Clinical trials report. Vascular effects beyond blood pressure: the CAMELOT study.
Explore the source record for details and available documents.
Comment↗
Biomedical subjects
Michael A Weber
Publications and source records attributed to Michael A Weber.
A global view of atherothrombosis: baseline characteristics in the Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance (CHARISMA) trial.
BACKGROUND: The manifestations of atherothrombosis such as myocardial infarction, ischemic stroke, limb ischemia, or cardiovascular death pose a global health care burden. Additional therapies to decrease ischemic events in patients with established vascular disease or at risk for developing vascular disease are necessary. We sought to characterize the risk factors and treatments of a diverse contemporary population of patients with atherothrombosis. METHODS: The CHARISMA trial has enrolled 15,603 patients from around the world. Patients with established coronary, cerebrovascular, or peripheral arterial disease, or those at high risk of developing atherothrombosis due to multiple risk factors, have been randomized to receive either the adenosine diphosphate receptor antagonist clopidogrel or placebo, in addition to background therapy with low- to moderate-dose aspirin. RESULTS: A high percentage of enrolled patients are being treated with statins and angiotensin-converting enzyme inhibitors. In the CHARISMA population, a total of 75.6% of the population had an abnormal body mass index: 42.2% were overweight and 33.4% were obese, with particularly high rates in the United States, especially of morbid obesity. Correspondingly, the prevalence of diabetes was 42%. CONCLUSION: The CHARISMA trial will further characterize atherothrombosis and provide insight into the role of dual antiplatelet therapy in improving outcomes in patients with multiple risk factors or established vascular disease. Of note, the rates of obesity and diabetes in patients with atherothrombosis throughout the world are particularly alarming.
Adult↗
The role of the new beta-blockers in treating cardiovascular disease.
The beta-adrenergic receptor blockers play an important role in the management of cardiovascular disease, including hypertension and chronic heart failure. However, concerns regarding safety and tolerability with currently available agents can limit their use. The beta-blockers vary with regard to several pharmacologic properties, including beta1/beta2 selectivity, intrinsic sympathomimetic activity, and, with the newest beta-blockers, vasodilation. These pharmacologic differences may result in clinically important differences in tolerability and hemodynamic properties. Nebivolol is a novel beta-blocker with both a greater degree of selectivity for beta1-adrenergic receptors than other agents in this class and an ability to stimulate endothelial nitric oxide production, leading to vasodilation and other potential clinical effects. Published randomized, controlled, multicenter studies with nebivolol have shown that once-daily treatment significantly reduces systolic and diastolic blood pressure in patients with mild-to-moderate hypertension, compared with placebo, in a dose-dependent manner, and is well tolerated, with an adverse event profile similar to that of placebo. When compared with other beta-blockers as well as with other antihypertensive classes of agents in head-to-head trials, nebivolol demonstrated similar antihypertensive efficacy and a lower incidence of adverse events. Nebivolol has also been shown to significantly reduce morbidity and mortality in a large population of elderly patients with chronic heart failure, independent of left ventricular ejection fraction. Nebivolol is currently available in Europe for the management of hypertension and is expected to be available soon in the United States.
Adolescent↗
Ambulatory blood pressure monitoring in the primary care setting: assessment of therapy on the circadian variation of blood pressure from the MICCAT-2 Trial.
BACKGROUND: We conducted a large-scale, practice-based trial (MICCAT-2) to evaluate the effects of telmisartan alone and in combination with a diuretic on 24-h blood pressure (BP) profiles, including the early morning period, a time when cardiovascular risk is excessive. METHODS: Patients with hypertension, either untreated or currently on treatment, were started on, or switched to, the angiotensin receptor blocker telmisartan 40 mg daily; after 2 weeks, if office blood pressure (BP) remained > or =140/85 mmHg, the dose was increased to 80 mg; and if necessary, hydrochlorothiazide 12.5 mg was added after a further 4 weeks and continued for a final 4-week period. Twenty-four-hour ambulatory blood pressure monitoring (ABPM) was performed at baseline and at the end of the treatment period. Baseline and treatment ABPM measurements were completed in 1619 patients. RESULTS: There were highly significant reductions in both the daytime (-11.8/-7.2 mmHg) and night-time (-9.6/-5.7 mmHg) mean BP following telmisartan alone or in combination with the diuretic. Evaluation of the 24-h profiles showed evidence for sustained pharmacodynamic effects of telmisartan over the entire dosing period. Ninety-five (6%) patients had a marked surge in early morning BP defined as >30 mmHg post-awakening change in systolic BP. The average reduction of in the early morning (post-awakening) BP in the entire cohort was -11.5/-7.0 mmHg (P<0.001; reductions were similar for monotherapy and combination therapy groups. The early morning post-awakening BPs fell by an average of -17.2/-10.1 mmHg in patients with large morning BP surges (P<0.05 versus non-surge patients). CONCLUSIONS: In a community based study using ambulatory BP monitoring, telmisartan-based therapy induced highly significant reductions in systolic and diastolic BP over 24 h and was particularly effective in reducing BP during the early morning period.
Aged↗
Managing the patient at risk for a second stroke.
Cerebrovascular disease is a major cause of mortality world-wide, and the prevalence is expected to increase as a result of projected demographic trends. Aggressive antihypertensive therapy is one intervention that has proven highly effective in reducing the risk of stroke, with relatively small blood pressure reductions affording measurable benefit even in patients not conventionally considered hypertensive. Comparative clinical trials are revealing evidence of differential impacts of antihypertensive classes on the incidence of cerebrovascular disease that will probably be important for therapeutic choice in patients with risk factors for stroke. In particular, the role of the renin-angiotensin system in cerebrovascular disease has come under scrutiny as a result of evidence that angiotensin II receptor blockers (ARBs), but perhaps not angiotensin converting enzyme inhibitors, can reduce the risk of a first stroke to a greater degree than might be expected from their effects on blood pressure alone. Although preclinical evidence suggests that there are differential effects of the type 1 and type 2 receptor activation, the clinical relevance of this is not yet known. Furthermore, the effect on the incidence of stroke conferred by blood pressure control in the early morning hours - the time when the incidence of strokes peaks--has not been tested. Some evidence for the beneficial effect of an ARB on secondary stroke prevention comes from the MOrbidity and mortality after Stroke --Eprosartan compared with nitrendipine in Secondary prevention study (MOSES), which showed that the ARB protected against cerebro- and cardiovascular events in hypertensive patients with a previous stroke over and above the protection offered by blood pressure control. These hypotheses are among those being examined in two current large-scale trials: the Prevention Regimen For Effectively avoiding Second Strokes (PRoFESS), and The ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial (ONTARGET) Trial Programme.
Antihypertensive Agents↗
Results of the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial by geographical region.
OBJECTIVE: To examine regional differences in the Controlled ONset Verapamil INvestigation of Cardiovascular Endpoints (CONVINCE) trial. DESIGN: Double-blind, randomized, international clinical trial. SETTING: Six hundred and sixty-one clinical centers in 15 countries. PATIENTS: Hypertensive volunteers (n = 16,602) with > or =1 additional cardiovascular risk factor, grouped into four regions: USA (n = 8144), Canada (n = 3405), Western Europe (Spain, UK, Italy, Sweden, Germany; n = 2048) or 'other' (Bulgaria, Israel, Mexico, Czech Republic, Hungary, Poland, Slovakia, Brazil; n = 2879); subgroupings included country and state/province within the USA and Canada. INTERVENTIONS: Randomized to COER-verapamil or the investigator's choice of either atenolol or hydrochlorothiazide, titrated and additional drugs added as required. MAIN OUTCOME MEASURES: Baseline characteristics; blood pressure control, medication adherence and lost-to-follow-up at 2 years; and composite primary endpoint (stroke, myocardial infarction, cardiovascular death) by regional groupings. RESULTS: Regional differences were found at baseline for age, gender, blood pressure, percentage receiving antihypertensive drug therapy, initial choice of atenolol or hydrochlorothiazide, and risk factor profile. Blood pressure control rates increased markedly during follow-up in all regions, but varied significantly by region. Blood pressure control, medication adherence and lost-to-follow-up rates were poorest in the USA. After adjustment for baseline differences, the primary-event rate for each region was significantly lower than for the USA. Although baseline factors, blood pressure control and event rates varied by region, treatment differences did not. CONCLUSION: Despite differences in baseline and follow-up measures across geographical regions, the absence of treatment differences by region suggests that the overall findings of CONVINCE are robust.
Aged↗
The efficacy and safety of low- and high-dose fixed combinations of irbesartan/hydrochlorothiazide in patients with uncontrolled systolic blood pressure on monotherapy: the INCLUSIVE trial.
This multicenter, prospective, open-label, single-arm study determined the efficacy and safety of irbesartan/hydrochlorothiazide (HCTZ) fixed combinations in patients (n=1005), aged 18 years and older, with uncontrolled systolic blood pressure (SBP) of 140-159 mm Hg (130-159 mm Hg for type 2 diabetes mellitus) after at least 4 weeks of antihypertensive monotherapy. Treatment was sequential: placebo (4-5 weeks), HCTZ 12.5 mg (2 weeks), irbesartan/HCTZ 150/12.5 mg (8 weeks), and irbesartan/HCTZ 300/25 mg (8 weeks). Enrolled patients (n=844) were aged 57.3+/-11.2 years; 52% were women, 23% were African American, and 14% were Hispanic. Thirty percent had type 2 diabetes mellitus, 46% had metabolic syndrome, and baseline blood pressure was 154.0+/-10.3/91.3+/-8.8 mm Hg. The mean change in SBP from placebo end to the primary end point, Week 18 (intent-to-treat population, n=736) was -21.5+/-14.3 mm Hg (p<0.001). The mean change in diastolic blood pressure (DBP) was -10.4+/-8.7 mm Hg (p<0.001). The mean Week 18 SBP/DBP was 132.9+/-13.8/81.1+/-9.7 mm Hg. Overall, 77% (95% confidence interval, 74%-80%) of patients achieved SBP goal (<140 mm Hg; <130 mm Hg for type 2 diabetes mellitus); 83% (95% confidence interval, 80%-86%) achieved DBP goal (<90 mm Hg; <80 mm Hg for type 2 diabetes mellitus); and 69% (95% confidence interval, 66%-72%) achieved dual SBP/DBP goal. Treatments were well tolerated. This irbesartan/HCTZ treatment regimen achieved SBP goals in more than 75% of patients uncontrolled on monotherapy.
Adult↗
Is there more to life than blood pressure?
Explore the source record for details and available documents.
Amlodipine↗
Efficacy of combination therapy for systolic blood pressure in patients with severe systolic hypertension: the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study.
Systolic hypertension is predominant among patients over 50 years of age, is a more important cardiovascular risk factor than diastolic blood pressure, and is more difficult to control than diastolic blood pressure. Consequently, the Seventh Report of the Joint National Committee on Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC 7) recommends combination therapy as first-line treatment for patients with stage 2 hypertension. In the Systolic Evaluation of Lotrel Efficacy and Comparative Therapies (SELECT) study, 24-hour ambulatory blood pressure monitoring was used to identify patients with systolic hypertension and to determine the impact of 8 weeks of treatment with either amlodipine besylate/benazepril HCl 5/20 mg combination therapy (n=149), amlodipine besylate 5 mg (n=146), or benazepril HCl 20 mg (n=148). Combination therapy was significantly more effective in reducing systolic blood pressure and pulse pressure than either monotherapy (p<0.0001). Significantly greater percentages of patients in the combination group compared with either monotherapy achieved blood pressure control (p<0.0001). Adverse events were low in all three treatment arms, with less peripheral edema in the combination group than in the amlodipine-treated group. The combination of amlodipine besylate/benazepril HCl given to patients with stage 2 systolic hypertension resulted in significantly greater reductions in blood pressure and pulse pressure than those seen with monotherapy and was at least as well tolerated as the separate components. This data supports the recommendation of the JNC 7 for the use of combination therapy in patients with stage 2 hypertension.
Aged↗
Comparative antihypertensive efficacy of angiotensin receptor blocker-based treatment in African-American and white patients.
Blood pressure (BP) reductions with agents that block the renin-angiotensin system are regarded as less effective as monotherapy in African Americans than other ethnic groups. This practice-based study compares the efficacy of an angiotensin receptor blocker-based regimen in African-American and Caucasian patients. Included in the 10-week study were 173 African-American and 1296 Caucasian patients. Efficacy was based on differences in 24-hour ambulatory BP. After baseline ambulatory BP monitoring and office BPs were obtained, all patients were started or switched to the angiotensin receptor blocker telmisartan, 40-80 mg daily, plus hydrochlorothiazide 12.5 mg daily (if needed for office BP control: <140/90 mm Hg). More African Americans required the addition of a low-dose thiazide diuretic than Caucasians (47.3% vs. 34.9%; p=0.021). Once patients with white coat hypertension were excluded (i.e., those with baseline ambulatory BP monitoring <130/80 mm Hg), ambulatory BP monitoring changes were similar between groups. A greater proportion of African Americans than Caucasians without white coat hypertension also needed combination therapy (52.1% vs. 39.5%; p=0.04). While achievement of BP goal was similar between groups by office criterion (<140/90 mm Hg), differences were noted by ambulatory BP monitoring (<130/80 mm Hg) (48.0% in African American vs. 63.2% in Caucasians; p=0.01) despite the same BP reductions, reflecting higher baseline values in African Americans. We conclude that an angiotensin receptor blocker as part of a BP-lowering strategy is effective in previously untreated African-American patients, although a higher proportion will require the use of a diuretic compared with Caucasians.
Adult↗
Expanding the definition and classification of hypertension.
Cardiovascular abnormalities are frequently the cause, as well as the effect, of elevated blood pressure. As such, early cardiovascular disease (CVD) may be established before identifiable blood pressure thresholds are crossed. To identify individuals at risk for CVD at an earlier point in the disease process, as well as to avoid labeling persons as hypertensive who are at low risk for CVD, the Hypertension Writing Group proposes incorporating the presence or absence of cardiovascular risk factors, early disease markers, and target organ damage into the definition and classification scheme of hypertension. To describe both the complexity and progressive nature of hypertension, the following definition is proposed: "Hypertension is a progressive cardiovascular syndrome arising from complex and interrelated etiologies. Early markers of the syndrome are often present before blood pressure elevation is observed; therefore, hypertension cannot be classified solely by discrete blood pressure thresholds. Progression is strongly associated with functional and structural cardiac and vascular abnormalities that damage the heart, kidneys, brain, vasculature, and other organs and lead to premature morbidity and death." Classification of hypertension must involve assessing global cardiovascular risk to situate an individual's risk for CVD and events along a continuum. As knowledge of early CVD continues to evolve, the approach to classifying individuals along that continuum can be expected to evolve accordingly. The four categories currently used to classify hypertension are normal, prehypertension, and stages 1 and 2 hypertension. The population identified with prehypertension includes a subgroup with early CVD. We believe it would be preferable to classify all individuals as either normal or hypertensive, based on their cardiovascular evaluation, using the four categories of normal and stages 1, 2, and 3 hypertension.
Antihypertensive Agents↗
Angiotensin-II receptor blockers for hypertension and heart failure: quality of life and outcomes.
Quality of life (QoL) is a component of disease and its management that may affect compliance with pharmacotherapy, and thus the success of treatment. Patients' QoL scores are important indicators of the progression of disease and effects of treatment. In hypertension, QoL parameters include medication side effects, depression, and sexual function. In heart failure, parameters include New York Heart Association functional class (men only), exercise tolerance, dyspnea, medication side effects, and costs of therapy. Medication side effects are negatively related to QoL and persistence with therapy. In hypertension, QoL is improved directly by meaningful blood pressure reductions. Overall, angiotensin-II receptor blockers have a low incidence of side effects and provide improved QoL compared with standard therapies for patients with hypertension or heart failure.
Angiotensin II Type 1 Receptor Blockers↗
Blood pressure dependent and independent effects of antihypertensive treatment on clinical events in the VALUE Trial.
The Valsartan Antihypertensive Long-term Use Evaluation (VALUE) trial was designed to test whether, for the same achieved blood pressures, regimens based on valsartan or amlodipine would have differing effects on cardiovascular endpoints in high risk hypertension. But inequalities in blood pressure, favouring amlodipine, throughout the multiyear trial precluded comparison of outcomes. A technique of serial median matching, applied at 6 months when treatment adjustments intended to achieve control of blood pressure were complete, created 5006 valsartan-amlodipine patient pairs matched exactly for systolic blood pressure, age, sex, and the presence or absence of previous coronary disease, stroke, or diabetes. Subsequent combined cardiac events, myocardial infarction, stroke, and mortality were almost identical in the two cohorts, but admission to hospital for heart failure was significantly lower with valsartan. Reaching blood pressure control (systolic <140 mm Hg) by 6 months, independent of drug type, was associated with significant benefits for subsequent major outcomes; the blood pressure response after just 1 month of treatment predicted events and survival.
Amlodipine↗
Clinical trials report. Consequences of new-onset diabetes during the treatment of hypertension.
Explore the source record for details and available documents.
Comment↗
Effect of antihypertensive monotherapy and combination therapy on arterial distensibility and left ventricular mass.
BACKGROUND: Angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers (CCBs) increase arterial compliance and decrease left ventricular mass in hypertensive patients. This study examined whether combined therapy has greater arterial and cardiac effects than doubled doses of the individual drugs. METHODS: This prospective, randomized, open-label study enrolled 106 patients aged >/=18 years with mild-to-moderate hypertension. Patients were randomized to 5 mg of amlodipine or 20 mg of benazepril for 2 weeks; then, depending on randomization assignment, they were force-titrated to 10 mg of amlodipine or 40 mg of benazepril monotherapy, or to combination amlodipine (5 mg) and benazepril (20 mg) treatment for 22 weeks. Arterial distensibility was assessed using the DynaPulse ambulatory system, and left ventricular mass was assessed by echocardiography. RESULTS: Combination therapy (0.71% +/- 0.51% mL/mm Hg) increased arterial distensibility more than amlodipine (0.28% +/- 0.69% mL/mm Hg; P =.008) or benazepril (0.39% +/- 0.62% mL/mm Hg; P =.03) monotherapies. Left ventricular mass decreased more with combination treatment (65 +/- 56 g) than with amlodipine (28 +/- 4 g; P <.02); the difference from benazepril (42 +/- 50 g) was not significant. CONCLUSIONS: Combined ACE inhibitor and CCB treatment was more efficacious than high doses of the individual agents in increasing arterial compliance and reducing left ventricular mass. These findings indicate that appropriately selected combinations of antihypertensive drugs might have enhanced cardioprotective effects.
Adult↗
Evaluation of antihypertensive therapy with the combination of olmesartan medoxomil and hydrochlorothiazide.
BACKGROUND: Most patients with hypertension require more than one agent to control blood pressure (BP). The purpose of this study was to assess the efficacy and safety of the angiotensin II receptor blocker olmesartan medoxomil in combination with hydrochlorothiazide (HCTZ). METHODS: This was a randomized, double-blind, factorial design study. After a placebo run-in period, eligible patients (n = 502) with a baseline mean seated diastolic blood pressure (SeDBP) of 100 to 115 mm Hg were randomized to one of 12 groups: placebo, olmesartan medoxomil monotherapy (10, 20, or 40 mg/day, HCTZ monotherapy (12.5 or 25 mg/day), or one of six groups of olmesartan medoxomil/HCTZ combination therapy. The primary endpoint was the change in mean trough SeDBP from baseline at week 8. Statistical analyses were conducted to determine whether at least one combination produced a larger reduction in SeDBP at week 8 than the individual corresponding component doses, but did not compare BP reductions with different combination doses. RESULTS: Olmesartan medoxomil plus HCTZ produced greater reductions in both SeDBP and seated systolic blood pressure (SeSBP) at week 8 than did monotherapy with either component. All olmesartan medoxomil/HCTZ combinations significantly reduced SeDBP and SeSBP compared with placebo in a dose-dependent manner. Reductions from baseline in mean trough SeSBP/SeDBP were 3.3/8.2 mm Hg, 20.1/16.4 mm Hg, and 26.8/21.9 mm Hg with placebo, olmesartan medoxomil/HCTZ 20/12.5 mg, and olmesartan medoxomil/HCTZ 40/25 mg, respectively. All treatments were well tolerated. CONCLUSIONS: Olmesartan medoxomil/HCTZ combination therapy produced BP reductions of up to 26.8/21.9 mm Hg and was well tolerated.
Adult↗
Rationale and design of the avoiding cardiovascular events through combination therapy in patients living with systolic hypertension (ACCOMPLISH) trial: the first randomized controlled trial to compare the clinical outcome effects of first-line combination therapies in hypertension.
Reducing blood pressure (BP) to target levels is a major priority in preventing clinical events in hypertension. Typically this requires more than one drug, and recent guidelines on hypertension management therefore recommend starting with combination treatment in many patients. Diuretics have often been part of such therapy, usually paired with angiotensin converting enzyme (ACE) inhibitors or similar agents; but calcium channel blockers are also highly efficacious in reducing BP when combined with ACE inhibitors. In addition, these drug classes, separately and in combination, appear to have vasculoprotective properties. Because the primary goal of treating hypertension is to enhance survival and reduce cardiovascular outcomes, the Rationale and Design of Avoiding Cardiovascular events through COMbination therapy in Patients LIving with Systolic Hypertension (ACCOMPLISH) trial is designed as the first blinded and randomized study to prospectively compare the effects on these endpoints of two antihypertensive combinations, benazapril/hydrochlorothiazide (force titrated to 40/12.5 mg) and amlodipine besylate/benazapril (force titrated to 5/40 mg). The doses can be further titrated to 40/25 mg or 10/40 mg, and other classes of drugs can be added as needed for optimal BP control. The primary study endpoint is a composite of cardiovascular mortality and morbidity. The study will be performed in hypertensive patients (systolic BP > or = 160 mm Hg or currently on antihypertensive therapy) with risk factors for cardiovascular events (prior events, target organ damage, kidney disease, or diabetes). A total of 6300 subjects will be randomized to each group with the expectation that a total of 1642 primary endpoints will occur during a 5-year period, providing 90% power to detect the 15% relative reduction in events (alpha = 0.05) hypothesized to favor the amlodipine besylate/benazapril group. The ACCOMPLISH study will be performed in the United States and Europe. The first patient was randomizedduring 2003, and the trial should conclude in 2008.
Antihypertensive Agents↗
Predictors of in-hospital mortality in 1333 patients with acute myocardial infarction complicated by cardiogenic shock treated with primary percutaneous coronary intervention (PCI); Results of the primary PCI registry of the Arbeitsgemeinschaft Leitende Kardiologische Krankenhausärzte (ALKK).
Aims Acute myocardial infarction complicated by cardiogenic shock is associated with an exceedingly high mortality, even if patients are treated with early reperfusion therapy. The aim of this study was to evaluate predictors of in-hospital mortality of a large cohort of consecutive patients with cardiogenic shock treated with primary percutaneous coronary intervention (PCI). Methods and results Between July 1994 and March 2001 all interventions performed in 80 centres in Germany were prospectively entered into the primary PCI registry of the ALKK. A total of 9422 procedures were registered, of these 1333 (14.2%) were performed in patients with cardiogenic shock. Total in-hospital mortality was 46.1% and was dependent on TIMI flow grade after PCI, with mortality rates of 78.2%, 66.1% and 37.4% in patients with TIMI 0/1, TIMI 2 and TIMI 3 flow, respectively. In a multivariate analysis left main disease, TIMI <3 flow after PCI, older age, three-vessel disease and longer time-intervals between symptom onset and PCI were significant independent predictors of mortality. The relative number of PCIs performed in patients with cardiogenic shock did not change significantly from 1995-2000. There was a significant decrease in mortality over the years (P for trend 0.02). Conclusions In-hospital mortality in patients with acute myocardial infarction complicated by cardiogenic shock remains high, even with early interventional therapy. However, our data demonstrate that the PCI in these high-risk patients is feasible in a wide spectrum of community hospitals with acceptable success rates. Our results seen in connection with the results of the randomized SHOCK study advocate an early invasive approach in younger patients with cardiogenic shock, while the best strategy in elderly patients is still a matter of debate.
Angioplasty, Balloon, Coronary↗