Multiple injuries in peacetime and wartime estimate of severity of injury by the Injury Severity Score and Polytraumaschlüssel

The aim of this study was to evaluate the efficacy and tolerability of valsartan, a new angiotensin II receptor antagonist, versus atenolol in the treatment of severe primary hypertension. A total of 103 adult out-patients were randomised to receive either valsartan 160 mg or atenolol 100 mg once daily for 6 weeks. If necessary, additional blood pressure (BP) control could be provided as add-on therapy. Both valsartan and atenolol decreased mean sitting diastolic BP (DBP) and mean sitting systolic BP (SBP): least squares mean change from baseline in DBP; valsartan, -20.0 mm Hg; atenolol, -20.4 mm Hg: in SBP; valsartan, -30.0 mm Hg; atenolol, -25.5 mm Hg. There was no statistically significant difference between the treatment groups. Add-on hydrochlorothiazide (HCTZ) 25 mg was required by 97.2% of patients receiving atenolol and 83.6% of patients receiving valsartan; additional verapamil SR 240 mg was also required by 58.3% of patients receiving atenolol and 64.2% receiving valsartan. Valsartan was well tolerated, with a comparable incidence of treatment-related adverse experiences in both groups. In conclusion valsartan 160 mg is as well tolerated and effective as atenolol 100 mg in lowering BP in severely hypertensive patients.     

Age-race subgroup compared with renin profile as predictors of blood pressure response to antihypertensive therapy. Department of Veterans Affairs Cooperative Study Group on Antihypertensive Agents

CONTEXT: Renin profiling and age-race subgroup may help select single-drug therapy for stage 1 and stage 2 hypertension. OBJECTIVE: To compare the plasma renin profiling and age-race subgroup methods as predictors of response to single-drug therapy in men with stage 1 and 2 hypertension as defined by the Joint National Committee on Prevention, Detection, Evaluation and Treatment of High Blood Pressure. DESIGN: The Veterans Affairs Cooperative Study on Single-Drug Therapy of Hypertension, a randomized controlled trial. SETTING: Fifteen Veterans Affairs hypertension centers. PATIENTS: A total of 1105 ambulatory men with entry diastolic blood pressure (DBP) of 95 to 109 mm Hg, of whom 1031 had valid plasma and urine samples for renin profiling. INTERVENTIONS: Randomization to 1 of 6 antihypertensive drugs: hydrochlorothiazide, atenolol, captopril, clonidine, diltiazem (sustained release), or prazosin. MAIN OUTCOME MEASURE: Treatment response as assessed by percentage achieving goal DBP (<90 mm Hg) in response to a single drug that corresponded to patients' renin profile vs a single drug that corresponded to patients' age-race subgroup. RESULTS: Clonidine and diltiazem had consistent response rates regardless of renin profile (76%, 67%, and 80% for low, medium, and high renin, respectively, for clonidine and 83%, 82%, and 83%, respectively, for diltiazem for patients with baseline DBP of 95-99 mm Hg). Hydrochlorothiazide and prazosin were best in low- and medium-renin profiles; captopril was best in medium- and high-renin profiles (low-, medium-, and high-renin response rates were 82%, 78%, and 14%, respectively, for hydrochlorothiazide; 88%, 67%, and 40%, respectively, for prazosin; and 51%, 83%, and 100%, respectively, for captopril for patients with baseline DBP of 95-99 mm Hg). Response rates for patients with baseline DBP of 95 to 99 mm Hg by age-race subgroup ranged from 70% for clonidine to 90% for prazosin for younger black men, from 50% for captopril to 97% for diltiazem for older black men, from 70% for hydrochlorothiazide to 92% for atenolol for younger white men, and from 84% for hydrochlorothiazide to 95% for diltiazem for older white men. Patients with a correct treatment for their renin profile but incorrect for age-race subgroup had a response rate of 58.7%; patients with an incorrect treatment for their renin profile but correct for age-race subgroup had a response rate of 63.1% (P = .30). After controlling for DBP and interactions with treatment group, age-race subgroup (P<.001) significantly predicted response to single-drug therapy, whereas renin profile was of borderline significance (P= .05). CONCLUSIONS: In these men with stage 1 and stage 2 hypertension, therapeutic responses were consistent with baseline renin profile, but age-race subgroup was a better predictor of response.     

A study of losartan, alone or with hydrochlorothiazide vs nifedipine GITS in elderly patients with diastolic hypertension

We conducted a randomised, double-blind, parallel design study comparing the efficacy and tolerability of the angiotensin II receptor antagonist, losartan, alone or with low-dose hydrochlorothiazide (HCTZ) to the dihydropyridine calcium channel blocker, nifedipine GITS (gastro-intestinal therapeutic system), in elderly patients (> or =65 years old) with a diastolic blood pressure (DBP) between 95 and 115 mm Hg. After a placebo wash out period, 140 patients were randomly assigned to receive either losartan 50 mg or nifedipine GITS 30 mg. Patients were evaluated at 4-week intervals during a 12-week treatment period. Patients receiving losartan had HCTZ 12.5 mg added and increased to 25 mg to reduce DBP <90 mm Hg. Patients receiving nifedipine GITS had their dose increased to 60 mg and 90 mg to reduce DBP <90 mm Hg. Efficacy, tolerability and quality of life were assessed during the 12 weeks on each regimen. Patients treated with the losartan regimen (n = 73) had reductions in trough sitting DBP of -10, -13, and -13 mm Hg after 4, 8, and 12 weeks of therapy, respectively. Patients receiving the nifedipine GITS regimen (n = 67) had DBP reductions of -14, -15, and -15 mm Hg, respectively. There were no significant differences in the DBP response between the treatment groups except at week 4 (P < 0.05). Similar reductions in systolic BP (SBP) between the two treatment groups were observed at all time points. The percentages of patients in the two treatment groups reaching goal DBP (<90 mm Hg or DBP > or =90 mm Hg with a reduction from a baseline of > or =10 mm Hg) were comparable (81% on the losartan regimen and 90% on the nifedipine GITS regimen). There were significantly more adverse events reported in patients receiving nifedipine GITS when compared to the losartan regimen (54% vs 36%, P < 0.05). A patient-reported symptom inventory also showed that swollen ankles was bothersome in significantly more patients treated with the nifedipine GITS regimen when compared to the losartan regimen (24% vs 5%, P = 0.001). Thus, in elderly patients with diastolic hypertension, a regimen of losartan alone or with HCTZ has similar efficacy to a regimen of nifedipine GITS with greater tolerability and less symptom bother due to swollen ankles.     

The treatment of severe hypertension with trandolapril, verapamil, and hydrochlorothiazide. Trandolapril/Verapamil Multicenter Study Group

A multiple drug regimen consisting of trandolapril, verapamil and hydrochlorothiazide (HCTZ) were sequentially added in an open-label evaluation of patients with severe hypertension. Ninety patients (58 white and 32 black patients) were titrated on one or more drugs and followed for a 19-week maintenance period. Statistically significant (P = 0.001) mean (+/-s.d.) decreases in supine diastolic blood pressure (DBP) were 9.0 (+/-9.3) mm Hg for trandolapril, 13.9 (+/-11.0) mm Hg for the trandolapril + verapamil (TV) combination, and 19.0 (+/-12.3) mm Hg when hydrochlorothiazide was added to the combination. The decrease in BP observed on TV combination therapy plus HCTZ was significantly (P = 0.001) greater than the decrease observed for the TV combination, which was significantly (P = 0.001) greater than the decrease observed for trandolapril monotherapy. Clinical responder rates were 44.8%, 56% and 77.7% for trandolapril monotherapy, trandolapril + verapamil combination therapy and triple therapy, respectively. Black and white patients had similar response rates, but black patients appeared to benefit more from the addition of HCTZ; 20% of black patients achieved a post-treatment supine DBP <90 mm Hg compared to 12.8% of white patients. This study demonstrates that the addition of verapamil to trandolapril has an additive effect on BP that is maintained throughout the day.     

A case report of two siblings with familial leukoencephalopathy in normotensive male adults with alopecia and lumbago

The aim of the study was to examine the hypotensive efficacy and tolerance of bisoprolol in elderly patients. Sixty patients (40 <65 years and 20 >65 years) with mild-to-moderate essential hypertension (diastolic blood pressure (DBP) between 95 and 109 mm Hg) were included in the study. After a 2-week run-in period on placebo, patients began bisoprolol therapy (5 mg/d) for 12 weeks. After 4 weeks the dose was increased to 10 mg/d in those with a DBP > or =95 mm Hg. Additionally, in 10 patients over 65 years old, 24-h ambulatory BP monitoring (ABPM) was performed, after placebo and after bisoprolol (5 mg) administration. The hypotensive efficacy of bisoprolol in the elderly and younger patients was similar. Before and after treatment the mean difference of systolic BP (SBP) was 19.6 +/- 12.5 mm Hg and DBP 9.6 +/- 6.2 mm Hg in the younger patients and 16.1 +/- 13.6 mmHg and 9.5 +/- 6.0 mmHg in the elderly patients. Bisoprolol produced a similar reduction in heart rate (23.1% vs 17.1%) in the estimated groups. The tolerance of bisoprolol was good in both groups. There were no significant differences in adverse drug reactions between the groups.     

Indomethacin does not attenuate the hypotensive effect of trandolapril

This is a randomised, double-blind, placebo-controlled, four-way crossover study to determine if indomethacin attenuates the hypotensive effect of trandolapril. Twenty-three hypertensive patients (diastolic blood pressure (DBP) 95-115) requiring NSAID were recruited. Seventeen completed the study. Three week treatment periods: trandolapril 2 mg od and indomethacin 25 mg tds, trandolapril 2 mg and placebo, indomethacin and placebo, placebo and placebo. Clinic and ambulatory BP after 3 weeks of each treatment. Study had 85% power to detect a 5 mm Hg difference in BP (s.d. 7 mm Hg). End of treatment clinic BPs were: 152.9/98 mm Hg (95% CI 147.2, 158.6/95.8, 101.4) with placebo and placebo; 150.4/94.9 mm Hg (95% CI 144.7, 156.1/92.1, 97.7) with trandolapril and indomethacin; 148.2/96.5 mm Hg (95% CI 142.5, 153.9/93.7, 99.3) with trandolapril and placebo; and 156.6/97.4 mm Hg (95% CI 150.9, 162.3/94.6, 100.2) with indomethacin and placebo. There were no significant interactions between trandolapril and indomethacin for clinic systolic BP (SBP) (P = 0.79) or clinic DBP (P = 0.87). When trandolapril treatments (placebo or with indomethacin) were compared to treatments without trandolapril (placebo or indomethacin), trandolapril lowered clinic SBP by 5.4 mm Hg (P = 0.047) and DBP by 2.3 mm Hg (P = 0.08). Mean ambulatory BP was: 140.6/88.2 mm Hg (trandolapril and placebo); 142.8/89.7 mm Hg (trandolapril and indomethacin); 149.6/95.0 mm Hg, (indomethacin and placebo); 147.7/94.0 mm Hg (placebo and placebo). Compared with placebo, trandolapril and placebo lowered BP by 6.5/7.5 mm Hg (P < 0.001, SBP; P < 0.001, DBP). Compared with indomethacin, trandolapril and indomethacin lowered BP by 5.0/5.5 mm Hg (P = 0.001, SBP; P < 0.001, DBP). In the present study trandolapril 2 mg lowered clinic SBP and ambulatory BP, but indomethacin did not attenuate this. Indomethacin had no significant effect on either clinic or ambulatory BP. The antihypertensive effects of trandolapril in this study were modest. Patient selection factors may have contributed to the observed responses, but it seems unlikely from these data that a clinically important drug interaction has occurred.     

Epidemiology of extrapulmonary tuberculosis among persons with AIDS in the United States

We compared the antihypertensive efficacy of once-daily amlodipine (AM) versus nitrendipine (NTR) by 24-h ambulatory blood pressure monitoring (24-h ABPM) in 32 patients with mild to moderate essential hypertension (EH). After a 2-week single-blind, placebo run-in period, patients were randomized in a double-blind, parallel fashion: 14 received AM 5 mg and 18 NTR 10 mg. After 2 weeks, dose was adjusted if necessary (AM 10 mg or NTR 20 mg) and continued for another 6-week period. At the end of the placebo period and during the last week of treatment, patients underwent 24-h ABPM. Initial office BP mean values were similar in both groups (169.8 +/- 14/102.5 +/- 6 vs. 167.1 +/- 14/98.7 +/- 5 mm Hg, respectively, p = NS). A comparable decrease in office mean values of systolic BP (SBP, -22.3 +/- 13 vs. -19.1 +/- 16 mm Hg) and diastolic BP (DBP, -12.0 +/- 5 vs. -8.1 +/- 8 mm Hg) was observed. Nevertheless, 24-h ABPM mean values differed significantly between patients treated with AM or NTR with regard to 24-h SBP (120.0 +/- 10 vs. 132.5 +/- 1 mm Hg, p = 0.01). Moreover, the average decrease in 24-h SBP (-19.3 +/- 6 vs. -5.2 +/- 11 mm Hg, p = 0.0036) and 24-h DBP (-10.7 +/- 4 vs. -3.7 +/- 6 mm Hg, p = 0.0047) was higher in the AM group, with no changes in 24-h heart rate (HR). At equivalent once-daily dosage, AM was more effective than NTR in decreasing BP assessed by 24-h ABPM.     

Valsartan, a new angiotensin II antagonist: antihypertensive effects over 24 hours

This study was done to assess the antihypertensive efficacy of once-daily valsartan 20 mg, 80 mg, 160 mg, and 320 mg over 24 hours using ambulatory blood pressure monitoring (ABPM). A total of 217 adult outpatients with uncomplicated essential hypertension (office mean sitting diastolic blood pressure [DBP] of > or = 95 to < or = 115 mm Hg) participated in this multicenter, double-masked, placebo-controlled study. Patients were randomized to receive valsartan 20 mg, 80 mg, 160 mg, 320 mg, or placebo for 8 weeks. Twenty-four-hour ABPM was done at baseline and after 8 weeks of treatment. All valsartan doses produced significant decreases in average ambulatory systolic blood pressure (SBP) and DBP over 24 hours compared with placebo. A trend to greater reductions compared with placebo was observed for doses of valsartan 80 mg and greater (80 mg, -6.61 mm Hg DBP, -11.04 mm Hg SBP; 160 mg, -5.51 mm Hg DBP, -10.61 mm Hg SBP; 320 mg, -8.44 mm Hg DBP, -14.34 mm Hg SBP) compared with valsartan 20 mg (-3.52 mm Hg DBP, -5.92 mm Hg SBP). Valsartan produced consistent reductions compared with placebo during both day (> 6 AM to < or = 10 PM) and night (> 10 PM to < or = 6 AM). However, in all groups, the circadian pattern of blood pressure over 24 hours was preserved and was similar to that observed at baseline (but shifted into the normotensive range in a parallel fashion). The data show that single daily doses of valsartan 80 mg and greater provide effective control of both DBP and SBP over a 24-hour period without loss of diurnal variation.     

Antihypertensive effects of combined lisinopril and hydrochlorothiazide in elderly patients with systodiastolic or systolic hypertension: results of a multicenter trial

This study was aimed at evaluating the antihypertensive effect of lisinopril and hydrochlorothiazide administered in the fixed combination of 20 and 12.5 mg, respectively, on clinic and 24-h blood pressure in elderly patients (age, 68.8 +/- 5.8 years, mean +/- SD) with mild-to-moderate essential systodiastolic or isolated systolic hypertension. After a washout period of 4 weeks, patients received once daily lisinopril combined with hydrochlorothiazide for a 6-week period. At the end of the washout and treatment periods, clinic blood pressure was assessed 24 h after dosing, and 24-h ambulatory blood pressure was monitored, taking blood pressure readings every 15 min. Pretreatment clinic blood pressure was 171.3 +/- 14.0/103.7 +/- 5.1 mm Hg (systolic/diastolic) in the group with systodiastolic hypertension (n = 405) and 179.6 +/- 9.4/83.6 +/- 5.4 mm Hg in the group with isolated systolic hypertension (n = 165). The corresponding 24-h average blood pressures were 144.1 +/- 13.9/88.7 +/- 8.4 mm Hg (n = 114) and 150.7 +/- 15.5/80.8 +/- 9.4 mm Hg (n = 40). Clinic blood pressure was significantly reduced by treatment in both groups. This was the case also for ambulatory blood pressure, which was reduced by 9.6 +/- 0.9%/9.9 +/- 0.9% in systodiastolic and by 11.8 +/- 1.3%/8.5 +/- 1.5% in isolated patients with systolic hypertension (p < 0.05 at least for all differences). The antihypertensive effect was similar in patients older and younger than 70 years. In all groups, it was manifest both during the day and the nighttime and was still significant after 24 h. Thus single daily administration of combined lisinopril-hydrochlorothiazide effectively reduces blood pressure in elderly patients with hypertension.     

A randomised crossover comparison of reserpine and sustained-release nifedipine in hypertension

OBJECTIVE: To compare the effectiveness of the combination of hydrochlorothiazide (HCT) plus sustained-release nifedipine with the combination of HCT plus reserpine in lowering high blood pressure (BP) unresponsive to HCT monotherapy. DESIGN: An open, randomised crossover drug trial. SETTING: Outpatients' clinic in Parirenyatwa Hospital, Harare, a tertiary referral centre. SUBJECTS: 32 Black patients of both sexes with newly diagnosed or previously treated hypertension aged between 21 and 65 years who had a BP > 140/95 after receiving HCT 25 mg daily for four weeks were studied. INTERVENTION: Patients were kept on HCT 25 mg daily and were randomised to receive either reserpine 0.25 mg daily or nifedipine (Adalat Retard) 20 mg bd for four weeks. This was followed by a two week washout period during which patients received HCT 25 mg daily only. After the washout period patients were crossed over to the alternative treatment for four weeks. Patients were kept on HCT 25 mg daily throughout the trial. MAIN OUTCOME MEASURES: The main outcome measure was the fall in BP which was taken as the difference between the BP at baseline and the BP at the end of each treatment period. Both systolic blood pressure (SBP) and diastolic blood pressure (DBP) measurements were taken. RESULTS: Both second line drugs were effective in lowering SBP and DBP and there was no significant difference between them. Nifedipine reduced SBP by 18.9 mmHg (95% CI 12.1 to 25.7) and DBP by 9.6 mmHg (95% CI 7.2 to 12.0). Reserpine reduced SBP by 15.9 mmHg (95% CI 8.4 to 23.4) and DBP by 11.1 mmHg (95% CI 7.5 to 14.6). However, only two patients attained the target DBP of < or = 90 mmHg after each active treatment period. CONCLUSION AND RECOMMENDATIONS: Since both agents were equally effective in reducing both SBP and DBP and reserpine is much cheaper than nifedipine, it is recommended that for a developing country like Zimbabwe, the combination of HCT and reserpine at the above doses should be used as the first step to treat mild to moderate hypertension without evidence of end organ damage. However, further trials should compare BP lowering effects as well as end organ protection offered by the trial drugs.     

Vectorcardiographic evaluation of myocardial infarct size: departure parameters are superior to conventional spatial parameters

OBJECTIVE: To measure the effects of losartan and amlodipine on peripheral capillary microcirculation in hypertension. SETTING: Medical out-patient clinic, Basel, in a university teaching hospital. METHODS: After a 4-week placebo run-in period 20 patients aged 50 +/- 8 (range 36-65) years with mild-to-moderate hypertension were randomly allocated to receive active treatment with losartan 50 mg titrated to losartan 50 mg/hydrochlorothiazide (HCT) 12.5 mg, or amlodipine 5 mg titrated to 10 mg for a 12 week period. Titration was performed if diastolic blood pressure (BP) was > or=90 mm Hg after 6 weeks of treatment. BP measurements as well as video capillary microscopy of the finger nailfold at the end of the placebo period and after 12 weeks of active treatment were compared. Capillary blood cell velocity was measured at rest and immediately, 1 min and 2 min after local finger cooling. RESULTS: After 3 months of treatment with amlodipine (n = 10) and losartan titrated to losartan-HCT (n = 10) sitting BP decreased significantly from 160 +/- 7/103 +/- 4 mm Hg and 147 +/- 7/98 +/- 6 mm Hg to 131 +/- 10/86 +/- 7 mm Hg and 134 +/- 17/89 +/- 9 mm Hg, respectively (P < 0.01). After local finger cooling the area under the curve (AUC) of capillary blood cell velocities was 1.13 +/- 0.58 mm (median +/- s.d.) at baseline and increased to 1.94 +/- 1.15 (P < 0.05) in losartan/losartan-HCT treated patients. In amlodipine treated patients the increase in AUC of capillary blood cell velocity did not reach the level of statistical significance (1.59 +/- 1.36 to 2.14 +/- 1.05 mm). CONCLUSION: This small trial shows that the area under the curve of capillary blood cell velocity increases in hypertensive patients treated with both losartan/losartan-HCT and amlodipine compared with baseline values.     

Ramipril and felodipine: a comparison of the efficacy and safety of monotherapy versus combination therapy

A multinational, double-blind, randomised study was conducted to investigate the efficacy and safety of a low-dose combination of the angiotensin converting enzyme inhibitor, ramipril, and the calcium antagonist, felodipine ER, in 642 patients with mild to moderate hypertension [supine diastolic blood pressure (DBP) = 95-115 mm Hg]. After a 4-week single-blind placebo run-in, patients were randomly allocated to once-daily felodipine extended release (ER; 2.5 mg), ramipril (2.5 mg) or felodipine ER/ramipril (2.5/2.5 mg) for 12 weeks. In the intention-to-treat analysis, mean DBP decreased significantly (p < 0.0001) after felodipine ER, ramipril and the combination (-9.1, -9.8 and -11.4 mm Hg, respectively). The decrease was significantly greater with the combination than with felodipine ER monotherapy (p = 0.02). The number of responding patients (final DBP < or = 90 mm Hg or a decrease of > or = 10 mm Hg) was also higher with the combination than with felodipine ER or ramipril monotherapy (65.1%, 53.1%, 55.7%, respectively). There were no differences between the three groups with respect to the incidence of adverse events overall or those considered treatment-related. There were fewer cases of peripheral oedema with combination therapy than with felodipine ER monotherapy. Thirty-three patients (5.1%) withdrew from the study because of adverse events, but there was no clear pattern with regard to the specific events leading to withdrawal. There were no clinically relevant changes in laboratory or clinical safety variables. Ramipril/felodipine ER 2.5/2.5 mg is an appropriate starting dosage when initiating combination antihypertensive therapy.     

Low dosages of felodipine ER once daily as monotherapy in elderly hypertensive patients: effect on ambulatory blood pressure and quality of life

OBJECTIVE: To establish the efficacy of 24-h ambulatory and casual blood pressure (BP) reduction, and the tolerability of once daily felodipine extended release (ER) 2.5 mg and felodipine ER 5 mg as monotherapy. DESIGN: Randomised, double-blind placebo controlled 6 weeks parallel study. SETTING: From 15 general practices centres (with 19 GPs) in the region of the University of Maastricht, The Netherlands. SUBJECTS: A total of 129 subjects aged 50-80 years with primary hypertension were screened; 27 men and 61 women with a casual diastolic BP of 100-115 mm Hg and/or a systolic BP of less than 200 mm Hg entered the study. MAIN OUTCOME MEASURES: Casual and 24-h ambulatory BP and a subjective symptom assessment (SSA) questionnaire after 6 weeks of therapy. RESULTS: After correlation for placebo response the mean casual systolic/diastolic BP (SBP/DBP) reduction was 10/5 mm Hg (NS) and 12/10 mm Hg (P < 0.05) for felodipine ER 2.5 and 5 mg, respectively. By using 24-h ambulatory BP measurements these reduction were 6/4 mm Hg (NS) and 13/8 mm Hg (P < 0.05), respectively. No significant difference for SBP and DBP was found during the night time between felodipine 2.5 and placebo (-1/0). Felodipine ER 5 mg lowered the BP load significantly during both daytime and night time but felodipine ER 2.5 mg only for DBP during the daytime. There was a significant difference for the number of responders between placebo (28%) vs felodipine ER 2.5 mg (55%) and ER 5.0 mg (59%). Both felodipine dosages and placebo were comparable in (a low) number of adverse events and results of the SSA. CONCLUSIONS: During daytime felodipine ER 2.5 mg and 5 mg are effective in BP lowering in elderly hypertensive patients. However, only felodipine ER mg is effective in reducing BP during night time (22.00-7.00). Only felodipine ER 5 mg has a significant reducing effect on BP load during day and night time. Both felodipine ER 2.5 and ER 5.0 have a significant effect on the responder rate. It appeared from this study that compared to placebo, and in contrast with felodipine ER 5 mg, the ER form of felodipine 2.5 mg has no BP lowering effect during night time in elderly patients. To assess the effectivity during night time of felodipine ER 2.5 mg in an individual patient it is recommendable to measure the BP at the end of the dose interval.     

Valsartan and hydrochlorothiazide in patients with essential hypertension. A multiple dose, double-blind, placebo controlled trial comparing combination therapy with monotherapy

OBJECTIVE: This study compares the antihypertensive efficacy and tolerability of valsartan, a novel angiotensin II antagonist, given with hydrochlorothiazide (HCTZ) vs placebo or vs valsartan or HCTZ alone. DESIGN: 871 adult out-patients with essential hypertension participated in this double-blind study. Patients were randomised in equal number to receive either combination therapy of valsartan (80 mg or 160 mg) and HCTZ (12.5 mg or 25 mg), or valsartan (80 mg or 160 mg) or HCTZ (12.5 mg or 25 mg) alone, or placebo. Patients were treated once daily for 8 weeks and assessed at 2, 4 and 8 weeks after randomisation. MAIN OUTCOME MEASURES: The primary efficacy variable was change from baseline in mean sitting diastolic blood pressure (MSDBP) at end-point. The secondary variable was change in mean sitting systolic blood pressure (MSSBP) from baseline to end-point. RESULTS: All active treatments produced a statistically significant difference in MSDBP (P < 0.001) from baseline to end-point compared with placebo. Similar results were obtained for MSSBP. All combination regimens produced a statistically significantly greater reduction in MSDPB and MSSBP than the corresponding monotherapies. Dizziness and headache were the most common treatment-related adverse experiences reported. Hypokalaemia, associated with the use of thiazide diuretics, was more commonly reported in the higher dose HCTZ 25 mg groups. CONCLUSIONS: Valsartan 80 mg and 160 mg act additively with HCTZ 12.5 mg or 25 mg to lower MSDBP and MSSBP in patients with essential hypertension. The addition of HCTZ to valsartan 80 mg or 160 mg was well tolerated.     

Optimization of antihypertensive therapy with a novel, extended-release formulation of diltiazem: results of a practice-based clinical study

Although the effectiveness of diltiazem for the treatment of patients with hypertension has been well demonstrated in numerous placebo-controlled and comparative clinical trials, most physicians have had some concern about its efficacy and have used it predominantly in patients with mild hypertension. Few large-scale studies have evaluated the efficacy and safety of higher dosages of diltiazem for the treatment of patients with hypertension, and few have evaluated the use of diltiazem in patients with more severe hypertension. Tiazac (Forest Pharmaceuticals, Inc., St. Louis, Missouri), a new, extended-release formulation of diltiazem, provides 24-hour blood pressure control with a single daily dose of up to 360 mg. The Study of Titration and Response to Tiazac (START) is an ongoing practice-based, open-label, multicenter study designed to evaluate the efficacy and safety profiles of Tiazac at greater-than-traditional doses in hypertensive patients and to assess the ability of Tiazac to decrease the rate-pressure product, a surrogate marker for cardiac workload. Patients were eligible for study entry whether their hypertension was newly diagnosed or previously treated with a different formulation of diltiazem or any other antihypertensive agent. Normotensive (sitting diastolic blood pressure [SDBP] < 90 mm Hg) subjects and those with mild (SDBP 90 to 99 mm Hg), moderate (SDBP 100 to 109 mm Hg), severe (SDBP 110 to 119 mm Hg), and very severe (SDBP > or = 120 mm Hg) hypertension were assessed at baseline (visit 1), visit 2 (10 to 14 days after visit 1), and visit 3 (25 to 28 days after visit 1). A total of 3082 patients were enrolled, and data from 2802 assessable patients (i.e., those who completed visits 1, 2, and 3) were analyzed. No subjects were lost to follow-up as a result of adverse effects. All subjects received a starting dose of Tiazac 180 mg or 240 mg once daily, and doses were titrated upward to 360 mg once daily as clinically indicated. Blood pressure reduction matched the severity of hypertension in all patients. Subjects who were switched from another diltiazem formulation demonstrated further decreases in SDBP. Antihypertensive monotherapy with Tiazac was well tolerated. This interim START report demonstrates that a daily dose of up to 360 mg of diltiazem is optimal in terms of both control of hypertension and patient compliance. It also provides the practice-based physician with useful clinical information on dose titration and response to a new formulation of an approved drug and supports the efficacy and safety profiles of diltiazem documented in previous well-controlled clinical trials.     

An elective-titration study of the comparative effectiveness of two angiotensin II-receptor blockers, irbesartan and losartan. Irbesartan/Losartan Study Investigators

This multicenter, randomized, double-masked, elective-titration study was designed to compare the effectiveness, safety, and tolerability of irbesartan and losartan, two angiotensin II subtype AT1-receptor blockers, in the treatment of patients with mild-to-moderate hypertension. After a 3-week, single-masked, placebo lead-in period, 432 patients with a mean seated diastolic blood pressure (SeDBP) of 95 to 115 mm Hg were randomly allocated to receive either irbesartan 150 mg once daily (n = 213) or losartan 50 mg once daily (n = 219). At week 4, if SeDBP at trough (i.e., 24 +/- 3 hours after the previous dose) was > or = 90 mm Hg, the daily dose was doubled (to irbesartan 300 mg or losartan 100 mg). At week 8, if trough SeDBP was > or = 90 mm Hg, hydrochlorothiazide 12.5 mg once daily was added to the regimen; consistent with the prescribing information for losartan, the dose of losartan was reduced to 50 mg once daily on the addition of hydrochlorothiazide. A total of 370 patients (178 irbesartan and 192 losartan) were evaluable for efficacy. The mean change in trough SeDBP at week 8, the primary efficacy end point, was significantly greater in patients receiving irbesartan monotherapy than in those receiving losartan monotherapy (-10.2 mm Hg vs -7.9 mm Hg, respectively). At week 12, reductions in trough SeDBP and seated systolic blood pressure were greater with irbesartan treatment than with losartan treatment (-13.8 mm Hg vs -10.8 mm Hg and -18.0 mm Hg vs -13.9 mm Hg, respectively), and a greater proportion of irbesartan patients responded to therapy (i.e., trough SeDBP < 90 mm Hg or reduction in trough SeDBP > or = 10 mm Hg) compared with losartan patients (78% vs 64%, respectively). Both regimens were well tolerated.     

Hydrochlorothiazide is superior to isradipine for reduction of left ventricular mass: results of a multicenter trial. The Isradipine Study Group

OBJECTIVES: We sought to determine the efficacy of isradipine in reducing left ventricular (LV) mass and wall thickness in hypertensive patients. BACKGROUND: LV hypertrophy on the echocardiogram is a strong predictor of cardiovascular events. Reduction of LV mass may be a desirable goal of drug therapy for hypertension. However, although thiazide diuretic drugs have been advocated as first-line therapy for hypertension, their efficacy in reducing LV mass has been questioned. METHODS: Patients with mild to moderate diastolic hypertension and LV mass in excess of 1 SD of normal values were randomized to isradipine (n = 89) or hydrochlorothiazide therapy (n = 45). Evaluations were obtained at baseline, after 3 and 6 months of treatment and 2 weeks after treatment was stopped. RESULTS: At 6 months, LV mass decreased by 43 +/- 45 g (mean +/- SD) with hydrochlorothiazide (p < 0.001) but only by 11 +/- 48 g with isradipine (p = NS; between-group comparison, p < 0.001). Two weeks after drug therapy was stopped, LV mass remained 24 +/- 41 g lower than that at baseline in the hydrochlorothiazide group (p = 0.003) but only 7 +/- 50 g lower in the isradipine group (p = NS). Septal and posterior wall thicknesses were significantly and equally reduced with both isradipine and hydrochlorothiazide. Greater LV mass reduction with hydrochlorothiazide was related to a 2.8 +/- 3.3-mm reduction of LV cavity size with hydrochlorothiazide but no reduction with isradipine. At 6 months of treatment, diastolic blood pressure (BP) by design was equally reduced in both treatment groups. At 3 months, systolic BP was reduced by 17 +/- 15 mm Hg with isradipine and by 26 +/- 15 and 25 +/- 17 mm Hg at 3 and 6 months, respectively, with hydrochlorothiazide (p = 0.003, between-group comparison). However, on stepwise multivariable regression analysis, treatment selection (partial r2 = 0.082, p = 0.001), change in average 24-h systolic BP (partial r2 = 0.032, p = 0.029) and change in average sitting systolic BP (partial r2 = 0.017, p = 0.096) were predictive of LV mass reduction. CONCLUSIONS: Despite an equivalent reduction of diastolic BP, 6 months of therapy with hydrochlorothiazide is associated with a substantial reduction of LV mass, greater than that with isradipine. The superior efficacy of hydrochlorothiazide for LV mass reduction is associated with a greater reduction of systolic BP as well as drug selection itself. These data may have important therapeutic implications.     

Evaluation of the antihypertensive efficacy of lisinopril and captopril associated with hydrochlorothiazide by ambulatory measurement of arterial pressure

The objective of this study was to evaluate the efficacy, particularly in terms of the 24-hour cover, and the safety of lisinopril 20 mg + hydrochlorothiazide 12.5 mg 5L/HCTZ) and captopril 50 mg + hydrochlorothiazide 25 mg (C/HCTZ) in patients with essential HT requiring two-agent therapy. Twenty patients with a diastolic blood pressure (DBP) between 95 and 120 mmHg after 2 weeks of placebo were randomised to receive, under double-blind conditions, either L/HCTZ or C/HCTZ as a single daily dose for 4 weeks. Clinical examination, laboratory tests and 24-hour ambulatory blood pressure monitoring (ABPM) were performed at the end of the placebo and active treatment periods. L/HCTZ and C/HCTZ significantly lowered SBP and DBP on occasional recordings and on ABPM. The mean fall in blood pressure on ABPM (SBP, DBP, mean of 24-hour recording, diurnal and nocturnal) at 4 weeks was greater with L/HCTZ than with C/HCTZ. Both treatments were effective for 24 hours and did not alter the circadian cycle. The clinical and laboratory safety was good. The blood pressure figures obtained by ABPM were lower than on occasional recordings, emphasising the value of this technique in the evaluation of a patient's poor response to antihypertensive treatment.     

Comparative antihypertensive effectiveness of once-daily mibefradil and diltiazem CD. Mibefradil Hypertension Study Group

This multicenter, double-masked, randomized, forced-titration, parallel-group trial was designed to determine whether we could confirm the results of a previous trial that demonstrated a significantly greater antihypertensive effect for mibefradil compared with diltiazem CD. Two hundred thirty-nine patients with uncomplicated mild-to-moderate essential hypertension and a baseline sitting diastolic blood pressure (SDBP) between 95 and 114 mm Hg were randomized to receive once-daily treatment with mibefradil 50 mg (n = 119) or diltiazem CD 180 mg (n = 120). After 4 weeks of treatment, all patients underwent forced titration to mibefradil 100 mg or diltiazem CD 360 mg for an additional 8 weeks. After 12 weeks of active treatment, the mean reduction from baseline in trough SDBP was significantly greater with mibefradil than with diltiazem CD (-14.3 +/- 6.6 mm Hg vs -11.7 +/- 7.4 mm Hg, respectively). In addition, significantly more patients receiving mibefradil had a decrease in SDBP > or = 10 mm Hg or a decrease to < or = 90 mm Hg by week 12 than did patients receiving diltiazem CD (82% vs 72%, respectively). The tolerability of mibefradil and diltiazem CD were comparable, with similar percentages of patients in both groups reporting at least one adverse event (21% vs 22%, respectively) that was considered to be at least remotely related to the study drug. The results of this study confirm those of the previous trial. Once-daily treatment with mibefradil 100 mg is significantly more effective than diltiazem CD 360 mg in lowering both diastolic and systolic blood pressure. Both drugs are well tolerated.     

Stress-management training for essential hypertension: a controlled study

Forty three patients with essential hypertension participated in a study on the effectiveness of stress-management training for essential hypertension. After 6-9 clinic and 48 self-measured readings of systolic and diastolic blood pressures (SBP and DBP), 22 patients were treated with a program based on education, relaxation, and problem-solving training; and another 21 patients were assigned to a waiting list control group. At post-treatment, mean reductions of clinic BP (17/13 mm Hg vs. 6.9/4.7 mm Hg for SBP/DBP), percentages of subjects who achieved at least a 5 mm Hg reduction (86/86% vs. 48/48% for SBP/DBP) and percentages of subjects who in addition achieved a normotensive level (59/68% vs. 29/14% for SBP/DBP) were significantly higher in the treated group than in the control group. Concerning self-measured BP, the effectiveness of the stress-management training was not so considerable (mean reductions of 3.6/2.4 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 52/38% for SBP/DBP), but it was significant and maintained in a 4-month follow-up assessment (mean reductions of 4/2 mm Hg and percentages of subjects who achieved a 5 mm Hg reduction of 48/33% for SBP/DBP). It is suggested that stress-management training can be beneficial for treatment of essential hypertension.