Antihypertensive effects of beta-blockers administered once daily: 24-hour measurements

Whole-day automated ambulatory blood pressure (BP) monitoring was used to assess the duration of the antihypertensive actions of the beta-blockers atenolol (50 to 100 mg; n = 20) and acebutolol (400 to 800 mg; n = 19) each given once daily at 9 AM. When compared with its pretreatment 24-hour average, atenolol decreased diastolic BP by 10 +/- 2 mm Hg (p less than 0.01) and systolic BP by 12 +/- 2 mm Hg (p less than 0.01). Acebutolol decreased the 24-hour diastolic BP by 11 +/- 1 mm Hg (p less than 0.01) and systolic BP by 13 +/- 2 mm Hg (p less than 0.01). More specifically, a comparison of the two drugs during the final 6 hours (3 AM to 9 AM) of the dosing interval showed that the mean decrease in diastolic BP of 10.2 +/- 1.5 mm Hg with acebutolol was greater (p less than 0.05) than the decrease of 6.2 +/- 1.3 mm Hg with atenolol. Moreover, this final 6-hour effect of atenolol was less (p less than 0.01) than that observed during the first 18 hours of the day. The late effects of acebutolol did not change significantly from its early effects. The two agents also differed in their trough (final 2-hour decrease in diastolic BP) and peak (maximum 2-hour decrease in diastolic BP) effects: for atenolol the peak-to-trough difference was 7.8 +/- 3.1 mm Hg (p less than 0.05), whereas for acebutolol it was 3.8 +/- 4.2 mm Hg (N.S.). This study confirms the efficacy of atenolol and acebutolol.(ABSTRACT TRUNCATED AT 250 WORDS)     

Comparison of lisinopril versus atenolol for mild to moderate essential hypertension.

The antihypertensive effects and safety profiles of lisinopril (10 to 40 mg) and atenolol (50 to 100 mg) were compared in a randomized, double-blind, parallel group trial in 144 patients with essential hypertension. After 8 weeks of therapy, seated blood pressure (BP) decreased by 26/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. Lisinopril produced a greater reduction (p less than 0.05) in sitting systolic BP than did atenolol. Standing BP decreased by 25/15 mm Hg with lisinopril and by 19/14 mm Hg with atenolol. No important changes in hematologic and biochemical profiles were seen with either drug. Eleven patients, 7 receiving lisinopril and 4 receiving atenolol, were withdrawn because of adverse experiences; another 3 patients defaulted during treatment, 1 in the lisinopril group and 2 in the atenolol group. Both drugs were well-tolerated and are therefore suitable for first-line therapy in essential hypertension.     

Assessing duration of antihypertensive effects with whole-day blood pressure monitoring

The whole-day blood pressure response to once-daily and twice-daily administration of a combination of captopril and hydrochlorothiazide was measured in a study of elderly patients (aged 59 to 78 years) with mild to moderate hypertension. Whole-day automated ambulatory blood pressure profiles were obtained at baseline, after 8 weeks of therapy with a combination of 25 mg of captopril and 15 mg of hydrochlorothiazide twice daily, and again after 8 weeks of once-daily therapy with 50 mg of captopril and 25 mg of hydrochlorothiazide. Average systolic and diastolic whole-day blood pressures significantly decreased from baseline during both twice-daily treatment (mean +/- SEM change, 18 [+/- 3]/10 [+/- 2] mm Hg) and once-daily treatment (11 [+/- 2]/9 [+/- 1] mm Hg). While the decrease in systolic blood pressure during once-daily therapy was less than that during twice-daily therapy for the group as a whole, 16 of 19 patients achieved normal systolic (less than 140 mm Hg) and diastolic (less than 90 mm Hg) blood pressures throughout the day during the once-daily regimen. During once-daily therapy, the blood pressure reductions were sustained throughout the 24-hour period, and were not attenuated during the final 2 to 4 hours before the next dose. A subgroup of 5 patients were identified who appeared unresponsive to both twice-daily and once-daily antihypertensive treatment. Despite hypertensive office-measured blood pressures at entry to the study, 4 of these 5 patients actually had normotensive whole-day blood pressure averages at baseline (mean, 131 [+/- 7]/81 [+/- 4] mm Hg). Thus, whole-day ambulatory blood pressure monitoring is a valuable tool for testing treatment responses. It demonstrated that once-daily treatment with low doses of captopril and hydrochlorothiazide was as effective as twice-daily administration in decreasing diastolic pressures throughout the day, but was slightly less effective in decreasing systolic pressures. Additionally, the monitoring identified apparently normotensive patients in whom treatment may not be indicated.     

Sustained antihypertensive actions of a dual angiotensin-converting enzyme neutral endopeptidase inhibitor, sampatrilat, in black hypertensive subjects.

Our objective was to evaluate the safety and antihypertensive efficacy of sampatrilat, a novel dual inhibitor of both angiotensin-converting enzyme (ACE) and neutral endopeptidase (NEP), in subjects poorly responsive to ACE inhibitor monotherapy. The ability of sampatrilat (50 to 100 mg daily) (n = 28) to lower blood pressure was compared with that of the ACE inhibitor lisinopril (10 to 20 mg daily) (n = 30) using a double-blind, randomized, parallel group study design over a 56-day treatment period in black hypertensives. Changes in systolic (SBP) and diastolic (DBP) blood pressure were determined using repeated ambulatory blood pressure (ABP) monitoring. Both sampatrilat and lisinopril decreased plasma ACE concentrations after 28 and 56 days. The decrease in plasma ACE concentrations (U/L) was greater after lisinopril (-9.33 +/- 0.52) as compared with sampatrilat (-6.31 +/- 0.70) (P = .0001) therapy. Lisinopril, but not sampatrilat, increased plasma renin activity. Lisinopril produced a transient decrease in mean 24-h ABP (mm Hg) at 28 days (SBP = -9.0 +/- 2.3, DBP = -5.7 +/- 1.3; P < .01), which returned to pretreatment values by 56 days of therapy. Alternatively, sampatrilat produced a sustained decrease in mean ABP over the 56-day treatment period (day 28: SBP = -7.3 +/- 1.8, DBP = -5.2 +/- 1.2; P < .01: day 56: SBP = -7.8 +/- 1.5; DBP = -5.2 +/- 0.95; P < 0.01) with a greater treatment effect on DBP than that of lisinopril at day 56 (P = .05). Treatment-emergent adverse events were noted to be similar between both treatment groups. We conclude that the antihypertensive actions of ACE/NEP inhibitor monotherapy in black subjects offers a novel therapeutic approach to patients otherwise resistant to the sustained antihypertensive actions of ACE inhibitor monotherapy.     

Reproducibility of Blood Pressure Values in Normotensive Subjects

The reproducibility of whole-day blood pressure (BP) averages was evaluated in 56 normal volunteers. Blood pressure was monitored using a non-invasive automatic device that measured BP at 7.5 minute intervals for a 24h period. The whole-day systolic BP averages were closely similar on the two study days, 119 10 (S.D) and 117 11 mm Hg. A difference between the two whole-day averages of systolic blood pressure of greater than 10 mm Hg was found in 10 subjects. Values for the diastolic BP averages were 75 7 and 73 8 mm Hg with differences of greater than 5 mm Hg found in 15 subjects. Strong consistency of BP averages during the separate study days was also found for shorter monitoring periods: the 2h period (8 AM to 10 AM), the daytime period (6AM to 10PM) and the nighttime period (10PM to 6AM). Thus, blood pressure values obtained using a non-invasive ambulatory monitoring device are reproducible in the majority of normotensive control subjects.     

Pulse pressure lowering effect of dual blockade with candesartan and lisinopril vs. high-dose ACE inhibition in hypertensive type 2 diabetic subjects: a CALM II study post-hoc analysis

BACKGROUND: Elevated pulse pressure (PP) is strongly associated with micro- and macrovascular complications in type 2 diabetic patients. We examined the effect of 12 months of dual blockade with candesartan and lisinopril vs. high-dose lisinopril monotherapy on ambulatory PP in hypertensive type 2 diabetic patients from the CALM (Candesartan and Lisinopril Microalbuminuria Trial) II study. METHODS: The CALM II study was a 12-month prospective, randomized, parallel-group, double-masked study that included 75 type 1 and type 2 diabetic subjects with hypertension. Participants were randomized for treatment with either high-dose lisinopril (40 mg once daily (o.d.)) or for dual blockade treatment with candesartan (16 mg o.d.) and lisinopril (20 mg o.d.). In this article, we present data from the post-hoc subgroup of 51 type 2 diabetic subjects who completed the full 12-month study period with successful ambulatory blood pressure (BP) measurements at both baseline and follow-up visits. RESULTS: Baseline 24-h BP values were similar in the two groups (24-h systolic BP (SBP) 130 +/- 12 vs. 127 +/- 9, 24-h diastolic BP (DBP) 77 +/- 8 vs. 74 +/- 7, and 24-h PP 53 +/- 8 vs. 53 +/- 7 mm Hg, for the lisinopril and dual blockade groups, respectively, P > 0.2 for all). Compared with lisinopril monotherapy, dual blockade treatment caused a highly significant reduction in 24-h PP levels (-5 +/- 5 mm Hg, P = 0.003), albeit the difference in the BP lowering effect between the treatment groups did not differ significantly for 24-h systolic (P = 0.21) or diastolic (P = 0.49) BP. Dual blockade treatment significantly lowered 24-h SBP (-5 +/- 11 mm Hg, P = 0.03), but not 24-h DBP (-2 +/- 7 mm Hg, P = 0.29), whereas in the lisinopril group, the opposite effect was observed (24-h SBP -1 +/- 9 mm Hg, P = 0.45, 24-h SBP -3 +/- 7 mm Hg, P = 0.03). CONCLUSIONS: Twelve months of dual blockade with candesartan and lisinopril significantly reduced PP when compared with high-dose monotherapy with lisinopril. Larger studies are needed to confirm this observation, and to evaluate whether this effect translates into a greater degree of end-organ protection from dual blockade treatment than from conventional angiotensin-converting enzyme (ACE) inhibition.     

Weighted Fourier analysis of blood pressure curves after lisinopril versus atenolol administration in young hypertensives

OBJECTIVE: To evaluate and compare the effects of lisinopril versus atenolol administration on the diurnal blood pressure profile and the nocturnal blood pressure fall in young mild-to-moderate essential hypertensives.METHODS: Thirty patients were studied. After a 2-week placebo run-in period, they were single-blind randomly assigned to receive 20 mg lisinopril or 100 mg atenolol. Using a SpaceLabs 90207 device, their ambulatory blood pressure was measured before and after 12 weeks of therapy. The readings were analysed using Fourer series with four harmonics. RESULTS: Lisinopril and atenolol administration significantly decreased office and ambulatory blood pressure values compared with the placebo period. The daily blood pressure curves obtained from Fourier analysis showed that the circadian rhythm was not altered by lisinopril and atenolol administration. From the night:day ratio for the nocturnal blood pressure fall, we found that atenolol administration minimized the average night-time blood pressure dip by increasing the number of non-dippers. In contrast, lisinopril administration did not modify the day-night difference, preserving the nocturnal blood pressure fall. CONCLUSION: Lisinopril and atenolol administration as a first-step treatment of young essential hypertensives produced comparable degrees of diurnal control of arterial pressure. The blood pressure fall at night in patients treated with atenolol was slightly less than that found with lisinopril treatment.     

Little Effect of Ordinary Antihypertensive Therapy on Nocturnal High Blood Pressure in Patients with Sleep Disordered Breathing

The antihypertensive effects of four different antihypertensive medications (β-blocking agent, atenolol 50 mg; calcium-antagonist, isradipine SRO [slow release] 2.5 mg; diuretic, hydrochlorothiazide [HCTZ] 25 mg; and angiotension converting enzyme-inhibitor, spirapril 6 mg) on obese patients with sleep disordered breathing and hypertension were compared by the ambulatory blood pressure measurement (ABPM).Eighteen patients were randomized in a double-blind, crossover fashion to receive each of the four different medications for 8 weeks. ABPM was performed at baseline and after an 8-week treatment with these medications. A 2- to 3-week washout period occurred both at baseline and between each of the four medications. Three patients were omitted from statistical analysis because of technical problems of ABPM.Atenolol, isradipine SRO, and spirapril decreased significantly (P < .01) the mean 24-h systolic blood pressure, whereas HCTZ did not. The mean 24-h diastolic blood pressure decreased significantly after all four medications: 12 (SD ± 14) mm Hg with atenolol, 7 (SD ± 10) mm Hg with isradipine SRO, 3 mm Hg (SD ± 14) with HCTZ, and 6 (SD ± 15) mm Hg with spirapril (P < .01). During nighttime none of the medications reduced the mean diastolic or systolic blood pressure significantly. According to the 24-h blood pressure curve the influence of these four medications during the whole measurement period was not similar. Atenolol and spirapril lost their antihypertensive effect during the early morning hours. The antihypertensive effect of HCTZ varied markedly from hour to hour. The trough-to-peak ratio of no medication was >0.50.Negative correlation was observed between the apnea time and the mean systolic 24-h (r = −0.604, P = NS) and the mean systolic nocturnal blood pressure change (r = −0.590, P = NS).Our study revealed that the daytime high blood pressure was quite easily controlled by the ordinary monotherapy in these patients with partial upper airway obstruction and hypertension. Instead none of the medications used decreased nocturnal high blood pressure markedly.     

Short-term systemic hemodynamic adaptation to beta-adrenergic inhibition with atenolol in hypertensive patients

Early systemic hemodynamic adjustments to antihypertensive therapy with the cardioselective beta inhibitor, atenolol, were investigated in 12 hospitalized men, mean age 52 years, with uncomplicated mild-to-moderate essential hypertension. Twice daily measurements of cardiac output (CO) by CO2 rebreathing, blood pressure by cuff, and heart rate were performed in all subjects for 3 days before and 5 days after initiation of oral atenolol therapy (50 or 100 mg daily). Cardiac output by CO2 rebreathing was checked with dye dilution just before, and 4 hours and 4 days after the start of therapy. Plasma volume (radioiodinated albumin) was measured before therapy and on Day 5 of therapy. The CO results obtained with the two methods were not significantly different (r = 0.88, p less than 0.01, n = 12). A reduction in heart rate, 18 +/- 2 beats/min (mean +/- SE), occurred in all patients while taking atenolol. By 4 hours after the first dose of atenolol, CO fell from 5.49 +/- 0./30 to 4.24 +/- 0.21 liters/min (p less than 0.01), while the control mean arterial pressure (MAP) of 108 +/- 4 mm Hg was not significantly changed, 110 +/- 4 mm Hg. At 24 hours, CO returned near baseline (5.10 +/- 0.21 liters/min) but MAP was reduced (95 +/- 3 mm Hg, p less than 0.001) and remained so thereafter. CO remained at baseline at 48 hours (5.50 +/- 0.29 liters/min) but fell again (p less than 0.01) to 4.81 +/- 0.11 on Day 4 and to 4.68 +/- 0.25 liters/min on Day 5 of atenolol therapy. Plasma volume, 3110 +/- 100 ml before therapy, was reduced to 2850 +/- 100 by Day 5 of atenolol therapy (p less than 0.01). The findings indicate a delayed onset of the antihypertensive action of atenolol. The transient return to baseline of CO on Day 2 and 3 of atenolol therapy suggests a reverse autoregulatory adjustment to the initial fall in CO.     

Lisinopril versus atenolol: Decrease in systolic versus diastolic blood pressure with converting enzyme inhibition

In a multicenter, parallel, double-blind study, lisinopril, a new converting enzyme inhibitor, was compared with atenolol in the treatment of mild to moderate essential hypertension. Four hundred ninety patients were randomized to once-a-day treatment with lisinopril 20 mg or atenolol 50 mg for 4 weeks, and the doses of lisinopril or atenolol were increased at 4-week intervals up to 80 mg or 200 mg, respectively, if sitting diastolic blood pressure (SDBP) was not well controlled. Lisinopril and atenolol reduced SDBP to a similar extent. All reductions from baseline in sitting diastolic and systolic blood pressure were significant (p less than 0.01). Lisinopril produced a significantly greater reduction (p less than 0.01) in sitting systolic blood pressure (SSBP) than atenolol. The predominant reduction in SSBP could not be explained on the basis of age, race, or severity of hypertension. It is suggested that the increase in arterial compliance reported for converting enzyme inhibitors could explain the predominant decrease in systolic blood pressure.     

Effects of diuretic therapy in low-, normal- and high-renin isolated systolic systemic hypertension

In 30 patients with isolated systolic systemic hypertension, diuretic therapy decreased body weight from 71.33 +/- 2.67 to 70.37 +/- 2.65 kg (p less than 0.0005) and the systolic blood pressure from 174 +/- 3 to 156 +/- 3 mm Hg (p less than 0.0005). Diastolic blood pressure and heart rate did not change significantly. Plasma renin activity increased from 2.25 +/- 0.33 to 4.27 +/- 0.43 ng/ml/hour (p less than 0.0005) and urinary aldosterone from 9 +/- 1 to 16 +/- 2 micrograms/24 hours (p less than 0.005). The antihypertensive effect of diuretics was significantly related only to the pretreatment plasma renin activity (r = -0.50, n = 30, p less than 0.05), and therefore the greatest decrease in systolic blood pressure occurred in the low-renin group, whereas the smallest occurred in the high-renin group (-22 +/- 2 vs -3 +/- 9 mm Hg, p less than 0.005). The diastolic blood pressure was significantly decreased only in the low-renin group (-7 +/- 2 mm Hg, p less than 0.005). There were no significant changes in blood pressure in 11 untreated control patients. These results indicate that diuretics are effective antihypertensive agents in most patients with low- and normal-renin isolated systolic systemic hypertension.     

24-hour blood pressure behavior in patients with untreated and treated hypertension in comparison with normotensive patients

Blood pressure was continuously monitored over 24 h in 201 patients with mild to moderate essential hypertension using a noninvasive method. Measurements were made both before and after 6 months of antihypertensive treatment and the data were compared to results from 100 normotensive patients. The frequency with which blood pressure values above 140/90 mm Hg occurred during the 24-h period proved to be the most reliable parameter for distinguishing between hypertensive and normotensive profiles. The blood pressures of all patients could be normalized (less than 140/90 mm Hg) on single or combined drug therapy as assessed by casual measurement. However, significant differences were observed between the 24-h profiles of the treated patients and the control group. The mean 24-h blood pressure, the mean day and nighttime blood pressures, the mean hourly pressure, and the frequency of increased blood pressure values were all significantly higher in the patients on medication as compared to the normotensive controls. This would suggest that normotension, as defined by the control group, cannot be attained with antihypertensive medication. In conclusion, 24-h continuous blood pressure monitoring allows a better evaluation of blood pressure profiles and consequently, will be of greater value in assessing cardiovascular risk than occasional random measurements.     

Effect of aerobic exercise training on patients with systemic arterial hypertension

One hundred five patients with established diastolic hypertension were enrolled in an exercise program to examine the effect of aerobic conditioning on blood pressure. In four patients, the decrease in mean blood pressure was less than 5 mm Hg; in all others, there was a significant decline in arterial blood pressure. In 58 patients who were not taking drug medication in the pre-exercise period, mean blood pressure decreased by 15 mm Hg. Of 47 patients receiving drug therapy during the pre-exercise period, 24 were able to discontinue all medication. Mean blood pressure in this group fell from 116.9 +/- 6.5 mm Hg to 97.2 +/- 9.2 mm Hg as a result of exercise. In patients still taking antihypertensive drugs, mean pressure decreased from 120.9 +/- 28.8 mm Hg to 104.4 +/- 17.9 mm Hg after three months of exercise. It is concluded that in patients physically and emotionally able to exercise, a significant decline in blood pressure can be achieved.     

Time course of regression of left ventricular hypertrophy in hypertensive patients treated with atenolol

Regression of left ventricular hypertrophy occurs with a number of antihypertensive drugs, but the time course of this regression has not been defined clearly. We obtained echocardiograms at baseline and serially (on seven occasions) during a 1 year treatment period with the beta-adrenergic receptor inhibitor atenolol in 12 patients with previously untreated essential hypertension. To ensure control of blood pressure in all patients throughout the study, it was necessary to add a thiazide diuretic to the therapy of five patients. Baseline blood pressure was 155/100 mm Hg and fell to 136/84 mm Hg; there was a 20% reduction in heart rate. Posterior and septal wall thicknesses were reduced from 1.16 +/- 0.03 to 1.06 +/- 0.02 cm (p less than .05) and from 1.28 +/- 0.07 to 1.18 +/- 0.06 cm (p less than .05), respectively; this reduction became significant initially at 4 weeks. Left ventricular mass decreased from 144 +/- 9 to 127 +/- 7 g/m2 (p less than .05) and this fall first became statistically significant at 6 months. Significant reduction in electrocardiographic voltages was also seen at 6 months. Therefore, regression of left ventricular hypertrophy with atenolol-induced blood pressure control occurred as early as 4 weeks after starting therapy and was maintained thereafter without apparent compromise of left ventricular systolic function.     

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.     

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.     

Circadian behavior of blood pressure and heart rate following orthotopic heart transplantation. Studies before and during antihypertensive therapy

The de novo hypertension, which develops in most cardiac transplant recipients within the first postoperative months, is multicausal, though toxic side-effects of cyclosporin A seem to play a key role. In order to analyze the circadian behavior of arterial blood pressure and heart rate after cardiac transplantation (HTX) and to evaluate the effect of an antihypertensive regimen on these parameters, 24-h noninvasive ambulatory blood pressure and heart rate monitoring was performed in 10 hypertensive cardiac transplant recipients on cyclosporin A (mean age 42.3 +/- 11.2 years, 14.3 +/- 8.3 months after HTX) before antihypertensive therapy and after introduction of an antihypertensive regimen with the ACE-inhibitor enalapril plus furosemide alone or combined with verapamil. The study demonstrated a complete loss of the usual nocturnal decline in blood pressure in cardiac transplant recipients (mean systolic and diastolic blood pressure 149 +/- 8 and 102 +/- 7 mm Hg during daytime and 152 +/- 8 and 104 +/- 9 mmHg at night). Antihypertensive therapy lowered the blood pressure level effectively, but did not influence the circadian pattern (mean systolic and diastolic blood pressure 121 +/- 8 and 81 +/- 4 mmHg during daytime and 121 +/- 9 and 83 +/- 3 mmHg at night, all p less than or equal to 0.001). Heart rate, in contrast, showed a significant, though in comparison to normal, a blunted decrease at night (mean heart rate 94 +/- 6 beats per min during daytime and 84 +/- 8 beats per min at night, p less than or equal to 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of indapamide SR in the treatment of hypertensive patients with type 2 diabetes

BACKGROUND: To evaluate the effect of the sustained-release formulation of indapamide (indapamide SR) in type 2 diabetic patients with mild-to-moderate hypertension and its possible side effects, particularly on glucose metabolism and lipid profiles. METHODS: A total of 64 patients randomly received 1.5 mg of indapamide SR or placebo once daily for 3 months. The effects were evaluated by 24-h ambulatory blood pressure monitor, fasting blood sampling for biochemistry, lipid profiles, and frequently sampled intravenous glucose tolerance test. RESULTS: The changes in standing and supine blood pressure (BP) were significant (154.7 +/- 9.4/94 +/- 2.9 mm Hg v 134.4 +/- 5.1/82.4 +/- 5 mm Hg and 155 +/- 9.8/94.6 +/- 3.6 mm Hg v 135.1 +/- 4.9/82.1 +/- 4.7 mm Hg) in the indapamide group, but not in the placebo group. According to the 24-h ambulatory blood pressure monitor reading, a significant reduction was observed in not only in the whole-day mean BP (mean systolic BP/mean diastolic BP, 149 +/- 19.3/87.6 +/- 11.3 mm Hg v 135.7 +/- 12.6/79.6 +/- 9 mm Hg) but also the whole-day mean median arterial pressure (109 +/- 12.7 mm Hg v 98.7 +/- 8.2 mm Hg) for the indapamide group, but not the placebo group. There were no changes in biochemical data including serum sodium, potassium, chloride, uric acid, alanine aminotransferase, aspartate aminotransferase, blood urea nitrogen, creatinine, lipid profiles, fasting blood glucose, insulin, hemoglobin Alc, and glucose metabolism parameters (insulin sensitivity, glucose effectiveness, and acute insulin response) from frequently sampled intravenous glucose tolerance test after indapamide or placebo therapy. CONCLUSIONS: Indapamide SR can significantly lower the whole-day BP in hypertensive patients with type 2 diabetes. Also, it did not alter or aggravate patients' lipid profiles, glucose metabolism, and did not exert possible side effects of hypokalemia and hyperuricemia. Therefore, monotherapy with indapamide SR should be suggested in type 2 diabetic patients with mild-to-moderate hypertension.     

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.     

Changes in home versus clinic blood pressure with antihypertensive treatments: a meta-analysis

Home blood pressure (HBP) monitoring is recommended for assessing the effects of antihypertensive treatment, but it is not clear how the treatment-induced changes in HBP compare with the changes in clinic blood pressure (CBP). We searched PubMed using the terms "home or self-measured blood pressure," and selected articles in which the changes in CBP and HBP (using the upper arm oscillometric method) induced by antihypertensive drugs were presented. We performed a systematic review of 30 articles published before March 2008 that included a total of 6794 subjects. As there was significant heterogeneity in most of the outcomes, a random effects model was used for the meta-analyses. The mean changes (+/-SE) in CBP and HBP (systolic/diastolic) were -15.2+/-0.03/-10.3+/-0.03 mm Hg and -12.2+/-0.04/-8.0+/-0.04 mm Hg respectively, although there were wide varieties of differences in the reduction between HBP and CBP. The reductions in CBP were correlated with those of HBP (systolic BP; r=0.66, B=0.48, diastolic BP; r=0.71, B=0.52, P<0.001). In 7 studies that also included 24-hour BP monitoring, the reduction of HBP was greater than that of 24-hour BP in systolic (HBP; -12.6+/-0.06 mm Hg, 24-hour BP; -11.9+/-0.04 mm Hg, P<0.001). In 5 studies that included daytime and nighttime systolic BP separately, HBP decreased 15% more than daytime ambulatory BP and 30% more than nighttime ambulatory BP. In conclusion, HBP falls approximately 20% less than CBP with antihypertensive treatments. Daytime systolic BP falls 15% less and nighttime systolic BP falls 30% less than home systolic BP.