Patients with Rheumatic Diseases do not have an Increased Risk of MRSA Carrier Status.

INTRODUCTION: The aim of this study was to determine the prevalence of methicillin-resistant Staphylococcus aureus (MRSA) both in rheumatologic and non-rheumatologic rehabilitation centers. In addition, we sought to evaluate the practice value of existing screening recommendations of the German Commission for Hospital Hygiene and Infection Prevention (KRINKO). METHODS: The analysis was performed in four rehabilitation clinics (rheumatology, psychosomatic medicine, oncology, and cardiology) with at least 200 patients per clinic tested for MRSA. RESULTS: Nine (1.1%) of the 842 patients were colonized with MRSA. Only five of them should have been tested according to the commission's recommendations. The prevalence was 0.5% (n = 207) in rheumatologic, 0.9% (n = 224) in psychosomatic, 1.4% (n = 209) in oncologic and 1.5% (n = 202) in cardiologic patients. We found a greater exposure to risk factors in cardiologic and oncologic patients. Among patients with carrier status, a higher percentage was exposed to three potential risk factors not applied by the commission. CONCLUSIONS: The prevalence of MRSA in our cohort correlates with data from previous studies. The low percentage among rheumatologic patients suggests that they are not more likely to reveal MRSA carrier status than other patient groups and that long-term immunosuppression does not necessarily represent a risk factor for MRSA colonization. Since only five out of nine patients with carrier status would have been detected following the recommendations of the KRINKO, further studies on potential risk factors are warranted.

Impact of left ventricular filling parameters on outcome of patients undergoing trans-catheter aortic valve replacement.

AIM: To assess the impact of left ventricular (LV) filling parameters on outcomes following trans-catheter aortic valve replacement (TAVR). METHODS AND RESULTS: A total of 526 TAVR patients were compared with 300 patients with severe aortic stenosis (AS) treated conservatively. Clinical variables were collected along with echocardiographic data at baseline, 1 month, and 6 months after study entry. End points included all-cause mortality and the combination of death and heart failure admission. LV filling parameters associated with mortality included reduced A wave velocity (P = 0.005) and shorter deceleration time (DT) (P = 0.0005). DT was superior to all other parameters (P = 0.05) apart from patients with atrial fibrillation in whom E/e' was better. Short DT (<160 ms) was associated with lower survival than long DT (≥220 ms; P = 0.002) or intermediate DT (P = 0.05), even after adjustment for age, gender, stroke volume index (SVI), and co-morbidities. However, patients with short baseline DT exhibited greater improvement in DT, E/A, and systolic pulmonary pressure at follow-up than patients with baseline DT ≥160 ms (P < 0.05 for all time x group interactions). Most importantly, among patients with short DT, TAVR was associated with better survival than conservative treatment (46 ± 7 vs. 28 ± 12% at 3 years, P = 0.05), even after adjustment for age, gender, and SVI (P = 0.05). CONCLUSION: Short DT is an independent predictor of adverse outcome following TAVR. Nevertheless, LV filling parameters improve in most patients post TAVR, and TAVR is associated with improved survival compared with conservative therapy, even in patients with evidence of elevated LV filling. Thus, evidence of elevated LV filling should not be viewed as a contraindication for TAVR.

The FDA's Final Rule on Expedited Safety Reporting: Statistical Considerations.

In March 2011, a Final Rule for expedited reporting of serious adverse events took effect in the United States for studies conducted under an Investigational New Drug (IND) application. In December 2012, the U.S. Food and Drug Administration (FDA) promulgated a final Guidance describing the operationalization of this Final Rule. The Rule and Guidance clarified that a clinical trial sponsor should have evidence suggesting causality before defining an unexpected serious adverse event as a suspected adverse reaction that would require expedited reporting to the FDA. The Rule's emphasis on the need for evidence suggestive of a causal relation should lead to fewer events being reported but, among those reported, a higher percentage actually being caused by the product being tested. This article reviews the practices that were common before the Final Rule was issued and the approach the New Rule specifies. It then discusses methods for operationalizing the Final Rule with particular focus on relevant statistical considerations. It concludes with a set of recommendations addressed to Sponsors and to the FDA in implementing the Final Rule.

Investigators' Experience With Expedited Safety Reports Prior to the FDA's Final IND Safety Reporting Rule.

Prior to enactment of the final investigational new drug application (IND) safety reporting rule, an attempt was made to document the effort expended at investigative sites in processing IND safety reports from sponsors and to assess the effect of these expedited reports on trial conduct. Investigators were asked to (1) prospectively document time to process IND safety reports and (2) retrospectively review safety reports from a previous 3-month period, documenting resultant actions. In this limited sample, sites spent a median of 0.25 hours per report at a median cost of US$22. Few expedited safety reports were retrospectively said to have changed study conduct or informed consent. However, a low response rate and the concentration of clinical sites in a single therapeutic area preclude generalizing these results. The authors discuss the challenges in gaining investigators' cooperation to evaluate the impact of regulatory requirements. Better methods to facilitate this type of research will enrich the scientific basis of future clinical trial regulation and guidance.

Industry Practices for Expedited Reporting to Investigators Conducting Research Under an IND.

Due to investigators' complaints about the volume and limited interpretability of expedited safety reports received in Investigational New Drug (IND) studies, the authors surveyed industry sponsors in late 2009 about their reporting practices. An Internet-enabled survey was submitted to 51 industry sponsors. Ten (20%) complete surveys were returned, 9 of which came from large pharmaceutical/biotechnology companies. Although the response rate in this study was low, considering the consolidation present in this sector, the preponderance of responses from large pharmaceutical companies provides a useful description of the safety reporting practices of a significant sector within the medical products industry. Sponsors described extensive safety-specialized resources for reporting individual events to the FDA and IND investigators. Aggregate reports, when prepared, were provided to the FDA but rarely to investigators. Sponsors reported receiving complaints from investigators about excessive volume and limited relevance of individual safety reports. These data suggest that investigators would likely benefit if industry sponsors decreased reporting of individual cases that are not readily interpretable and instead reported meaningful safety information from aggregate analyses.

Optimizing Expedited Safety Reporting for Drugs and Biologics Subject to an Investigational New Drug Application.

In September 2010, the US Food and Drug Administration (FDA) published a final rule governing the requirements for expedited safety reporting for products subject to an investigational new drug application. The rule clarified the types of safety information that qualify for expedited reporting. Its intent was to improve the overall quality of safety reporting by reducing the number of uninterpretable individual reports sent to the FDA and clinical investigators. In December 2011, we surveyed pharmaceutical and biotechnology sponsors regarding their safety reporting practices. We convened a group of experts and a biostatistics work group to review the survey results and identify gaps between current practice and the final safety reporting rule. Most sponsors had not changed their approach to expedited reporting of serious adverse events. We devised recommendations to help sponsors optimize their premarket safety systems to reduce the number of uninformative expedited reports and ensure recognition of important safety issues for an investigational drug as early as possible in development.

Portfolio of clinical research in adult cardiovascular disease as reflected in ClinicalTrials.gov.

BACKGROUND: Cardiovascular medicine is widely regarded as a vanguard for evidence-based drug and technology development. Our goal was to describe the cardiovascular clinical research portfolio from ClinicalTrials.gov. METHODS AND RESULTS: We identified 40 970 clinical research studies registered between 2007 and 2010 in which patients received diagnostic, therapeutic, or other interventions per protocol. By annotating 18 491 descriptors from the National Library of Medicine's Medical Subject Heading thesaurus and 1220 free-text terms to select those relevant to cardiovascular disease, we identified studies that related to the diagnosis, treatment, or prevention of diseases of the heart and peripheral arteries in adults (n = 2325 [66%] included from review of 3503 potential studies). The study intervention involved a drug in 44.6%, a device or procedure in 39.3%, behavioral intervention in 8.1%, and biological or genetic interventions in 3.0% of the trials. More than half of the trials were postmarket approval (phase 4, 25.6%) or not part of drug development (no phase, 34.5%). Nearly half of all studies (46.3%) anticipated enrolling 100 patients or fewer. The majority of studies assessed biomarkers or surrogate outcomes, with just 31.8% reporting a clinical event as a primary outcome. CONCLUSIONS: Cardiovascular studies registered on ClinicalTrials.gov span a range of study designs. Data have limited verification or standardization and require manual processes to describe and categorize studies. The preponderance of small and late-phase studies raises questions regarding the strength of evidence likely to be generated by the current portfolio and the potential efficiency to be gained by more research consolidation.

Participants' perspectives on safety monitoring in clinical trials.

BACKGROUND: Minimizing the risk to study participants is an essential requirement of ethical research. Respecting the rights of subjects is also paramount, which includes respecting their autonomy by making available important information about the evolving safety profile of an investigational product as the trial progresses. Little is known about what trial participants understand and expect regarding monitoring and communication of serious adverse events during the conduct of a trial in which they have agreed to participate. PURPOSE: To explore understanding and expectations of potential trial participants concerning monitoring and communication of serious adverse events during a clinical trial. METHODS: A professional moderator led four 90-min, in-person focus groups: two groups with individuals who had never participated in a clinical trial and two groups with people who had. After relevant research terms were defined and existing regulations were explained, discussion focused on how participants expected safety to be monitored and communicated during the conduct of a clinical trial. Group comments were video-recorded and transcribed and then analyzed by the investigators. RESULTS: The 27 racially diverse focus group members were largely unaware of existing safeguards and regulations to manage risk in clinical trials. Many people expressed a desire for increased transparency about serious adverse events during the trial as well as shortened reporting deadlines. Focus group members also spontaneously expressed concerns about potential financial conflicts of interest in monitoring and reporting serious adverse events. LIMITATIONS: This was a single-site, qualitative study and is not meant to establish the prevalence of beliefs. CONCLUSIONS: Potential trial participants have limited understanding and a wide range of expectations about how safety monitoring in clinical trials should be managed and communicated. The overall tenor of opinion suggests unease about participant safety and a desire to have more information conveyed by sponsors to investigators and, in some cases, by investigators to participants. Additional study in other regions and settings may be useful to more broadly explore the range of participants' beliefs and expectations. In the meantime, engaging patient advocates in the design of clinical trials and clearly communicating to trial participants the plan for oversight of their safety may help ease the types of concerns expressed in this study.

Use of central institutional review boards for multicenter clinical trials in the United States: a review of the literature.

BACKGROUND: To improve the efficiency of conducting multicenter clinical trials, the Food and Drug Administration, the Office of Human Research Protections, and the Department of Health and Human Services have expressed support for using a centralized institutional review board (IRB) process. However, research institutions differ in their willingness to defer to central IRBs. PURPOSE: We aimed to review and describe peer-reviewed journal articles on the use of central IRBs for multicenter clinical trials in the United States in an effort to inform the policy discussion about central IRBs. METHODS: We used a PubMed search and consulted IRB experts and the bibliographies of other reviews to identify relevant commentaries and empirical studies. RESULTS: Our search identified 33 articles related to the use of central IRBs for multicenter trials in the United States. Of these, 22 were commentary pieces and 11 were empirical studies. LIMITATIONS: Our review was restricted to journal articles about the use of central IRBs for multicenter clinical trials in the United States. CONCLUSIONS: There is limited empirical work on the use of central IRBs for multicenter trials in the United States. Most published studies focused on problems in efficiency associated with redundant local reviews of multicenter studies and the potential benefits of a centralized system. Because the absence of studies on the use of central IRBs may be due to their infrequent use, additional work is needed to generate data on the use of central IRBs and to elucidate and address the concerns that research institutions have about deferring ethical review to a central IRB.

Using central IRBs for multicenter clinical trials in the United States.

Research institutions differ in their willingness to defer to a single, central institutional review board (IRB) for multicenter clinical trials, despite statements from the FDA, OHRP, and NIH in support of using central IRBs to improve the efficiency of conducting trials. The Clinical Trials Transformation Initiative (CTTI) supported this project to solicit current perceptions of barriers to the use of central IRBs and to formulate potential solutions. We held discussions with IRB experts, interviewed representatives of research institutions, and held an expert meeting with diverse stakeholder groups and thought leaders. We found that many perceived barriers relate to conflating responsibilities of the institution with the ethical review responsibilities of the IRB. We identified the need for concrete tools to help research institutions separate institutional responsibilities from ethical responsibilities required of the IRB. One such tool is a document we created that delineates these responsibilities and how they might be assigned to each entity, or, in some cases, both entities. This tool and project recommendations will be broadly disseminated to facilitate the use of central IRBs in multicenter trials. The ultimate goal is to increase the nation's capacity to efficiently conduct the large number of high-quality trials.

Risk of Guillain-Barré syndrome after meningococcal conjugate vaccination.

PURPOSE: A new meningococcal conjugate vaccine (MCV4) was introduced in 2005. Shortly after, case reports of Guillain-Barré syndrome (GBS), a serious demyelinating disease, began to be reported to the Vaccine Adverse Event Reporting System. In 2006, the Centers for Disease Control and Prevention and the Food and Drug Administration requested the evaluation of GBS risk after MCV4 vaccination. We conducted a study to assess the risk of GBS after MCV4 vaccination using health plan administrative and claims data together with the review of primary medical records of potential cases. METHODS: Retrospective cohort study among 12.6 million 11- to 21-year-old members of five US health plans with a total membership of 50 million. Automated enrollment and medical claims data from March 2005 through August 2008 were used to identify the population, the vaccinations administered, and the medical services associated with possible GBS. Medical records were reviewed and adjudicated by a neurologist panel to confirm cases of GBS. The study used distributed data analysis methods that minimized sharing of protected health information. RESULTS: We confirmed 99 GBS cases during 18,322,800 person-years (5.4/1,000,000 person-years). More than 1.4 million MCV4 vaccinations were observed. No confirmed cases of GBS occurred within 6 weeks after vaccination. The upper 95% CI for the attributable risk of GBS associated with MCV4 is estimated as 1.5 cases per 1,000,000 doses. CONCLUSIONS: Among members of five US health plans, MCV4 vaccination was not associated with increased GBS risk.

Characteristics of clinical trials registered in ClinicalTrials.gov, 2007-2010.

CONTEXT: Recent reports highlight gaps between guidelines-based treatment recommendations and evidence from clinical trials that supports those recommendations. Strengthened reporting requirements for studies registered with ClinicalTrials.gov enable a comprehensive evaluation of the national trials portfolio. OBJECTIVE: To examine fundamental characteristics of interventional clinical trials registered in the ClinicalTrials.gov database. METHODS: A data set comprising 96,346 clinical studies from ClinicalTrials.gov was downloaded on September 27, 2010, and entered into a relational database to analyze aggregate data. Interventional trials were identified and analyses were focused on 3 clinical specialties-cardiovascular, mental health, and oncology-that together encompass the largest number of disability-adjusted life-years lost in the United States. MAIN OUTCOME MEASURES: Characteristics of registered clinical trials as reported data elements in the trial registry; how those characteristics have changed over time; differences in characteristics as a function of clinical specialty; and factors associated with use of randomization, blinding, and data monitoring committees (DMCs). RESULTS: The number of registered interventional clinical trials increased from 28,881 (October 2004-September 2007) to 40,970 (October 2007-September 2010), and the number of missing data elements has generally declined. Most interventional trials registered between 2007 and 2010 were small, with 62% enrolling 100 or fewer participants. Many clinical trials were single-center (66%; 24,788/37,520) and funded by organizations other than industry or the National Institutes of Health (NIH) (47%; 17,592/37,520). Heterogeneity in the reported methods by clinical specialty; sponsor type; and the reported use of DMCs, randomization, and blinding was evident. For example, reported use of DMCs was less common in industry-sponsored vs NIH-sponsored trials (adjusted odds ratio [OR], 0.11; 95% CI, 0.09-0.14), earlier-phase vs phase 3 trials (adjusted OR, 0.83; 95% CI, 0.76-0.91), and mental health trials vs those in the other 2 specialties. In similar comparisons, randomization and blinding were less frequently reported in earlier-phase, oncology, and device trials. CONCLUSION: Clinical trials registered in ClinicalTrials.gov are dominated by small trials and contain significant heterogeneity in methodological approaches, including reported use of randomization, blinding, and DMCs.

Patient-focused intervention to improve long-term adherence to evidence-based medications: a randomized trial.

BACKGROUND: Nonadherence to cardiovascular medications is a significant public health problem. This randomized study evaluated the effect on medication adherence of linking hospital and community pharmacists. METHODS: Hospitalized patients with coronary artery disease discharged on aspirin, ß-blocker, and statin who used a participating pharmacy were randomized to usual care or intervention. The usual care group received discharge counseling and a letter to the community physician; the intervention group received enhanced in-hospital counseling, attention to adherence barriers, communication of discharge medications to community pharmacists and physicians, and ongoing assessment of adherence by community pharmacists. The primary end point was self-reported use of aspirin, ß-blocker, and statin at 6 months postdischarge; the secondary end point was a ≥ 75% proportion of days covered (PDC) for ß-blocker and statin through 6 months postdischarge. RESULTS: Of 143 enrolled patients, 108 (76%) completed 6-month follow-up, and 115 (80%) had 6-month refill records. There was no difference between intervention and control groups in self-reported adherence (91% vs 94%, respectively, P = .50). Using the PDC to determine adherence to ß-blockers and statins, there was better adherence in the intervention versus control arm, but the difference was not statistically significant (53% vs 38%, respectively, P = .11). Adherence to ß-blockers was statistically significantly better in intervention versus control (71% vs 49%, respectively, P = .03). Of 85 patients who self-reported adherence and had refill records, only 42 (49%) were also adherent by PDC. CONCLUSIONS: The trend toward better adherence by refill records with the intervention should encourage further investigation of engaging pharmacists to improve continuity of care.

Monitoring the quality of conduct of clinical trials: a survey of current practices.

BACKGROUND: There is a little empirical evidence to determine which, if any, monitoring practices best achieve the goals of trial monitoring set forth in ICH E6 under the variable circumstances of different clinical trial settings. PURPOSE: The purpose of this project was to describe current methods of monitoring clinical trials and to explore the rationale for the use of those methods. METHODS: An electronic survey of known monitoring practices was developed and sent to over 200 organizations involved in conducting clinical research. The survey collected information on institutional demographics, methods of overall study oversight, use of risk-based monitoring and factors that influence assessments of risk, and details on quality assurance and monitoring practices. RESULTS: Seventy-nine organizations completed the survey; our analysis included the 65 organizations that indicated they perform clinical trials. Data from the survey indicate that a wide variety of monitoring practices are currently being employed. Eighty-three percent of respondents use centrally available data to evaluate site performance, but only 12% of respondents always or frequently used centralized monitoring to replace on-site visits. Eighty-seven percent of respondents indicated that they always performed on-site visits. This varied by type of organization, with 31% of academic coordinating centers/cooperative groups/government organizations always performing on-site monitoring visits versus 84% of other organizations. The rationale for using a specific monitoring approach does not appear to be based on empirical evidence. Fifty-four percent of respondents stated that 'usual practice' determined the frequency with which they conducted on-site monitoring visits. LIMITATIONS: The overall response rate to our survey was only 30%; thus, we may not have captured the full variance of current monitoring practices, and our responding sample may not be representative. CONCLUSION: These findings underscore the necessity of research to provide an evidence base for monitoring practice.

Association between mortality and persistent use of beta blockers and angiotensin-converting enzyme inhibitors in patients with left ventricular systolic dysfunction and coronary artery disease.

Beta blockers and angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are evidence-based medications for chronic heart failure, but little is known about the persistent use and clinical effectiveness of these medications. We evaluated the longer-term use of beta blockers and ACEIs/ARBs in patients with left ventricular systolic dysfunction and coronary artery disease. Patients with an ejection fraction <40% and coronary artery disease who had a cardiac catheterization from April 1994 through December 2005 were identified. Long-term patterns of beta-blocker and ACEI/ARB use were categorized as persistent, new, previous, or no use based on information from routine follow-up surveys. Characteristics among medication-use groups were explored, and survival associated with persistent use was determined. Of 3,187 patients identified for the beta-blocker analysis, 1,339 (42.0%) had persistent use. Conditional on surviving for > or = 2 follow-up surveys, the adjusted risk of death was statistically significantly lower with persistent use versus no use (hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.65 to 0.82) and new use versus no use (HR 0.81, 95% CI 0.68 to 0.97). Adjusted risk of death was not statistically significantly different between persistent or new use of an evidence-based beta blocker and persistent use of a nonevidence-based beta blocker (HR 0.96, 95% CI 0.78 to 1.17). Of 3,166 patients identified for the ACEI/ARB analysis, 1,347 (42.5%) had persistent use. There was no statistically significant association between adjusted mortality and persistent use (HR 0.93, 95% CI 0.81 to 1.05), new use (HR 0.86, 95% CI 0.71 to 1.03), or previous use (HR 0.88, 95% CI 0.73 to 1.07) compared with no ACEI/ARB use. In conclusion, persistent and new use of beta blockers was associated with survival, but evidence-based beta blockers did not appear superior to nonevidence-based beta blockers. We were unable to demonstrate a statistically significant association between persistent ACEI/ARB use and survival.

Scientific evidence underlying the ACC/AHA clinical practice guidelines.

CONTEXT: The joint cardiovascular practice guidelines of the American College of Cardiology (ACC) and the American Heart Association (AHA) have become important documents for guiding cardiology practice and establishing benchmarks for quality of care. OBJECTIVE: To describe the evolution of recommendations in ACC/AHA cardiovascular guidelines and the distribution of recommendations across classes of recommendations and levels of evidence. DATA SOURCES AND STUDY SELECTION: Data from all ACC/AHA practice guidelines issued from 1984 to September 2008 were abstracted by personnel in the ACC Science and Quality Division. Fifty-three guidelines on 22 topics, including a total of 7196 recommendations, were abstracted. DATA EXTRACTION: The number of recommendations and the distribution of classes of recommendation (I, II, and III) and levels of evidence (A, B, and C) were determined. The subset of guidelines that were current as of September 2008 was evaluated to describe changes in recommendations between the first and current versions as well as patterns in levels of evidence used in the current versions. RESULTS: Among guidelines with at least 1 revision or update by September 2008, the number of recommendations increased from 1330 to 1973 (+48%) from the first to the current version, with the largest increase observed in use of class II recommendations. Considering the 16 current guidelines reporting levels of evidence, only 314 recommendations of 2711 total are classified as level of evidence A (median, 11%), whereas 1246 (median, 48%) are level of evidence C. Level of evidence significantly varies across categories of guidelines (disease, intervention, or diagnostic) and across individual guidelines. Recommendations with level of evidence A are mostly concentrated in class I, but only 245 of 1305 class I recommendations have level of evidence A (median, 19%). CONCLUSIONS: Recommendations issued in current ACC/AHA clinical practice guidelines are largely developed from lower levels of evidence or expert opinion. The proportion of recommendations for which there is no conclusive evidence is also growing. These findings highlight the need to improve the process of writing guidelines and to expand the evidence base from which clinical practice guidelines are derived.

Comparative effectiveness of beta-blockers in elderly patients with heart failure.

BACKGROUND: Whether beta-blockers (BBs) other than carvedilol, metoprolol succinate, and bisoprolol fumarate (evidence-based beta-blockers [EBBBs]) improve survival in patients with heart failure (HF) is unknown. We compared the effectiveness of EBBBs vs non-EBBBs on survival. METHODS: Our study population included North Carolina residents at least 65 years old who were eligible for Medicare and Medicaid with pharmacy benefits and had had at least 1 hospitalization for HF during the period 2001 through 2004. Primary outcome was survival from 30 days to 1 year. Secondary outcomes included number and days of rehospitalizations for HF and number of outpatient visits. Cohorts were defined by BB class (EBBBs, non-EBBBs, or no BBs) in first 30 days after discharge from index hospitalization for HF. Outcomes were analyzed using inverse probability-weighted (IPW) estimators with propensity score adjustment. RESULTS: Of 11,959 patients, 40% were nonwhite, 79% were female, and 26% were at least 85 years old. Fifty-nine percent received no BB, 23% received EBBBs, and 18% received non-EBBBs. One-year adjusted mortality rates were 28.3% (no BBs), 22.8% (non-EBBBs), and 24.2% (EBBBs). The IPW-adjusted comparisons of 1-year mortality outcomes for either non-EBBBs or EBBBs compared with no BBs were statistically significant (P = .002 for both), but there was no statistical difference between the 2 BB groups (P = .43). The IPW-adjusted mean numbers of rehospitalizations for HF were 0.33 (no BBs), 0.29 (non-EBBBs), and 0.41 (EBBBs), with statistically more rehospitalizations in patients receiving EBBBs compared with no BBs (P = .002) and with non-EBBBs (P < .001). CONCLUSION: In this elderly population, the comparative effectiveness of EBBBs vs non-EBBBs was similar for 1-year survival, whereas the rehospitalization rate was higher for patients receiving EBBBs.

Early and long-term outcomes of heart failure in elderly persons, 2001-2005.

BACKGROUND: The treatment of chronic heart failure has improved during the past 2 decades, but little is known about whether the improvements are reflected in trends in early and long-term mortality and hospital readmission. METHODS: In a retrospective cohort study of 2 540 838 elderly Medicare beneficiaries hospitalized with heart failure between January 1, 2001, and December 31, 2005, we examined early and long-term all-cause mortality and hospital readmission and patient- and hospital-level predictors of these outcomes. RESULTS: Unadjusted in-hospital mortality declined from 5.1% to 4.2% during the study (P < .001), but 30-day, 180-day, and 1-year all-cause mortality remained fairly constant at 11%, 26%, and 37%, respectively. Nearly 1 in 4 patients were readmitted within 30 days of the index hospitalization, and two-thirds were readmitted within 1 year. Controlling for patient- and hospital-level covariates, the hazard of all-cause mortality at 1 year was slightly lower in 2005 than in 2001 (hazard ratio, 0.98; 95% confidence interval, 0.97-0.99). The hazard of readmission did not decline significantly from 2001 to 2005 (hazard ratio, 0.99; 95% confidence interval, 0.98-1.00). CONCLUSIONS: Early and long-term all-cause mortality and hospital readmission rates remain high and have improved little with time. The need to identify optimal management strategies for these clinically complex patients is urgent.