- Clinical Evaluation of the CorCap Cardiac Support Device in Patients With Dilated Cardiomyopathy
- Long-Term Impact of Disease Management in a Large, Diverse Heart Failure Population
- Effects of Angiotensin Converting Enzyme Inhibition in Patients With Stable Coronary Artery Disease: The Prevention of Events With Angiotensin Converting Enzyme Inhibition (PEACE) Trial: The PEACE Study Investigators
- Randomized, Blinded Trial on Perioperative Metoprolol Versus Placebo for Diabetic Patients Undergoing Non-Cardiac Surgery
- Impact of Glucose-Insulin-Potassium on Mortality and Morbidity in Over 20,000 Patients With Acute Myocardial Infarction: The CREATE-ECLA International Trial
- Impact of Low Molecular Weight Heparin (Reviparin) in Reducing Death and Reinfarction in Patients With Acute Myocardial Infarction and ST Elevation MI
- SHock Inhibition Evaluation with AzimiLiDe (SHIELD): A Randomized Placebo Controlled Trial of Azimilide in Reducing ICD Therapies
- African American Heart Failure Trial: Efficacy of a Fixed Dose Combination of Isosorbide Dinitrate and Hydralazine in Heart Failure
- Metabolic Effects of Carvedilol versus Metoprolol in Patients with Type 2 Diabetes and Hypertension: Results of the GEMINI Trial
- Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness: The ESCAPE Trial
- Syncope Evaluation in the Emergency Department Study (SEEDS)
- Effect of Rimonabant on Weight Reduction and Weight Maintenance: RIO-NORTH AMERICA (RIO-NA) Trial
- Coronary Artery Revascularization Prior to Major Elective Vascular Surgery and Long-Term Outcome: The Coronary Artery Revascularization Prophylaxis (CARP) Trial
- ARBITER 2: A Double-Blind, Placebo-Controlled Study of Long-Acting Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins
- Cost-Effectiveness of ICD Therapy in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
- A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia
- A Randomized, Double-Blind, Placebo-Controlled Trial of Glycoprotein IIb/IIIa Inhibition With Abciximab in Patients with Diabetes Undergoing Percutaneous Coronary Intervention (ISAR-SWEET Trial)
- Rescue Angioplasty Versus Conservative Therapy or Repeat Thrombolysis (REACT) Trial for Failed Reperfusion in AMI –
- Figures & Tables
- Info & Metrics
Clinical Evaluation of the CorCap Cardiac Support Device in Patients With Dilated Cardiomyopathy
Douglas L. Mann, MD, The Michael E. DeBakey Veterans Affairs Medical Center and Baylor College of Medicine, Houston, Texas
Background: Progressive left ventricular (LV) remodeling is part of the unfavorable natural history in patients with heart failure (HF). The CorCap Cardiac Support Device (CSD) is a mesh device that is implanted around the heart to reduce wall stress and the first therapy specifically designed to address LV remodeling. Early clinical studies have shown that the CSD is safe and associated with improvements in LV structure and function and patient symptoms. Design: This multicenter prospective trial enrolled 300 patients with NYHA Class III-IV HF and dilated cardiomyopathy. 193 patients underwent mitral valve repair/replacement (MVR) and were randomized to either MVR alone or MVR plus CSD. 107 patients were randomized to either continued optimal medical therapy alone or with the CSD. Patients were followed to a common closing date 12 months after the last patient was enrolled (median follow up 22 months). Results: The primary endpoint was a clinical composite with patients classified as improved, same or worsened based upon the occurrence of death, a major cardiac procedure indicative of HF progression and a change in NYHA class. Compared to the control group, the CSD group had more patients “improved” (38% vs. 27%) and fewer patients “worsened” (37% vs. 45%), yielding an odds ratio of 1.73 (1.07, 2.79; p = 0.02). The CSD group had fewer major cardiac procedures (e.g. transplant, LVAD) compared to controls (19 vs. 33; p = 0.01), a greater reduction in LV end diastolic (p = 0.009) and systolic volumes (p= 0.017) and a greater improvement in sphericity index (p=0.026). Quality of life (Minnesota Living with HF and SF 36) was significantly improved in the CSD group (p=0.05 and p = 0.015 respectively). Repeat hospitalizations and adverse events were not different between the two groups. Summary: In patients with progressive HF who are symptomatic despite optimal medical therapy, CSD implant reverses the natural history of HF, as indicated by an improvement in LV size and shape, an improved clinical score, fewer major cardiac procedures, and improvements in quality of life. This innovative therapy represents a new and effective approach for patients with enlarged hearts.
Long-Term Impact of Disease Management in a Large, Diverse Heart Failure Population
Autumn D. Galbreath, San Antonio, TX
Background: The goal of disease management (DM) is to improve health outcomes and reduce cost. While early studies suggested DM may be useful in heart failure (HF), its long-term impact in a large, diverse group is unknown. We performed a randomized, controlled trial of telephonic DM in a group of 1069 community-based patients (age 70.9 ± 10.3) with systolic (EF 35 ± 9 %) or echo-confirmed diastolic HF to assess the impact of DM over an 18-month period. Methods: Data were collected at baseline and at 6 month intervals. Survival analysis was performed by Kaplan-Meier method, with subgroup analyses for type of HF, age, gender, and diabetes. Healthcare utilization was defined after extensive record review attempting to account for all inpatient and outpatient visits, medications and diagnostic tests. We obtained data on 92% of the patients, in nearly 53,000 health-related encounters. Total cost per patient was defined by adding estimated costs for the observed encounters, excluding the cost of the DM. Results: Kaplan-Meier analysis showed DM patients had a reduced mortality rate (p=0.037), with DM patients surviving an average of 76 days longer than controls. Subgroup analysis showed DM had beneficial outcomes in systolic HF (HR 0.62, p=0.040) that was more pronounced in NYHA class III and IV. While improvements in NYHA class were more likely with DM (p<0.001), 6 minute walk (6MW) data from 217 patients in whom data were available at each visit showed no significant benefit from DM (p=0.08). Total and CHF-related healthcare utilization, including medications, office or emergency department visits, procedures, or hospitalizations were not decreased by DM. Repeated measures ANOVA for cost by group showed no significant differences, even in the higher NYHA class groups. Conclusions: Participation in DM resulted in a survival benefit, most notably in symptomatic systolic HF patients. Though DM was associated with improved NYHA class, 6MW test results did not improve. Healthcare utilization was not reduced by DM, and it conferred no cost savings. Disease management in HF results in modest improvement in life expectancy, but does not improve objective measures of functional capacity, and does not reduce cost.
Effects of Angiotensin Converting Enzyme Inhibition in Patients With Stable Coronary Artery Disease: The Prevention of Events With Angiotensin Converting Enzyme Inhibition (PEACE) Trial: The PEACE Study Investigators
Writing Group: E. Braunwald, MD*; M.J. Domanski, MD; S.E. Fowler, PhD; N.L. Geller, PhD; B.J. Gersh, MD; J. Hsia, MD; M.A. Pfeffer, M.D., PhD*; M.M. Rice, PhD; Y.D. Rosenberg, MD; J.L. Rouleau, MD. *Co-Chairs
Background: Angiotensin-converting-enzyme (ACE) inhibitors are effective in reducing the risk of heart failure, myocardial infarction (MI), and death from cardiovascular causes in patients with left ventricular systolic dysfunction or heart failure. ACE inhibitors have also been shown to reduce atherosclerotic complications in patients who have vascular disease without heart failure. Methods: PEACE tested the hypothesis that patients with stable coronary artery disease and normal or slightly reduced left ventricular function derive therapeutic benefit from addition of ACE inhibitors to modern conventional therapy. The trial was a double-blind, placebo-controlled study in which 8290 patients were randomly assigned to trandolapril at a target dose of 4 mg per day (4158 patients) or matching placebo (4132 patients). Results: The mean (±SD) age of the patients was 64±8 years, the mean blood pressure 133±17/78±10 mm Hg, and the mean left ventricular ejection fraction 58±9 percent. Patients received intensive treatment, with 72 percent having undergone coronary revascularization and 70 percent receiving lipid-lowering drugs. The incidence of the primary end point – death from cardiovascular causes, MI, or coronary revascularization – was 21.9 percent in the trandolapril group, and 22.5 percent in the placebo group (hazard ratio, 0.96; 95 percent confidence interval, 0.88 to 1.06; P=0.43) over a median follow-up of 4.8 years. Conclusions: In patients with stable coronary heart disease and preserved left ventricular function who are receiving contemporary therapy and in whom the rate of cardiovascular events is lower than in previous trials of ACE inhibitors in patients with vascular disease, there is no evidence that the addition of an ACE inhibitor provides further benefit in terms of death from cardiovascular causes, MI, or coronary revascularization.
Randomized, Blinded Trial on Perioperative Metoprolol Versus Placebo for Diabetic Patients Undergoing Non-Cardiac Surgery
Anne Benedicte Juul, Jørn Wetterslev, Allan Kofoed-Enevoldsen, Torben Callesen, Gorm Jensen, Christian Gluud, and The DIPOM Group, Copenhagen Trial Unit, H:S Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark
Introduction: Trials suggest that perioperative β-blockade reduces cardiac events in patients at risk of myocardial ischemia undergoing non-cardiac surgery. Diabetes confers high risk of cardiac morbidity and mortality. Methods: The DIabetic POstoperative Mortality and Morbidity Trial is an investigator-controlled, centrally randomized, placebo-controlled, blinded multicenter trial. We compared metoprolol 100 mg daily vs placebo on mortality and cardiovascular morbidity in β-blocker naive diabetic patients above 39 years undergoing non-cardiac surgery. Metoprolol was given during hospitalization to a maximum of 7 days beginning the evening before surgery. Primary outcome was the composite of all-cause mortality, acute myocardial infarction, unstable angina, or congestive heart failure. We aimed at 1000 patients (one-year incidence of primary outcome in the placebo arm=30%, minimal relevant difference=10%, power=90%, alfa=5%). Results: 2066 patients were eligible; 921 were randomized, 462 to metoprolol and 459 to placebo. Mean treatment duration was 4.6 vs 4.9 days. Day 1–7, 10–68% vs 5–59% received no intervention (contraindication or discharge), but heart rate (±SD) was significantly lower in the metoprolol group (75±13 vs 84±14, P<0.001). Median follow up was 18 months (range, 6 to 30). Primary outcome incidence was 99/462 (21%) in the metoprolol vs 93/459 (20%) in the placebo group (logrank test, P=0.66). Multivariate Cox regression intention-to-treat analysis showed hazard ratio 1.10 (95% CI 0.82 to 1.46, P=0.53) adjusting for age, gender, history of coronary heart disease, and malignant disease. The incidence of all-cause mortality was 74/462 (16%) vs 72/459 (16%) (logrank test, P=0.88). Per protocol analyses (n=733) and analyses of secondary outcomes showed similar results. Proportion of serious adverse events incidence was 7.1% in the metoprolol vs 5.2% in the placebo group (χ2-test, P>0.2). Conclusion: Short-term perioperative metoprolol did not significantly affect mortality and cardiac morbidity or adverse events in diabetic patients undergoing non-cardiac surgery, but 95% CIs were wide. The dose, duration, drug, and intervention group need reconsideration. Larger, blinded, placebo-controlled trials are warranted.
Impact of Glucose-Insulin-Potassium on Mortality and Morbidity in Over 20,000 Patients With Acute Myocardial Infarction: The CREATE-ECLA International Trial
Shamir R. Mehta, MD, Associate Professor of Medicine McMaster University and Hamilton Health Sciences Hamilton, Canada, on behalf of the CREATE-ECLA Investigators
Purpose: Cardiovascular disease is the leading cause of death globally with 80% of acute myocardial infarctions (AMI) occurring in developing countries. Yet, few low cost interventions have been evaluated that are globally applicable. Glucose-insulin-potassium (GIK) is a promising therapy, proposed in the 1950’s and improves myocardial energetics, and ventricular function; and decreases free fatty acids, and serious ventricular arrhythmias in AMI. Several small trials have been promising, but none have been conclusive. A meta-analysis of 16 trials on a total of 4,994 patients indicates an 18% reduction in mortality, but with wide confidence intervals (0.68 to 0.98; p=0.03). Given the global importance of GIK, these results need confirmation. Design: Randomized controlled, multicentre, international trial, utilizing a partial 2x2 factorial design (in which low molecular weight heparin is also evaluated). Sample Size: > 20,000 GIK/control patients Population Studied: Over 20,000 patients with ST segment elevation myocardial infarction (STEMI) presenting within 12 hours from 518 centers in 21 regions, (India, China, South America, Pakistan, North America, Europe, and the Middle East) with mean age of 58.6 years and 77.8% males. The trial was organized and coordinated at McMaster University and Hamilton Health Sciences, Hamilton, Canada. Interventions(s): Patients were randomized to receive glucose-insulin-potassium (GIK) intravenous infusion for 24 hours or usual care. Power Calculations: 20,000 GIK/control patients will yield an expected power of over 95% to detect a 15% relative risk reduction, assuming a 10% cumulative event rate of mortality at 30 days in the control group. Outcome: The primary outcome is 30 day all-cause mortality. Secondary outcomes include non-fatal cardiac arrest, cardiogenic shock and re-infarction at 7 and 30 days. Results: Overall, 20,201 patients were randomized: 10,107 to Control and 10,088 to GIK. Evidence based therapies were used in a very high proportion of patients. Mortality from any cause occurred in 9.7% of control patients and 10.0% of GIK patients (HR 1.03, 95% CI 0.95–1.13, P=0.45. The rates of cardiac arrest were 1.5% control and 1.4% GIK (P=ns), cardiogenic shock 6.3% and 6.6% (P=ns) and reinfarction 2.4% and 2.3% (p=ns). However, we find a significant reduction in recurrent ischemia at 7 days (6.5% vs 4.6%, HR 0.85, P=0.004), which was sustained at 30 days (P=0.036). The pre-specified subgroup analyses were consistent with the overall result on mortality, including diabetics, those presenting with heart failure and those receiving thrombolytic therapy or primary PCI. In an exploratory subgroup of those patients receiving primary PCI or tPA, there was a significant reduction in mortality, however this should be interpreted with caution as it was not a pre-specified analysis. Conclusions: In this large, international randomized trial, high dose GIK infusion had no impact on mortality, cardiac arrest or cardiogenic shock in patients with acute STEMI. Sponsors: There are no sponsors for this trial.
Impact of Low Molecular Weight Heparin (Reviparin) in Reducing Death and Reinfarction in Patients With Acute Myocardial Infarction and ST Elevation MI
CREATE Investigators, McMaster University, Hamilton, Canada
Background: Despite extensive investigation, no antithrombotic or newer anti-platelet drug has been shown to reduce mortality in AMI when given to patients receiving reperfusion therapy or aspirin. We therefore evaluated the effects of reviparin, a low molecular weight heparin given for 7 days in addition to usual therapy on the primary outcome of death, reinfarction, or strokes at 7 and 30 days. Methods: 15,570 patients with ST segment elevation or new bundle branch block, presenting within 12 hours of symptom onset were randomized to receiving reviparin (based on their weight) or placebo subcutaneously twice daily for 7 days. Results: The primary composite outcome (death, myocardial infarction and strokes) was significantly reduced from 10.9% in the placebo group to 9.6% in the Reviparin group (hazard ratio of 0.87, 95% confidence intervals of 0.79 to 0.96; p=0.006). These benefits persisted at 30 days [1056 (13.6%) versus 921 (11.8%); p=0.001] with significant reductions in mortality [877 (11.3%) versus 766 (9.8%), hazard ratio of 0.87, 95% CI of 0.79 to 0.86; p=0.005] and reinfarction [199 (2.6%) versus 154 (2.0%), hazard ratio of 0.77, 95% CI of 0.62 to 0.95, p=0.014), with no significant differences in strokes (80 versus 64; p=0.193). There was a significant increase in life-threatening bleeds not included in the primary outcome (17 (0.2%) versus 7 (0.1%), p=0.07), but the absolute excess is small (2 per 1000) compared to the reductions in the primary outcome (17 per 1000) or mortality (15 per 1000), indicating that the benefits clearly outweigh the risks. Reviparin treatment was significantly better when treatment was initiated very early after symptom onset [0.2 hrs: hazard ratio of 0.70, >2 to 4 hrs: hazard ratio of 0.81 (p=0.032), >4 to 8 hrs: hazard ratio of 0.85 (p=0.047), >8 hrs: hazard ratio of 1.06; P for trend=0.041] Conclusions: Reviparin significantly reduces mortality and reinfarction, without an increase in overall stroke rates. There is a small absolute excess of life-threatening bleeds, but the benefits clearly outweigh the risks, especially in those treated within 8 hrs of symptom onset.
SHock Inhibition Evaluation with AzimiLiDe (SHIELD): A Randomized Placebo Controlled Trial of Azimilide in Reducing ICD Therapies
P. Dorian*, S. Hohnloser, H.R. Al-Khalidi, J.M. Brum, M. Borggrefe, D.S. Tatla, J. Brachmann, R. Myerburg, D. Cannom, M. Vanderlaan, M.J. Holroyde, C.M. Pratt, on Behalf of the SHIELD Investigators. *St Michael’s Hospital, Toronto, Canada.
Background: Although implanted cardioverter defibrillators (ICDs) effectively treat sustained ventricular tachyarrhythmias, up to 50% of ICD recipients eventually require concomitant antiarrhythmic drug therapy to prevent symptomatic arrhythmia recurrences and hence reduce the number of device therapies. Methods and Results: A total of 633 ICD recipients were enrolled in a randomized, double-blind, placebo-controlled study to evaluate the effect of daily doses of 75 mg or 125 mg of azimilide on recurrent symptomatic ventricular tachyarrhythmias and ICD therapies. Total all-cause shocks plus symptomatic ventricular tachycardia (VT) terminated by antitachycardia pacing (ATP) were significantly reduced by azimilide, with relative risk reductions of 57% (HR=0.43, 95% CI [0.26 to 0.69], p=0.0006) and 47% (HR=0.53 to 95% CI [0.34 to 0.83], p=0.0053) at 75 mg and 125 mg doses, respectively. The reductions in all-cause shocks on both doses of azimilide did not achieve statistical significance. The incidence of all appropriate ICD therapies (shocks or ATP terminated VT) was reduced significantly among patients on 75 mg azimilide (HR=0.52, 95% CI [0.30 to 0.89], p=0.01698) and on 125 mg azimilide (HR=0.38, 95% CI [0.22 to 0.65], p=0.0004). Five patients in the azimilide groups and 1 patient in the placebo group had torsade de pointes; all were successfully treated by the device. One patient on 75 mg azimilide had severe, but reversible neutropenia. Conclusion: Azimilide significantly reduced the recurrence of VT or ventricular fibrillation (VF) terminated by shocks or ATP in ICD patients, thereby reducing the burden of symptomatic ventricular tachyarrhythmia.
African American Heart Failure Trial: Efficacy of a Fixed Dose Combination of Isosorbide Dinitrate and Hydralazine in Heart Failure
A.L. Taylor, S. Ziesche, C. Yancy, P. Carson, R. D’Agostino, K. Ferdinand, M. Taylor, K. Adams, M. Sabolinski, M. Worcel, J. Cohn, and the A-HeFT Investigators
Background: The African-American Heart Failure trial explores the hypothesis that nitric oxide enhancing (NOE) therapy with a fixed-dose combination of isosorbide dinitrate and hydralazine (ISDN/HYD) may provide additional benefit in advanced heart failure in African-Americans, a subgroup previously noted to have a favorable response to this therapy and in whom data shows less robust nitric oxide bioavailability. Methods: 1,050 African-American patients with NYHA Class III-IV heart failure with dilated ventricles were randomized to receive a fixed-dose combination of ISDN/HYD or placebo added to standard background heart failure therapy including neurohormonal blockade. The primary endpoint was a composite score weighting all cause mortality, first heart failure hospitalization and change in quality of life (QoL). Results: The study was terminated prematurely due to significantly higher mortality in the placebo group than in the ISDN/HYD group, (10.2% versus 6.2%, p=0.02) over a mean drug exposure of 10 months. The mean primary composite score, as well as all of its individual components were significantly improved when ISDN/HYD was compared to placebo: composite score, -0.1±1.9 versus -0.5±2.0, p=0.01; all cause mortality was reduced by 43%, Hazard Ratio,0.57, p=0.01, first hospitalization for heart failure was reduced by 33%, (16.4% versus 22.4%, p=0.001), and Quality of Life was improved, -5.6±20.6 versus -2.7±21.2, p=0.02, with lower QoL scores indicating better QoL. Conclusion: The African American Heart Failure trial has demonstrated the efficacy and survival advantage of a fixed-dose combination of ISDN/HYD added to standard background heart failure therapy including neurohormonal blockade in African American patients with advanced heart failure. These results confirm the benefit of nitric oxide enhancing (NOE) medication in the treatment of heart failure in African Americans.
Metabolic Effects of Carvedilol versus Metoprolol in Patients with Type 2 Diabetes and Hypertension: Results of the GEMINI Trial
George L. Bakris, MD, Rush University Medical Center, Chicago; Vivian Fonseca, MD, Tulane University, New Orleans; Richard E. Katholi, MD, St. John’s Hospital, Springfield; Janet B. McGill, MD, Washington University School of Medicine, St. Louis; Franz Messerli, MD, St. Luke’s-Roosevelt, New York; Robert A. Phillips, MD, Ph.D, Lenox Hill Hospital/New York University, New York; Philip Raskin, MD, University of Texas, Dallas; Jackson T. Wright, Jr., MD, Ph.D, Case Western Reserve University, Cleveland; Rosemary Oakes, MS, GlaxoSmithKline, Philadelphia; Mary Ann Lukas, MD, GlaxoSmithKline, Philadelphia; Karen M. Anderson, PhD, GlaxoSmithKline, Philadelphia; David S.H. Bell, MD, University of Alabama, Birmingham for the GEMINI Investigators
Background: β-blockers (β-Bs) decrease cardiovascular risk while worsening metabolic control in patients (pts) with hypertension (HTN) and Type 2 diabetes (DM). GEMINI (Glycemic Effects in Diabetes Mellitus: Carvedilol-Metoprolol Comparison in Hypertensives) is a randomized, double-blind trial that compared the effects of β-Bs with different pharmacological profiles on glycemic and metabolic control in pts with DM and HTN receiving renin-angiotensin system (RAS) blockade. We tested the hypothesis that carvedilol (C), known to improve insulin sensitivity, is superior to metoprolol tartrate (M) in maintaining glycemic control in the presence of RAS blockers. Methods: 1235 pts, age 30–80 years with DM (HbA1c >6.5<8.5%) and HTN (>130/80mmHg) receiving RAS blockers were randomized to C 6.25–25 mg (n=498) or M 50–200 mg (n=737), each given twice daily and followed for up to 35 weeks. Hydrochlorothiazide 12.5 mg and a dihydropyridine calcium antagonist were added, if needed, to achieve blood pressure (BP) target. The primary endpoint was the difference between groups in mean change from baseline HbA1c after 5 months of maintenance therapy. Also assessed were change from baseline HbA1cby treatment, treatment effect on BP, insulin sensitivity (Homeostatic model assessment [HOMA-IR]) and microalbuminuria (MAU). Results: C and M differed significantly in mean change in HbA1c from baseline (0.13% ± 0.05, 95%CI -0.22, -0.04, p=0.004). HbA1c increased with M (0.15% ± 0.04%; p<0.001) but not C (0.02% ± 0.04%; p=0.65). HbA1c increases of >1% were seen in 14.2% of M vs. 7% of C pts; odds ratio (OR) 0.46, 95%CI (0.30, 0.70); p<0.001). HOMA-IR improved with C (-9.1%; p=0.004) but not M (-2.0%; p=0.48); the treatment difference was -7.2%, 95%CI (-13.8,-0.2), p=0.04. More pts withdrew for worsening glycemic control from M (2.2%) vs. C (0.6%), p=0.04. Achieved BP was similar between groups. Mean doses needed to achieve target BP were 17.5 mg bid for C and 128 mg bid for M. MAU development was less frequent with C (6.4% , C vs. 10.3% , M; OR 0.60, 95%CI (0.36, 0.97); p=0.04). Conclusion: Carvedilol in the presence of RAS blockade has a neutral effect on glycemic control and improves components of the metabolic syndrome in contrast to metoprolol, in people with DM and HTN.
Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness: The ESCAPE Trial
Monica R. Shah, MD, MHS, MSJ, Columbia University Medical Center, New York, NY; The ESCAPE Investigators and ESCAPE Study Coordinators
Background: Recent studies have raised concern that use of indwelling pulmonary artery catheters (PAC) may lead to increased mortality in hospitalized patients. ESCAPE, a multicenter randomized controlled trial sponsored by NHLBI, tested whether PAC use would improve clinical outcomes in patients hospitalized with recurrent heart failure. Methods: Patients were randomly assigned to therapy guided by clinical assessment and PAC or clinical assessment alone (CLIN). The target in both arms was resolution of clinical congestion, with PAC targets of pulmonary capillary wedge (PCW) pressure <15 and right atrial pressure <8 mm Hg. The protocol did not specify medications, but inotropes were discouraged. The primary endpoint was days neither dead nor hospitalized during 6 mos, with secondary endpoints of time to death or rehospitalization, exercise, quality of life, and echocardiographic changes. Results: A total of 433 patients from 26 sites were enrolled. The average age was 56, with 74% male, 40% minority, and LVEF 20%. Severity of illness was reflected by average SBP 105.6, Na 137, BUN 35, and Cr 1.5 mg/dL, and was more evident in the concurrent PAC registry. Use of PAC did not significantly affect the primary endpoint (HR 1.00; CI, 0.83–1.21), time to death, death plus hospitalization, or days hospitalized. PAC-associated complications occurred in 9 PAC patients vs 1 CLIN (4.2% vs 0.5%, p=0.01), with no PAC-related deaths. Exercise and quality of life endpoints improved in both groups with a trend for greater improvement with PAC, which reached significance for time trade-off at all timepoints after randomization. Conclusions: Use of PAC to lower PCW without a specified treatment regimen did not impact mortality and hospitalization in the randomized ESCAPE population, a result consistent with previous randomized PAC trials in heart failure. If therapy to lower filling pressures can enhance the value of life perceived by patients, future trials should test noninvasive measurements and specific treatment strategies that could be used to better tailor therapy without PAC.
Syncope Evaluation in the Emergency Department Study (SEEDS)
Win K. Shen, Wyatt W. Decker, Peter A. Smars, Deepi G. Goyal, Ann E. Walker, David O. Hodge, Jane M. Trusty, Karen M. Brekke, Arshad Jahangir, Peter A. Brady, Thomas M. Munger, Bernard J. Gersh, Stephen C. Hammill, Robert L. Frye, Mayo Clinic, Rochester, MN
Purpose: The primary aim and central hypothesis of the study are that a designated syncope unit in the emergency department (ED) improves diagnostic yield and reduces hospital admission for patients with syncope who are at intermediate risk for an adverse cardiovascular outcome. Methods: In this prospective, randomized, single-center study, patients were randomly allocated to 2 treatment arms: syncope unit evaluation and standard care (controls). All patients met the American College of Emergency Physicians policy statement for consideration of hospital admission. The primary end points of the study were 1) diagnostic yield and 2) hospital admission rate at the time of ED dismissal. The syncope unit included continuous rhythm monitoring up to 6 hours, hourly orthostatic BP examination, availability of tilt table testing, carotid sinus massage with continuous BP and HR monitoring, echocardiogram, and electrophysiology consultation. In the controls, patients were evaluated for syncope according to routine care in the ED. The 2 groups were compared with χ2 test for independence of categorical variables. Wilcoxon rank sum test was used for continuous variables. Survival was estimated with the Kaplan-Meier method. Results: One hundred three consecutive patients (53 women; mean age, 64±17 years) entered the study. Fifty-one patients were randomized to the syncope unit. For the syncope unit and standard care patients, the presumptive diagnosis was established in 34 (67%) and 5 (10%) patients (P<0.001), respectively, hospital admission was required for 22 (43%) and 51 (98%) patients (P<0.001), and total patient-hospital days was reduced from 140 to 64. Actuarial survival was 97% and 90% (P=0.30) and survival free from recurrent syncope was 88% and 89% (P=0.72) at 2 years for the syncope unit and standard care groups, respectively. Conclusions: The novel syncope unit designed for this study significantly improved diagnostic yield in the emergency department and reduced hospital admission and total length of hospital stay without affecting recurrent syncope and all-cause mortality among intermediate-risk patients. Observations from our study provide benchmark data for improving patient care and effectively utilizing health care resources.
Effect of Rimonabant on Weight Reduction and Weight Maintenance: RIO-NORTH AMERICA (RIO-NA) Trial
F. Xavier Pi-Sunyer, St Luke’s/Roosevelt Hospital Center—Columbia University, New York, NY
Background: Rimonabant is the first selective cannabinoid type 1 (CB1) blocker developed to manage cardiovascular risk factors such as obesity and smoking. Phase II studies established the efficacy of this compound in obesity and smoking cessation. A large program of phase III trials conducted in over 6600 overweight/obese subjects has been set up. Two recently completed clinical trials in overweight or obese subjects with untreated dyslipidemia (rio-lipids) or with or without comorbidities (RIO-Europe) showed significant weight loss with positive effects on lipid and glycemic profiles together with a favorable safety profile suggesting that rimonabant may become an important tool in the management of cardiovascular risk factors. Methods: RIO-NA is a multicenter, randomized, double-blind, placebo-controlled, parallel-group, fixed dose study conducted in Canada and USA over a 2-year period to assess the effect of rimonabant on weight reduction and weight maintenance. Subjects with BMI≥ 30 kg/m2 or BMI>27 kg/m2 with comorbidities were treated for 1 year with either rimonabant 5 mg, rimonabant 20 mg, or placebo using a randomization ratio of 2:2:1. After 1 year of treatment, subjects on rimonabant were re-randomized to receive either the same dose of rimonabant or placebo using a randomization ratio of 1:1. Primary efficacy endpoints were weight loss, weight maintenance at 1 year and, and prevention of weight regain between the 1st and 2nd years. Secondary endpoints include lipid concentration, fasting glucose/insulin homeostasis. Safety was evaluated throughout the study. Results: 3040 patients were studied: 80.7% women and 19.3% men, with mean (SD), age 45.0 (11.6) years, BMI 37.6 (6.5) kg/m2, weight 104.4 (21.3) kg, waist circumference 105.8 (15.3) cm. The results on body weight, waist circumference and metabolic profile parameters (HDL-cholesterol, triglyceride and insulin sensitivity) were consistent with the previously reported trials. The efficacy and good safety profile with rimonabant at 20mg was maintained throughout the two year’s treatment. Information is provided for medical and scientific purpose only, rimonabant is not yet licensed.
Coronary Artery Revascularization Prior to Major Elective Vascular Surgery and Long-Term Outcome: The Coronary Artery Revascularization Prophylaxis (CARP) Trial
Edward O. McFalls, Herbert B. Ward, VA Med Ctr/Univ of Minnesota, Minneapolis, MN; Thomas Edward Moritz, VA Med Ctr, Chicago, IL; Steven Goldman, VA Med Ctr, Tuczon, AZ; William C. Krupski, VA Med Ctr/Univ of Colorado, Denver, CO; Fred Littooy, VA VA Med Ctr/Univof Loyola, Chicago, IL; Gordon Pierpont, Steven Santilli, VA Med Ctr/Univ of Minnesota, Minneapolis, MN; Joseph Rapp, VA Med Ctr, San Francisco, CA; Brack Hattler, VA Med Ctr, Denver, CO; Kendrick Shrunk, VA Medical Center, San Francisco, CA; Connie Jaenicke, VA Med Ctr/Univ of Minnesota, Minneapolis, MN; Lizy Thotapurathu, Nancy Ellis, Dominic J. Reda, William G. Henderson, VA Med Ctr, Chicago, IL
Aim: The objective was to determine whether coronary artery revascularization prior to elective vascular surgery improves outcome. Design: This multicenter randomized controlled trial involved 18 Veterans Affairs Medical Centers and was funded by the Cooperative Studies Program. The primary end-point was long-term survival and analysis was done by an intention to treat. Results: Over 4 years, 5859 patients were screened prior to vascular surgery and 510 (9%) were enrolled and randomized to either coronary artery revascularization or no revascularization prior to surgery. The surgical indications were an abdominal aortic aneurysm in 33% or lower extremity arterial occlusive disease in 67%. Seventy-four percent of the study patients were at increased cardiac risk by either the Eagle’ criteria, the Revised Cardiac Risk Index or a high-risk stress imaging test. Among the patients undergoing preoperative coronary artery revascularization, percutaneous coronary intervention was performed in 59% and bypass surgery was performed in 41%. Procedural related deaths following coronary artery revascularization occurred in 1.7% of the patients, and there were no complications related to stroke, loss of limb, or dialysis. The median time from randomization to vascular surgery was 54 days in the coronary revascularization group and 18 days in the no revascularization group (P<0.001). At a median time of 2.7 years following randomization, mortality in the revascularization group was 22% and in the no revascularization group was 23% (P=0.92; with relative risk of 0.98, and a 95% confidence interval of 0.70 to 1.37). Within 30-days following vascular surgery, mortality was 3.1% in the coronary revascularization group and 3.4% in the no revascularization group (P=0.87). A myocardial infarction, defined by any elevation in troponins following vascular surgery, occurred in 11.6% of the revascularization group and 14.3% of the no revascularization group (p=0.37). Conclusions: Among patients undergoing elective vascular surgery, preoperative coronary artery revascularization does not alter outcome. Based on these data, coronary artery revascularization prior to elective vascular surgery among patients with stable ischemic heart disease is not supported.
ARBITER 2: A Double-Blind, Placebo-Controlled Study of Long-Acting Niacin on Atherosclerosis Progression in Secondary Prevention Patients Treated With Statins
Allen J. Taylor, Walter Reed Army Medical Ctr, Washington, DC, United States
Background: Niacin reduces coronary heart disease morbidity and mortality when taken either alone or in combination with statins. However, the incremental impact of adding niacin to background statin therapy is unknown. Methods: Double-blind, randomized, placebo controlled study of once-daily extended-release niacin (1000 mg) added to background statin therapy in 167 patients (mean age 67 years) with known coronary heart disease and low levels of HDL-C (<45 mg/dL). The primary endpoint was the change in common carotid intima-media thickness (CIMT) after 1 year. Results: Baseline CIMT (0.884 ± 0.234 mm), LDL-C (89 ± 20 mg/dL) and HDL-C (40 ± 7 mg/dL) were comparable in the placebo and niacin groups. Adherence to niacin exceeded 90% and 149 pts (89.2%) completed the study. HDL-C increased 21% (39 to 47 mg/dL) in the niacin group. After 12 months, mean CIMT increased significantly in the placebo group (+ 0.044 ± 0.100 mm; P<.001), and was unchanged in the niacin group (+0.014 ± 0.104 mm; P = .23). Although the overall difference in IMT progression between the niacin and placebo groups was not statistically significant (P = .08), niacin significantly reduced the rate of IMT progression in subjects without insulin resistance (P = .026). Clinical cardiovascular events occurred in 3 pts treated with niacin (3.8%) and 7 pts treated with placebo (9.6%; P = .20). Conclusions: The addition of extended-release niacin to statin therapy slowed progression of atherosclerosis among individuals with known CHD and moderately-low HDL-C.
Cost-Effectiveness of ICD Therapy in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
Daniel B. Mark, Charlotte L. Nelson, Kevin J. Anstrom, Sana M. Al-Khatib, Anastasios A. Tsiatis, Jeanne Poole, George Johnson, Jill Anderson, Patricia A. Cowper, Nancy E. Clapp-Channing, Linda Davidson-Ray, Kerry L. Lee, Gust H. Bardy for the SCD-HeFT Investigators
The SCD-HeFT RCT reported a 23% reduction in all cause mortality with single-lead, shock-only ICD therapy (Rx) versus state-of-the-art medical therapy alone and no mortality benefit for amiodarone therapy. We evaluated the costs of amiodarone and ICD Rx and cost effectiveness of ICD Rx for primary prevention of SCD in NYHA class II and III stable heart failure using the empirical data collected in SCD-HeFT (median follow-up 46 mos). Costs out to 5 yrs for US patients were assessed empirically using medical billing information and charge to cost corrections (>95% complete) for hospitalizations, resource use data from the case report form, and the Medicare Fee Schedule for outpatient and physician costs. Protocol ICDs were priced at $17,500 (including lead) with outpatient implantation. Amiodarone was priced using 90% of the Red Book AWP. Cost data were modeled using the empirical cost database, adding in the need for late generator replacements with ICD Rx (base case generator life was 5 yrs), as well as late ICD complications and equipment modifications. The empiric SCD-HeFT data were also used in an age-based Cox model to calculate a life expectancy for each study patient. Cost effectiveness of ICD Rx was calculated as incremental life expectancy divided by incremental lifetime costs. Costs from 0–3 mos were amiodarone $3829, placebo $2568, and ICD $24,366. Five-Yr cumulative costs were amiodarone $49,443; placebo $43,078; and ICD $61,968. Lifetime costs were placebo $90,759 and ICD $159,147 (undiscounted). Life expectancies were placebo 8.41 yrs, ICD 10.87 yrs (undiscounted). Discounting at 3%, the CE ratio for ICD Rx was $33,192 per life-year added. Results were robust over a wide range of sensitivity analyses. For subgroups, CE ratios were $33,603 for ischemics and $32,170 for non-ischemics, $25,517 for NYHA class II assuming NYHA class by ICD interaction. Without the interaction, CE ratio was $34,714 for NYHA class II and $44,809 for NYHA class III. In conclusion, in stable NYHA class II and III heart failure with EF<35%, amiodarone is no more effective than placebo but is more expensive. ICD therapy is both more effective and more expensive but represents an economically attractive way to increase societal health benefits.
A Comparison of Lipid and Glycemic Effects of Pioglitazone and Rosiglitazone in Patients With Type 2 Diabetes and Dyslipidemia
Ronald B. Goldberg, MD, PhD, Division of Endocrinology, Metabolism and Diabetes, University of Miami School of Medicine, Miami, Fla; David M. Kendall, MD, International Diabetes Center, Park Nicollet Institute, Minneapolis, Minn; Mark A. Deeg, MD, PhD, Division of Endocrinology and Metabolism, Department of Veterans Affairs and the Indiana University School of Medicine, Indianapolis, Indiana; John B. Buse, MD, PhD, Divisions of Endocrinology and of General Medicine, University of North Carolina School of Medicine, Chapel Hill, NC; Anthony J. Zagar, MS; Jane A. Pinaire, PhD; Meng H. Tan, MD, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind; Mehmood A. Khan, MD, Takeda Pharmaceuticals North America, Lincolnshire, Ill; Alfonso T. Perez, MD, Takeda Global Research and Development Center, Lincolnshire, Ill; and Scott J. Jacober, DO, Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Ind
Introduction: Diabetic dyslipidemia (low HDL-C, high triglycerides [TGs] and predominance of small dense LDL) is a common cardiovascular risk factor in patients with type 2 diabetes (T2D). The thiazolidinediones, pioglitazone (PIO) and rosiglitazone (ROSI), have both glucose-lowering and lipid-altering effects. Prior reports have suggested that these agents may have different effects on lipid parameters. Methods: PIO and ROSI were compared in a randomized, double-blind, multicenter trial in patients with T2D (WHO criteria) and dyslipidemia (fasting TG levels ≥150 and <600 mg/dL; fasting LDL-C levels ≤130 mg/dL). Subjects discontinued any prior T2D monotherapy and were randomized (PIO, n = 400; ROSI, n = 402) to receive placebo washout for 4 weeks followed by 24 weeks of either PIO or ROSI monotherapy. At 12 weeks, PIO (30 mg qd) and ROSI (4 mg qd) were titrated to the maximally effective doses of 45 mg qd and 4 mg bid, respectively. Patients received no other lipid-lowering therapies prior to or during the study. Results: There were no clinically significant baseline differences between treatments. The mean change in HbA1c from baseline to week 24 was similar for PIO and ROSI (-0.7 ± 0.1 vs. -0.6 ± 0.1%). Conclusions: This study demonstrates that PIO and ROSI exert different effects on plasma lipids. PIO is associated with significant improvements versus ROSI in TG, HDL-C, non-HDL-C, and LDL particle concentration and size, despite similar effects on glycemic control. Whether these differences on lipid measures translate into differences for the future risk of CVD has not been determined ⇓
A Randomized, Double-Blind, Placebo-Controlled Trial of Glycoprotein IIb/IIIa Inhibition With Abciximab in Patients with Diabetes Undergoing Percutaneous Coronary Intervention (ISAR-SWEET Trial)
Julinda Mehilli, Adnan Kastrati, Albert Schömig, MD, Deutsches Herzzentrum, Technische Universität, Munich, Germany
Background: Diabetic patients are at increased risk of adverse outcomes after percutaneous coronary interventions. Although subset analyses suggest particular benefit from the administration of abciximab in diabetic patients, no dedicated large randomized trials have been performed in diabetic patients undergoing percutaneous coronary intervention, and certainly not after pretreatment with a high loading dose of clopidogrel. Methods and Results: This study enrolled 701 diabetic patients with coronary artery disease who underwent an elective percutaneous coronary intervention after pretreatment with a 600 mg dose of clopidogrel >2 hours prior to the procedure: 351 patients were randomly assigned to abciximab and 350 patients to placebo. The primary endpoint of the trial was the composite incidence of death and myocardial infarction at 1 year. The frequency of angiographic restenosis (diameter stenosis ≥50%) was the secondary endpoint. The incidence of death or myocardial infarction was 8.3% in the abciximab group and 8.6% in the placebo group (P=0.91), relative risk of 0.97 [95% confidence interval, 0.58–1.62]. The incidence of angiographic restenosis was 28.9% in the abciximab group and 37.8% in the placebo group (P=0.01), relative risk of 0.76 [0.62–0.94]. The incidence of target lesion revascularization was 23.2% in the abciximab group and 30.4% in the placebo group (P=0.03). Conclusions: The findings of this study do not support a significant impact of abciximab on the risk of death and myocardial infarction in diabetic patients undergoing percutaneous coronary interventions after pretreatment with a 600 mg loading dose of clopidogrel at least 2 hours before the procedure. The present findings show, however, that abciximab reduces the risk of restenosis in diabetic patients receiving coronary bare metal stents.
Rescue Angioplasty Versus Conservative Therapy or Repeat Thrombolysis (REACT) Trial for Failed Reperfusion in AMI –
A.H.Gershlick, R. Wilcox, Sarah Hughes, Suzanne Stevens, Amanda Stephens–Lloyd, K Abrams, for the REACT Investigators
Up to 40% of patients suffering acute myocardial infarction fail to adequately reperfuse (achieve TIMI Grade 3 patency) following thrombolysis. Subsequent treatment options (percutaneous coronary intervention (RPCI), heparin (Conservative), or repeat thrombolysis (R-Lysis)) are currently non-evidence-based. The REACT trial is a UK-based randomised comparison of rescue angioplasty, repeat lysis (fibrin-specific) or conservative therapy in patients with failed thrombolysis. It examines safety and clinical outcomes to one year in 427 patients recruited till March 2004 at 35 UK hospitals. Patients receiving standard treatment ((any) lysis and aspirin) within 6 hours of onset of pain with <50% resolution of ST changes on ECG at 90 minutes were included. Exclusion criteria included age >85 yrs, cardiogenic shock, hypertension and low body weight. Primary endpoint is composite MACE (death/re-infarction/severe heart failure/CVA) at 6 months. Demographics: male 79.2%: mean age 61.1 (11) years: 42.5% anterior MI at presentation, 55% inferior. 48% current smokers, 14.1% diabetics, 37.5% hypertensive. Streptokinase was first lytic in 60%. The median time from pain-first lytic was 140 mins (2.3 hrs), with a door-needle time of 27 mins. Randomised (fibrin-specific) R-lysis was administered median 330 mins (5.5 hrs) after onset of pain, and RPCI 414 mins (6.9 hrs) (time difference 84 mins (1.4 hrs). Results: 30 day data (time to first primary endpoint) shows improved event-free survival with RPCI: survival rates: RPCI 88.9% versus R-Lysis 77.4%; versus Conservative 75.2% (p=0.009). RPCI versus Conservative HR= 0.42 (95% CI 0.23–0.76)(p=0.004) and versus R-Lysis HR = 0.46 (95% CI 0.25–0.84 (p=0.012). Benefit was seen in all components of the end-point. At 6 months; survival rates: RPCI 84.6% versus R-Lysis 68.7%; versus Conservative 70.1% (p=0.004). RPCI versus Conservative HR= 0.47 (95% CI 0.28- 0.79)(p=0.004) and versus R-Lysis HR = 0.45 (95% CI 0.27–0.75 (p=0.002). Conclusion: REACT demonstrates for the first time that following failed lysis, RPCI provides best clinical outcome.
- Clinical Evaluation of the CorCap Cardiac Support Device in Patients With Dilated Cardiomyopathy
- Long-Term Impact of Disease Management in a Large, Diverse Heart Failure Population
- Syncope Evaluation in the Emergency Department Study (SEEDS)
- Effect of Rimonabant on Weight Reduction and Weight Maintenance: RIO-NORTH AMERICA (RIO-NA) Trial
- Cost-Effectiveness of ICD Therapy in the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT)
- Figures & Tables
- Info & Metrics