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Peter Sever

Publications and source records attributed to Peter Sever.

10 recordsLinked to original sources
PubMed2006

Potential synergy between lipid-lowering and blood-pressure-lowering in the Anglo-Scandinavian Cardiac Outcomes Trial.

AIMS: A prespecified objective of the Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) was to assess whether any synergistic effects were apparent between the lipid-lowering and blood-pressure-lowering regimens in preventing cardiovascular events. METHODS AND RESULTS: A total of 19 257 hypertensive subjects were randomized to an amlodipine-based regimen or an atenolol-based regimen. Of these, 10 305 subjects with total cholesterol < or =6.5 mmol/L were further randomized to atorvastatin 10 mg daily or placebo. In this analysis, the effects of atorvastatin were compared with placebo on coronary heart disease (CHD), cardiovascular and stroke events in those assigned amlodipine-based and atenolol-based regimens. In the ASCOT lipid-lowering arm (LLA), overall, atorvastatin reduced the relative risk of the primary endpoint of non-fatal myocardial infarction and fatal CHD events by 36% (HR 0.64, CI 0.50-0.83, P=0.0005), total cardiovascular events by 21% (HR 0.79, CI 0.69-0.90, P=0.0005), and stroke by 27% (HR 0.73, CI 0.56-0.96, P=0.024). However, atorvastatin reduced the relative risk of CHD events by 53% (HR 0.47, CI 0.32-0.69, P<0.0001) among those allocated the amlodipine-based regimen, and by 16% (HR 0.84, CI 0.60-1.17, p: n.s.) among those allocated the atenolol-based regimen (P=0.025 for heterogeneity). There were no significant differences between the effects of atorvastatin on total cardiovascular events or strokes among those assigned amlodipine (HR 0.73, CI 0.60-0.88, P<0.005 and HR 0.69, CI 0.45-1.06, P: n.s., respectively) or atenolol (HR 0.85, CI 0.71-1.02, P: n.s and HR 0.76, CI 0.53-1.08, P: n.s, respectively). Differences in blood pressure and lipid parameters (placebo corrected) between the two antihypertensive treatment limbs could not account for the differences observed in CHD outcome. CONCLUSION: These findings of an apparent interaction between atorvastatin and an amlodipine-based regimen in the prevention of CHD events are of borderline significance, and hence generate an hypothesis that merits independent evaluation in other trials.

Adult↗
PubMed2006

Candesartan- and atenolol-based treatments induce different patterns of carotid artery and left ventricular remodeling in hypertension.

BACKGROUND AND PURPOSE: Angiotensin receptor blocker (ARB)-based treatment reduces cardiovascular events and stroke more than does beta-blocker-based treatment despite similar blood pressure (BP) reduction. We investigated whether these treatments have different effects on cardiac and large-artery remodelling and evaluated the relation of arterial remodelling to hemodynamic changes in subjects with hypertension. METHODS: We compared the treatment effects of an ARB (candesartan cilexetil)-based regimen and a beta-blocker (atenolol)-based regimen for 52 weeks on common carotid artery (CCA) and left ventricular structure in hypertensive patients in a randomized, double-blind study. Clinic brachial BP and 24-hour ambulatory BP, carotid BP, left ventricular mass index, CCA intima-media thickness, lumen diameter, intima-media area, and carotid blood flow were measured. Distensibility, circumferential tensile stress, Young's elastic modulus (E(m)), and shear stress (tau) in the CCA were also calculated. RESULTS: Both candesartan and atenolol reduced intima-media thickness and intima-media area and increased distensibility to similar extents after 52 weeks of treatment. Despite similar reductions in BP, treatment with atenolol resulted in a lesser reduction in left ventricular mass index, a decrease in lumen diameter, and a reduction in carotid blood flow compared with candesartan. CONCLUSIONS: BP-independent effects of ARB on cardiac and arterial structure may contribute to the beneficial effects of these agents on cardiovascular disease.

Adrenergic beta-Antagonists↗
PubMed2006

New hypertension guidelines from the National Institute for Health and Clinical Excellence and the British Hypertension Society.

A joint initiative between the National Institute for Health and Clinical Excellence (NICE) and the British Hypertension Society (BHS) has led to the publication of new guidelines for the management of hypertension in the community. Recent trial evidence highlighting the increased incidence of new-onset diabetes in those exposed to beta-blocker-based treatment regimens, with or without diuretics, compared with those based on calcium channel blockers (CCBs) or angiotensin-converting enzyme (ACE-Is) inhibitors has led to a recommendation that in the uncomplicated patient, beta-blockers are no longer considered suitable options for first-line therapy. Together with mounting evidence that age and ethnicity dictate blood pressure (BP) responsiveness to different classes of antihypertensive drugs, the ACD algorithm is now proposed (formerly ABCD), with ACE inhibitors (ACE-Is) (or angiotensin receptor blockers [ARBs] when ACE-Is are poorly tolerated) preferred in younger patients and CCBs or diuretics preferred for older patients and in black patients of any age. Pathophysiological considerations have influenced proposals for combination therapies with CCBs or diuretics added to ACE-Is in younger patients and vice versa in older patients. Health economic analyses have clearly indicated the cost effectiveness of CCBs which are now elevated to equal standing with diuretics in older patients.

Adrenergic beta-Antagonists↗
PubMed2004

Regression of left ventricular mass in hypertensive patients treated with perindopril/indapamide as a first-line combination: the REASON echocardiography study.

BACKGROUND: Increase in left ventricular mass (LVM) may be linked to morbidity and mortality in hypertensive patients. Arterial stiffness, systolic blood pressure (BP), and pulse pressure (PP) seem to be the main determinants of LVM. The perindopril/indapamide combination normalizes systolic BP, PP, and arterial function to a greater extent than atenolol. The aim of this study was to compare the effects of perindopril (2 mg)/indapamide (0.625 mg) first-line combination with atenolol (50 mg) on LVM reduction in hypertensive patients. METHODS: Two hundred fourteen patients with essential hypertension participating in the PREterax in Regression of Arterial Stiffness in a ContrOlled Double-BliNd (REASON), randomized, double-blind, parallel-group study, underwent M-mode two-dimensional-guided echocardiography. RESULTS: Perindopril/indapamide and atenolol were both effective at brachial BP reduction during the 12-month period. The systolic BP reduction was significantly greater with perindopril/indapamide than with atenolol (-21.2 v -15.3 mm Hg), whereas the reduction in diastolic BP was similar between treatment groups (-12.1 v -11.3 mm Hg). Reduction in LVM was higher with perindopril/indapamide than with atenolol. The between-group difference was significant for LVM (-13.6 v -4.3 g, P = .027), LVM/body surface area (LVMI1, P = .032), and LVM/body height2.7 (LVMI2, P = .013). The 124 patients with LV hypertrophy at baseline showed greatest LVM regression (LVM: -22.5 v -8.9 g, P = .009; LVMI1, P = .031; LVMI2, P = .028). The reduction in LVM adjusted for brachial systolic BP and heart rate was still significantly greater with perindopril/indapamide than with atenolol. CONCLUSIONS: Treatment, based on a first-line perindopril/indapamide combination in hypertensive patients, was more effective than atenolol on regression of echocardiographic indices of LVM and LV hypertrophy.

Adult↗
PubMed2004

The VALUE trial: a commentary.

The Valsartan Antihypertensive Long-Term Use Evaluation (VALUE) Trial compared coronary heart disease outcome in two anti-hypertensive treatment strategies based on either an angiotensin receptor blocker, valsartan, or a calcium channel blocker (CCB), amlodipine. In both patient groups a diuretic was added, if necessary, in an attempt to achieve blood pressure (BP) goals. Follow-up of over 15,000 patients was maintained for 4.2 years. There were no differences in the primary composite endpoint of cardiac morbidity and mortality (which included interventional procedures, hospitalised heart failure, non-fatal myocardial infarction and fatal coronary heart disease, however myocardial infarction and stroke events occurred less commonly on amlodipine than on valsartan the former achieving statistical significance [p=0.02 and p=0.08 respectively]). There was a non-significant excess of hospitalised heart failure on amlodipine (p=0.012). However, lower BPs early in the trial probably accounted for most of the observed benefits in favour of the CCB. The angiotensin receptor blocker arm was associated with less new onset diabetes. The results of VALUE add further support to the evidence that blood pressure control is the major determinant in outcome in trials of antihypertensive therapy.

Amlodipine↗
PubMed2002

Comparison of the effects of antihypertensive treatment with angiotensin II blockade and beta-blockade on carotid wall structure and haemodynamics: protocol and baseline demographics.

Several systemic factors have been shown to contribute to the acceleration of large vessel atheroma. Correction of these factors leads to a reduction in the progression of plaque formation and associated arterial wall thickness. Atheroma remains, however, a focal disease, developing at characteristic sites within the arterial tree. These sites are typically at areas of vessel branching or marked curvature, and correspond to regions of high tensile stress and low sheer stress, leading to the hypothesis that local haemodynamic factors and vessel wall mechanics potentiate the focal development of atheroma. Current assessment of vascular haemodynamics suffers from an inability to handle complex flow, and does not allow accurate determination of locally varying flow, and shear stress patterns. The application of computational fluid dynamic (CFD) flow simulation techniques to ultrasound and local pressure data, however, allows a comprehensive, non-invasive appraisal of haemodynamic flow parameters to be performed. The Candesartan cilexetil and Atenolol Carotid Haemodynamic Endpoint Trial (CACHET) study compares the effects of two antihypertensive regimens, one b-blocker-based, the other angiotensin receptor blocker based, on carotid intima-media thickness. The collection of ultrasound and pressure data on each subject provides a unique opportunity to apply these data to the CFD model to study the effects of these antihypertensive regimens on local fluid dynamics. This will lead to a greater understanding of the relationship of these factors to atheroma formation and regression.

Adrenergic beta-Antagonists↗
PubMed2002

The SCOPE trial. Study on Cognition and Prognosis in the Elderly.

The Study on Cognition and Prognosis in the Elderly (SCOPE) was designed to provide outcome data on cardiovascular endpoints and cognitive function in 4500 elderly hypertensive patients randomised to the angiotensin receptor blocker, candesartan, or to placebo and followed up for 4.5 years. The primary endpoint of combined cardiovascular mortality, non-fatal myocardial infarction and non-fatal stroke was not significantly reduced by active treatment (relative risk reduction 11%, p=0.19). There was also no significant difference in the decline of cognitive function between the two treatment arms. Active treatment of the placebo group (mainly hydrochlorothiazide) reduced the blood pressure differences between the treatment arms to only 3.2/1.6 mmHg, thus markedly reducing the overall power of the study. In a number of non-prespecified subgroup analyses, advantages of candesartan over placebo were reported.

Aged↗
PubMedDate not supplied

VALUE: analysis of results.

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Angiotensin II Type 1 Receptor Blockers↗