Comparison of blood pressure and angiotensin responses to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme inhibitor enalapril in essential hypertension

OBJECTIVE: To compare the responses of angiotensin II (Ang II) and blood pressure to the renin inhibitor Ro 42-5892 and the angiotensin converting enzyme (ACE) inhibitor enalapril. SUBJECTS: Eight non-sodium-restricted patients with mild-to-moderate essential hypertension. DESIGN: A single-blind crossover study. Ro 42-5892 (600 mg orally, once a day) and enalapril (20 mg orally, once a day) were given for 8 days before detailed investigations were carried out. METHODS: Ambulatory blood pressure was measured directly for 24 h by the Oxford technique on three occasions. Off-treatment and on day 8 of treatment with Ro 42-5892 and with enalapril. Ang II was measured by radioimmunoassay after separation by high-performance liquid chromatography. RESULTS: Plasma renin activity and Ang II were lowered by 83% [95% confidence interval (CI) 61-105] and 68% (95% CI 49-87), respectively, 0.5-1 h after Ro 42-5892, but after only 3 h values had returned to baseline. Unlike this rapid and short-term suppression of Ang II, the maximal antihypertensive response to Ro 42-5892 (fall in blood pressure 12.9/9.0 mmHg) occurred only after 6 h. Blood pressure returned to baseline after 8 h. In response to enalapril, Ang II was maximally suppressed by 63% (95% CI 32-94) after 2 h and by 83% (95% CI 76-90) after 8 h. Despite early maximal Ang II suppression, the maximal antihypertensive response to enalapril occurred only after 12 h (fall in blood pressure 25.3/16.3 mmHg). With this compound a significant antihypertensive effect was still present 24 h after dosing. CONCLUSIONS: Compared with enalapril at 20 mg once a day, repeated oral administration of a single dose of Ro 42-5892 at 600 mg caused only short-term suppression of Ang II and blood pressure. Suppression of Ang II and reduction in blood pressure were temporally dissociated, both with the ACE inhibitor and the renin inhibitor. This implies that the blood pressure lowering effect of these inhibitors is caused partly by Ang II suppression outside the circulation.     

Comparison of isolated hepatocytes and tissue slices for study of liver hypothermic preservation/reperfusion injury

BACKGROUND/AIMS: Effective protection from the risk of variceal bleeding is achieved when the hepatic venous pressure gradient is reduced to 12 mmHg or at least by 20% of baseline values. Such a marked decrease is rarely achieved with propranolol, and new agents or combinations of them are now being explored. The present randomized study investigated whether chronic treatment with the combination of propranolol plus molsidomine, a preferential venous dialator that reduces hepatic venous pressure gradient and does not cause pharmacological tolerance, achieves greater reduction in hepatic venous pressure gradient than propranolol alone. METHODS: A hemodynamic study was performed in 34 patients with cirrhosis with portal hypertension in baseline conditions and after 3 months of chronic oral treatment with propranolol alone (n = 19) or propranolol plus molsidomine (n = 15). RESULTS: Propranolol produced a significant reduction in hepatic venous pressure gradient (-16%, p < 0.01). Propranolol plus molsidomine also caused a slight but significant decrease in hepatic venous pressure gradient (-9%, p < 0.05). Hepatic blood flow and the hepatic and intrinsic clearance of indocyanine green were significantly reduced by propranolol. The combined administration of propranolol+molsidomine significantly reduced hepatic blood flow but not hepatic and intrinsic clearance of indocyanine green. Both treatment groups produced similar reduction in azygos blood flow, heart rate and cardiac output. However, contrary to propranolol alone, propranolol plus molsidomine did not increase cardiopulmonary pressures. CONCLUSIONS: The current study shows that although the combined administration of propranolol plus molsidomine prevents some of the adverse effects of propranolol on liver function and cardiopulmonary pressures, it does not achieve a greater reduction in hepatic venous pressure gradient than propranolol alone and therefore, does not support the use of this combined therapy for the pharmacological treatment of portal hypertension.     

A case of intraplacental choriocarcinoma associated with placental hemangioma

Disorders in peripheral microcirculation are observed in arterial hypertension and may be improved by antihypertensive treatment. In this pilot study the authors measured capillary blood cell velocity in the finger nailfold in 14 patients (mean age 50 +/- 14 years, range 30-71 years; 9 men, 5 women) with mild-to-moderate essential hypertension. After a 3-week placebo period, patients received double-blind randomized treatment with either 0.2- to 0.4-mg moxonidine (n=7) or 2.5- to 5.0-mg cilazapril (n=7). Finger nailfold video capillaroscopy was performed at baseline and after 8 weeks of treatment. Blood pressure was measured by conventional office technique. Capillary blood cell velocity, 1 minute after local finger cooling, increased in the Moxonidine group (0.65 +/- 0.53 mm/sec to 1.13 +/- 0.77 mm/sec; p<0.05) after 8 weeks treatment compared to the baseline. The increase in the Cilazapril group from 0.79 +/- 0.45 mm/sec to 0.93 +/- 1.03 mm/sec did not reach a level of statistical significance. Blood pressure decreased from 151 +/- 8/101 +/- 5 to 147 +/- 6/98 +/- 7 mmHg in the Moxonidine group and from 164 +/- 12/102 +/- 6 to 140 +/- 9/93 +/- 9 mmHg in the cilazapril group. Moxonidine increased nailfold capillary blood cell velocity 1 minute after local finger cooling in patients with mild-to-moderate hypertension. This improvement of the peripheral microcirculation may be associated with reversal of vascular dysfunction in hypertension.     

Appropriate Blood Pressure Control in NIDDM (ABCD) Trial

The ABCD (Appropriate Blood Pressure Control in Diabetes) Trial is a large, prospective, randomized clinical trial of 950 patients with non-insulin-dependent diabetes mellitus (NIDDM) designed to compare the effects of intensive blood pressure control with moderate control on the prevention and progression of diabetic nephropathy, retinopathy, cardiovascular disease, and neuropathy in NIDDM. The secondary objective is to determine equivalency of the effects of a calcium channel blocker (nisoldipine) and an angiotensin-converting-enzyme inhibitor (enalapril) as a first-line antihypertensive agent in the prevention and/or progression of these diabetic vascular complications. The study consists of two study populations aged 40-74 years, 470 hypertensive patients (diastolic blood pressure of > or = 90.0 mmHg at time of randomization) and 480 normotensive patients (diastolic blood pressure of 80.0 mmHg at time of randomization). The study duration is 5 years and is scheduled to end in May of 1998. Patients are randomized to receive either intensive antihypertensive drug therapy or moderate antihypertensive drug therapy. Patients are also randomized to nisoldipine or enalapril, with open-label medications added if further blood pressure control is necessary. The primary outcome measure is glomerular filtration rate as assessed by 24-h creatinine clearance. Secondary outcome measures are urinary albumin excretion, left ventricular hypertrophy, retinopathy, and neuropathy. Cardiovascular morbidity and mortality will also be evaluated. Given the data showing the impact of hypertension on complications in NIDDM, the ABCD Trial is designed to determine if intensive antihypertensive therapy will be more efficacious than moderate antihypertensive therapy on the outcome of diabetic complications in NIDDM.     

Response of hypertension to conventional antihypertensive treatment and/or steroidogenesis inhibitors in Cushing's syndrome

OBJECTIVES: To evaluate the effect of conventional antihypertensive drugs and/or inhibitors of steroid production in the management of hypertension in Cushing's syndrome. DESIGN: A retrospective open clinical study with pre- and post-treatment assessment. SETTING: A university hospital, where patients were initially admitted and then followed-up in an ambulatory clinic over a period of 6 years. SUBJECTS: Forty consecutive hypertensive patients with Cushing's syndrome. INTERVENTIONS: Patients were divided into two groups according to the different management of hypertension. The first group (group 1) of 28 patients included those treated with antihypertensive drugs at full dose (diuretics, calcium antagonists, angiotensin converting enzyme [ACE] inhibitors, as single agents or in combination). The second group (group 2) of 12 patients received ketoconazole alone. MAIN OUTCOME MEASURES: Blood pressure variations compared to pre-treatment levels. RESULTS: Blood pressure normalization was obtained in four of the 28 patients of group 1. In 12 of the remaining patients, ketoconazole, an inhibitor of steroid production, was subsequently added and this normalized blood pressure in all but the one in whom cortisol was not decreased. In the 12 patients of group 2, ketoconazole alone lowered blood pressure within normal limits in all but one who had long-standing hypertension. CONCLUSIONS: In hypertensive patients with Cushing's syndrome, conventional antihypertensive therapy is mostly ineffective. Blood pressure response is satisfactory only after the restoration of normal cortisol levels, indicating the need for a specific treatment for hypertension in this disorder.     

Comparison of the angiotensin II antagonist losartan with the angiotensin converting enzyme inhibitor enalapril in patients with essential hypertension

OBJECTIVE: To evaluate the blood pressure lowering efficacy as well as tolerability and safety of the angiotensin II antagonist losartan compared with that of the angiotensin converting enzyme inhibitor enalapril in patients with mild-to-moderate essential hypertension. DESIGN AND METHODS: The study was a multicentre, double-blind, double-dummy, randomized, parallel study. Patients (n = 407) with diastolic blood pressure > or = 95 and < or = 120 mmHg at the end of a 2-week baseline placebo period were randomly allocated to receive either 50 mg losartan once a day or 20 mg enalapril once a day for 12 weeks. Blood pressure, clinical and laboratory safety, specific symptoms including coughing determined using a symptoms questionnaire and metabolic variables were examined at baseline and at weeks 6 and 12. RESULTS: Both losartan and enalapril decreased systolic and diastolic blood pressure from baseline at weeks 6 and 12. Blood pressure changes from baseline at trough (22-26 h after the dose) did not differ between the two groups in the per-protocol analysis. Response to treatment at trough was excellent or good (diastolic blood pressure < 90 mmHg or reduction in diastolic blood pressure of 10 mmHg) in 51 and 53% of the patients in the losartan and enalapril groups, respectively. Enalapril administration increased dry coughing symptoms whereas losartan did not. The incidence of dry coughing was 1.0 and 12.2% as a spontaneously reported discomfort at week 12 and 3.0 and 15.1% as a clinical adverse experience in the losartan and enalapril groups, respectively. The difference from baseline at week 12 in the incidence of dry coughing between the two groups was 14.9% as a specific symptom in the symptoms questionnaire. Losartan reduced serum uric acid concentration, whereas effects on other metabolic parameters did not differ between the groups. CONCLUSIONS: Losartan is an effective and well-tolerated antihypertensive drug showing similar blood-pressure-lowering efficacy to that of enalapril at trough. However, in contrast to enalapril, losartan does not increase the incidence of dry coughing. Thus, the angiotensin II antagonist losartan provides a promising new approach to treatment of hypertension.     

Use of antihypertensive drugs and trends in blood pressure in the elderly

BACKGROUND: During the 1980s data became available from randomized trials concerning the clear benefits of treating hypertension in the elderly. In three large communities, we examined the impact of these findings on rates of treatment, use of specific antihypertensive drugs, and rates of elevated blood pressure as well as distributions of levels. METHODS: In 1981 the National Institute on Aging initiated population-based cohort studies in the residents of three communities who were 65 years and older. East Boston, Mass; Washington and Iowa counties, Iowa; and New Haven, Conn. Participation rates ranged from 80% to 85% across sites with 10,294 community-dwelling participants in the combined cohorts. Baseline evaluation included inhome blood pressure assessment and medication inventory. Repeated in-home evaluations occurred 3 and 6 years after baseline and follow-up rates ranged from 71% to 88%. RESULTS: Use of antihypertensive drugs increased over time in all three communities: the age- and sex-adjusted rates of use were between 14% and 32% higher in 1988 and 1989 relative to 1982 and 1983. Parallel declines in the use of thiazide diuretics occurred in all three populations along with large increases in the use of angiotensin-converting enzyme inhibitors and calcium channel blockers. In East Boston and New Haven mean systolic blood pressure decreased substantially over time and the prevalence of elevated systolic pressure (> or = 160 mmHg) decreased overall as well as by age and sex. In Iowa the mean levels of systolic blood pressure were lowest at baseline and increased slightly. CONCLUSIONS: The reported evidence about the benefits of treatment for hypertension in the elderly was followed by substantial increases in treatment rates. The use of drugs with proven efficacy declined while the use of newer agents with theoretical advantages, not yet tested in clinical trials of mortality, increased. In the United States, the ongoing therapeutic efforts to lower elevated blood pressure in elderly populations may be contributing to the continuing decline in cardiovascular and stroke mortality.     

Long-term evaluation of combined antihypertensive therapy with lisinopril and a thiazide diuretic in patients with essential hypertension

For the treatment of hypertension, the combination of an angiotensin-converting enzyme (ACE) inhibitor and a thiazide diuretic is supported by multiple lines of evidence, because these drugs have synergistic action and are expected to cancel out each other's adverse side effects. However, the long-term outcome of this combination antihypertensive therapy is not entirely clear. In the present multicenter open trial, we investigated the long-term efficacy and safety of combined antihypertensive therapy with an ACE inhibitor, lisinopril, and a thiazide diuretic, trichlormethiazide. A total of 466 patients with essential hypertension were treated with lisinopril alone (monotherapy group, n = 360) or with a combination of lisinopril with trichlormethiazide (combination therapy group, n = 106) for 1 year. The average blood pressure was effectively lowered to below 150/90 mmHg in both the monotherapy and the combination therapy groups throughout the study period. The average maintenance dose of lisinopril was lower when combined with thiazide than when given alone (9.8 vs. 11.5 mg/day, p < 0.001). Dry cough was the major side effect of lisinopril; no severe adverse effects were observed. The incidence of cough was not significantly different between the monotherapy group (13.1%) and the combination therapy group (11.3%). The increase in serum potassium observed in the monotherapy group was reversed by the concurrent use of the thiazide diuretic in the combination therapy group. Fasting blood glucose was significantly reduced in the monotherapy group; the reduction observed in the combination therapy group was not significant. Thus, the present results provide useful information as to the effectiveness and safety of combined antihypertensive therapy with lisinopril and a thiazide in comparison with monotherapy with lisinopril.     

Long-term therapeutic effects of ace inhibitor and calcium antagonists on hypertensive vascular lesions in M-SHRSP

1. Our results indicate that the drugs used in this study are very effective in malignant hypertension therapy. 2. For M-SHRSP treated with highly effective antihypertensive drugs, if blood pressure remains under 200 mmHg over the long-term, the structures of the small arteries and/or arterioles stay as well preserved as they do in WKY. 3. For M-SHRSP treated with drugs with a lower antihypertensive effect, the occurrence of cerebrovascular lesions and angionecrosis in the various organs are suppressed significantly, even though blood pressure remains over 250 mmHg over the long-term. Based upon effect alone, there is no difference between ACEI and a calcium antagonist. However, inhibition of the proliferation of vascular smooth muscle cells is more potent in the former than in the latter. 4. These results suggest that ACEI might have the potential to suppress smooth muscle cell proliferation independent of high blood pressure.     

Low-dose reserpine/thiazide combination in first-line treatment of hypertension: efficacy and safety compared to an ACE inhibitor

The concept of initiating treatment of mild-to-moderate hypertension with a low-dose combination of reserpine and the thiazide clopamide in comparison to monotherapy with an ACE inhibitor was investigated. A total of 127 adult outpatients with diastolic blood pressure between 100 and 114 mmHg were randomized into this double-blind, parallel group study. After a 2-week wash-out period and a subsequent 2-week placebo run-in period, they were allocated to once-daily treatment with 0.1 mg reserpine plus 5 mg clopamide (R/C), or 5 mg enalapril. If diastolic blood pressure was not normalized after 3 weeks of therapy (i.e. DBP < 90 mmHg), the dosage was doubled from week 4 to 6. The primary efficacy variables were the change from baseline in mean sitting diastolic and systolic blood pressure (DBP/SBP) after 3 weeks of therapy. Secondary variables included the change in DBP and SBP after 6 weeks of therapy, the BP normalization rates at 3 and 6 weeks and, concerning tolerability, the rates of adverse events after 6 weeks of therapy. An intent-to-treat analysis was performed. The reserpine/ clopamide and enalapril groups did not differ with regard to demographic and baseline characteristics (mean age 57 or 58 years, respectively; 63% or 56% males, respectively; mean SBP/DBP after the 2-week placebo period = 156 mmHg/104 mmHg in both groups). After 3 weeks of treatment with one capsule daily, mean SBP/DBP reduction from baseline (24 h after last medication intake) in the R/C combination group was -19.6/ -17.0 mmHg, in the enalapril group -6.1/ -9.5 mmHg (between-group comparison: 2p < 0.01 for both parameters). The normalization rates for DBP (< 90 mmHg) were 64.1% (R/C) and 28.6% (enalapril) (2p < 0.01). Adverse events that were considered possibly or definitely drug-related by the investigator were noted in 11 patients (17.2%) in the R/C group and in 9 patients (14.3%) in the enalapril group (NS). Two patients in the enalapril group discontinued the study prematurely due to adverse events (cough; skin eruption). In the treatment of mild-to-moderate hypertension, a low-dose combination of reserpine and clopamide once a day is considerably more effective than, and as tolerable as, 5-10 mg of enalapril once a day. These findings suggest that treatment with a combination of different antihypertensives with different modes of action in low doses is a rational alternative to conventional monotherapy in the first-line treatment of hypertension. Besides, the "old" reserpine-diuretic regimen also in these days appears to be a rational alternative to "modern" monotherapies.     

Progression of nephropathy in long-term diabetics with proteinuria and effect of initial anti-hypertensive treatment

The rate of progression of nephropathy was studied in 6 young male diabetics with intermittent proteinuria (Albustix) and in 10 young male diabetics with constant proteinuria by measuring glomerular filtration rate (GFR), renal plasma flow (RPF), and urinary albumin excretion by exact techniques. Albumin excretion was elevated in both the recumbent and the erect position in patients with intermittent proteinuria. GFR and RPF were at the same level as in diabetics without proteinuria, and no deterioration in renal function was noted during a mean control period of 32 months. In the patients with constant proteinuria the fall rate during a mean period of 33.6 months for GFR and RPF was 0.91 ml/min/month +/- 0.68 (S.D.) and 4.38 ml/min/month +/- 3.23 (S.D.) respectively. Initial fall rate in GFR correlated well with long-term fall rate, both of which were studied in 7 patients. In the same patients there was a positive correlation between the fall rate in GFR and diastolic blood pressure as well as albumin clearance. In 8 patients with constant proteinuria and mean blood pressure of 159/101 mmHg, antihypertensive treatment was started with propranolol alone or combined with hydralazine and furosemide. During a treatment period of 47 days blood pressure was reduced to 143/93 mmHg, and in the same period urinary albumin excretion was reduced significantly from a mean value of 3547 mug/min to 2414 mug/min (P less than 0.01). Further control studies will clarify whether end-stage of renal insufficiency will be postponed by antihypertensive treatment.     

Identification of a transforming growth factor alpha-like molecule in human seminal plasma

In a double-blind controlled trial, 91 middle-aged and elderly women with mild to moderate hypertension who were not on antihypertensive medication were randomly assigned to treatment with magnesium aspartate-HCl (20 mmol Mg/d) or placebo for 6 mo. Magnesium aspartate-HCl in the given dose was well-tolerated and was not associated with an increased frequency of diarrhea compared with placebo. At the end of the study, systolic blood pressure had fallen by 2.7 mm Hg (95% CI -1.2, 6.7; P = 0.18) and diastolic blood pressure by 3.4 mm Hg (1.3, 5.6; P = 0.003) more in the magnesium group than in the placebo group. Blood pressure response was not associated with baseline magnesium status, as measured by dietary magnesium intake and urinary magnesium excretion. Urinary magnesium excretion in the magnesium group increased by 50% during the intervention period. No changes were seen in other biochemical indexes, including serum concentrations of total and high-density-lipoprotein cholesterol. The findings suggest that oral supplementation with magnesium aspartate-HCl may lower blood pressure in subjects with mild to moderate hypertension.     

Laparoscopic repair of chronic traumatic diaphragmatic hernia: case report and review of the literature

This study compared the efficacy and tolerability of nisoldipine coat core (CC) 10-40 mg o.d. and hydrochlorothiazide (HCTZ) 25-50 mg o.d. Patients with mild-to-moderate essential hypertension received either nisoldipine CC 10 mg o.d. or HCTZ 25 mg o.d. Treatment was titrated at two-weekly intervals as necessary. The primary efficacy endpoint was a defined reduction in diastolic blood pressure (DBP). Response rates were similar for both the nisoldipine CC- and HCTZ-treated groups (74% and 70%, respectively). Secondary efficacy endpoints were reductions in both diastolic and systolic blood pressures (SBP). At treatment endpoint, the change from baseline in SBP was 16.2 mmHg for the nisoldipine CC group and 14.9 mmHg for the HCTZ group. Both drugs were well tolerated, and adverse events were generally minor and typical of these antihypertensive agents. Drug-related adverse events were greater in the nisoldipine CC- than the HCTZ-treated patients (50% and 37%, respectively). Nisoldipine CC was shown to demonstrate antihypertensive efficacy similar to HCTZ in the treatment of mild-to-moderate hypertension.     

Trends in blood pressure levels and control of hypertension in Finland from 1982 to 1997

OBJECTIVE: To assess the trends in blood pressure levels and hypertension control in Finland from 1982 to 1997. DESIGN: Four independent cross-sectional population surveys conducted in 1982, 1987, 1992 and 1997. SETTING: From 1982 to 1997, the provinces of North Karelia and Kuopio in eastern Finland and the region of Turku-Loimaa in southwestern Finland were surveyed. From 1992 to 1997, the Helsinki-Vantaa region in southern Finland was surveyed. PARTICIPANTS: Men and women aged 25-64 years were selected randomly from the national population register. The total number of participants was 27 623. MAIN OUTCOME MEASURES: We assessed mean systolic and diastolic blood pressure, prevalence of hypertension (subjects with systolic blood pressure > or = 160 mmHg or diastolic blood pressure > or = 95 mmHg or current use of antihypertensive drug treatment) and antihypertensive drug treatment and quality of hypertension care among hypertensive persons. RESULTS: Mean systolic blood pressure and the prevalence of hypertension decreased significantly in all areas except among men in the Helsinki-Vantaa region. The fall in mean diastolic pressure was significant only in eastern Finland. The proportion of hypertensives who were unaware of their condition fell from 45.5 to 24.1% in men and from 27.2 to 15.7% in women. At the same time, the proportion of hypertensives with adequately controlled blood pressure (systolic pressure < 160 mmHg and diastolic pressure < 95 mmHg) increased from 9.4 to 23.5% in men and from 16.0 to 36.7% in women. CONCLUSION: Hypertension care in Finland has improved significantly during the last 15 years. However, the situation is still far from optimal. It is obvious that the biggest problem in hypertension care has shifted from detection to adequate treatment of high blood pressure.     

Effects of amlodipine on 24-hour ambulatory blood pressure profiles, electrocardiographic monitoring, and left ventricular mass and function in black patients with very severe hypertension

In a 3-month, open-label study, 54 consecutive black patients with very severe hypertension were treated with amlodipine. Very severe hypertension was defined as an average sitting diastolic blood pressure (BP) > or = 115 mmHg and < or = 140 mmHg as a mean of 10 readings over a 30-minute period using an automatic BP measuring device and a mean 24-hour diastolic ambulatory blood pressure (ABP) > or = 110 mmHg and < or = 140 mmHg). Serial changes in 24-hour ABP and electrocardiographic monitoring, left ventricular (LV) mass index, and LV systolic function were evaluated. Mean 24-hour ABP was reduced from 181 +/- 14/119 +/- 6 to 140 +/- 15/92 +/- 9 mmHg at 3 months (P < 0.0001). Target BP (mean 24-hour diastolic ABP < 90 mmHg) was achieved in 35% of the patients. The reduction in BP was sustained for 24 hours after drug administration. Simultaneous BP measurements using the automatic BP measuring device were significantly different from the ABP measurements before and after treatment, suggesting a marked "white coat" pressor effect. At baseline, frequent or complex ventricular arrhythmias (> 30 ventricular extrasystoles per hour, ventricular couplets) were present in 2 (4%) patients, with no significant change after treatment. Left ventricular mass index regressed from 140 +/- 50 to 111 +/- 30 g/m2 at 3 months (P < 0.03); LV performance was not adversely affected. Adverse effects were few and tended to disappear during the treatment period. All of the clinical laboratory parameters tested remained unchanged. In this group of patients, treatment with amlodipine showed a marked and sustained antihypertensive action as demonstrated by 24-hour ABP monitoring, and was well tolerated and associated with LV mass regression without adverse effect on systolic cardiac function. Further, a low rate of complex ventricular arrhythmias was documented.     

Glucose and lipid metabolism during long-term antihypertensive treatment with indapamide in non-insulin-dependent diabetic patients

Thirty-nine patients with diabetes and hypertension were treated with indapamide for 24 weeks to study the effects of that drug on glucose and lipid metabolism. The drug was administered at a dose of 2 mg once per day in the morning as a single drug (26 patients) or in combination with other antihypertensive drugs (13 patients), including calcium antagonists, angiotensin-converting enzyme inhibitors, an alpha-blocker, or a beta-blocker. Blood pressure was reduced in both groups during treatment, and no alteration of glycemic control or lipid metabolism was observed. One patient complained of a mild headache, but treatment was continued. The results indicate that indapamide is useful for the long-term treatment of hypertension in diabetic patients, either alone or in combination with other antihypertensive agents.     

Experience in using acupuncture reflexotherapy combined with weight-reducing diet therapy in hypertension

AIM: To study the effectiveness of acupuncture in combination with unload diet against hypertension. MATERIALS AND METHODS: 137 patients with mild hypertension have undergone unload diet therapy or therapeutic fasting in combination with acupuncture. Acupuncture therapy was carried out according to the physiological model. The unload diet therapy was performed according to the method of Iu. S. Nikolaev and consisted of voluntary fasting. RESULTS: The treatment resulted in a decrease of cholesterol levels and blood pressure, positive trend in ECG. For 3 years 20 patients with mild hypertension had normal blood pressure. They kept on diet, had short-term courses of fasting, exercised in free-choice regimen. CONCLUSION: Acupuncture in combination with diet therapy are recommended for treatment of blood hypertension. They can be used alone or in combination with drug therapy.     

Fixed combination verapamil SR/trandolapril

Urapidil is a peripheral postsynaptic alpha 1-adrenoceptor antagonist with central agonistic action at serotonin 5-HT1A receptors. It reduces blood pressure by decreasing peripheral vascular resistance. Oral urapidil decreases blood pressure in patients with mild to moderate essential hypertension and associated risk factors such as hyperlipidaemia or type 2 (non-insulin-dependent) diabetes mellitus with no effect on heart rate. The antihypertensive efficacy of urapidil is similar to that of most comparators in patients with mild to moderate essential or secondary hypertension and no concomitant risk factors. However, the antihypertensive efficacy of urapidil was lower than that of hydrochlorothiazide in a well designed trial. Lipid levels and glucose metabolism are not adversely affected and may improve with urapidil in patients with lipid or glucose abnormalities. Urapidil can be safely combined with other antihypertensive agents such as hydrochlorothiazide and nifedipine and improves blood pressure control in previous nonresponders to monotherapy. Intravenous urapidil reduces blood pressure in patients with pre-eclampsia or hypertension in pregnancy and in patients with hypertensive crises or peri- or postoperative hypertension. The decrease in blood pressure is similar to that observed after nifedipine, enalaprilat, sodium nitroprusside and dihydralazine, greater than that of ketanserin according to 1 larger study, and greater than that of sublingual nitroglycerin in 1 trial in patients with nonsurgical hypertensive crises and pulmonary oedema. However, more patients responded to treatment with urapidil than with enalaprilat or nifedipine. Heart rate is less likely to be altered by urapidil than with some comparator drugs. Urapidil appears to be well tolerated, with most adverse events being mild and transient. The incidence of adverse events with urapidil is similar to that with prazosin, metoprolol, atenolol, sodium nitroprusside and hydrochlorothiazide and less than that with nifedipine and clonidine. Urapidil may not be as well tolerated as captopril and, in 1 study, more urapidil than nitrendipine recipients discontinued treatment because of adverse events. Conclusions: urapidil reduces blood pressure without altering heart rate. The oral formulation is an effective choice in patients with hypertension and concomitant dyslipidaemia or type 2 diabetes mellitus, in whom the drug does not adversely affect and may improve lipid profiles and glucose metabolism. The intravenous formulation is effective in controlling various hypertensive crises and hypertension associated with pregnancy or surgery and is similar to or better than other first-line agents used in these conditions. Thus, urapidil may be a useful alternative to currently available antihypertensive agents.     

Studies with prazosin--a new effective hypotensive agent. I. Open clinical study of prazosin in combination with other antihypertensive agents

The use of prazosin, a new antihypertensive agent, in combination with other conventional antihypertensive agents, in a hospital outpatient clinic setting, was studied in a mixed group of 104 hypertensive patients. Prazosin effectively lowered the lying and standing blood pressure in the majority of patients whose blood pressure was uncontrolled or poorly controlled before the introduction of prazosin. Blood pressure control was adequately maintained in patients who were given prazosin because of the occurrence of side effects of other antihypertensive medication. No significant change in renal function attributable to prazosin was found in patients with normal or impaired renal function.     

A multifactorial trial design to assess combination therapy in hypertension. Treatment with bisoprolol and hydrochlorothiazide

BACKGROUND: The safety and effectiveness of different dosages and combinations of antihypertensive agents can be efficiently studied using a multifactorial trial design. In consultation with the Cardio-Renal Division of the Food and Drug Administration, we conducted a randomized, double-blind, placebo-controlled, 3 x 4 factorial trial of bisoprolol, a beta 1-selective adrenergic blocking agent, and hydrochlorothiazide. METHODS: A total of 512 patients with mild to moderate essential hypertension were randomized to once-daily treatment with bisoprolol (0, 2.5, 10, or 40 mg), hydrochlorothiazide (0, 6.25, or 25 mg), and all possible combinations. Diastolic and systolic blood pressures were monitored during this 12-week trial. RESULTS: The effects of bisoprolol and hydrochlorothiazide were additive with respect to reductions in diastolic and systolic blood pressures over the dosage ranges studied. The addition of hydrochlorothiazide (or bisoprolol) to therapy with bisoprolol (or hydrochlorothiazide) produced an incremental reduction in blood pressure. Dosages of hydrochlorothiazide as low as 6.25 mg/d contributed a significant antihypertensive effect. A hydrochlorothiazide dosage of 6.25 mg/d produced significantly less hypokalemia and less of an increase in uric acid levels than a dosage of 25 mg/d. The low-dose combination of bisoprolol, 2.5 mg/d, and hydrochlorothiazide, 6.25 mg/d, reduced diastolic blood pressure to lower than 90 mm Hg in 61% of patients and demonstrated a safety profile that compared favorably with that of placebo. CONCLUSIONS: The utility of factorial design trials to characterize dose-response relationships and to test the potential interactions between various antihypertensive agents has been demonstrated. The combination of low dosages of bisoprolol and hydrochlorothiazide may be a rational alternative to conventional stepped-care therapy for the initial treatment of patients with mild to moderate hypertension.