Effect of fish oil on ventricular tachyarrhythmia and death in patients with implantable cardioverter defibrillators: the Study on Omega-3 Fatty Acids and Ventricular Arrhythmia (SOFA) randomized trial

Context  Very-long-chain n-3 polyunsaturated fatty acids (omega-3 PUFAs) from fish are thought to reduce risk of sudden death, possibly by reducing susceptibility to cardiac arrhythmia. Objective  To study the effect of supplemental fish oil vs placebo on ventricular tachyarrhythmia or death. Design, Setting, and Patients  The Study on Omega-3 Fatty acids and ventricular Arrhythmia (SOFA) was a randomized, parallel, placebo-controlled, double-blind trial conducted at 26 cardiology clinics across Europe. A total of 546 patients with implantable cardioverter-defibrillators (ICDs) and prior documented malignant ventricular tachycardia (VT) or ventricular fibrillation (VF) were enrolled between October 2001 and August 2004. Patients were randomly assigned to receive 2 g/d of fish oil (n = 273) or placebo (n = 273) for a median period of 356 days (range, 14-379 days). Main Outcome Measure  Appropriate ICD intervention for VT or VF, or all-cause death. Results  The primary end point occurred in 81 (30%) patients taking fish oil vs 90 (33%) patients taking placebo (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.64-1.16; P = .33). In prespecified subgroup analyses, the HR was 0.91 (95% CI, 0.66-1.26) for fish oil vs placebo in the 411 patients who had experienced VT in the year before the study, and 0.76 (95% CI, 0.52-1.11) for 332 patients with prior myocardial infarctions. Conclusion  Our findings do not indicate evidence of a strong protective effect of intake of omega-3 PUFAs from fish oil against ventricular arrhythmia in patients with ICDs. Trial Registration  clinicaltrials.gov Identifier: NCT00110838      

Implantable defibrillators for the prevention of mortality in patients with nonischemic cardiomyopathy: a meta-analysis of randomized controlled trials

Context  Implantable cardioverter defibrillator (ICD) therapy is effective in primary and secondary prevention of sudden cardiac death among patients with prior myocardial infarction and depressed ejection fraction. However, conclusive evidence of survival benefit in patients with nonischemic cardiomyopathy (NICM) is still lacking. Objective  To determine whether ICD therapy reduces all-cause mortality in patients with NICM. Data Sources  MEDLINE (1966-2004), EMBASE (1991-2004), the Cochrane Central Register of Controlled Trials (through first quarter, 2004), reports presented at scientific meetings (2003-2004), and bibliographic review of secondary sources. Search terms included defibrillator, randomized controlled trials, clinical trials, andsudden death. Study Selection  Eligible studies were prospective randomized controlled trials of ICD or combined cardiac resynchronization therapy and defibrillator (CRT-D) vs medical therapy enrolling at least some individuals with NICM and reporting all-cause mortality as an outcome. Of 675 potentially relevant articles screened initially, 8 reports of randomized trials enrolling a total of 2146 patients with NICM were included. Data Extraction  Included studies were reviewed to determine the number of patients randomized, mean duration of follow-up, primary end point, mortality of ICD cohort, and mortality of control cohort. Data Synthesis  Five primary prevention trials enrolling 1854 patients with NICM were identified; pooled analysis suggested a significant reduction in total mortality among patients randomized to ICD or CRT-D vs medical therapy (risk ratio [RR], 0.69; 95% confidence interval [CI], 0.55-0.87; P = .002). Mortality reduction remained significant even after elimination of CRT-D trials. Two of the 3 secondary prevention trials presented subgroup estimates for ICD efficacy in NICM. Pooled analysis of these secondary prevention trials (n = 256 patients with NICM) indicated an equivalent but nonsignificant mortality reduction with ICD therapy (RR, 0.69; 95% CI, 0.39-1.24; P = .22). Analysis of all 7 trials combined demonstrated a statistically significant 31% overall reduction in mortality with ICD therapy (RR, 0.69; 95% CI, 0.56-0.86; P = .002). Conclusion  ICD therapy appears to significantly reduce mortality in selected patients with NICM.      

First documented rhythm and clinical outcome from in-hospital cardiac arrest among children and adults

Context  Cardiac arrests in adults are often due to ventricular fibrillation (VF) or pulseless ventricular tachycardia (VT), which are associated with better outcomes than asystole or pulseless electrical activity (PEA). Cardiac arrests in children are typically asystole or PEA. Objective  To test the hypothesis that children have relatively fewer in-hospital cardiac arrests associated with VF or pulseless VT compared with adults and, therefore, worse survival outcomes. Design, Setting, and Patients  A prospective observational study from a multicenter registry (National Registry of Cardiopulmonary Resuscitation) of cardiac arrests in 253 US and Canadian hospitals between January 1, 2000, and March 30, 2004. A total of 36 902 adults (18 years) and 880 children (<18 years) with pulseless cardiac arrests requiring chest compressions, defibrillation, or both were assessed. Cardiac arrests occurring in the delivery department, neonatal intensive care unit, and in the out-of-hospital setting were excluded. Main Outcome Measure  Survival to hospital discharge. Results  The rate of survival to hospital discharge following pulseless cardiac arrest was higher in children than adults (27% [236/880] vs 18% [6485/36 902]; adjusted odds ratio [OR], 2.29; 95% confidence interval [CI], 1.95-2.68). Of these survivors, 65% (154/236) of children and 73% (4737/6485) of adults had good neurological outcome. The prevalence of VF or pulseless VT as the first documented pulseless rhythm was 14% (120/880) in children and 23% (8361/36 902) in adults (OR, 0.54; 95% CI, 0.44-0.65; P<.001). The prevalence of asystole was 40% (350) in children and 35% (13 024) in adults (OR, 1.20; 95% CI, 1.10-1.40; P = .006), whereas the prevalence of PEA was 24% (213) in children and 32% (11 963) in adults (OR, 0.67; 95% CI, 0.57-0.78; P<.001). After adjustment for differences in preexisting conditions, interventions in place at time of arrest, witnessed and/or monitored status, time to defibrillation of VF or pulseless VT, intensive care unit location of arrest, and duration of cardiopulmonary resuscitation, only first documented pulseless arrest rhythm remained significantly associated with differential survival to discharge (24% [135/563] in children vs 11% [2719/24 987] in adults with asystole and PEA; adjusted OR, 2.73; 95% CI, 2.23-3.32). Conclusions  In this multicenter registry of in-hospital cardiac arrest, the first documented pulseless arrest rhythm was typically asystole or PEA in both children and adults. Because of better survival after asystole and PEA, children had better outcomes than adults despite fewer cardiac arrests due to VF or pulseless VT.      

Fish and omega-3 fatty acid intake and risk of coronary heart disease in women

Context  Higher consumption of fish and omega-3 fatty acids has been associated with a lower risk of coronary heart disease (CHD) in men, but limited data are available regarding women. Objective  To examine the association between fish and long-chain omega-3 fatty acid consumption and risk of CHD in women. Design, Setting, and Participants  Dietary consumption and follow-up data from 84 688 female nurses enrolled in the Nurses' Health Study, aged 34 to 59 years and free from cardiovascular disease and cancer at baseline in 1980, were compared from validated questionnaires completed in 1980, 1984, 1986, 1990, and 1994. Main Outcome Measures  Incident nonfatal myocardial infarction and CHD deaths. Results  During 16 years of follow-up, there were 1513 incident cases of CHD (484 CHD deaths and 1029 nonfatal myocardial infarctions). Compared with women who rarely ate fish (<1 per month), those with a higher intake of fish had a lower risk of CHD. After adjustment for age, smoking, and other cardiovascular risk factors, the multivariable relative risks (RRs) of CHD were 0.79 (95% confidence interval [CI], 0.64-0.97) for fish consumption 1 to 3 times per month, 0.71 (95% CI, 0.58-0.87) for once per week, 0.69 (95% CI, 0.55-0.88) for 2 to 4 times per week, and 0.66 (95% CI, 0.50-0.89) for 5 or more times per week (P for trend = .001). Similarly, women with a higher intake of omega-3 fatty acids had a lower risk of CHD, with multivariable RRs of 1.0, 0.93, 0.78, 0.68, and 0.67 (P<.001 for trend) across quintiles of intake. For fish intake and omega-3 fatty acids, the inverse association appeared to be stronger for CHD deaths (multivariate RR for fish consumption 5 times per week, 0.55 [95% CI, 0.33-0.90] for CHD deaths vs 0.73 [0.51-1.04]) than for nonfatal myocardial infarction. Conclusion  Among women, higher consumption of fish and omega-3 fatty acids is associated with a lower risk of CHD, particularly CHD deaths.      

Omega-3 polyunsaturated fatty acid intake and islet autoimmunity in children at increased risk for type 1 diabetes

Context  Cod liver oil supplements in infancy have been associated with a decreased risk of type 1 diabetes mellitus in a retrospective study. Objective  To examine whether intakes of omega-3 and omega-6 fatty acids are associated with the development of islet autoimmunity (IA) in children. Design, Setting, and Participants  A longitudinal, observational study, the Diabetes Autoimmunity Study in the Young (DAISY), conducted in Denver, Colorado, between January 1994 and November 2006, of 1770 children at increased risk for type 1 diabetes, defined as either possession of a high diabetes risk HLA genotype or having a sibling or parent with type 1 diabetes. The mean age at follow-up was 6.2 years. Islet autoimmunity was assessed in association with reported dietary intake of polyunsaturated fatty acids starting at age 1 year. A case-cohort study (N = 244) was also conducted in which risk of IA by polyunsaturated fatty acid content of erythrocyte membranes (as a percentage of total lipids) was examined. Main Outcome Measure  Risk of IA, defined as being positive for insulin, glutamic acid decarboxylase, or insulinoma-associated antigen-2 autoantibodies on 2 consecutive visits and still autoantibody positive or having diabetes at last follow-up visit. Results  Fifty-eight children developed IA. Adjusting for HLA genotype, family history of type 1 diabetes, caloric intake, and omega-6 fatty acid intake, omega-3 fatty acid intake was inversely associated with risk of IA (hazard ratio [HR], 0.45; 95% confidence interval [CI], 0.21-0.96; P = .04). The association was strengthened when the definition of the outcome was limited to those positive for 2 or more autoantibodies (HR, 0.23; 95% CI, 0.09-0.58; P = .002). In the case-cohort study, omega-3 fatty acid content of erythrocyte membranes was also inversely associated with IA risk (HR, 0.63; 95% CI, 0.41-0.96; P = .03). Conclusion  Dietary intake of omega-3 fatty acids is associated with reduced risk of IA in children at increased genetic risk for type 1 diabetes.      

6-month androgen suppression plus radiation therapy vs radiation therapy alone for patients with clinically localized prostate cancer: a randomized controlled trial

Context  Survival benefit in the management of high-grade clinically localized prostate cancer has been shown for 70 Gy radiation therapy combined with 3 years of androgen suppression therapy (AST), but long-term AST is associated with many adverse events. Objective  To assess the survival benefit of 3-dimensional conformal radiation therapy (3D-CRT) alone or in combination with 6 months of AST in patients with clinically localized prostate cancer. Design, Setting, and Patients  A prospective randomized controlled trial of 206 patients with clinically localized prostate cancer who were randomized to receive 70 Gy 3D-CRT alone (n = 104) or in combination with 6 months of AST (n = 102) from December 1, 1995, to April 15, 2001. Eligible patients included those with a prostate-specific antigen (PSA) of at least 10 ng/mL, a Gleason score of at least 7, or radiographic evidence of extraprostatic disease. Main Outcome Measures  Time to PSA failure (PSA >1.0 ng/mL and increasing >0.2 ng/mL on 2 consecutive visits) and overall survival. Results  After a median follow-up of 4.52 years, patients randomized to receive 3D-CRT plus AST had a significantly higher survival (P = .04), lower prostate cancer–specific mortality (P = .02), and higher survival free of salvage AST (P = .002). Kaplan-Meier estimates of 5-year survival rates were 88% (95% confidence interval [CI], 80%-95%) in the 3D-CRT plus AST group vs 78% (95% CI, 68%-88%) in the 3D-CRT group. Rates of survival free of salvage AST at 5 years were 82% (95% CI, 73%-90%) in the 3D-CRT plus AST group vs 57% (95% CI, 46%-69%) in the 3D-CRT group. Conclusion  The addition of 6 months of AST to 70 Gy 3D-CRT confers an overall survival benefit for patients with clinically localized prostate cancer.      

Influence of cardiopulmonary resuscitation prior to defibrillation in patients with out-of-hospital ventricular fibrillation

Context  Use of automated external defibrillators (AEDs) by first arriving emergency medical technicians (EMTs) is advocated to improve the outcome for out-of-hospital ventricular fibrillation (VF). However, adding AEDs to the emergency medical system in Seattle, Wash, did not improve survival. Studies in animals have shown improved outcomes when cardiopulmonary resuscitation (CPR) was administered prior to an initial shock for VF of several minutes' duration. Objective  To evaluate the effects of providing 90 seconds of CPR to persons with out-of-hospital VF prior to delivery of a shock by first-arriving EMTs. Design  Observational, prospectively defined, population-based study with 42 months of preintervention analysis (July 1, 1990-December 31, 1993) and 36 months of postintervention analysis (January 1, 1994-December 31, 1996). Setting  Seattle fire department–based, 2-tiered emergency medical system. Participants  A total of 639 patients treated for out-of-hospital VF before the intervention and 478 after the intervention. Intervention  Modification of the protocol for use of AEDs, emphasizing approximately 90 seconds of CPR prior to delivery of a shock. Main Outcome Measures  Survival and neurologic status at hospital discharge determined by retrospective chart review as a function of early (<4 minutes) and later (4 minutes) response intervals. Results  Survival improved from 24% (155/639) to 30% (142/478) (P=.04). That benefit was predominantly in patients for whom the initial response interval was 4 minutes or longer (survival, 17% [56/321] before vs 27% [60/220] after; P = .01). In a multivariate logistic model, adjusting for differences in patient and resuscitation factors between the periods, the protocol intervention was estimated to improve survival significantly (odds ratio, 1.42; 95% confidence interval, 1.07-1.90; P = .02). Overall, the proportion of victims who survived with favorable neurologic recovery increased from 17% (106/634) to 23% (109/474) (P = .01). Among survivors, the proportion having favorable neurologic function at hospital discharge increased from 71% (106/150) to 79% (109/138) (P<.11). Conclusion  The routine provision of approximately 90 seconds of CPR prior to use of AED was associated with increased survival when response intervals were 4 minutes or longer.      

Azithromycin for the secondary prevention of coronary heart disease events: the WIZARD study: a randomized controlled trial

Context  Several lines of evidence have implied an association between Chlamydia pneumoniae infection and atherogenesis. Objective  To determine the effect of 12 weeks of antibiotic therapy on coronary heart disease events in patients with stable coronary artery disease and known C pneumoniae exposure. Design, Setting, and Participants  Randomized, placebo-controlled trial of 7747 adults with previous myocardial infarction that had occurred at least 6 weeks previously (median, 2.6 years) and a C pneumoniae IgG titer of 1:16 or more. Patients were recruited from 271 clinical practices in North America, Europe, Argentina, and India, from October 10, 1997, to July 22, 2001. Intervention  The patients received either azithromycin (600 mg/d for 3 days during week 1, then 600 mg/wk during weeks 2-12; n = 3879) or placebo (n = 3868). Main Outcome Measures  The primary event was the first occurrence of death from any cause, nonfatal reinfarction, coronary revascularization, or hospitalization for angina. Patients were followed up until 1038 events accrued. Results  After a median of 14 months of follow-up, there was no significant risk reduction in the likelihood of a primary event with azithromycin vs placebo (7% [95% confidence interval, -5% to 17%], P = .23). Analysis of hazard ratios suggested early benefits of azithromycin on the primary event and on death or reinfarction, but these decreased over time. There were no significant risk reductions for any of the components of the primary end point including death (8%), recurrent myocardial infarction (7%), revascularization procedures (5%), or hospitalizations for angina (-1%). Adverse events related to study drug were reported by 13.2% of those randomized to receive azithromycin, predominantly a result of diarrhea, compared with 4.6% randomized to receive placebo, and resulted in discontinuation of drug in 1.6% of those taking azithromycin and 0.4% taking placebo. Conclusion  Among stable patients with previous myocardial infarction and with evidence of C pneumoniae exposure, a 3-month course of azithromycin did not significantly reduce the clinical sequelae of coronary heart disease.      

Effect of a mediterranean-style diet on endothelial dysfunction and markers of vascular inflammation in the metabolic syndrome: a randomized trial

Context  The metabolic syndrome has been identified as a target for dietary therapies to reduce risk of cardiovascular disease; however, the role of diet in the etiology of the metabolic syndrome is poorly understood. Objective  To assess the effect of a Mediterranean-style diet on endothelial function and vascular inflammatory markers in patients with the metabolic syndrome. Design, Setting, and Patients  Randomized, single-blind trial conducted from June 2001 to January 2004 at a university hospital in Italy among 180 patients (99 men and 81 women) with the metabolic syndrome, as defined by the Adult Treatment Panel III. Interventions  Patients in the intervention group (n = 90) were instructed to follow a Mediterranean-style diet and received detailed advice about how to increase daily consumption of whole grains, fruits, vegetables, nuts, and olive oil; patients in the control group (n = 90) followed a prudent diet (carbohydrates, 50%-60%; proteins, 15%-20%; total fat, <30%). Main Outcome Measures  Nutrient intake; endothelial function score as a measure of blood pressure and platelet aggregation response to L-arginine; lipid and glucose parameters; insulin sensitivity; and circulating levels of high-sensitivity C-reactive protein (hs-CRP) and interleukins 6 (IL-6), 7 (IL-7), and 18 (IL-18). Results  After 2 years, patients following the Mediterranean-style diet consumed more foods rich in monounsaturated fat, polyunsaturated fat, and fiber and had a lower ratio of omega-6 to omega-3 fatty acids. Total fruit, vegetable, and nuts intake (274 g/d), whole grain intake (103 g/d), and olive oil consumption (8 g/d) were also significantly higher in the intervention group (P<.001). The level of physical activity increased in both groups by approximately 60%, without difference between groups (P = .22). Mean (SD) body weight decreased more in patients in the intervention group (–4.0 [1.1] kg) than in those in the control group (–1.2 [0.6] kg) (P<.001). Compared with patients consuming the control diet, patients consuming the intervention diet had significantly reduced serum concentrations of hs-CRP (P = .01), IL-6 (P = .04), IL-7 (P = 0.4), and IL-18 (P = 0.3), as well as decreased insulin resistance (P<.001). Endothelial function score improved in the intervention group (mean [SD] change, +1.9 [0.6]; P<.001) but remained stable in the control group (+0.2 [0.2]; P = .33). At 2 years of follow-up, 40 patients in the intervention group still had features of the metabolic syndrome, compared with 78 patients in the control group (P<.001). Conclusion  A Mediterranean-style diet might be effective in reducing the prevalence of the metabolic syndrome and its associated cardiovascular risk.      

Risk of death with atypical antipsychotic drug treatment for dementia: meta-analysis of randomized placebo-controlled trials

Context  Atypical antipsychotic medications are widely used to treat delusions, aggression, and agitation in people with Alzheimer disease and other dementia; however, concerns have arisen about the increased risk for cerebrovascular adverse events, rapid cognitive decline, and mortality with their use. Objective  To assess the evidence for increased mortality from atypical antipsychotic drug treatment for people with dementia. Data Sources  MEDLINE (1966 to April 2005), the Cochrane Controlled Trials Register (2005, Issue 1), meetings presentations (1997-2004), and information from the sponsors were searched using the terms for atypical antipsychotic drugs (aripiprazole, clozapine, olanzapine, quetiapine, risperidone, and ziprasidone), dementia, Alzheimer disease, and clinical trial. Study Selection  Published and unpublished randomized placebo-controlled, parallel-group clinical trials of atypical antipsychotic drugs marketed in the United States to treat patients with Alzheimer disease or dementia were selected by consensus of the authors. Data Extraction  Trials, baseline characteristics, outcomes, all-cause dropouts, and deaths were extracted by one reviewer; treatment exposure was obtained or estimated. Data were checked by a second reviewer. Data Synthesis  Fifteen trials (9 unpublished), generally 10 to 12 weeks in duration, including 16 contrasts of atypical antipsychotic drugs with placebo met criteria (aripiprazole [n = 3], olanzapine [n = 5], quetiapine [n = 3], risperidone [n = 5]). A total of 3353 patients were randomized to study drug and 1757 were randomized to placebo. Outcomes were assessed using standard methods (with random- or fixed-effects models) to calculate odds ratios (ORs) and risk differences based on patients randomized and relative risks based on total exposure to treatment. There were no differences in dropouts. Death occurred more often among patients randomized to drugs (118 [3.5%] vs 40 [2.3%]. The OR by meta-analysis was 1.54; 95% confidence interval [CI], 1.06-2.23; P = .02; and risk difference was 0.01; 95% CI, 0.004-0.02; P = .01). Sensitivity analyses did not show evidence for differential risks for individual drugs, severity, sample selection, or diagnosis. Conclusions  Atypical antipsychotic drugs may be associated with a small increased risk for death compared with placebo. This risk should be considered within the context of medical need for the drugs, efficacy evidence, medical comorbidity, and the efficacy and safety of alternatives. Individual patient analyses modeling survival and causes of death are needed.      

Effect of frequent nocturnal hemodialysis vs conventional hemodialysis on left ventricular mass and quality of life: a randomized controlled trial

Context  Morbidity and mortality rates in hemodialysis patients remain excessive. Alterations in the delivery of dialysis may lead to improved patient outcomes. Objective  To compare the effects of frequent nocturnal hemodialysis vs conventional hemodialysis on change in left ventricular mass and health-related quality of life over 6 months. Design, Setting, and Participants  A 2-group, parallel, randomized controlled trial conducted at 2 Canadian university centers between August 2004 and December 2006. A total of 52 patients undergoing hemodialysis were recruited. Intervention  Participants were randomly assigned in a 1:1 ratio to receive nocturnal hemodialysis 6 times weekly or conventional hemodialysis 3 times weekly. Main Outcome Measures  The primary outcome was change in left ventricular mass, as measured by cardiovascular magnetic resonance imaging. The secondary outcomes were patient-reported quality of life, blood pressure, mineral metabolism, and use of medications. Results  Frequent nocturnal hemodialysis significantly improved the primary outcome (mean left ventricular mass difference between groups, 15.3 g, 95% confidence interval [CI], 1.0 to 29.6 g; P = .04). Frequent nocturnal hemodialysis did not significantly improve quality of life (difference of change in EuroQol 5-D index from baseline, 0.05; 95% CI, –0.07 to 0.17; P = .43). However, frequent nocturnal hemodialysis was associated with clinically and statistically significant improvements in selected kidney-specific domains of quality of life (P = .01 for effects of kidney disease and P = .02 for burden of kidney disease). Frequent nocturnal hemodialysis was also associated with improvements in systolic blood pressure (P = .01 after adjustment) and mineral metabolism, including a reduction in or discontinuation of antihypertensive medications (16/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional hemodialysis group; P < .001) and oral phosphate binders (19/26 patients in the nocturnal hemodialysis group vs 3/25 patients in the conventional dialysis group; P < .001). No benefit in anemia management was seen with nocturnal hemodialysis. Conclusion  This preliminary study revealed that, compared with conventional hemodialysis (3 times weekly), frequent nocturnal hemodialysis improved left ventricular mass, reduced the need for blood pressure medications, improved some measures of mineral metabolism, and improved selected measures of quality of life. Trial Registration  isrctn.org Identifier: ISRCTN25858715      

Sex and racial differences in the use of implantable cardioverter-defibrillators among patients hospitalized with heart failure

Context  Practice guidelines recommend implantable cardioverter-defibrillator (ICD) therapy for patients with heart failure and left ventricular ejection fraction of 30% or less. The influence of sex and race on ICD use among eligible patients is unknown. Objective  To examine sex and racial differences in the use of ICD therapy. Design, Setting, and Patients  Observational analysis of 13 034 patients admitted with heart failure and left ventricular ejection fraction of 30% or less and discharged alive from hospitals in the American Heart Association's Get With the Guidelines–Heart Failure quality-improvement program. Patients were treated between January 2005 and June 2007 at 217 participating hospitals. Main Outcome Measures  Use of ICD therapy or planned ICD therapy at discharge. Results  Among patients eligible for ICD therapy, 4615 (35.4%) had ICD therapy at discharge (1614 with new ICDs, 527 with planned ICDs, and 2474 with prior ICDs). ICDs were used in 375 of 1329 eligible black women (28.2%), 754 of 2531 white women (29.8%), 660 of 1977 black men (33.4%), and 2356 of 5403 white men (43.6%) (P < .001). After adjustment for patient characteristics and hospital factors, the adjusted odds of ICD use were 0.73 (95% confidence interval, 0.60-0.88) for black men, 0.62 (95% confidence interval, 0.56-0.68) for white women, and 0.56 (95% confidence interval, 0.44-0.71) for black women, compared with white men. The differences were not attributable to the proportions of women and black patients at participating hospitals or to differences in the reporting of left ventricular ejection fraction. Conclusions  Less than 40% of potentially eligible patients hospitalized for heart failure received ICD therapy, and rates of use were lower among eligible women and black patients than among white men.      

Androgen suppression and radiation vs radiation alone for prostate cancer: a randomized trial

Context  Comorbidities may increase the negative effects of specific anticancer treatments such as androgen suppression therapy (AST). Objectives  To compare 6 months of AST and radiation therapy (RT) to RT alone and to assess the interaction between level of comorbidity and all-cause mortality. Design, Setting, and Patients  At academic and community-based medical centers in Massachusetts, between December 1, 1995, and April 15, 2001, 206 men with localized but unfavorable-risk prostate cancer were randomized to receive RT alone or RT and AST combined. All-cause mortality estimates stratified by randomized treatment group and further stratified in a postrandomization analysis by the Adult Comorbidity Evaluation 27 comorbidity score were compared using a log-rank test. Main Outcome Measure  Time to all-cause mortality. Results  As of January 15, 2007, with a median follow-up of 7.6 (range, 0.5-11.0) years, 74 deaths have occurred. A significant increase in the risk of all-cause mortality (44 vs 30 deaths; hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.1-2.9; P = .01) was observed in men randomized to RT compared with RT and AST. However, the increased risk in all-cause mortality appeared to apply only to men randomized to RT with no or minimal comorbidity (31 vs 11 deaths; HR, 4.2; 95% CI, 2.1-8.5; P < .001). Among men with moderate or severe comorbidity, those randomized to RT alone vs RT and AST did not have an increased risk of all-cause mortality (13 vs 19 deaths; HR, 0.54; 95% CI, 0.27-1.10; P = .08). Conclusions  The addition of 6 months of AST to RT resulted in increased overall survival in men with localized but unfavorable-risk prostate cancer. This result may pertain only to men without moderate or severe comorbidity, but this requires further assessment in a clinical trial specifically designed to assess this interaction. Trial Registration  clinicaltrials.gov Identifier: NCT00116220      

Implantable cardioverter-defibrillators: expanding indications and technologies

Context  Sudden cardiac death (SCD) is a major challenge facing contemporary cardiology. For an increasing number of patients, the current standard of care for the treatment and prevention of SCD is the implantable cardioverter-defibrillator (ICD). Since its introduction, there have been numerous advances in ICD technology, and indications for its use have expanded greatly in the past year. Objective  To highlight the evolving indications for and the numerous advances in ICD technology, with emphasis on primary and secondary prophylaxis of SCD. Evidence Acquisition  Electronic literature search of the Pubmed and MEDLINE databases from January 1996 to July 2005, using the Medical Subject Heading implantable defibrillator. Abstracts and titles were reviewed to identify English-language randomized controlled trials that included an ICD group and a non-ICD group and that had end points of all-cause mortality, cardiac death, and/or arrhythmic mortality as the main outcome. A further MEDLINE search was conducted to identify randomized controlled trials of cardiac resynchronization therapy (CRT) with a CRT and a non-CRT group (including both mortality and other end points). Other studies were included that clarify aspects of device function and other relevant issues. A total of 22 trials were identified. Evidence Synthesis  ICD implantation improves survival in patients with a history of life-threatening ventricular arrhythmia. More recent evidence shows that ICD implantation also improves survival as primary prophylaxis against SCD in patients at high risk for ventricular arrhythmias, including those with left ventricular ejection fraction (LVEF) of 35% or less and New York Heart Association class II or III heart failure and those with a history of myocardial infarction and LVEF of 30% or less. Cardiac resynchronization improves symptoms, quality of life, and survival for patients with advanced heart failure and intraventricular conduction delays and ventricular dyssynchrony. Conclusions  ICDs have been shown to improve survival as both primary and secondary prophylaxis in an expanding population of patients. Ongoing ICD research may continue to delineate groups with survival benefit from ICDs, and the use and indications of these devices in clinical practice will continue to expand.      

Effect of neurolytic celiac plexus block on pain relief, quality of life, and survival in patients with unresectable pancreatic cancer: a randomized controlled trial

Context  Pancreatic cancer is an aggressive tumor associated with high mortality. Optimal pain control may improve quality of life (QOL) for these patients. Objective  To test the hypothesis that neurolytic celiac plexus block (NCPB) vs opioids alone improves pain relief, QOL, and survival in patients with unresectable pancreatic cancer. Design, Setting, and Patients  Double-blind, randomized clinical trial conducted at Mayo Clinic, Rochester, Minn. Enrolled (October 1997 and January 2001) were 100 eligible patients with unresectable pancreatic cancer experiencing pain. Patients were followed up for at least 1 year or until death. Intervention  Patients were randomly assigned to receive either NCPB or systemic analgesic therapy alone with a sham injection. All patients could receive additional opioids managed by a clinician blinded to the treatment assignment. Main Outcome Measures  Pain intensity (0-10 numerical rating scale), QOL, opioid consumption and related adverse effects, and survival time were assessed weekly by a blinded observer. Results  Mean (SD) baseline pain was 4.4 (1.7) for NCPB vs 4.1 (1.8) for opioids alone. The first week after randomization, pain intensity and QOL scores were improved (pain intensity, P.01 for both groups; QOL, P<.001 for both groups), with a larger decrease in pain for the NCPB group (P = .005). From repeated measures analysis, pain was also lower for NCPB over time (P = .01). However, opioid consumption (P = .93), frequency of opioid adverse effects (all P>.10), and QOL (P = .46) were not significantly different between groups. In the first 6 weeks, fewer NCPB patients reported moderate or severe pain (pain intensity rating of =" BORDER="0">5/10) vs opioid-only patients (14% vs 40%, P = .005). At 1 year, 16% of NCPB patients and 6% of opioid-only patients were alive. However, survival did not differ significantly between groups (P = .26, proportional hazards regression). Conclusion  Although NCPB improves pain relief in patients with pancreatic cancer vs optimized systemic analgesic therapy alone, it does not affect QOL or survival.      

Pacemaker and ICD generator reliability: meta-analysis of device registries

Context  Despite there being millions of pacemaker and implantable cardioverter-defibrillator (ICD) generator implants worldwide, little is known about device reliability. Objectives  To perform a meta-analysis of prospective pacemaker and ICD registries to determine annual rates of pacemaker and ICD malfunction and to identify trends in these rates. Data Sources  MEDLINE (January 1966 to April 2005), the Cochrane Central Register of Controlled Trials (through second quarter 2005), the Cochrane Database of Systematic Reviews (through second quarter 2005), and a bibliographic review of secondary sources. Search terms included pacemaker, artificial; defibrillators, implantable; registries; performance; and malfunction. Study Selection  Eligible registries were prospective; reported the number of patients with pacemaker, ICD, or both; and allowed determination of the annual number of device malfunctions. Of 1007 references screened, 3 registries meeting the selection criteria were identified and included 2.1 million pacemaker person-years and 14 821 ICD person-years of observation. Data Extraction  Included the annual number of patients with pacemakers and ICDs at risk of device failure and the annual number of generator malfunctions (1983-2004 for pacemakers, 1988-2004 for ICDs). A device malfunction was defined as an integral component failure that required device explantation prior to reaching elective replacement. Failures of pacemaker and ICD electrodes were not included in the study. Data Synthesis  There were 2981 pacemaker and 384 ICD generator malfunctions. Pacemaker reliability improved markedly during the 1980s (P for trend <.001) and the pacemaker malfunction rate remained low during the remainder of the study. Implantable cardioverter-defibrillator reliability improved during the first 10 study years (P for trend <.001). From 1998-2002, however, the ICD malfunction rate increased more than 4-fold (P for trend <.001), before decreasing substantially in the latter 2 years of the study. Overall, the mean (SE) annual ICD malfunction rate was about 20-fold higher than the pacemaker malfunction rate (26.5 [3.8] vs 1.3 [0.1] malfunctions per 1000 person-years, P<.001). Battery malfunctions were the most common cause of device failure. Conclusions  Pacemaker reliability has improved markedly. In contrast, after more than a decade of improving device reliability, the ICD malfunction rate transiently increased before experiencing substantial reductions in the latter 2 study years. Whether increasing device sophistication accounts for the observed decrease in reliability is not known. Continued monitoring of pacemaker and ICD performance is required.      

Evaluation and management of patients after implantable cardioverter-defibrillator shock

Context  There has been a tremendous increase in the use of implantable cardioverter-defibrillators (ICDs) after several large clinical trials demonstrated their ability to effectively reduce mortality in selected populations of patients with cardiac disease. Thus, the nonelectrophysiologist will often encounter patients who have received an ICD shock. Objective  To assess options for the evaluation and management of patients who have received an ICD shock. Evidence Acquisition  Literature search using the PubMed and MEDLINE databases to identify articles published from January 1990 to September 2006, using the Medical Subject Headings defibrillators, implantable; defibrillators, implantable/adverse effects; anti-arrhythmic agents; electric countershock; quality of life; tachycardia therapy; algorithm; ventricular tachycardia/diagnosis; and supraventricular tachycardia/diagnosis. Case reports were excluded and articles were limited to those published in English. Scientific statements and guidelines from the American College of Cardiology, the American Heart Association, and the Heart Rhythm Society were also reviewed, as were the reference lists of retrieved articles, to identify any additional articles for inclusion. Evidence Synthesis  There are multiple causes of both appropriate and inappropriate ICD shocks. Irrespective of appropriateness, receiving ICD shocks substantially impairs a patient's quality of life. A variety of techniques are available using ICD programming to reliably limit the occurrence of appropriate or inappropriate ICD shocks. Antiarrhythmic medications can also effectively reduce the occurrence of shocks. Conclusions  Through the use of effective ICD programming and antiarrhythmic medications, the occurrence of ICD shocks can be reduced while maintaining the lifesaving ability of the ICD. A basic understanding of the range of available options is fundamental for evaluation and management of the patient who has received an ICD shock.      

Prophylactic Oral Amiodarone for the Prevention of Arrhythmias that Begin Early After Revascularization, Valve Replacement, or Repair: PAPABEAR: a randomized controlled trial

Context  Atrial tachyarrhythmias after cardiac surgery are associated with adverse outcomes and increased costs. Previous trials of amiodarone prophylaxis, while promising, were relatively small and yielded conflicting results. Objective  To determine whether a brief perioperative course of oral amiodarone is an effective and safe prophylaxis for atrial tachyarrhythmias after cardiac surgery overall and in important subgroups. Design, Setting, and Patients  Double-blind randomized controlled trial of 601 patients listed for nonemergent coronary artery bypass graft (CABG) surgery and/or valve replacement/repair surgery between February 1, 1999, and September 26, 2003, at a tertiary care hospital. The patients were followed up for 1 year. Intervention  Oral amiodarone (10 mg/kg daily) or placebo administered 6 days prior to surgery through 6 days after surgery (13 days). Randomization was stratified for subgroups defined by age, type of surgery, and use of preoperative -blockers. Main Outcome Measure  Incidence of atrial tachyarrhythmias lasting 5 minutes or longer that prompted therapy by the sixth postoperative day. Results  Atrial tachyarrhythmias occurred in fewer amiodarone patients (48/299; 16.1%) than in placebo patients (89/302; 29.5%) overall (hazard ratio [HR], 0.52; 95% confidence interval [CI], 0.34-0.69; P<.001); in patients younger than 65 years (19 [11.2%] vs 36 [21.1%]; HR, 0.51 [95% CI, 0.28-0.94]; P = .02); in patients aged 65 years or older (28 [21.7%] vs 54 [41.2%]; HR, 0.45 [95% CI, 0.27-0.75]; P<.001); in patients who had CABG surgery only (22 [11.3%] vs 46 [23.6%]; HR, 0.45 [95% CI, 0.26-0.79]; P = .002); in patients who had valve replacement/repair surgery with or without CABG surgery (25 [23.8%] vs 44 [44.1%]; HR, 0.51 [95% CI, 0.31-0.84; P = .008); in patients who received preoperative -blocker therapy (27 [15.3%] vs 42 [25.0%]; HR, 0.58 [95% CI, 0.34-0.99]; P = .03); and in patients who did not receive preoperative -blocker therapy (20 [16.3%] vs 48 [35.8%]; HR, 0.40 [95% CI, 0.22-0.71]; P<.001), respectively. Postoperative sustained ventricular tachyarrhythmias occurred less frequently in amiodarone patients (1/299; 0.3%) than in placebo patients (8/302; 2.6%) (P = .04). Dosage reductions of blinded therapy were more common in amiodarone patients (34/299; 11.4%) than in placebo patients (16/302; 5.3%) (P = .008). There were no differences in serious postoperative complications, in-hospital mortality, or readmission to the hospital within 6 months of discharge or in 1-year mortality. Conclusion  Oral amiodarone prophylaxis of atrial tachyarrhythmias after cardiac surgery is effective and may be safe overall and in important patient subgroups. Clinical Trials Registration  ClinicalTrials.gov Identifier: NCT00251706      

Fenoldopam mesylate for the prevention of contrast-induced nephropathy: a randomized controlled trial

Context  The development of contrast-induced nephropathy in patients undergoing invasive cardiac procedures is associated with a marked increase in cardiovascular morbidity and mortality. Fenoldopam mesylate, a specific agonist of the dopamine-1 receptor, preserves renal blood flow after iodinated contrast administration and has shown promise in ameliorating contrast nephropathy in previous observational and small randomized trials. Objective  To examine the efficacy of fenoldopam mesylate in preventing contrast nephropathy after invasive cardiovascular procedures. Design  Prospective, placebo-controlled, double-blind, multicenter randomized trial with serial serum creatinine levels measured at a central biochemistry laboratory (at baseline and 1, 24, 48, and 72 to 96 hours after study drug administration) and 30-day clinical follow-up. Patients and Setting  Between March 2001 and July 2002, 315 patients with creatinine clearance less than 60 mL/min (1.00 mL/s) at 28 centers in the United States were randomized to receive fenoldopam mesylate (n = 157) or placebo (n = 158). Interventions  Patients were hydrated and randomized to receive intravenous fenoldopam (0.05 µg/kg/min titrated to 0.10 µg/kg/min) vs matching placebo, starting 1 hour prior to angiography and continuing for 12 hours. Main Outcome Measure  Contrast-induced nephropathy, defined as an increase of 25% or more in serum creatinine level within 96 hours postprocedure. Results  Mean (SD) patient age was 70 (11) years, and 49% had diabetes mellitus. Mean (SD) baseline creatinine clearance was 29.0 (10.0) mL/min (0.48 [0.16] mL/s) (range, 7.5-56.8 mL/min [0.12-0.94 mL/s]), and 157 (108) mL of contrast was administered during the procedures. The primary end point of contrast-induced nephropathy occurred in 33.6% of patients assigned to receive fenoldopam vs 30.1% assigned to receive placebo (relative risk, 1.11; 95% confidence interval, 0.79-1.57; P = .61). There were no significant differences in the 30-day rates of death (2.0% vs 3.8%, P = .50), dialysis (2.6% vs 1.9%, P = .72), or rehospitalization (17.6% vs 19.9%, P = .66) in fenoldopam vs placebo randomized patients, respectively. Conclusion  The selective dopamine-1 agonist fenoldopam mesylate does not prevent further renal function deterioration after contrast administration in patients with chronic renal insufficiency.      

Comparison of conventional-dose vs high-dose conformal radiation therapy in clinically localized adenocarcinoma of the prostate: a randomized controlled trial

Context  Clinically localized prostate cancer is very prevalent among US men, but recurrence after treatment with conventional radiation therapy is common. Objective  To evaluate the hypothesis that increasing the radiation dose delivered to men with clinically localized prostate cancer improves disease outcome. Design, Setting, and Patients  Randomized controlled trial of 393 patients with stage T1b through T2b prostate cancer and prostate-specific antigen (PSA) levels less than 15 ng/mL randomized between January 1996 and December 1999 and treated at 2 US academic institutions. Median age was 67 years and median PSA level was 6.3 ng/mL. Median follow-up was 5.5 (range, 1.2-8.2) years. Intervention  Patients were randomized to receive external beam radiation to a total dose of either 70.2 Gy (conventional dose) or 79.2 Gy (high dose). This was delivered using a combination of conformal photon and proton beams. Main Outcome Measure  Increasing PSA level (ie, biochemical failure) 5 years after treatment. Results  The proportions of men free from biochemical failure at 5 years were 61.4% (95% confidence interval, 54.6%-68.3%) for conventional-dose and 80.4% (95% confidence interval, 74.7%-86.1%) for high-dose therapy (P<.001), a 49% reduction in the risk of failure. The advantage to high-dose therapy was observed in both the low-risk and the higher-risk subgroups (risk reduction, 51% [P<.001] and 44% [P = .03], respectively). There has been no significant difference in overall survival rates between the treatment groups. Only 1% of patients receiving conventional-dose and 2% receiving high-dose radiation experienced acute urinary or rectal morbidity of Radiation Therapy Oncology Group (RTOG) grade 3 or greater. So far, only 2% and 1%, respectively, have experienced late morbidity of RTOG grade 3 or greater. Conclusions  Men with clinically localized prostate cancer have a lower risk of biochemical failure if they receive high-dose rather than conventional-dose conformal radiation. This advantage was achieved without any associated increase in RTOG grade 3 acute or late urinary or rectal morbidity.