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Background: A daily single capsule (polycap) of 3 blood pressure (BP) lowering drugs (hydrochlorthiazide, 12.5 mg; atenolol, 50 mg; ramipril, 5 mg) at low doses, simvastatin (20 mg), and aspirin (100 mg) has been demonstrated to be well tolerated and to reduce BP and low-density lipoprotein cholesterol. We examined the incremental effects of 2 (full dose) plus K(+) supplementation versus single polycap (low dose) on risk factors and tolerability.Methods and Results: After a run-in period, 518 individuals with previous vascular disease or diabetes mellitus from 27 centers in India were randomly assigned to a single-dose polycap or to 2 capsules of the polycap plus K(+) supplementation for 8 weeks. The effects on BP, heart rate (HR), serum lipids, serum and urinary K(+), and tolerability were assessed using an intention-to-treat analysis. The full-dose polycap (plus K(+) supplementation) reduced BP by a further 2.8 mm Hg systolic and 1.7 mm Hg diastolic, compared with that observed with the low-dose polycap (P=0.003; P=0.001), but there were no differences in HR (0.1 bpm). The differences in total and low-density lipoprotein cholesterol between the full-dose and low-dose polycap was 7.2 mg/dL (P=0.014) and 6.6 mg/dL (P=0.006), respectively, but there were no differences in high-density lipoprotein cholesterol or triglycerides. The rates of discontinuation of the study drug after randomization were similar in the 2 groups (6.9% low dose versus 7.8% full dose).Conclusions: The full-dose polycap (plus K(+) supplementation) reduces BP and low-density lipoprotein cholesterol to a greater extent compared with the low dose, with similar tolerability. Therefore, the full-dose polycap should potentially lead to larger benefits. Clinical Trial Registration- URL: http://www.ctri.nic.in. Unique identifier: CTRI/2010/091/000054. [ABSTRACT FROM AUTHOR]

Objective Longer QRS duration on the ECG is associated with increased cardiovascular (CV) mortality. To evaluate potential mechanisms, we examined in this study the relationship between QRS duration and left ventricular (LV) mass and LV end systolic and end diastolic volume in patients with known CV disease or high-risk diabetes. Methods In a substudy of the ONTARGET/TRANSCEND (Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trial/Telmisartan Randomised Assessment Study in ACE Intolerant Subjects with Cardiovascular Disease) clinical trials, 368 patients had a cardiac magnetic resonance scan to measure LV mass, LV end systolic volume, LV end diastolic volume and LV ejection fraction at baseline and after 2 years of follow-up. Relationships between QRS duration on the 12-lead ECG and LV mass and volumes were evaluated at both assessments. Results Each 10-ms increase in QRS duration both within and above the normal reference range was associated with an 8.3% (95% CI 6.7% to 9.9%) increase in LV mass, a 9.2% (95% CI 7.4% to 10%) increase in LV end diastolic volume and a 7.8% (95% CI 6.4% to 9.3%) increase in LV end systolic volume. QRS duration increased with body size, but associations with LV mass and volumes remained strong after indexing measurements to height(2.7) (p<0.001 for all) and were similar for subjects with an otherwise normal and abnormal ECG. Conclusion A longer QRS duration both within and above the normal reference range is associated with a greater LV mass and larger LV end systolic and end diastolic volumes. This may explain the known association of longer QRS duration with increased CV mortality. [ABSTRACT FROM AUTHOR]

BACKGROUND: Glomerular filtration rate and albuminuria are risk factors for cardiovascular disease and markers of renal function. OBJECTIVE: To examine the contribution of estimated glomerular filtration rate (eGFR) and urinary albumin-creatinine ratio beyond that of traditional cardiovascular risk factors to classification of patient risk for cardiovascular and renal outcomes. DESIGN: Prospective cohort study that pooled all patients of ONTARGET (ONgoing Telmisartan Alone and in combination with Ramipril Global Endpoint Trial) and TRANSCEND (Telmisartan Randomized Assessment Study in Angiotensin-Converting-Enzyme-Inhibitor Intolerant Subjects with Cardiovascular Disease). PATIENTS: 27,620 patients older than 55 years with documented cardiovascular disease, who were followed for a mean of 4.6 years. MEASUREMENTS: Baseline eGFR, urinary albumin-creatinine ratio, and cardiovascular risk factors. Outcomes were all-cause mortality; a composite of cardiovascular death, myocardial infarction, stroke, and hospitalization for heart failure; long-term dialysis; and a composite of long-term dialysis and doubling of serum creatinine level. RESULTS: Lower eGFRs and higher urinary albumin-creatinine ratios were associated with the primary cardiovascular composite outcome (for example, an adjusted hazard ratio of 2.53 [95% CI, 1.61 to 3.99] for an eGFR <30 mL/min per 1.73 m(2) and a very high urinary albumin-creatinine ratio). However, adding information about eGFR and urinary albumin-creatinine ratio to the risk reclassification analyses led to no meaningful decrease in the proportion of patients assigned to the intermediate-risk category (31% without vs. 32% with renal information). In contrast, eGFR and urinary albumin-creatinine ratio were strongly associated with risk for long-term dialysis and greatly improved both model calibration and risk stratification capacity when added to traditional cardiovascular risk factors (65% assigned to intermediate-risk categories without renal information vs. 18% with renal information). LIMITATION: Creatinine levels were not standardized. CONCLUSION: In patients with high vascular risk, eGFR and urinary albumin-creatinine ratio add little to traditional cardiovascular risk factors for stratifying cardiovascular risk but greatly improve risk stratification for renal outcomes. PRIMARY FUNDING SOURCE: Boehringer Ingelheim, Population Health Research Institute, and the European Commission. [ABSTRACT FROM AUTHOR]

BACKGROUND: Contrast-induced nephropathy is common in patients with coronary angiography. Mechanistically, forced euvolemic diuresis with mannitol and furosemide ought to prevent contrast-induced nephropathy. Our objectives are to: (1) undertake a randomized trial testing this hypothesis, and (2) conduct a meta-analysis of our findings with 2 earlier studies. STUDY DESIGN: (1) Randomized allocation-concealed controlled trial with blinded ascertainment of outcomes, and (2) random-effects meta-analysis of 3 trials. SETTING & PARTICIPANTS: Single-center study of consenting adults with serum creatinine level greater than 1.7 mg/dL undergoing coronary angiography; patients unable to tolerate fluid challenge or receiving dialysis were excluded. Two previous trials had randomly assigned 159 patients. INTERVENTION: Forced euvolemic diuresis with saline, mannitol, and furosemide compared with saline hydration controls. All patients were pretreated with at least 500 mL of half-normal saline before angiography; during and 8 hours after, urine output was replaced milliliter per milliliter with half-normal saline. OUTCOMES & MEASUREMENTS: The primary outcome was contrast-induced nephropathy within 48 hours of the procedure, defined as a 0.5-mg/dL absolute or 25% relative increase in creatinine level. RESULTS: Overall, 92 patients were allocated to intervention (n = 46) or control (n = 46). Mean age was 64 +/- 14 (SD) years, 23% were women, 37% had diabetes, 47% used oral furosemide, mean creatinine level was 2.8 +/- 1.6 mg/dL, and most patients (72%) underwent diagnostic catheterization. Patients had a net positive fluid balance (389 +/- 958 mL for intervention versus 655 +/- 982 mL for controls; P = 0.2). Contrast-induced nephropathy occurred in 23 (50%) intervention patients versus 13 (28%) controls (relative risk, 1.77; 95% confidence interval, 1.03 to 3.05; P = 0.03; adjusted odds ratio, 3.73; P = 0.03). Within 48 hours, creatinine level had increased by 0.8 +/- 1.1 mg/dL with intervention versus 0.2 +/- 0.6 mg/dL for controls (P = 0.002). Overall, 11 (12%) patients died or required dialysis, with no difference according to allocation status (P = 0.5). Random-effects meta-analysis of published data (3 trials; 251 patients) suggests furosemide-based interventions lead to significant harm compared with hydration: pooled relative risk, 2.15; 95% confidence interval, 1.37 to 3.37; I(2) = 0%. LIMITATIONS: Small single-center study that cannot determine whether harms were related to furosemide, mannitol, or a combination. CONCLUSIONS: Forced euvolemic diuresis led to a significantly increased risk of contrast-induced nephropathy. This strategy should be abandoned, and our results suggest that oral furosemide therapy perhaps should be held before angiography. Copyright © 2009 National Kidney Foundation, Inc. [ABSTRACT FROM AUTHOR]

Background: Angiotensin-receptor blockers (ARBs) blunt progression of advanced diabetic nephropathy, but their long-term renal effects in other patients are not clear.Objective: To examine the long-term renal effects of telmisartan versus placebo in adults at high vascular risk.Design: Randomized trial. Patients were randomly assigned by a central automated system between November 2001 and May 2004 and were followed until March 2008. Participants and investigators were blinded to intervention status.Setting: Multicenter, multinational study.Patients: 5927 adults with known cardiovascular disease or diabetes with end-organ damage but without macroalbuminuria or heart failure who cannot tolerate angiotensin-converting enzyme inhibitors.Intervention: Telmisartan, 80 mg/d (n = 2954), or matching placebo (n = 2972) plus standard treatment for a mean of 56 months.Measurements: Composite renal outcome of dialysis or doubling of serum creatinine, changes in estimated glomerular filtration rate (GFR), and changes in albuminuria.Results: No important difference was found in the composite renal outcome with telmisartan (58 patients [1.96%]) versus placebo (46 patients [1.55%]) (hazard ratio, 1.29 [95% CI, 0.87 to 1.89]; P = 0.20). Among the telmisartan and placebo groups, 7 and 10 patients had dialysis and 56 and 36 patients had doubling of serum creatinine, respectively (hazard ratio, 1.59 [CI, 1.04 to 2.41]; P = 0.031). Albuminuria increased less with telmisartan than with placebo (32% [CI, 23% to 41%] vs. 63% [CI, 52% to 76%]; P < 0.001). Decreases in estimated GFR were greater with telmisartan than with placebo (mean change in estimated GFR, -3.2 mL/min per 1.73 m(2) [SD, 18.3] vs. -0.26 mL/min per 1.73 m(2) [SD, 18.0]; P < 0.001).Limitation: Only 17 participants had dialysis.Conclusion: In adults with vascular disease but without macroalbuminuria, the effects of telmisartan on major renal outcomes were similar to those of placebo. [ABSTRACT FROM AUTHOR]

Background: Results from a retrospective analysis of the Studies of Left Ventricular Dysfunction (SOLVD) study suggest that angiotensin-converting-enzyme (ACE) inhibitors may be less effective in patients receiving aspirin. We aimed to confirm or refute this theory.Methods: We used the Peto-Yusuf method to undertake a systematic overview of data for 22060 patients from six long-term randomised trials of ACE inhibitors to assess whether aspirin altered the effects of ACE inhibitor therapy on major clinical outcomes (composite of death, myocardial infarction, stroke, hospital admission for congestive heart failure, or revascularisation).Findings: Baseline characteristics, and prognosis in patients allocated placebo, differed strikingly between those who were and were not taking aspirin at baseline. Results from analyses of all trials, except SOLVD, did not suggest any significant differences between the proportional reductions in risk with ACE inhibitor therapy in the presence or absence of aspirin for the major clinical outcomes (p=0.15), or in any of its individual components, except myocardial infarction (interaction p=0.01). Overall, ACE inhibitor therapy significantly reduced the risk of the major clinical outcomes by 22% (p<0.0001), with clear reductions in risk both among those receiving aspirin at baseline (odds ratio 0.80, [99% CI 0.73-0.88]) and those who were not (0.71 [99% CI 0.62-0.81], interaction p=0.07).Interpretation: Considering the totality of evidence on all major vascular outcomes in these trials, there is only weak evidence of any reduction in the benefit of ACE-inhibitor therapy when added to aspirin. However, there is definite evidence of clinically important benefits with respect to these major clinical outcomes with ACE-inhibitor therapy, irrespective of whether concomitant aspirin is used. [ABSTRACT FROM AUTHOR]

PURPOSE: To determine whether the management of heart failure by specialized multidisciplinary heart failure disease-management programs was associated with improved outcomes. BACKGROUND: The advent of angiotensin-converting enzyme inhibitors, beta-blockers, and spironolactone has revolutionized the management of heart failure. Randomized double-blind studies have demonstrated survival benefits of these drugs in heart failure patients. Nevertheless, in spite of these advances, heart failure continues to be a syndrome of poor outcomes. 1–4 There is also evidence that a significant portion of heart failure patients does not receive this evidence-based therapy that reduces morbidity and mortality. 5–7 Various disease-management programs have been proposed and tested to improve the quality of heart failure care. Most of these programs are specialized multidisciplinary heart failure clinics lead by cardiologists or heart failure specialists and conducted by nurses or nurse practitioners. Similar to the Department of Veterans Affairs (VA) multidisciplinary geriatric assessment clinics, these clinics also use many other services, including pharmacists, dietitians, physical therapists, and social workers. Some of these programs also have an affiliated home health service. Several observation studies, using mostly pre- and postcomparison designs, have demonstrated the effectiveness of these programs in the process of care, resource use, healthcare costs, and clinical outcomes in patients with heart failure. 8 Risk of hospitalization was reduced by 50% to 85% in six of the studies. 8 Subsequently, several randomized trials were conducted to determine the effectiveness of these programs. The purpose of this systematic review was to determine the effectiveness of these programs on mortality and hospitalization rates of heart failure patients. METHODS: Published articles on human randomized trials involving... [ABSTRACT FROM AUTHOR]

Objective: To examine the relations between demographic factors, specific psychosocial factors, and cardiac rehabilitation attendance.Design: Cohort, repeated measures design.Setting: A large tertiary care centre in western CanadaPatients: 304 consecutive consenting patients discharged following acute myocardial infarction and/or coronary artery bypass graft surgery.Main Outcome Measures: The Jenkins self-efficacy expectation scales and activity checklists of behaviour performance for maintaining health and role resumption, modified version of the self-motivation inventory, and the shortened social support scale.Results: Those who had higher role resumption behaviour performance scores at two weeks after discharge were significantly less likely to attend cardiac rehabilitation programmes. At six months after discharge, those who attended cardiac rehabilitation demonstrated higher health maintenance self-efficacy expectation and behaviour performance scores. Health maintenance self-efficacy expectation and behaviour performance improved over time. Women reported less social support but showed greater improvement in health maintenance self-efficacy expectation. Changes in self-efficacy scores were unrelated to-but changes in health maintenance behaviour performance scores were strongly associated with-cardiac rehabilitation attendance.Conclusions: Cardiac patients and practitioners may have misconceptions about the mandate and potential benefits of rehabilitation programmes. Patients who resumed role related activities early and more completely apparently did not see the need to "rehabilitate" while those who attended cardiac rehabilitation programmes enhanced their secondary prevention behaviours. [ABSTRACT FROM AUTHOR]

Objective: To investigate the effects of prophylactic therapy with antiarrhythmic agents on mortality in patients with myocardial infarction.Data Sources and Study Selection: Data were obtained from all completed, published or unpublished, randomized, parallel controlled trials of antiarrhythmic agents, regardless of sample size. Investigators were contacted for data on patients excluded after randomization.Data Extraction: Data on mortality were extracted by one author and confirmed where necessary by the others.Data Synthesis: Mortality data from 138 trials on 98,000 patients were combined by the Yusuf-Peto adaptation of the Mantel-Haenszel method. There were 660 deaths among 11,712 patients allocated to receive class I agents and 571 deaths among 11,517 corresponding control patients (51 trials: odds ratio [OR], 1.14; 95% confidence interval [CI], 1.01 to 1.28; P = .03). Of 26,973 patients allocated to receive beta-blockers (class II agents), 1464 died compared with 1727 deaths among 26,295 control patients (55 trials: OR, 0.81; 95% CI, 0.75 to 0.87; P = .00001). Of 778 patients allocated to receive amiodarone (a class III agent), 77 died compared with 101 deaths in 779 control patients (eight trials: OR, 0.71; 95% CI, 0.51 to 0.97; P = .03). There were 982 deaths in 10,154 patients allocated to receive a class IV agent (calcium channel blockers) and 949 deaths in 10,188 control patients (24 trials: OR, 1.04; 95% CI, 0.95 to 1.14; P = .41).Conclusions: The routine use of class I antiarrhythmic agents after myocardial infarction is associated with increased mortality. beta-Blockers have been conclusively demonstrated to reduce mortality. The limited data on amiodarone appear promising. Data on calcium channel blockers remain unpromising. [ABSTRACT FROM AUTHOR]

Background: Moderate alcohol consumption may reduce cardiovascular events, but little is known about its effect on atrial fibrillation in people at high risk of such events. We examined the association between moderate alcohol consumption and the risk of incident atrial fibrillation among older adults with existing cardiovascular disease or diabetes.Methods: We analyzed data for 30 433 adults who participated in 2 large antihypertensive drug treatment trials and who had no atrial fibrillation at baseline. The patients were 55 years or older and had a history of cardiovascular disease or diabetes with end-organ damage. We classified levels of alcohol consumption according to median cut-off values for low, moderate and high intake based on guidelines used in various countries, and we defined binge drinking as more than 5 drinks a day. The primary outcome measure was incident atrial fibrillation.Results: A total of 2093 patients had incident atrial fibrillation. The age- and sex-standardized incidence rate per 1000 person-years was 14.5 among those with a low level of alcohol consumption, 17.3 among those with a moderate level and 20.8 among those with a high level. Compared with participants who had a low level of consumption, those with higher levels had an increased risk of incident atrial fibrillation (adjusted hazard ratio [HR] 1.14, 95% confidence interval [CI] 1.04-1.26, for moderate consumption; 1.32, 95% CI 0.97-1.80, for high consumption). Results were similar after we excluded binge drinkers. Among those with moderate alcohol consumption, binge drinkers had an increased risk of atrial fibrillation compared with non-binge drinkers (adjusted HR 1.29, 95% CI 1.02-1.62).Interpretation: Moderate to high alcohol intake was associated with an increased incidence of atrial fibrillation among people aged 55 or older with cardiovascular disease or diabetes. Among moderate drinkers, the effect of binge drinking on the risk of atrial fibrillation was similar to that of habitual heavy drinking. [ABSTRACT FROM AUTHOR]

Background: In patients with stable coronary artery disease, it remains unclear whether an initial management strategy of percutaneous coronary intervention (PCI) with intensive pharmacologic therapy and lifestyle intervention (optimal medical therapy) is superior to optimal medical therapy alone in reducing the risk of cardiovascular events.Methods: We conducted a randomized trial involving 2287 patients who had objective evidence of myocardial ischemia and significant coronary artery disease at 50 U.S. and Canadian centers. Between 1999 and 2004, we assigned 1149 patients to undergo PCI with optimal medical therapy (PCI group) and 1138 to receive optimal medical therapy alone (medical-therapy group). The primary outcome was death from any cause and nonfatal myocardial infarction during a follow-up period of 2.5 to 7.0 years (median, 4.6).Results: There were 211 primary events in the PCI group and 202 events in the medical-therapy group. The 4.6-year cumulative primary-event rates were 19.0% in the PCI group and 18.5% in the medical-therapy group (hazard ratio for the PCI group, 1.05; 95% confidence interval [CI], 0.87 to 1.27; P=0.62). There were no significant differences between the PCI group and the medical-therapy group in the composite of death, myocardial infarction, and stroke (20.0% vs. 19.5%; hazard ratio, 1.05; 95% CI, 0.87 to 1.27; P=0.62); hospitalization for acute coronary syndrome (12.4% vs. 11.8%; hazard ratio, 1.07; 95% CI, 0.84 to 1.37; P=0.56); or myocardial infarction (13.2% vs. 12.3%; hazard ratio, 1.13; 95% CI, 0.89 to 1.43; P=0.33).Conclusions: As an initial management strategy in patients with stable coronary artery disease, PCI did not reduce the risk of death, myocardial infarction, or other major cardiovascular events when added to optimal medical therapy. (ClinicalTrials.gov number, NCT00007657 [ClinicalTrials.gov].). [ABSTRACT FROM AUTHOR]