INSIGHT and NORDIL. International Nifedipine GITS study: Intervention as a Goal in Hypertension Treatment. Nordic Diltiazem Study.
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Biomedical subjects
Publications and source records attributed to A S Westheim.
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OBJECTIVES: The study aimed to assess the hemodynamic and neuroendocrine effects of candoxatril and frusemide compared with placebo in patients with mild chronic heart failure. BACKGROUND: Candoxatril is an atriopeptidase inhibitor. It increases circulating levels of atrial natriuretic peptide leading to natriuresis and diuresis, which alleviate the symptoms of a failing heart. METHODS: This was a multicenter, randomized, double-blind study. Forty-seven patients with mild stable chronic heart failure received candoxatril 400 mg/day, frusemide 40 mg/day or placebo for up to six weeks. Cardiac indices were determined at rest and during exercise, and blood samples were taken for laboratory analysis. Assessments were performed at baseline (day 0) and after six weeks (day 42). RESULTS: In comparison with placebo, both drugs significantly reduced mean pulmonary capillary wedge pressure following the first dose administration. Only candoxatril significantly reduced pulmonary capillary wedge pressure during exercise on day 0, while both drugs significantly reduced this parameter on day 42. Changes in the remaining hemodynamic parameters were comparable for both drugs relative to placebo. Frusemide significantly increased mean plasma renin activity (days 0 and 42), and the mean aldosterone concentration (day 42) in comparison with placebo, whereas candoxatril caused no significant changes in any of the hormonal parameters assessed. CONCLUSIONS: These results show that candoxatril, 400 mg/day, has a similar hemodynamic profile to frusemide, 40 mg/day, but it does not induce adverse neuroendocrine effects. Candoxatril therefore appears to offer a clinically significant advantage over frusemide, providing an alternative therapeutic approach to the treatment of patients with mild stable chronic heart failure.
Patients with heart failure are particularly susceptible to the negative effects of calcium channel blockers because the failing heart demonstrates a defect in the delivery of calcium to the contractile proteins, and an attenuation of the normal sympathetic reflexes. Currently these drugs have no place in the treatment of heart failure caused by systolic dysfunction of the left ventricle. Calcium channel blockers should probably not be described for patients with coronary artery disease and left ventricular dysfunction. When the patient needs additional treatment for angina and beta-blockers or nitrates have not given satisfactory results, it may be appropriate to prescribe amlodipine or felodipine.
Research has shown that lifestyle intervention has a promising effect in patients with coronary heart disease, but little is known about the practice of such intervention. To explore this issue a questionnaire was sent to all departments of internal medicine in Norway (N = 67). 58 hospitals responded. The results showed that most hospitals offered physical training (49 hospitals) and dietary intervention programmes (51 hospitals) to patients with coronary heart disease, but only six hospitals offered a smoking cessation programme. The hospitals expressed a desire to expand the existing programmes (especially dietary intervention) and establish new ones (in particular smoking cessation), but claimed that lack of personnel and funds limited their activity. Only a few hospitals record in the medical journal that a patient has been informed about the significance of changes in lifestyle.
The effect of alpha 1 adrenoceptor blockade (doxazosin, 4 mg daily) on maximal oxygen uptake (VO2 max) and physical endurance capacity in 16 mildly hypertensive, athletic men was investigated in a randomized, placebo-controlled, double-blind, two-period of 4 weeks, cross-over study. The maximal work load obtained during graded bicycle ergometer exercise and the VO2 max were reduced by 16 +/- 3 W (mean +/- SE) and 3 +/- 1 ml x kg-1 x min-1 on doxazosin (p < 0.001 for both), and the running time on 5000 m track increased by 43 +/- 12 sec (p < 0.05). Thus, alpha 1-blockade moderately reduces VO2 max and physical endurance capacity in mildly hypertensive athletic men. However, lower systolic blood pressure (9 +/- 4 mm Hg, p < 0.05) immediately after running, and unchanged heart rate suggest a safer performance of exercise.
Several studies have been published recently on the effect of calcium-antagonists in the treatment of hypertension and heart failure. Except for an American case-control study, in which negative results may have been caused by selection bias, other studies show that calcium-antagonists have a positive effect. They appear to reduce cardiovascular complications, lower mortality and slow down the progression of atherosclerosis. However, large trials of adequate design and force are in progress (STOP II, NORDIL, HOT, INSIGHT, ALLHAT). It is hoped that the results of these trials will clarify whether calcium-antagonist are warranted in the treatment of hypertension and associated cardiovascular disease.
Many hypertensive patients do not respond adequately to single-drug therapy and may therefore require two or more drugs to reach the treatment goal. The drugs used in combination therapy should have additive or synergistic effects on blood pressure. A potential benefit of combinations is to use lower doses of each drug, which may attenuate or abolish the occurrence of side effects. Different combinations are discussed, as well as the inhibition of compensatory mechanisms that may otherwise counteract the antihypertensive effect.
Resistant hypertension is a common disorder in general practice, and poses a challenge to clinicians. It is generally defined as failure to reduce blood pressure adequately despite the use of at least three different antihypertensive agents with different modes of action. The importance of recognizing expansion of plasma volume as a mediator of resistance to therapy is emphasized. Some patients may have white-coat hypertension. An even larger group of patients may fail to comply with the prescribed medication. A good physician-patient relationship is vital, and education of the patient is crucial for obtaining better adherence to the medication.
There is still a need of support for nonpharmacologic treatment of uncomplicated, mild-to-moderate essential hypertension. We investigated whether a low sodium-based diet implemented by a nutritionist could lower blood pressure and affect sympathetic activity. Middle-aged, otherwise healthy men with never-treated essential hypertension (n = 95) were randomized to an intervention group, a blood pressure control group, and a time control group. The intervention group was advised to use less sodium chloride in their diet, and if necessary, less saturated fat and decrease body weight. They attended regular clinic visits as did the blood pressure control group. After 1 year, the intervention group had achieved on average 72 mmol/24 h lower urinary sodium excretion (P < .001) and a decrease in body weight of 2.7 +/- 0.5 kg (P < .001). Both supine and standing mean blood pressure were on average 8 to 10 mm Hg lower after intervention compared with the two control groups (P < .001). Arterial plasma epinephrine, measured in all 40-year-old subjects (n = 30), decreased in parallel in all three groups (P < .05), indicating some habituation to the invasive procedure and clinic visits. However, the decrease in norepinephrine was significant (P < .001) only in the intervention group; it correlated with the weight loss (r = 0.76, P < .05) and was significantly higher (P < .05) than in both control groups. These results suggest that broad dietary advice (ie, low intake of sodium chloride, saturated fat and energy), implemented by a nutritionist, may have a significant blood pressure lowering effect and a favorable sympathicolytic effect in uncomplicated, mild-to-moderate essential hypertension.
The effect of alpha 1-adrenoceptor blockade (doxazosin, 4 mg daily) on maximal VO2 and physical endurance capacity in 16 mildly hypertensive, athletic men was investigated in a randomized, placebo-controlled, double-blind, two-period of 4 weeks, cross-over study. The maximal workload obtained during graded bicycle ergometer exercise and the corresponding maximal VO2 were reduced by 16 +/- 3 W (mean +/- SE), (P = .00003) and 3 +/- 1 mL/(kg.min) (P = .0004), respectively, on doxazosin compared with placebo. The running time on a 5000 m track increased by 43 +/- 12 sec on doxazosin (P = .04). Heart rate was unchanged during the running session. Systolic blood pressure was reduced by 9 +/- 4.1 mm Hg (P = .04) immediately after finishing 5000 m. Six subjects reported side effects from doxazosin (headache, fatigue, and leg pain). Thus, antihypertensive treatment with alpha 1-selective adrenoceptor blockade moderately, but significantly, reduces maximal O2 consumption and high intensity physical endurance capacity in mildly hypertensive athletic men. Significantly reduced systolic blood pressure and unchanged heart rate immediately after running, combined with unchanged heart rate during the race may, however, suggest a safer exercise performance.
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Explore the source record for details and available documents.
Explore the source record for details and available documents.
Explore the source record for details and available documents.