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Biomedical subjects

Michael A Weber

Publications and source records attributed to Michael A Weber.

At least 19 recordsLinked to original sources
PubMed2003

Effects of the selective aldosterone blocker eplerenone versus the calcium antagonist amlodipine in systolic hypertension.

Eplerenone is a highly selective aldosterone blocker, which is under development for the treatment of hypertension and heart failure. To assess its usefulness in older patients with systolic hypertension and widened pulse pressure, we compared the effects of eplerenone with amlodipine, on clinic blood pressure (BP) and pulse pressure and in a subset of the patients, ambulatory BP, vascular compliance, and urinary albumin excretion. The study involved 269 patients > or =50 years of age who were randomly assigned to either eplerenone (50 to 200 mg daily) or amlodipine (2.5 to 10 mg daily) in a double-blind titration to effect design. After 24 weeks of therapy, reductions in clinic systolic BP were similar for both treatments (eplerenone, -20.5+/-1.1 mm Hg; amlodipine, -20.1+/-1.1 mm Hg). Reductions in clinic diastolic BP were modestly larger on amlodipine (-6.9+/-0.7 mm Hg) compared with eplerenone (-4.5+/-0.7 mm Hg) (P=0.014). Pulse pressure was also reduced similarly from baseline by the 2 treatment groups (eplerenone, -15.9 mm Hg versus amlodipine, -13.4 mm Hg, P=0.07). Changes from baseline in pulse wave velocity after 24 weeks of therapy were statistically similar for eplerenone and amlodipine. In patients with microalbuminuria at baseline (>30 mg albumin/g creatinine), eplerenone reduced the urinary albumin/creatinine ratio by 52% compared with a reduction of 10% by amlodipine (P=0.04). Thus, eplerenone was as effective as amlodipine in lowering systolic BP and pulse pressure as well as pulse wave velocity in older patients with widened pulse pressure hypertension. Furthermore, eplerenone reduced microalbuminuria to a greater extent than amlodipine in this older patient group.

Aged↗
PubMed2003

Defining the antihypertensive properties of the angiotensin receptor blocker telmisartan by a practice-based clinical trial.

Traditional randomized controlled clinical trials are designed to define the specific properties of individual antihypertensive drugs but do not provide full information about their use in clinical practice. To carry out a large-scale practice-based open-label trial to evaluate the safety and efficacy of an angiotensin receptor blocker (ARB) in controlling blood pressure (BP) in the community setting, 703 practitioners recruited 2705 hypertensive patients. There were three groups: untreated at the time of study entry with uncontrolled BP (>/=140/90 mm Hg) (N = 1957); treated but uncontrolled on current monotherapy (N = 685); and treated and controlled, but with unacceptable side effects (N = 63). After stopping any previous treatment, patients received telmisartan (40 mg daily) for 2 weeks; the dose was increased to 80 mg if BP remained >/=130/85 mm Hg. Participants were then followed for a further 4 weeks. Blood pressure decreased by 18.9/12.3 mm Hg in the untreated group, by 13.1/7.9 mm Hg in the previously treated but uncontrolled group, and increased slightly by 3.5/1.3 mm Hg in the previously controlled group. Patients not responding adequately to the 40-mg telmisartan dose had an initial BP reduction of 7.3/4.5 mm Hg; titration to 80 mg gave an additional 7.5/5.0 mm Hg reduction and controlled BP (<140/90 mm Hg) in 44% of these titrated patients. Overall, control occurred in 56% of white patients; 52% of black patients (who responded well to dose titration); 60% of patients <65 years; and 46% of patients >/=65 years. Thus, in contrast with the relatively flat dose response effects in controlled parallel group trials, this practice-based trial has demonstrated the value of titrating telmisartan to its maximum dose in patients with inadequate BP responses to the initial dose, and has shown its efficacy across major demographic groups.

Adult↗
PubMed2003

Angiotensin II receptor blockers and cardiovascular outcomes: what does the future hold?

The ability of angiotensin-converting enzyme (ACE) inhibitors and angiotensin II receptor blockers (ARBs) to lower blood pressure (BP) is well established. ACE inhibitors (ACE-Is) have also been shown to improve the prognosis of a broad range of patients at high cardiovascular risk, including those with heart failure, post-myocardial infarction (MI), and nephropathy. These benefits suggest that interrupting the renin-angiotensin-aldosterone system (RAAS) with ACE-Is has a widespread vasculoprotective effect, provided that BP is also adequately controlled. Evidence that RAAS blockade by ARBs also improves long-term clinical outcomes in patients with cardiovascular disease has started to accumulate, and will be tested further during the coming years as a number of large-scale, prospective trials are completed. These trials are investigating the long-term protective effects of ARBs on morbidity and mortality in patients with hypertension, heart failure, diabetes mellitus, acute MI, or established vascular disease. The results should establish the extent to which ARBs exhibit the vasculoprotective properties demonstrated by ACE-Is in patients at high cardiovascular risk. If ARBs are found to provide benefits that are similar to, or even greater than ACE-Is, it may have important implications for drug selection, given the excellent tolerability of ARBs. Some studies are also investigating whether more extensive RAAS blockade using a combination of an ARB and an ACE-I will offer even greater protection than either agent alone.

Angiotensin Receptor Antagonists↗
PubMed2002

The 24-hour blood pressure pattern: does it have implications for morbidity and mortality?

The onset of adverse cardiovascular events demonstrates a circadian pattern that reaches a peak in the morning shortly after awakening and arising. A parallel, 24-hour cyclical pattern has also been observed in the activities of various physiologic measurements, including blood pressure, heart rate, sympathetic nervous system activity, and platelet adhesiveness. Although a direct link has not yet been established, it can be postulated that the early morning surge in blood pressure may be a factor in precipitating acute cardiovascular episodes. Similar to the early morning blood pressure surge, blood pressure variability throughout the day appears to be a further independent risk factor for hypertensive target organ damage. Thus, it is reasonable to select an antihypertensive agent that offers smooth and well-sustained blood pressure control for the full 24-hour dosing interval, including the vulnerable early morning period. The results of clinical trials using ambulatory blood pressure monitoring have shown that telmisartan, an angiotensin II receptor antagonist, possesses such properties. Whether or not these attributes of telmisartan might translate into improvements in cardiovascular morbidity and mortality will be explored in the Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial (ONTARGET). This study will compare the effects of telmisartan 80-mg monotherapy, ramipril 10-mg monotherapy, or a combination of telmisartan 80 mg plus ramipril 10 mg, on cardiovascular endpoints in patients at high risk of cardiovascular events, several of whom are likely to be hypertensive at baseline. Inclusion of the telmisartan plus ramipril treatment arm will allow investigation of the potential advantages presented by combining an angiotensin-converting enzyme inhibitor with an angiotensin II receptor antagonist.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed2002

Design of the Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial.

The Omapatrilat in Persons with Enhanced Risk of Atherosclerotic events (OPERA) trial is a large clinical trial of omapatrilat, a vasopeptidase inhibitor, in patients with stage 1 isolated systolic hypertension (ISH). OPERA is the first study to examine whether effective antihypertensive treatment can provide survival and clinical end point benefits in older persons with this common condition. This 5-year multinational, randomized, double-blind, parallel-group, placebo-controlled, forced-titration study will be conducted in approximately 12,600 subjects randomized by approximately 1100 study centers worldwide over a recruitment period of approximately 2 years. The primary objective of OPERA is to determine whether treatment with once-daily omapatrilat (target dose 40 mg) will reduce cardiovascular (CV) morbidity and mortality in older (> or = 65 years) men and women with enhanced risk for atherosclerotic events due to stage 1 ISH plus other risk factors for which currently there is no evidence-based requirement for treatment. Blood pressure inclusion criteria are systolic blood pressure (SBP) 140 to 159 mm Hg (SBP 125 to 139 mm Hg in diabetic individuals) and diastolic blood pressure (DBP) <90 mm Hg. The primary end point is defined as the composite of fatal/nonfatal stroke, fatal/nonfatal myocardial infarction, fatal/nonfatal heart failure, and other CV mortality. Secondary end points include the individual components of the primary end point, CV mortality, and major cardiovascular end points, as well as effects on cognitive function and initiation of treatment for diabetes. Additional analyses will be conducted in men and women, in diabetic patients, in different risk classes and according to prior evidence of vascular disease.

Arteriosclerosis↗
PubMed2002

Clinical implications of aldosterone blockade.

BACKGROUND: Aldosterone contributes to hypertension, cardiac and vascular remodeling, and heart failure. The significant risk reduction provided by the addition of spironolactone to standard therapy in patients with severe heart failure has renewed interest in aldosterone blockade. METHODS: This review describes recent clinical studies of eplerenone, a selective aldosterone blocker, in patients with hypertension. RESULTS: In a 16-week study, eplerenone was more effective than placebo or losartan in lowering systolic blood pressure (BP) and diastolic BP in black patients with mild to moderate hypertension. The BP-lowering efficacy of eplerenone was similar in blacks and whites. In a separate study in patients whose BP was controlled inadequately by angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers, addition of eplerenone significantly reduced systolic BP, and to a lesser extent, diastolic BP. There were no significant changes in potassium levels in this study. Eplerenone increased active renin and aldosterone levels, indicating that it blocks the renin-angiotensin-aldosterone system. Gynecomastia, or breast tenderness, was uncommon and occurred at a rate comparable to placebo. CONCLUSIONS: Eplerenone is a selective aldosterone blocker that effectively lowers BP in both white and black patients with hypertension and provides meaningful further antihypertensive efficacy when added to patients whose hypertension is inadequately controlled by angiotensin-converting enzyme inhibitors or angiotensin-receptor blockers.

Aldosterone↗
PubMed2002

The angiotensin II receptor blockers: opportunities across the spectrum of cardiovascular disease.

Angiotensin receptor blockers are a new class of agents that have made a major contribution to the treatment of hypertension. These agents effectively reduce blood pressure and are well tolerated. Other clinical trials have focused, however, on the much wider use of angiotensin receptor blockers in conditions such as congestive heart failure, postmyocardial infarction management, and diabetic nephropathy. Recent studies have provided evidence that these agents might confer target organ protection in hypertension that is equal to, and possibly better than, the benefits provided by conventional antihypertensive agents. Moreover, there is now little doubt that these drugs are effective alternatives to ACE inhibitors in heart failure and will become treatments of choice for patients with type 2 diabetes and nephropathy. Cardiovascular study outcomes have still not determined, however, whether high-risk patients would do better on angiotensin receptor blockers or angiotensin converting enzyme (ACE) inhibitors or a combination of both, except in cases of intolerance to ACE inhibitors.

Angiotensin II↗
PubMedDate not supplied

Principal results of the Controlled Onset Verapamil Investigation of Cardiovascular End Points (CONVINCE) trial.

CONTEXT: Hypertensive patients are often given a calcium antagonist to reduce cardiovascular disease risk, but the benefit compared with other drug classes is controversial. OBJECTIVE: To determine whether initial therapy with controlled-onset extended-release (COER) verapamil is equivalent to a physician's choice of atenolol or hydrochlorothiazide in preventing cardiovascular disease. DESIGN, SETTING, AND PARTICIPANTS: Double-blind, randomized clinical trial conducted at 661 centers in 15 countries. A total of 16 602 participants diagnosed as having hypertension and who had 1 or more additional risk factors for cardiovascular disease were enrolled between September 1996 and December 1998 and followed up until December 31, 2000. After a mean of 3 years of follow-up, the sponsor closed the study before unblinding the results. INTERVENTION: Initially, 8241 participants received 180 mg of COER verapamil and 8361 received either 50 mg of atenolol or 12.5 mg of hydrochlorothiazide. Other drugs (eg, diuretic, beta-blocker, or an angiotensin-converting enzyme inhibitor) could be added in specified sequence if needed. MAIN OUTCOME MEASURES: First occurrence of stroke, myocardial infarction, or cardiovascular disease-related death. RESULTS: Systolic and diastolic blood pressure were reduced by 13.6 mm Hg and 7.8 mm Hg for participants assigned to the COER verapamil group and by 13.5 and 7.1 mm Hg for partcipants assigned to the atenolol or hydrochlorothiazide group. There were 364 primary cardiovascular disease-related events that occurred in the COER verapamil group vs 365 in atenolol or hydrochlorothiazide group (hazard ratio [HR], 1.02; 95% confidence interval [CI], 0.88-1.18; P =.77). For fatal or nonfatal stroke, the HR was 1.15 (95% CI, 0.90-1.48); for fatal or nonfatal myocardial infarction, 0.82 (95% CI, 0.65-1.03); and for cardiovascular disease-related death, 1.09 (95% CI, 0.87-1.37). The HR was 1.05 (95% CI, 0.95-1.16) for any prespecified cardiovascular disease-related event and 1.08 (95% CI, 0.93-1.26) for all-cause mortality. Nonstroke hemorrhage was more common with participants in the COER-verapamil group (n = 118) compared with the atenolol or hydrochlorothiazide group (n = 79) (HR, 1.54 [95% CI, 1.16-2.04]; P =.003). More cardiovascular disease-related events occurred between 6 AM and noon in both the COER verapamil (99/277) and atenolol or hydrochlorothiazide (88/274) groups; HR, 1.15 (95% CI, 0.86-1.53). CONCLUSIONS: The CONVINCE trial did not demonstrate equivalence of a COER verapamil-based antihypertensive regimen compared with a regimen beginning with a diuretic or beta-blocker. When considered in the context of other trials of calcium antagonists, these data indicate that the effectiveness of calcium-channel therapy in reducing cardiovascular disease is similar but not better than diuretic or beta-blocker treatment.

Adrenergic beta-Antagonists↗