Multicenter, double-blind comparison of doxazosin and atenolol in patients with mild to moderate hypertension

In a double-blind multicenter study, the new alpha 1-adrenoceptor inhibitor doxazosin was compared with atenolol for efficacy, safety and effect on serum lipids. One hundred and twenty-six patients with mild to moderate hypertension were randomly assigned to receive either doxazosin (n = 63) or atenolol (n = 63). The mean final dosages, administered once daily, to obtain 24-hour blood pressure (BP) control were doxazosin 12 mg (range 1 to 16) and atenolol 91.8 mg (range 50 to 100). Of 12 doxazosin and 7 atenolol patient withdrawals from the study, 7 doxazosin and 4 atenolol patients withdrew for treatment-related reasons. No statistically significant differences between treatment groups were found after 20 weeks in changes from baseline in standing and sitting BPs measured 24 hours after administration. Sitting BP (systolic/diastolic) was reduced by 10.5/9.8 mm Hg after doxazosin treatment and by 10.9/10.7 mm Hg after atenolol therapy. Standing BP was reduced by 8.8/7.7 mm Hg after doxazosin administration and 9.7/9.3 mm Hg after treatment with atenolol. Supine BP was measured in a small cohort of the study population, and doxazosin had a smaller effect than atenolol. After 20 weeks of treatment, both drugs reduced heart rate with atenolol producing a statistically significantly greater decrease than doxazosin (standing, doxazosin 5 beats/min, atenolol 16.2 beats/min, p less than 0.001; sitting, doxazosin 5 beats/min, atenolol 13.1 beats/min, p less than 0.001). Side effects were reported by 37 patients receiving doxazosin therapy and 34 patients receiving atenolol therapy.(ABSTRACT TRUNCATED AT 250 WORDS)     

Importance of blood pressure control in left ventricular mass regression

Blood pressure (BP) reduction to 140/90 mm Hg or lower using renin-angiotensin-system blockers reportedly provides the greatest left ventricular (LV) mass regression; β-blockers have less effect. This study examined whether combination antihypertensive therapy would provide greater benefit. With a double-blind, parallel-group design, the effects of 3 different combinations, carvedilol controlled-release (CR)/lisinopril, atenolol/lisinopril, and lisinopril, on left ventricular mass index (LVMI) were assessed by MRI after 12 months. Patients were treated to achieve guideline-recommended BP (<140 mm Hg/<90 mm Hg; diabetes: <130 mm Hg/<80 mm Hg). Sample size was calculated to achieve 90% power to detect a 5 g/m² difference in mean change from baseline in LVMI between the carvedilol CR/lisinopril group and each of the other treatment groups. Of 287 patients randomized, more than 50% were titrated to maximum dosage; 73% reached targeted BP. At month 12 (last observation carried forward ≥ month 9) for 195 evaluable subjects, mean BP was similar in all groups (carvedilol CR/lisinopril: 128.8/77.9; atenolol/lisinopril: 128.7/76.5; lisinopril: 126.3/80.3 mm Hg). Compared with baseline, mean LVMI decreased to a similar extent in all groups (carvedilol CR/lisinopril: –6.3; atenolol/lisinopril: –6.7; lisinopril: –7.9 g/m²). Achievement of targeted BP control is more important than treatment regimen in achieving LV mass reduction.     

Concomitant administration of terazosin and atenolol for the treatment of essential hypertension

The safety and efficacy of once-daily terazosin hydrochloride administered concomitantly with once-daily atenolol for the treatment of essential hypertension were evaluated in this double-blind, multiclinic, placebo-controlled study. After each patient received 50 mg of atenolol daily for eight weeks, patients with a supine diastolic blood pressure (DBP) of 95 to 110 mm Hg and whose supine DBP had decreased at least 5 mm Hg were randomized to receive either terazosin (plus atenolol) or placebo (plus atenolol) for ten weeks. Patients assigned to the terazosin hydrochloride treatment group received increasing dosages (1,2,5, and 10 mg daily) [corrected] of terazosin at two-week intervals until the maximum dose was reached or until the supine DBP was decreased to less than 90 mm Hg. Terazosin-treated patients (n = 43) had significant mean decreases from the baseline in supine BP (systolic/diastolic = -8.8/-8.5 mm Hg) and standing BP (-10.9/-9.5 mm Hg), whereas the decreases in BP in the placebo-treated patients (n = 49; supine, -2.3/-2.6 mm Hg; standing, -1.4/-1.3 mm Hg) were not significant. When terazosin and placebo were compared, the differences in BP were significant. Terazosin-treated patients had significantly greater decreases in mean percent change of total cholesterol (-4.8%) and low-density lipoprotein plus very-low-density lipoprotein cholesterol (-6.3%) levels, compared with the placebo-treated patients (+0.6% and +1.1%, respectively). Concomitant administration of terazosin and atenolol to patients with essential hypertension was found to be safe and efficacious.     

Comparison of diltiazem and atenolol in young, physically active men with essential hypertension

The antihypertensive efficacy and effect on maximal exercise performance of diltiazem was evaluated and compared with atenolol in patients specifically selected on the basis of their being young and physically active. Diltiazem (sustained-release preparation, 90 mg twice daily) was administered to 14 patients (aged 33 +/- 2 years) and atenolol (50 mg once daily) to 13 patients (aged 30 +/- 2 years) with essential hypertension in a 16-week randomized, double-blind, parallel study. The 2 drugs had comparable antihypertensive effects at rest, with mean decreases of 18 and 17 mm Hg (p less than 0.001) for supine and standing diastolic blood pressure (BP), respectively, during diltiazem treatment, and mean decreases of 21 and 18 mm Hg (p less than 0.001) during atenolol treatment. During maximal graded exercise testing, systolic BP, diastolic BP, heart rate and heart rate-BP product were significantly reduced by both drugs. However, the reductions in systolic BP, heart rate and heart rate-BP product during exercise were considerably greater (p less than 0.001) with atenolol than with diltiazem. Maximal exercise performance was essentially unchanged with diltiazem and slightly (3%, p less than 0.05) reduced with atenolol. Thus, diltiazem is effective and well-tolerated single therapy for young patients with mild to moderate essential hypertension who lead a physically active life style and compares favorably with atenolol.     

Blood Pressure Control by Drug Group in the Antihypertensive and Lipid‐Lowering Treatment to Prevent Heart Attack Trial (ALLHAT)

Blood pressure (BP) control rates and number of antihypertensive medications were compared (average follow‐up, 4.9 years) by randomized groups: chlorthalidone, 12.5–25 mg/d (n=15,255), amlodipine 2.5–10 mg/d (n=9048), or lisinopril 10–40 mg/d (n=9054) in a randomized double‐blind hypertension trial. Participants were hypertensives aged 55 or older with additional cardiovascular risk factor(s), recruited from 623 centers. Additional agents from other classes were added as needed to achieve BP control. BP was reduced from 145/83 mm Hg (27% control) to 134/76 mm Hg (chlorthalidone, 68% control), 135/75 mm Hg (amlodipine, 66% control), and 136/76 mm Hg (lisinopril, 61% control) by 5 years; the mean number of drugs prescribed was 1.9, 2.0, and 2.1, respectively. Only 28% (chlorthalidone), 24% (amlodipine), and 24% (lisinopril) were controlled on monotherapy. BP control was achieved in the majority of each randomized group—a greater proportion with chlorthalidone. Over time, providers and patients should expect multidrug therapy to achieve BP <140/90 mm Hg in a majority of patients.     

Diltiazem as monotherapy for systemic hypertension: a multicenter, randomized, placebo-controlled trial

A multicenter, randomized, placebo-controlled, parallel group study of diltiazem in essential hypertension was carried out in 77 patients (40 diltiazem, 37 placebo) with stable supine diastolic blood pressure (BP) between 95 and 110 mm Hg. Patients were withdrawn from previous antihypertensive therapy for at least 4 weeks, titrated to the optimal dose, and followed for a total of 12 weeks during therapy. A diltiazem dose of 360 mg/day was required in 85% of the patients. Average BP in all positions was significantly (p less than 0.0001) reduced by diltiazem compared with placebo. With diltiazem, average supine BP fell from 156/100 mm Hg at baseline to 141/87 at end titration and 145/90 mm Hg at week 12, whereas average standing BP fell from 152/101 mm Hg to 136/90 and 143/91 mm Hg, respectively, at those times. There was no significant change in heart rate at week 12. Diltiazem tended to be more effective in older patients, but caused no increase in orthostatic BP drop. There were no statistically significant changes in BP in the placebo group. Two patients receiving placebo and 1 patient receiving diltiazem discontinued therapy as a result of adverse effects, and overall, side effects were only slightly more common with diltiazem treatment. Thus, diltiazem was effective and well tolerated single therapy for mild to moderate systemic hypertension and appears to compare favorably to most agents being used.     

Lisinopril versus enalapril: evaluation of trough:peak ratio by ambulatory blood pressure monitoring.

In 34 out-patients with essential hypertension, the antihypertensive effect and the trough-to-peak ratios of once-daily enalapril or lisinopril were compared by ambulatory blood pressure monitoring (ABPM) according to a crossover design. The drug dose was titrated and a thiazide diuretic was added if necessary to attain a target office BP of less than 140/90 mm Hg. Both drugs significantly lowered BP but the effect of lisinopril was greater (P < 0.009): day- and night-time mean BP fell from 152/98 and 135/84 mm Hg, respectively to 133/85 and 118/74 mm Hg with enalapril and to 129/83 and 116/70 mm Hg with lisinopril. BP goal was reached with an average dose of 18 mg enalapril with 8 mg hydrochlorothiazide and with 17 mg lisinopril combined with 6 mg diuretic. Trough:peak ratio values, which were calculated after Fourier analysis of ABPM data in individual patients, were independent of drug dose. The combination with the diuretic resulted in slightly higher trough:peak ratios than with ACE inhibitor monotherapy, but the difference was not significant. The median trough:peak ratio in patients when using enalapril-based therapy was 0.48 and, when taking lisinopril-based treatment, it was 0.65 (n = 28, P < 0.005). A significant correlation was found between trough:peak ratio and changes in daytime mean arterial pressure (MAP; Spearman r= 0.43) and night-time MAP (r= 0.66). When 24-h ABPM was performed starting 24 h after last drug intake, both ACE inhibitors still had a significant antihypertensive effect (P < 0.001), which was similar for both drugs. Eleven patients reported minor side effects. Four patients stopped ACE-inhibitor treatment because of cough. The data show that lisinopril has a longer duration of action than enalapril.     

Renin profile, race, and antihypertensive efficacy with atenolol and labetalol

In this randomised double-blind parallel study, we compared the efficacy of labetalol and atenolol in a group of black (n = 33) and white (n = 34) hypertensives with uncomplicated essential hypertension after obtaining pretreatment renin profiles. After single-blind placebo (14-21 days), patients with standing diastolic BP between 105-119 mmHg were randomised to receive either labetalol (100-800 mg twice daily) or atenolol (50-100 mg once daily) to achieve a DBP less than 90 mmHg. Dosage titration occurred at weekly intervals for labetalol and biweekly for atenolol. The supine BP decrease with atenolol was -18/-14 vs. -6/-6 mmHg in whites vs. blacks respectively. With labetalol, it was -13/-12 in whites and -2/-7 mmHg in blacks. Standing BPs were: -19/-14 vs. -4/-5, whites vs. blacks with atenolol and -17/-17 vs. -19/-9 mmHg with labetalol. Neither labetalol nor atenolol was as effective in black compared with white hypertensives. The atenolol but not labetalol BP response was positively correlated with pretreatment renin values.     

Atenolol plus nifedipine for mild to moderate systemic hypertension after fixed doses of either agent alone

Three therapies were used to treat 35 patients with mild to moderate systemic hypertension: (1) the cardioselective beta-adrenoceptor blocker atenolol, (2) the calcium antagonist nifedipine and (3) combination therapy for those who failed to reach the target diastolic blood pressure (BP) of less than 90 mm Hg with monotherapy. After an initial run-in placebo period, when the mean supine diastolic BP was 102 +/- 1 mm Hg (mean +/- standard error of the mean), patients were randomized (double-blind) to atenolol, 100 mg as a single daily dose or nifedipine (slow-release form), 20 mg twice daily, then to a washout dummy placebo period before crossover. Each period lasted 4 weeks. Supine, erect and exercise BP were recorded. Atenolol and nifedipine, in the same fixed doses but in combination, were given to 20 patients in whom either supine or erect diastolic BP exceeded 90 mm Hg after the period of monotherapy. Atenolol monotherapy reduced the erect diastolic BP to less than 90 mm Hg in 14 patients (40%); of the remainder, 1 patient responded only to fixed-dose nifedipine and 11 to combination therapy, yielding a total success rate of 74%. The combination gave enhanced control, as shown by a further decrease in supine and erect BP and by better control of exercise BP; these effects were achieved without an increased incidence of adverse effects. The mean reductions in supine diastolic BP were: atenolol, 9 +/- 2 mm Hg; nifedipine, 6 +/- 2 mm Hg; and combination therapy, 16 +/- 2 mm Hg (p less than 0.05 vs atenolol or nifedipine).(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparative efficacy of two different beta-blockers on 24-hour blood pressure control.

Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles. This study tests the hypothesis that differences that are especially noted in the early morning period, when cardiovascular risk is highest, in 24-hour blood pressure (BP) control exist between these 2 beta-blockers. This was a small, randomized open-label study with blinded end point evaluation in 36 hypertensive patients. All participants received hydrochlorothiazide 12.5 mg for 2 weeks before randomization to either 50 mg atenolol or metoprolol succinate given every morning; both treatments were force-titrated to 100 mg/d at 4 weeks. The primary end point was the change in early morning ambulatory systolic BP. Early morning (12 AM-6 AM) systolic BP differences were 3+/-14 mm Hg with atenolol vs -7+/-8 mm Hg with metoprolol succinate (P=.03). The overall 24-hour changes in systolic BP were 1+/-15 mm Hg with atenolol vs -9+/-11 mm Hg with metoprolol (P=.03). In conclusion, metoprolol succinate was more effective in sustaining 24-hour and early morning BP reductions compared with atenolol in a small group of hypertensive patients also treated with once-daily low-dose hydrochlorothiazide. It is possible that differences in outcome between atenolol-based and other therapies may be the result of inadequate dosing of atenolol, a medication that may not be effective for the entire 24-hour period.     

Twenty-four-hour ambulatory blood pressure monitoring efficacy of perindopril/indapamide first-line combination in hypertensive patients: the REASON study

BACKGROUND: Circadian blood pressure (BP) measurements provide more information on hypertensive complications than office BP measurements. The purpose of this study was to analyze the efficacy of the first-line combination of perindopril 2 mg plus indapamide 0.625 mg versus atenolol 50 mg on BP parameters and variability over 24 h in patients with hypertension. METHODS: A double-blind, randomized, controlled, 12-month study comparing perindopril/indapamide and atenolol was performed in 201 patients (age 55.0 years) with uncomplicated sustained essential hypertension. Ambulatory BP measurements (ABPM) were done every 15 min over 24 h. RESULTS: After 1 year of treatment, the decrease in systolic BP was significantly greater for perindopril/indapamide than for atenolol during the entire 24-h period (-13.8 v -9.2 mm Hg), the daytime and the nighttime periods (P <.01). Diastolic blood pressure (DBP) variations were comparable for the two groups (-7.2 v -8.3 mm Hg, NS). Pulse pressure (PP) reduction was also significantly greater for perindopril/indapamide than for atenolol (for the whole 24 h, -6.6 v -0.9 mm Hg, P <.001). The through to peak (T/P) BP ratio and the smoothness index were comparable in the two groups for DBP. For systolic blood pressure (SBP), higher values of the T/P ratio (0.80 v 0.59) and the smoothness index (1.45 v 0.98; P <.02) were achieved for the perindopril/indapamide combination than for atenolol. CONCLUSIONS: The perindopril/indapamide first-line combination decreased SBP and PP more effectively than atenolol. Moreover, the BP control effect was smooth and consistent throughout the 24-h dosing interval and BP reduction variability was lower than the one induced by atenolol.     

Effects of celecoxib on ambulatory blood pressure in hypertensive patients on ACE inhibitors

Nonselective nonsteroidal anti-inflammatory agents have been shown to attenuate the antihypertensive efficacy of ACE inhibitors with average increases in systolic blood pressure (BP) of 5 to 10 mm Hg. Less is known about the specific cyclooxygenase-2 (COX-2) inhibitors now widely used for the treatment of arthritis. The objective of this study was to determine the effects of celecoxib compared with placebo on 24-hour BP levels in ACE inhibitor-treated patients with hypertension. This was a randomized, double-blind, placebo-controlled, parallel-group clinical trial involving 178 men and women (mean age, 53 years) with essential hypertension who were treated and controlled with lisinopril monotherapy (10 to 40 mg daily). Baseline BP values were obtained using 24-hour ambulatory recordings. Patients received either celecoxib, 200 mg twice daily (twice the recommended dose for osteoarthritis) (n=91), or placebo (n=87) for 4 weeks, and changes in the 24-hour BP, body weight, and clinical laboratory parameters were assessed. Mean changes from baseline in the 24-hour systolic and diastolic BP were 2.6/1.5+/-0.9/0.6 mm Hg on celecoxib versus 1.0/0.3+/-1/0.6 mm Hg on placebo (P=0.34 for systolic BP; P=0.45 for diastolic BP). The proportion of patients whose 24-hour BP increased by at least 5, 10, 15, or 20 mm Hg were also similar on celecoxib and placebo. No changes in body weight, serum creatinine, or potassium occurred in either group. Thus, these data demonstrate that high doses of celecoxib have no significant effect on the antihypertensive effect of the ACE inhibitor lisinopril. The placebo-subtracted changes observed in 24-hour BP (1.6/1.2 mm Hg) are less than what has been reported for nonselective nonsteroidal anti-inflammatory agents in ACE inhibitor-treated patients.     

Comparison of doxazosin and atenolol in mild hypertension, and effects on exercise capacity, hemodynamics and left ventricular function

The effects of once-daily therapy with doxazosin (1 to 8 mg/day) on exercise capacity, left ventricular performance and hemodynamics (radionuclide ventriculography) were compared with those of atenolol (50 to 100 mg/day) and placebo in a randomized, double-blind crossover trial in 16 patients (9 men) with mild hypertension. Both medications controlled blood pressure (BP) to a similar degree (mean BP was 150 +/- 12, 137 +/- 17 and 141 +/- 14 mm Hg for placebo, atenolol and doxazosin, respectively) but by different mechanisms. Changes during maximal semierect bicycle exercise were similar to those seen at rest. Doxazosin decreased total peripheral resistance and maintained cardiac output, whereas atenolol decreased cardiac output. Exercise capacity (136 +/- 56 watts with placebo) was maintained by doxazosin (135 +/- 56 watts) but decreased with atenolol (122 +/- 55 watts). Compared with atenolol, doxazosin slightly increased the left ventricular ejection fraction at rest and during exercise. The significance of this study is in the choice of a first-line antihypertensive agent. Both are once-a-day medications that control BP. However, doxazosin does so by improving the abnormal physiology of essential hypertension and, consequently, does not adversely affect exercise performance.     

Comparative Efficacy of Two Different β-Blockers on 24-Hour Blood Pressure Control

Atenolol and metoprolol succinate, dosed once daily, have different pharmacokinetic profiles. This study tests the hypothesis that differences that are especially noted in the early morning period, when cardiovascular risk is highest, in 24-hour blood pressure (BP) control exist between these 2 β-blockers. This was a small, randomized open-label study with blinded end point evaluation in 36 hypertensive patients. All participants received hydrochlorothiazide 12.5 mg for 2 weeks before randomization to either 50 mg atenolol or metoprolol succinate given every morning; both treatments were force-titrated to 100 mg/d at 4 weeks. The primary end point was the change in early morning ambulatory systolic BP. Early morning (12 am –6 am ) systolic BP differences were 3±14 mm Hg with atenolol vs −7±8 mm Hg with metoprolol succinate ( P =.03). The overall 24-hour changes in systolic BP were 1±15 mm Hg with atenolol vs −9±11 mm Hg with metoprolol ( P =.03). In conclusion, metoprolol succinate was more effective in sustaining 24-hour and early morning BP reductions compared with atenolol in a small group of hypertensive patients also treated with once-daily low-dose hydrochlorothiazide. It is possible that differences in outcome between atenolol-based and other therapies may be the result of inadequate dosing of atenolol, a medication that may not be effective for the entire 24-hour period.     

A comparison of the tolerability of the direct renin inhibitor aliskiren and lisinopril in patients with severe hypertension

Patients with severe hypertension (>180/110 mm Hg) require large blood pressure (BP) reductions to reach recommended treatment goals (<140/90 mm Hg) and usually require combination therapy to do so. This 8-week, multicenter, randomized, double-blind, parallel-group study compared the tolerability and antihypertensive efficacy of the novel direct renin inhibitor aliskiren with the angiotensin converting enzyme inhibitor lisinopril in patients with severe hypertension (mean sitting diastolic blood pressure (msDBP)>or=105 mm Hg and <120 mm Hg). In all, 183 patients were randomized (2:1) to aliskiren 150 mg (n=125) or lisinopril 20 mg (n=58) with dose titration (to aliskiren 300 mg or lisinopril 40 mg) and subsequent addition of hydrochlorothiazide (HCTZ) if additional BP control was required. Aliskiren-based treatment (ALI) was similar to lisinopril-based treatment (LIS) with respect to the proportion of patients reporting an adverse event (AE; ALI 32.8%; LIS 29.3%) or discontinuing treatment due to AEs (ALI 3.2%; LIS 3.4%). The most frequently reported AEs in both groups were headache, nasopharyngitis and dizziness. At end point, ALI showed similar mean reductions from baseline to LIS in msDBP (ALI -18.5 mm Hg vs LIS -20.1 mm Hg; mean treatment difference 1.7 mm Hg (95% confidence interval (CI) -1.0, 4.4)) and mean sitting systolic blood pressure (ALI -20.0 mm Hg vs LIS -22.3 mm Hg; mean treatment difference 2.8 mm Hg (95% CI -1.7, 7.4)). Responder rates (msDBP<90 mm Hg and/or reduction from baseline>or=10 mm Hg) were 81.5% with ALI and 87.9% with LIS. Approximately half of patients required the addition of HCTZ to achieve BP control (ALI 53.6%; LIS 44.8%). In conclusion, ALI alone, or in combination with HCTZ, exhibits similar tolerability and antihypertensive efficacy to LIS alone, or in combination with HCTZ, in patients with severe hypertension.     

Amlodipine versus atenolol in essential hypertension

The efficacy and safety of amlodipine (2.5–10 mg) once daily was compared with atenolol (50–100 mg) once daily in patients with mild-to-moderate essential hypertension in a randomized, doubleblind, parallel, placebo-controlled study. A total of 125 patients were randomly allocated at the end of a 4-week run-in placebo period to 8 weeks of double-blind treatment with amlodipine (n = 41), atenolol (n = 43), or placebo (n = 41). The placebo group had small mean changes in supine and standing blood pressure compared with baseline. The mean blood pressure changes from baseline 24 hours postdose in the amlodipine group (mean daily dose 8.8 mg) were −12.8/−10.1 mm Hg for supine blood pressure and −11.5/−9.8 mm Hg for standing blood pressure (p < 0.001 compared with placebo), and for the atenolol group (mean daily dose 83.7 mg) the changes were −11.3/−11.7 mm Hg for supine blood pressure and −13.3/−12.3 mm Hg for standing blood pressure (p < 0.001 compared with placebo). There were no statistically significant blood pressure differences between active treatments. The responder rates for amlodipine, atenolol, and placebo were 61.1, 64.9, and 11.1%, respectively. The blood pressure values taken over the 24-hour period at final visit revealed that amlodipine and atenolol maintained the supine blood pressure ≤ 140/90 mm Hg throughout the period of observation; the corresponding time-effect curve for the placebo group was clearly in the hypertensive range. Heart rate was significantly lowered by atenolol only. Both amlodipine and atenolol were well tolerated. Only 1 patient was withdrawn due to adverse effects (development of peripheral edema, arthralgia and fatigue) related to amlodipine. This study demonstrates that once-daily therapy with amlodipine or atenolol was well tolerated in patients with mild-to-moderate essential hypertension and provided control of blood pressure throughout the 24-hour dosing interval.     

Lisinopril for the treatment of hypertension within the first 24 hours of acute ischemic stroke and follow-up

BACKGROUND: Hypertension immediately after acute ischemic stroke is associated with impaired morbidity and mortality, although there are few data on antihypertensive use immediately after ictus. This randomized, double-blinded, placebo-controlled, parallel-group study explored the hemodynamic effect and safety of oral lisinopril initiated within 24 h after an ictus. METHODS: Forty hypertensive (systolic blood pressure [BP] >/=140 or diastolic BP >/=90 mm Hg) acute ischemic stroke patients (14 lacunar, 13 partial anterior, 7 total anterior, 6 posterior circulation infarct) were randomized to 5 mg of oral lisinopril (n = 18) or matching placebo (n = 22). Dose was increased to 10 mg (or 2 x placebo) on day 7 if casual systolic BP was >/=140 mm Hg and continued to day 14. After the initial dose, automated BP levels were monitored for 16 h. The BP levels and stroke outcome measures were assessed at day 14, and all patients were followed to day 90. RESULTS: At h 4 after the first dose, systolic/diastolic BP change was -20 +/- 21/-6 +/- 10 mm Hg (mean +/- SE) in the lisinopril group and 1 +/- 11/0 +/- 8 mmHg in the placebo group (group differences: systolic BP, P < .05; diastolic BP, P = .07). With a daily dosing regime, systolic BP, mean arterial pressure (MAP), diastolic BP, and pulse pressure (PP) were significantly lower in the lisinopril group compared to the placebo group at day 14 (P < .01). Neurologic and functional measures were similar between groups at follow-up. CONCLUSIONS: Lisinopril, even at small dosages, is well tolerated and an effective hypotensive agent after acute ischemic stroke, gradually reducing BP by 4 h after oral first-dose administration. Oral lisinopril is now being studied in a larger outcome-based trial in acute hypertensive stroke patients.     

Efficacy and tolerability of a fixed-dose combination of telmisartan plus hydrochlorothiazide in patients uncontrolled with telmisartan monotherapy.

The antihypertensive effects of a telmisartan 80 mg/hydrochlorothiazide (HCTZ) 12.5 mg fixed-dose combination and telmisartan 80 mg monotherapy were compared in patients with a history of mild-to-moderate essential hypertension and inadequate BP control (DBP > or = 90 mm Hg) following 8 weeks of telmisartan monotherapy. At the end of this period, 491 patients (62.9% men; mean age 55.3 years) whose DBP was > or = 90 mm Hg were double-blind randomised to once-daily telmisartan 80 mg/HCTZ 12.5 mg (n = 246) or telmisartan 80 mg (n = 245). Trough (24 h post-dose) clinic BP was measured after 4 and 8 weeks of double-blind therapy. At the end of double-blind treatment, patients receiving telmisartan 80 mg/HCTZ 12.5 mg had significant additional decrements in clinic SBP/DBP over telmisartan 80 mg of -5.7/-3.1 mm Hg (P < 0.01). Most of the additional effect occurred during the first 4 weeks of treatment. The proportion of patients with normalised BP (SBP < 140 mm Hg and DBP < 90 mm Hg) was significantly greater in the telmisartan 80 mg/HCTZ 12.5 mg group than the telmisartan 80 mg group (41.5%vs 26.1%;P < 0.05). Both treatments were well tolerated. The incidence of adverse events was similar except for diarrhoea, which occurred more frequently in the telmisartan 80 mg/HCTZ 12.5 mg group, and oedema, which occurred more frequently in the telmisartan group. Our results indicate that a telmisartan 80 mg/HCTZ 12.5 mg fixed-dose combination confers significant additional BP reductions compared with continuation of telmisartan monotherapy in non-responders.     

Atenolol and eprosartan: differential effects on central blood pressure and aortic pulse wave velocity

BACKGROUND: Recent data suggest that atenolol may be inferior to other antihypertensive drugs in reducing cardiovascular risk in older individuals with hypertension, despite lowering peripheral blood pressure (BP). We hypothesized that that atenolol fails to reduce central BP as much as other agents. The aim of the present study was to compare the hemodynamic effects of atenolol and eprosartan in a double-blind, randomized, cross-over study. METHODS: After a 2-week placebo run-in, 21 subjects with never-treated hypertension underwent 6 weeks of therapy with atenolol (50 mg) and eprosartan (600 mg). Central BP and augmentation index were assessed using pulse wave analysis, and aortic pulse wave velocity was measured, at baseline and at the end of each treatment. RESULTS: Both drugs reduced peripheral BP to the same degree. However, there was a significantly greater reduction in central systolic BP with eprosartan (means +/- SEM: 16 +/- 3 v 11 +/- 2 mm Hg; P = .03). Despite identical reductions in mean pressure, atenolol reduced aortic pulse wave velocity more than eprosartan (0.8 +/- 0.1 v 0.5 +/- 0.1 m/sec; P = .005). Conversely, augmentation index and N-terminal pro-brain natiuretic peptide levels were reduced significantly after eprosartan (6% +/- 2% and 11 +/- 5 pg/mL, respectively) but were increased after atenolol (7% +/- 2% and 67 +/- 24 pg/mL, respectively). CONCLUSIONS: These data indicate that despite similar effects on peripheral BP and a greater effect on aortic stiffness, atenolol had less impact on central systolic BP than eprosartan because it failed to reduce wave reflection. This provides one potential explanation for the failure of atenolol to improve outcome in older patients with essential hypertension.     

Effects of candesartan cilexetil in patients with severe systemic hypertension. Candesartan Cilexetil Study Investigators.

The efficacy, tolerability, and safety of the potent angiotensin II receptor blocker candesartan cilexetil were evaluated in 217 adult patients (68% men, 41% black) with severe systemic hypertension on background therapy with hydrochlorothiazide (HCTZ) in a 4-week, multicenter, randomized, double-blind, placebo-controlled study. Patients with sitting diastolic blood pressure (BP) > or =110 mm Hg during the placebo run-in received HCTZ 12.5 mg once daily for 1 week. Those with sitting diastolic BP >95 mm Hg after the HCTZ run-in were randomized (2:1) to receive candesartan cilexetil 8 mg once daily (n = 141) or placebo (n = 76), plus HCTZ 12.5 mg. After 1 week of double-blind treatment, patients with sitting diastolic BP > or =90 mm Hg were uptitrated to candesartan cilexetil 16 mg once daily or matching placebo, plus HCTZ 12.5 mg; 84% required uptitration. Primary efficacy measurement was a change in trough (24+/-3 hours after treatment) sitting diastolic BP from the end of the HCTZ run-in to double-blind week 4. Mean changes in systolic and diastolic BP were significantly greater with candesartan cilexetil than with placebo, -11.3/-9.1 mm Hg versus -4.1/-3.1 mm Hg, p <0.001/p <0.001, respectively. Patients with higher sitting diastolic BP at the end of the HCTZ run-in tended to have greater decreases in BP (p <0.05). Most patients (53%) receiving candesartan cilexetil were responders (diastolic BP <90 mm Hg or > or =10 mm Hg decrease) and 32% were controlled (diastolic BP <90 mm Hg). Tolerability and safety profiles were similar in the candesartan and placebo groups. In conclusion, candesartan cilexetil 8 to 16 mg once daily was an effective and well-tolerated therapy for lowering BP when added to HCTZ 12.5 mg in a diverse population of patients with severe systemic hypertension in the United States.