Beta-blockers versus diuretics in hypertensive men: main results from the HAPPHY trial. Behavioral and physiological effects of a beta blocker and relaxation therapy on mild hypertensives. Placebo effect and adaptation to noninvasive monitoring of BP. Comparison of a chronotherapeutically administered beta blocker vs. a traditionally administered beta blocker in patients with hypertension. Cardiovascular risk and risk factors in a randomized trial of treatment based on the beta-blocker oxprenolol: the International Prospective Primary Prevention Study in Hypertension (IPPPSH). The IPPPSH Collaborative Group. Comparison of tamsulosin and naftopidil for efficacy and safety in the treatment of benign prostatic hyperplasia: a randomized controlled trial. Pharmaceutical care program for patients with uncontrolled hypertension. Report of a double-blind clinical trial with ambulatory blood pressure monitoring. Lowering blood pressure reduces renal events in type 2 diabetes. Effect of intensive blood pressure control with valsartan on urinary albumin excretion in normotensive patients with type 2 diabetes.
Men aged 40-64 years with mild to moderate hypertension [diastolic blood pressure (DBP) 100-130 mmHg] were randomized to treatment with a diuretic (n = 3272) or a beta-blocker (n = 3297), with additional drugs if necessary, to determine whether a beta-blocker based treatment differs from thiazide diuretic based treatment with regard to the prevention of coronary heart disease (CHD) events and death. Patients with previous CHD, stroke or other serious diseases, or with contraindications to diuretics or beta-blockers were excluded. If normotension (DBP less than 95 mmHg) was not achieved by monotherapy, other antihypertensive drugs were added, but the two basic drugs were not crossed over. Patients were assessed at 6-monthly intervals. The mean follow-up for end-points was 45.1 months. Blood pressure (BP) side effects and end-points were recorded in a standardized manner. Entry characteristics and the BP reduction achieved were very similar in both treatment groups. All analyses were made on an intention-to-treat basis. The incidence of CHD did not differ between the two treatment groups. The incidence of fatal stroke tended to be lower in the beta-blocker treated group than in the diuretic treated group. Total mortality and the total number of end-points were similar in both groups. The percentage of patients withdrawn due to side effects was similar, whereas the number of reported symptoms, according to a questionnaire, was higher for patients on beta-blockers. The incidence of diabetes did not differ between the two groups. Subgroup analyses did not detect a difference in the effect of beta-blockers compared with diuretics in smokers as opposed to non-smokers, and beta-blockers also had the same effects as diuretics in the quartile with the highest predicted risk for CHD. Beta-blockers and thiazide diuretics were approximately equally well tolerated. The two drugs had a similar BP reducing effect although additional drugs had to be given more often in the diuretic group. Antihypertensive treatment based on a beta-blocker or on a thiazide diuretic could not be shown to affect the prevention of hypertensive complications, including CHD, to a different extent. In this industrial-based study we compared the blood pressure (BP)-lowering effectiveness of relaxation, a beta blocker, and the combined use of these two treatments in 47 untreated, mildly hypertensive blue collar steel workers. Using a randomized two by two factorial design, patients received either nadolol or placebo drug daily, and either a relaxation training or an education program, each lasting 8 weeks. A pre-intervention and post-intervention stress test measured response of heart rate and BP to mental and physical tasks. BP assessments were done at baseline, post-intervention, 1 month, and 3 month follow-up. Change in several self-report measures was determined. Results showed that beta blocker was more effective in lowering BP than placebo, but relaxation was not more effective in lowering BP than health education. The combined effect of beta blocker and relaxation was not superior to beta blocker alone. Compliance with relaxation practice was not superior to compliance with medication. We conclude that pharmacologic treatment is superior to the relaxation therapy tested. Three 24 h ambulatory monitorings of BP were performed at two-week intervals in 21 untreated hypertensives (mean age 38 +/- 10 yrs, 13 males and 9 females). After the first baseline monitoring, the patients were randomised, according to a cross-over design, to one of the following sequences: no therapy to placebo or placebo to no therapy. At the end of each period, noninvasive ambulatory monitoring was performed. Mean +/- SE 24 h systolic (SBP) and diastolic (DBP) pressures recorded at the first monitoring were 129.2 +/- 3.5 mmHg and 81.7 +/- 2.3 mmHg respectively. At the second and third monitorings, mean 24 h BP differences versus baseline levels were -2.9 +/- 1.8 and -4.7 +/- 1.7 mmHg for SBP, and -2.0 +/- 1.1 and -2.7 +/- 1.5 mmHg for DBP. Both SBP and DBP differences at repeated monitorings were significant by analysis of variance (P less than 0.05). No significant effects on BP of treatment sequence or of placebo administration were found. Analysis of covariance showed a significant relationship between initial 24 h BP and subsequent mean 24 h BP differences (SBP: beta = -0.260, DBP: beta = -0.124). ANOVA performed on waking and sleeping BP separately showed the observed differences to be significant only during waking hours. Regression analysis showed that the decrease in 24 h BP at repeated monitorings was significantly related to the extent of 'white coat'-induced BP increase only for DBP (P = 0.022). For both 24 h SBP and DBP, however, a negative correlation between the alarm reaction to the presence of the physician and 24 h BP decrease at repeated monitorings was observed. It is concluded that noninvasive ambulatory monitoring is subject to adaptative phenomena but not to placebo effect. Factors influencing the defence reactions to manual measurements and to ambulatory monitoring might be partly different. Increasing systolic blood pressure and heart rate during the early morning results in increased myocardial oxygen demand. The use of beta blockers during this period may decrease cardiac workload, particularly in beta-blocker sensitive patients. The impact of a new chronotherapeutic beta blocker was assessed in 44 hypertensive patients. Patients were randomized to delayed-release propranolol (INP) dosed at 10 p.m. or to traditionally dosed propranolol (ILA) dosed at 8 a.m. for 4 weeks, following which they were switched to the alternative formulation for 4 weeks. Thirty-four-hour ambulatory blood pressure monitoring and pharmacokinetic measurements were obtained. INP and ILA resulted in significant reductions in mean 24-hour blood pressure (-9.0/-6.9 mm Hg and -10.4/-7.7 mm Hg, respectively). The top 25% of responders to high-dose propranolol (sensitive patients) were compared on each formulation. Mean trough reductions were -8.0/-6.7 mm Hg and -7.6/-5.8 mm Hg, respectively. Mean blood pressure reductions in the beta-blocker sensitive patients (n = 11) between 6 a.m. and noon were -15.2/-11.9 mm Hg on INP and -8.0/-4.6 mm Hg on ILA. Heart rate reduction was -14.1 bpm and double product reduction was -3319 in the INP patients between 6 a.m. and 12 noon compared with -10.5 and -2209 in the ILA patients. This study suggests that INP and ILA are effective once-a-day beta blockers, but the use of delayed-release propanolol results in a greater reduction in double product between 6 a.m. and noon in beta-blocker sensitive patients than does traditionally dosed propranolol. Myocardial infarction, sudden cardiac death, cerebrovascular accidents, blood pressure control and treatment tolerability were studied in a randomized double-blind trial conducted in 6357 men and women aged 40-64 years with uncomplicated essential hypertension (diastolic blood pressures 100-125 mmHg). At the start of the trial 3185 patients received treatment based on a beta-blocker (oxprenolol), while in the remaining 3172 placebo replaced oxprenolol. Supplementary drugs, excluding beta-blockers, were used as necessary in both treatment groups, with the aim of reducing diastolic pressure to 95 mmHg or less. Patients were followed for 3-5 years, a total of 25 651 patient years at risk. In most respects the two groups fared equally well; sudden death (relative risk [RR] 1.08; 95% confidence interval [Cl] 0.68 and 1.72), myocardial infarction (RR 0.83; Cl 0.59 and 1.16) and cerebrovascular accident (RR 0.97; Cl 0.64 and 1.47) rates were similar. Beta-blocker based therapy was associated with significantly lower average blood pressures, earlier ECG normalization, less hypokalaemia and fewer withdrawals from double-blind treatment for uncontrolled hypertension. Doctor-elicited and patient-assessed unwanted effects demonstrated overall good tolerability. In smokers the cardiac event rate was doubled. We propose that beta-blocker treatment effects depend on smoking status, with a significant interaction benefiting non-smoking men. Lower blood pressures during treatment were associated with substantially lower rates for cardiac as well as cerebrovascular events. Proportional hazards analysis also underlines the importance of other cardiovascular risk factors. The IPPPSH stresses the need for a comprehensive approach to the management of blood pressure and other risk factors in hypertensive patients. To compare the efficacy and safety of two alpha1a/alpha1d adrenoceptor (AR) antagonists with different affinity for the alpha1AR subtypes, tamsulosin and naftopidil, in the treatment of benign prostatic hyperplasia (BPH).
                Patients with BPH were randomized to receive either tamsulosin or naftopidil. The primary efficacy variables were the changes in the total International Prostate Symptom Score (IPSS), maximum flow rate on free uroflowmetry, and residual urine volume. The secondary efficacy variables were average flow rate, changes in the IPSS storage score, IPSS voiding score, and quality-of-life (QoL) Index score, from baseline to endpoint (12 weeks). Data on all randomized patients were included in the safety analyses for adverse effects and changes in blood pressure.
                Of the 185 patients enrolled data for 144 who were eligible for inclusion in the efficacy analysis were analysed (75 from the tamsulosin and 69 from the naftopidil group). There was no significant difference in any variable at baseline between the groups. There were statistically significant improvements for all primary and secondary variables in both groups, except for residual urine in the tamsulosin group. However, there was no significant intergroup difference in the improvement of any efficacy variable between the groups. The adverse effects were comparable, with no significant differences in systolic and diastolic blood pressure after treatment in both groups.
                This study suggests that naftopidil is as effective and safe as tamsulosin. Both drugs were effective in improving storage and voiding symptoms. However, there was no difference in clinical efficacy or adverse effects between the alpha1 AR antagonists with different affinity to alpha1 subtypes, alpha1a and alpha1d. Pharmaceutical care programs may be an option to improve blood pressure (BP) control in patients with uncontrolled hypertension. The aim of this study was to evaluate the efficacy of pharmaceutical care programs in treating patients with resistant hypertension.
                In a double-blind randomized clinical trial, 71 patients with uncontrolled BP were enrolled in a pharmaceutical care program or in a control group and underwent a series of cognitive tests. The primary outcome was change in ambulatory BP (ABP) between the baseline evaluation and the final visit 6 months later. The secondary outcomes were the frequency of drug-related problems and adherence as determined by plasma levels of hydrochlorothiazide.
                The delta-values between the intervention and control groups for ABP in the different daily periods, with the corresponding 95% confidence limits, adjusted for age and baseline BP were: 3 (-1 to 5), 2 (-2 to 4), and 5 (-1 to 6) mm Hg for 24 h, daily and nightly systolic BP, respectively. The corresponding values for diastolic BP were 1 (-1 to 3), 0 (-2 to 2), and 3 (-1 to 4) mm Hg, respectively. Hydrochlorothiazide was detected in the plasma in 21 of 27 patients in the intervention group that attended to all appointments and 24 of 30 patients in the control group (P = .904).
                The pharmaceutical care program tested in this trial was feasible and showed a trend for better BP control in patients with uncontrolled hypertension. BP is an important determinant of kidney disease among patients with diabetes. The recommended thresholds to initiate treatment to lower BP are 130/80 and 125/75 mmHg for people with diabetes and nephropathy, respectively. We sought to determine the effects of lowering BP below these currently recommended thresholds on renal outcomes among 11,140 patients who had type 2 diabetes and participated in the Action in Diabetes and Vascular disease: preterAx and diamicroN-MR Controlled Evaluation (ADVANCE) study. Patients were randomly assigned to fixed combination perindopril-indapamide or placebo, regardless of their BP at entry. During a mean follow-up of 4.3 yr, active treatment reduced the risk for renal events by 21% (P < 0.0001), which was driven by reduced risks for developing microalbuminuria and macroalbuminuria (both P < 0.003). Effects of active treatment were consistent across subgroups defined by baseline systolic or diastolic BP. Lower systolic BP levels during follow-up, even to <110 mmHg, was associated with progressively lower rates of renal events. In conclusion, BP-lowering treatment with perindopril-indapamide administered routinely to individuals with type 2 diabetes provides important renoprotection, even among those with initial BP <120/70 mmHg. We could not identify a BP threshold below which renal benefit is lost. Diabetes is the most common cause of renal failure in the United States, and data regarding the effects of aggressive blood pressure (BP) therapy in normotensive patients with type 2 diabetes are inadequate.
                A total of 129 type 2 diabetic patients with a BP of <140/80 to 90 mm Hg without overt albuminuria were randomized to either intensive BP control (diastolic BP goal 75 mm Hg) using an angiotensin II receptor blocker, valsartan, versus moderate BP control (diastolic BP 80 to 90 mm Hg with placebo initially) to evaluate the effect on the change in urinary albumin excretion (UAE) from baseline.
                The mean entrance BP was 126 +/- 8.8/84 +/- 2.4 mm Hg. The mean follow-up period was 1.9 +/- 1.0 years. During the follow-up period, the mean BP was 118 +/- 10.9/75 +/- 5.7 for the intensive v 124 10.9/80 6.5 mm Hg for the moderate BP groups (P < .001). No difference was observed in change in creatinine clearance or serum creatinine from baseline between the two groups. An analysis of covariance model for change in log (UAE + 1), adjusting for age, HBA(1c), duration of diabetes, baseline log (UAE + 1), sex, and ethnicity resulted in a significant treatment difference at 2 years (P = .007) with intensive BP control reducing log (UAE+1) compared with moderate BP control.
                Intensive BP control with valsartan to <120/80 mm Hg in normotensive patients with type 2 diabetes and normo- or microalbuminuria significantly decreased the progression of UAE and in some cases caused regression of UAE.
Based on the limited number of published RCTs, the BP lowering effect of alpha blockers is modest; the estimate of the magnitude of trough BP lowering of -8/-5 mmHg is likely an overestimate. There are no clinically meaningful BP lowering differences between different alpha blockers. The review did not provide a good estimate of the incidence of harms associated with alpha blockers because of the short duration of the trials and the lack of reporting of adverse effects in many of the trials.