[Guide for general practice. Much evidence favors broad use of fixed combinations].
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Biomedical subjects
Publications and source records attributed to J Scholze.
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AIMS: To investigate the dose-response relationship and contribution of verapamil SR and trandolapril given in combination once a day for the treatment of essential hypertension. METHODS: A randomized, double-blind, placebo controlled, factorial, 12 arm parallel group comparison with placebo, verapamil SR (120, 180 mg), trandolapril (0.5, 1.0, 2.0 mg) covering all combinations of both drugs. A 4 week placebo run-in period followed by 6 weeks of treatment. Four hundred and fifty-six patients from office practice (22 centres) with mild to moderate hypertension enrolled and 426 with diastolic pressure > or = 100 mm Hg at the end of run-in period were randomized. Main outcome measures were reduction in sitting systolic (SBP) and sitting diastolic (DBP) blood pressure. RESULTS: The combination of verapamil SR and trandolapril, particularly verapamil SR 180 mg and trandolapril 0.5 or 1.0 mg was significantly superior to both monocomponents at the same dose (P<0.05). For these combinations, the adjusted mean reductions in DBP from baseline to last visit were 14.1 and 16.0 mm Hg, respectively. Response surface analysis provided further evidence that these combinations were optimal for antihypertensive efficacy. All treatments were well tolerated. The incidence of adverse events did not differ significantly between treatment groups; the profile of adverse events on combination therapy was mild and consistent with that of each monocomponent. CONCLUSIONS: All dosage combinations of verapamil SR and trandolapril produced significantly greater reduction of blood pressure than the monotherapy at the same dosage. However, verapamil SR 180 mg in combination with trandolapril 1.0 mg was the dosage with the greatest blood pressure reduction and had the greatest effects compared with the monocomponents.
AIMS: To evaluate initial blood pressure effects of the angiotensin II antagonist losartan (L) immediately after switching from an ACE inhibitor (captopril, C). METHODS: Two-phase multicentre randomized study in 177 outpatients with mild to moderate essential hypertension. For 6 weeks all patients received 25 mg C twice daily. Then they were randomized double-blind to switch for another 6 weeks to 50 mg L once daily (n=110) or to maintain C (n=55). On the first day of the switch they underwent ambulatory blood pressure measurement (ABPM). RESULTS: Within 12 h of first dose, 31% of patients who switched to L had two consecutive systolic BP readings of 30 mmHg below their individual baseline value compared with 24% of patients who stayed on C. In 3% of patients with L and in 6% of the C patients systolic BP readings less than 100 mmHg were recorded within 12 h of first dose. The differences were not statistically significant. There were no clinical symptoms attributable to initial hypotension. During the 6 weeks double-blind therapy, 9% of L patients experienced at least one adverse event, compared with 16% of patients with C. CONCLUSIONS: In this study the angiotensin II antagonist losartan was effective and generally well tolerated when administered immediately after pretreatment with an ACE inhibitor.
In a 71-year-old woman with macroglossia and heart failure, a monoclonal protein (kappa-light chains) was found in the serum. Congestive heart failure was diagnosed on the basis of heart catheterization and echocardiography. The tongue biopsy showed numerous amyloid fibrils, and plasmacytosis was present in the bone marrow. All these findings indicated a restrictive cardiomyopathy as part of a primary systemic amyloidosis.
Regular conditioning has been well documented to exert a beneficial effect on cardiovascular risk factors and to improve overall cardiovascular health and to reduce the incidence of coronary disease. There are conflicting results concerning the effect of physical exercise on blood pressure (BP) in hypertensive patients and its importance in the treatment of hypertension. Therefore 10 male patients with mild arterial hypertension were studied in order to define the BP response to long-term aerobic training (60 min twice a week) under resting conditions, during standardised ergometric workload, during isometric exercise, during cold pressor testing and during 24-h BP monitoring. After 18 months of regular training there were significant reductions in arterial pressures at rest, during and after standardised ergometry and during isometric and cold pressor testing when compared with pre-training. The heart rate also decreased significantly during exercise testing thus implying a decrease in myocardial oxygen consumption. After long-term training, a reduction in systolic and diastolic BP could also be shown during 24-h ambulatory BP monitoring. These results demonstrate that long-term aerobic training leads to a decrease in systolic and diastolic BP at rest, during exercise and during 24-h BP monitoring and imply a beneficial effect in the management of hypertension that is nearly comparable to that of drug therapy.
The drug monotherapy of hypertension is successful in about half of the patients. The occurrence of relevant side-effects usually leads to a new treatment with an antihypertensive drug of another substance category (= sequential monotherapy). However, if normotension is not achieved despite good tolerance, the physician should combine two antihypertensive drugs with different modes of action. Similar to the monotherapy, a treatment procedure individually balanced to the patient-situation of the circulation, risk factors or coexisting diseases -determines success or failure. In the following, useful and clinically reliable combination options with first-line substance categories are described. Under the aspects of economy, pragmatism, and patient compliance, among other things it is dealt with reliable as well as new fixed combination preparations.
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OBJECTIVE: To identify appropriate dosages of ramipril and hydrochlorothiazide (HCT) when given in combination once a day for the treatment of essential hypertension. DESIGN: A 2- or 4-week placebo run-in followed by 6-week, double-blind, parallel-group phase: 4 x 3 factorial (2.5, 5 and 10 mg ramipril; 12.5 and 25 mg HCT; all six combinations; placebo). SETTING: Office practice (21 centres). PATIENTS AND PARTICIPANTS: Patients with mild-to-moderate essential hypertension (World Health Organization stage I-II; supine diastolic blood pressure 100-115 mmHg in last 2 weeks of run-in): 581 enrolled, 534 randomly assigned to double-blind therapy and 517 completed. MAIN OUTCOME MEASURES: Reduction in supine and standing blood pressure. RESULTS: In pairwise comparisons, the combinations of 5 mg ramipril with 12.5 and 25 mg HCT and 10 mg ramipril with 12.5 mg HCT consistently produced significantly greater blood pressure reductions than their respective components. Response surface analyses were performed, and a stairstep model was constructed to characterize the shape of the dose-response surface. The combinations involving 5 and 10 mg ramipril with 12.5 and 25 mg HCT were again more effective than their components. Withdrawals and adverse effects were minimal for all treatments. A large drop in serum potassium was observed on 25 mg HCT, but not on combination therapy. Addition of ramipril appeared to reduce the hyperuricaemic effect of HCT. CONCLUSIONS: Several dosage combinations of ramipril plus HCT produced significantly greater blood pressure reductions than the monotherapies at the same dosages. Overall, the combination of 5 mg ramipril and 25 mg HCT gave the best mean reduction. Combination therapy with ramipril plus HCT was safe and effective for patients with mild-to-moderate essential hypertension.
Angiotensin-converting enzyme (ACE) inhibitors are well established antihypertensives. Their effect on kidney function, however, seems to depend on the pathophysiological mechanisms underlying the clinical symptoms. In one part of the Perindopril and Therapeutic Safety Study (PUTS) the effect of a 6-week treatment with placebo or 4 mg/d of perindopril (Coversum, CAS 82834-16-0) on kidney function and albuminuria was investigated in 56 hypertensives with concomitant nephropathy. The study was performed as multicenter, randomized, placebo-controlled, double-blind study. The results show that perindopril reduced blood pressure effectively. The responder rate determined as a fall in blood pressure at least about 10 mmHg in the perindopril group was 39% vs. 21% in the placebo group. All investigated parameters of kidney function like serum creatinine, creatinine clearance, urinary excretion of albumin and alpha 1-microglobulin remained unchanged during the study. In a subgroup of patients with isolated albuminuria ACE inhibition reduced significantly the urinary albumin excretion (perindopril: -292 +/- 205 mg/g creat. vs. placebo: +61 +/- 48 mg/g creat: p < 0.05). From this study it can be concluded that in hypertension with concomitant nephropathy, except renovascular hypertension and hypertension in renal transplant recipients, ACE inhibition by perindopril will not impair kidney function. In the early phase of nephropathy with isolated albuminuria and normal serum creatinine perindopril improves albuminuria and seems to be even of benefit for the kidney.
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The diagnostic step-program in arterial hypertension can be divided in a so called basic program and in special differential-diagnostic programs. The basic evaluation for every hypertensive subject contains family and personal history, clinical investigation, blood pressure measurement, electrocardiogram, chest X-ray, blood tests (creatinine and potassium) and urine analysis. The extended basic program enables the evaluation of global cardiovascular risk. Furthermore other blood and urine examinations (including vanilmandelic acid), fundoscopy, echocardiography and sonography of the kidneys are of particular value for determining severity and etiology of the disease. After this program an extension of diagnostics can be renounced in about 90% of hypertensives.
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