeDBP) <110 mm Hg; or SeDBP 100-109 mm Hg when SeSBP <180 mm Hg) 3:1:1 to treatment with irbesartan 300 mg/hydrochlorothiazide (HCTZ) 25 mg combination therapy (n=328), irbesartan 300 mg monotherapy (n=106) or HCTZ monotherapy 25 mg (n=104). Treatment was initiated at half dose, with forced titration to full dose after two weeks followed by ten further weeks' treatment. The primary efficacy variable was the mean reduction in SeSBP from baseline to week 8. Baseline characteristics were similar between groups, with mean baseline blood pressure approximately 162/98 mm Hg; the mean age was 55 years. At week 8 there was a reduction in SeSBP of 27.1 mm Hg with irbesartan/HCTZ, compared with 22.1 mm Hg with irbesartan monotherapy (P=0.0016) and 15.7 mm Hg with HCTZ (P<0.0001). Both the rate of decline and the total degree of decline achieved were greatest with irbesartan/HCTZ and least with HCTZ. A significantly greater percentage of patients reached a treatment goal of SeSBP <140 mm Hg and SeDBP <90 mm Hg by week 8 with irbesartan/HCTZ (53.4%), compared with irbesartan (40.6%; P=0.0254) and HCTZ (20.2%; P<0.0001) alone. Treatment was well tolerated in all three-treatment groups with a slight increase in adverse events in the combination therapy group. In conclusion, irbesartan/HCTZ (300/25 mg) is well tolerated and achieves rapid and sustained reductions in both systolic blood pressure and diastolic blood pressure in patients with moderate hypertension.