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Biomedical subjects

R Fagard

Publications and source records attributed to R Fagard.

At least 505 records · Page 28Linked to original sources
PubMedDate not supplied

Subgroup and per-protocol analysis of the randomized European Trial on Isolated Systolic Hypertension in the Elderly.

BACKGROUND: In 1989, the European Working Party on High Blood Pressure in the Elderly started the double-blind, placebo-controlled, Systolic Hypertension in Europe Trial to test the hypothesis that antihypertensive drug treatment would reduce the incidence of fatal and nonfatal stroke in older patients with isolated systolic hypertension. This report addresses whether the benefit of antihypertensive treatment varied according to sex, previous cardiovascular complications, age, initial blood pressure (BP), and smoking or drinking habits in an intention-to-treat analysis and explores whether the morbidity and mortality results were consistent in a per-protocol analysis. METHODS: After stratification for center, sex, and cardiovascular complications, 4695 patients 60 years of age or older with a systolic BP of 160 to 219 mm Hg and diastolic BP less than 95 mm Hg were randomized. Active treatment consisted of nitrendipine (10-40 mg/d), with the possible addition of enalapril maleate (5-20 mg/d) and/or hydrochlorothiazide (12.5-25 mg/d), titrated or combined to reduce the sitting systolic BP by at least 20 mm Hg, to below 150 mm Hg. In the control group, matching placebo tablets were employed similarly. RESULTS: In the intention-to-treat analysis, male sex, previous cardiovascular complications, older age, higher systolic BP, and smoking at randomization were positively and independently correlated with cardiovascular risk. Furthermore, for total (P = .009) and cardiovascular (P = .09) mortality, the benefit of antihypertensive drug treatment weakened with advancing age; for total mortality (P = .05), the benefit increased with higher systolic BP at entry, while for fatal and nonfatal stroke (P = .01), it was most evident in nonsmokers (92.5% of all patients). In the perprotocol analysis, active treatment reduced total mortality by 24% (P = .05), reduced all fatal and nonfatal cardiovascular end points by 32% (P<.001), reduced all strokes by 44% (P = .004), reduced nonfatal strokes by 48% (P = .005), and reduced all cardiac end points, including sudden death, by 26% (P = .05). CONCLUSIONS: In elderly patients with isolated systolic hypertension, stepwise antihypertensive drug treatment, starting with the dihydropyridine calcium channel blocker nitrendipine, improves prognosis. The per-protocol analysis suggested that treating 1000 patients for 5 years would prevent 24 deaths, 54 major cardiovascular end points, 29 strokes, or 25 cardiac end points. The effects of antihypertensive drug treatment on total and cardiovascular mortality may be attenuated in very old patients.

Aged↗
PubMedDate not supplied

Influence of beta 1- versus beta 2-adrenoceptor blockade on left ventricular function in humans.

Pharmacological and radio-ligand binding studies have recently indicated the existence of beta 2-adrenoceptors in the human heart. Their physiological role, however, remains to be elucidated. The present study investigated in 17 normal, young volunteers the effect on resting left ventricular (LV) function of two types of beta-blockers; a predominant beta 1-adrenoceptor antagonist (atenolol, 50 mg once daily) and ICI 118,551 (20 mg t.i.d.), a new, predominant beta 2-antagonist. LV function was assessed using M-mode echocardiograms and systolic time intervals. Atenolol, ICI 118,551, and placebo were given according to a randomized, double-blind, cross-over protocol. As compared with placebo, both drugs caused a decrease in resting heart rate, but the reduction by ICI 118,551 was less pronounced. Systolic blood pressure was only reduced by atenolol 8 mm Hg on average. Cardiac output was decreased to the same extent following treatment with atenolol (-20%) as after ICI 118,551 (-17%). These decreases in cardiac output were related to the beta-blocker-induced bradycardia, since stroke volumes were not affected during either selective beta 1- or beta 2-blockade. In addition, all other echocardiographic variables reflecting LV pump function, such as fractional shortening, velocity of diameter change and of displacements, pre-ejection period, and the ratio of PEP/LVET, were not different from placebo. We conclude that in normal young subjects, global LV pump function is not affected by beta 1- or by beta 2-blockade, despite the negative chronotropic effect of both drugs.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic beta-Antagonists↗
PubMedDate not supplied

Exercise performance and training in cardiac patients with atrial fibrillation.

PURPOSE: Exercise training in cardiac patients with chronic atrial fibrillation (AF) has received little attention in the literature. Therefore, this study compared exercise performance and the effect of an exercise training program over a period of 3 months in patients with and without AF. METHODS: Data in patients with AF (n = 19) were compared with a control group of patients in sinus rhythm (n = 44), drawn from a database of 2,116 patients. Patients performed a maximal exercise test on the bicycle until exhaustion before and after an ambulatory exercise training program where exercise training was offered 3 times a week for 3 months. RESULTS: Before training, peak oxygen uptake (VO2) was significantly lower in patients with AF compared with the control group (1271 +/- 368 versus 1496 +/- 414 mL/min, P < 0.05). Exercise training significantly increased peak VO2 in both groups (+31%, P < 0.001 in AF and +25%, P < 0.001 in the control group). The gain in peak VO2 did not significantly differ between both groups. A significant decrease in resting heart rate was achieved in both groups after exercise training. AF was also a significant and independent determinant of peak VO2 in the total database, but not of the change in peak VO2. CONCLUSIONS: Exercise training significantly improves exercise performance in cardiac patients with AF. AF affects exercise performance but does not impair the beneficial effects of training. Patients with chronic AF should therefore not be dissuaded from participating in exercise training after a cardiac event.

Aged↗
PubMedDate not supplied

Alpha-adrenoceptor blockade by tibalosine: hemodynamic and humoral effects at rest and during exercise, and effect of opioid receptor antagonism.

In a randomized double-blind protocol, 12 healthy male volunteers were studied twice at rest and during exercise after pretreatment for 1 week with placebo or 150 mg daily of the new alpha 1-adrenoceptor antagonist tibalosine. Six subjects received, on both experimental days, an intravenous infusion of saline and the other six received the opioid receptor antagonist naloxone. Combined measurements taken during rest and exercise showed tibalosine, on average, to decrease mean intraarterial pressure by 4.7 mm Hg and heart rate by 3.5 beats/min. Urinary volume and sodium excretion were transiently reduced by tibalosine as compared with placebo. Opioid antagonism by naloxone stimulated the pituitary-adrenal axis, but had no effect on the influence of tibalosine, as shown by hemodynamic, respiratory, and most humoral measurements. However, on interruption of exercise, opioid antagonism counteracted the inhibition of the plasma renin-angiotensin system by tibalosine, probably through the naloxone-induced increase in epinephrine release. In conclusion tibalosine reduced blood pressure at rest and during exercise independently of opioidergic mechanisms. This hypotensive action may be accompanied by sodium and fluid retention.

Adrenergic alpha-Antagonists↗
PubMedDate not supplied

Antihypertensive action and serotonin-induced platelet aggregation during long-term ketanserin treatment in hypertensive patients.

Ketanserin (3 X 40 mg daily) was administered during 6 weeks in 14 patients with mild to moderate essential hypertension using a double-blind, placebo-controlled, crossover design. Ketanserin decreased (p less than 0.01) the recumbent blood pressure from 159/104 to 153/97 mm Hg and the recumbent heart rate from 75 to 72 beats/min. Platelet aggregation induced by 5-hydroxytryptamine (5-HT), whether or not amplified by threshold doses of collagen, was not inhibited; however, it was reduced in 10 normal volunteers after a single oral dose of 40 mg ketanserin. The results suggest that long-term treatment with ketanserin reduces blood pressure; whereas 5-HT receptor inhibition could not be demonstrated when assessed by platelet aggregation.

Adult↗
PubMedDate not supplied

INDANA: a meta-analysis on individual patient data in hypertension. Protocol and preliminary results.

The overall effect of antihypertensive drug treatment has been well documented. The proportion of patients who benefit varies according to their baseline cardiovascular risk, and is small for the majority of people treated. Some investigators propose limiting the treatment target population to patients at high cardiovascular risk, but several assumptions must be made to justify this procedure. The INDANA project is a meta-analysis based on individual patient data, and thus offers the opportunity to check the validity of these assumptions. Its main objective is to identify responders (and non-responders) in the drug treatment of hypertension. The rationale and methods for such an approach are presented here, with the solution for some technical problems. The conclusion of the data collection has shown that the project is feasible. The results of the main analysis should be available in 1996, and should contribute to the selection of responders and to the individualization of the treatment of hypertension.

Humans↗