Approach to Multimorbidity Burden Classification and Outcomes in Older Adults With Heart Failure.

BACKGROUND: The optimal approach to classifying multimorbidity burden in assessing treatment-associated outcomes using real-world data remains uncertain. We assessed whether 2 measurement approaches to characterize multimorbidity influenced observed associations of ß-blocker use with outcomes in adults with heart failure (HF). METHODS: We conducted a retrospective study on adults with HF from 4 integrated health care delivery systems. Multimorbidity burden was characterized by either (1) simple counts of chronic conditions or (2) a weighted multiple chronic conditions score using data from electronic health records. We assessed the impact of these 2 approaches to characterizing multimorbidity on associations between exposure to ß-blockers and subsequent all-cause death, hospitalization for HF, and hospitalization for any cause. RESULTS: The study population characterized by a count of chronic conditions included 9988 adults with HF who had a mean (SD) age of 76.4 (12.5) years, with 48.7% women and 24.7% racial/ethnic minorities. The cohort characterized by weighted multiple chronic conditions included 10,082 adults with HF who had a mean (SD) age of 76.4 (12.4) years, 48.9% women, and 25.5% racial/ethnic minorities. The multivariable associations of risks of death or hospitalizations for HF or for any cause associated with incident ß-blocker use were similar regardless of how multimorbidity burden was characterized. CONCLUSIONS: Simple counts of chronic conditions performed similarly to a weighted multimorbidity score in predicting outcomes using real-world data to examine clinical outcomes associated with ß-blocker therapy in HF. Our findings challenge conventional wisdom that more complex measures of multimorbidity are always necessary to characterize patients in observational studies examining therapy-associated outcomes.

Adverse Events After Initiating Angiotensin-Converting Enzyme Inhibitor/Angiotensin II Receptor Blocker Therapy in Individuals with Heart Failure and Multimorbidity.

BACKGROUND: Current clinical practice guidelines recommend routine kidney function and serum potassium testing within 30 days of initiating angiotensin-converting enzyme inhibitor (ACEI) or angiotensin II receptor blocker (ARB) therapy. However, evidence is lacking on whether routine follow-up testing reduces therapy-related adverse events in adults with heart failure and if multimorbidity influences the association between laboratory testing and these adverse events. METHODS: We conducted a retrospective cohort study among adults with heart failure from 4 US integrated health care delivery systems. Multimorbidity was defined using counts of chronic conditions. Patients with outpatient serum creatinine and potassium tests in the 30 days after starting ACEI or ARB therapy were matched 1:1 to patients without follow-up tests. We evaluated the association of follow-up testing with 30-day all-cause mortality and hospitalization with acute kidney injury or hyperkalemia using Cox regression. RESULTS: We identified 3629 matched adults with heart failure initiating ACEI or ARB therapy between January 1, 2005, and December 31, 2012. Follow-up testing was not significantly associated with 30-day all-cause mortality (adjusted hazard ratio [aHR] 0.45, 95% confidence interval [CI] 0.14; 1.39) and hospitalization with hyperkalemia (aHR 0.73, 95% CI, 0.33; 1.61). However, follow-up testing was significantly associated with hospitalization with acute kidney injury (aHR, 1.40, 95% CI, 1.01; 1.94). Interaction between multimorbidity burden and follow-up testing was not statistically significant in any of the outcome models examined. CONCLUSIONS: Routine laboratory monitoring after ACEI or ARB therapy initiation was not associated with risk of 30-day all-cause mortality or hospitalization with hyperkalemia across the spectrum of multimorbidity burden in a cohort of patients with heart failure.

Cognitive impairment, age, quality of life, and treatment strategy for atrial fibrillation in older adults: The SAGE-AF study.

BACKGROUND: Atrial fibrillation (AF) treatment includes anticoagulation for high stroke risk individuals and either rate or rhythm control strategies. We aimed to investigate the impact of age, geriatric factors, and medical comorbidities on choice of rhythm versus rate control strategy in older adults. METHODS: Patients with AF aged ≥65 years with CHA2 DS2 VASc score ≥2 and eligible for anticoagulation were recruited for the Systematic Assessment of Geriatric Elements-AF (SAGE-AF) prospective cohort study. An interview that included measures of HRQoL, cognitive function, vision, hearing, and frailty was performed. The association between these elements and AF treatment strategy was examined by multivariable logistic regression models. RESULTS: One thousand two hundred forty-four participants (mean age 76 years; 49% female; 85% non-Hispanic white) were enrolled. Rate and rhythm control were used in 534 and 710 participants, respectively. Compared to participants <75 years, those ≥75 were more likely to be treated with a rate control strategy (age 75-84 adjusted odds ratio [aOR] 1.37 [95% CI 0.99, 1.88]; age 85+ aOR = 2.05, 95% CI 1.30, 3.21). Those treated with a rate control strategy were more likely to have cognitive impairment (aOR = 1.50, 95% CI 1.13, 1.99), and peripheral vascular disease (PVD) (aOR = 1.82, 95% CI 1.22, 2.72) but less likely to have visual impairment (aOR 0.73 [0.55, 0.98]), congestive heart failure (CHF; aOR 0.68 [0.49, 0.94]) or receive anticoagulation (aOR 0.53, 95% CI 0.36, 0.78). CONCLUSION: Older age, cognitive impairment, and PVD were associated with use of rate control strategy. Visual impairment, CHF, and anticoagulation use were associated with a rhythm control strategy. There was no difference in HRQoL between the rate and rhythm control groups. This study suggests that certain geriatric elements may be associated with AF treatment strategies. Further study is needed to evaluate how these decisions affect outcomes.

Noncardiac-Related Morbidity, Mobility Limitation, and Outcomes in Older Adults With Heart Failure.

BACKGROUND: To examine the individual and combined associations of noncardiac-related conditions and mobility limitation with morbidity and mortality in adults with heart failure (HF). METHODS: We conducted a retrospective cohort study in a large, diverse group of adults with HF from five U.S. integrated healthcare delivery systems. We characterized patients with respect to the presence of noncardiac conditions (<3 vs ≥3) and/or mobility impairment (defined by the use/nonuse of a wheelchair, cane, or walker), categorizing them into four subgroups. Outcomes included all-cause death and hospitalizations for HF or any cause. RESULTS: Among 114,553 adults diagnosed with HF (mean age: 73 years old, 46% women), compared with <3 noncardiac conditions/no mobility limitation, adjusted hazard ratios (HR) for all-cause death among those with <3 noncardiac conditions/mobility limitation, ≥3 noncardiac conditions/no mobility limitation, ≥3 noncardiac conditions/mobility limitation (vs) were 1.40 (95% CI, 1.31-1.51), 1.72 (95% CI, 1.69-1.75), and 1.93 (95% CI, 1.85-2.01), respectively. We did not observe an increased risk of any-cause or HF-related hospitalization related to the presence of mobility limitation among those with a greater burden of noncardiac multimorbidity. Consistent findings regarding mortality were observed within groups defined according to age, gender, and HF type (preserved, reduced, mid-range ejection fraction), with the most prominent impact of mobility limitation in those <65 years of age. CONCLUSIONS: There is an additive association of mobility limitation, beyond the burden of noncardiac multimorbidity, on mortality for patients with HF, and especially prominent in younger patients.

Comparison of Inappropriate Shocks and Other Health Outcomes Between Single- and Dual-Chamber Implantable Cardioverter-Defibrillators for Primary Prevention of Sudden Cardiac Death: Results From the Cardiovascular Research Network Longitudinal Study of Implantable Cardioverter-Defibrillators.

BACKGROUND: In US clinical practice, many patients who undergo placement of an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden cardiac death receive dual-chamber devices. The superiority of dual-chamber over single-chamber devices in reducing the risk of inappropriate ICD shocks in clinical practice has not been established. The objective of this study was to compare risk of adverse outcomes, including inappropriate shocks, between single- and dual-chamber ICDs for primary prevention. METHODS AND RESULTS: We identified patients receiving a single- or dual-chamber ICD for primary prevention who did not have an indication for pacing from 15 hospitals within 7 integrated health delivery systems in the Longitudinal Study of Implantable Cardioverter-Defibrillators from 2006 to 2009. The primary outcome was time to first inappropriate shock. ICD shocks were adjudicated for appropriateness. Other outcomes included all-cause hospitalization, heart failure hospitalization, and death. Patient, clinician, and hospital-level factors were accounted for using propensity score weighting methods. Among 1042 patients without pacing indications, 54.0% (n=563) received a single-chamber device and 46.0% (n=479) received a dual-chamber device. In a propensity-weighted analysis, device type was not significantly associated with inappropriate shock (hazard ratio, 0.91; 95% confidence interval, 0.59-1.38 [P=0.65]), all-cause hospitalization (hazard ratio, 1.03; 95% confidence interval, 0.87-1.21 [P=0.76]), heart failure hospitalization (hazard ratio, 0.93; 95% confidence interval, 0.72-1.21 [P=0.59]), or death (hazard ratio, 1.19; 95% confidence interval, 0.93-1.53 [P=0.17]). CONCLUSIONS: Among patients who received an ICD for primary prevention without indications for pacing, dual-chamber devices were not associated with lower risk of inappropriate shock or differences in hospitalization or death compared with single-chamber devices. This study does not justify the use of dual-chamber devices to minimize inappropriate shocks.

Use of Risk Models to Predict Death in the Next Year Among Individual Ambulatory Patients With Heart Failure.

Importance: The clinical practice guidelines for heart failure recommend the use of validated risk models to estimate prognosis. Understanding how well models identify individuals who will die in the next year informs decision making for advanced treatments and hospice. Objective: To quantify how risk models calculated in routine practice estimate more than 50% 1-year mortality among ambulatory patients with heart failure who die in the subsequent year. Design, Setting, and Participants: Ambulatory adults with heart failure from 3 integrated health systems were enrolled between 2005 and 2008. The probability of death was estimated using the Seattle Heart Failure Model (SHFM) and the Meta-Analysis Global Group in Chronic Heart Failure (MAGGIC) risk calculator. Baseline covariates were collected from electronic health records. Missing covariates were imputed. Estimated mortality was compared with actual mortality at both population and individual levels. Main Outcomes and Measures: One-year mortality. Results: Among 10 930 patients with heart failure, the median age was 77 years, and 48.0% of these patients were female. In the year after study enrollment, 1661 patients died (15.9% by life-table analysis). At the population level, 1-year predicted mortality among the cohort was 9.7% for the SHFM (C statistic of 0.66) and 17.5% for the MAGGIC risk calculator (C statistic of 0.69). At the individual level, the SHFM predicted a more than 50% probability of dying in the next year for 8 of the 1661 patients who died (sensitivity for 1-year death was 0.5%) and for 5 patients who lived at least a year (positive predictive value, 61.5%). The MAGGIC risk calculator predicted a more than 50% probability of dying in the next year for 52 of the 1661 patients who died (sensitivity, 3.1%) and for 63 patients who lived at least a year (positive predictive value, 45.2%). Conversely, the SHFM estimated that 8496 patients (77.8%) had a less than 15% probability of dying at 1 year, yet this lower-risk end of the score range captured nearly two-thirds of deaths (n = 997); similarly, the MAGGIC risk calculator estimated a probability of dying of less than 25% for the majority of patients who died at 1 year (n = 914). Conclusions and Relevance: Although heart failure risk models perform reasonably well at the population level, they do not reliably predict which individual patients will die in the next year.

Risk factors for adverse outcomes by left ventricular ejection fraction in a contemporary heart failure population.

BACKGROUND: Although heart failure (HF) is a syndrome with important differences in response to therapy by left ventricular ejection fraction (LVEF), existing risk stratification models typically group all HF patients together. The relative importance of common predictor variables for important clinical outcomes across strata of LVEF is relatively unknown. METHODS AND RESULTS: We identified all members with HF between 2005 and 2008 from 4 integrated healthcare systems in the Cardiovascular Research Network. LVEF was categorized as preserved (LVEF ≥ 50% or normal), borderline (41%-49% or mildly reduced), and reduced (≤ 40% or moderately to severely reduced). We used Cox regression models to identify independent predictors of death and hospitalization by LVEF category. Among 30094 ambulatory adults with HF, mean age was 74 years and 46% were women. LVEF was preserved in 49.5%, borderline in 16.2%, and reduced in 34.3% of patients. During a median follow-up of 1.8 years (interquartile range, 0.8-3.1), 8060 (26.8%) patients died, 8108 (26.9%) were hospitalized for HF, and 20272 (67.4%) were hospitalized for any reason. In multivariable models, nearly all tested covariates performed similarly across LVEF strata for the outcome of death from any cause, as well as for HF-related and all-cause hospitalizations. CONCLUSIONS: We found that in a large, diverse contemporary HF population, risk assessment was strikingly similar across all LVEF categories. These data suggest that, although many HF therapies are uniquely applied to patients with reduced LVEF, individual prognostic factor performance does not seem to be significantly related to level of left ventricular systolic function.

Baseline and follow-up laboratory monitoring of cardiovascular medications.

BACKGROUND: Laboratory monitoring of medications is typically used to establish safety prior to drug initiation and to detect drug-related injury following initiation. It is unclear whether black box warnings (BBWs) as well as evidence- and consensus-based clinical guidelines increase the likelihood of appropriate monitoring. OBJECTIVE: To determine the proportion of patients newly initiated on selected cardiovascular medications with baseline assessment and follow-up laboratory monitoring and compare the prevalence of laboratory testing for drugs with and without BBWs and guidelines. METHODS: This cross-sectional study included patients aged 18 years or older from a large multispecialty group practice who were prescribed a cardiovascular medication (angiotensin converting enzyme inhibitors, angiotensin II receptor blockers, amiodarone, digoxin, lipid-lowering agents, diuretics, and potassium supplements) between January 1 and July 31, 2008. The primary outcome measure was laboratory test ordering for baseline assessment and follow-up monitoring of newly initiated cardiovascular medications. RESULTS: The number of new users of each study drug ranged from 49 to 1757 during the study period. Baseline laboratory test ordering across study drugs ranged from 37.4% to 94.8%, and follow-up laboratory test ordering ranged from 20.0% to 77.2%. Laboratory tests for drugs with baseline laboratory assessment recommendations in BBWs were more commonly ordered than for drugs without BBWs (86.4% vs 78.0%, p < 0.001). Drugs with follow-up monitoring recommendations in clinical guidelines had a lower prevalence of monitoring (33.1% vs 50.7%, p < 0.001). CONCLUSIONS: Baseline assessment of cardiovascular medication monitoring is variable. Quality measurement of adherence to BBW recommendations may improve monitoring.

The Cardiovascular Research Network: a new paradigm for cardiovascular quality and outcomes research.

BACKGROUND: A clear need exists for a more systematic understanding of the epidemiology, diagnosis, and management of cardiovascular diseases. More robust data are also needed on how well clinical trials are translated into contemporary community practice and the associated resource use, costs, and outcomes. METHODS AND RESULTS: The National Heart, Lung, and Blood Institute recently established the Cardiovascular Research Network, which represents a new paradigm to evaluate the epidemiology, quality of care, and outcomes of cardiovascular disease and to conduct future clinical trials using a community-based model. The network includes 15 geographically distributed health plans with dedicated research centers, National Heart, Lung, and Blood Institute representatives, and an external collaboration and advisory committee. Cardiovascular research network sites bring complementary content and methodological expertise and a diverse population of approximately 11 million individuals treated through various health care delivery models. Each site's rich electronic databases (eg, sociodemographic characteristics, inpatient and outpatient diagnoses and procedures, pharmacy, laboratory, and cost data) are being mapped to create a standardized virtual data warehouse to facilitate rapid and efficient large-scale research studies. Initial projects focus on (1) hypertension recognition and management, (2) quality and outcomes of warfarin therapy, and (3) use, outcomes, and costs of implantable cardioverter defibrillators. CONCLUSIONS: The Cardiovascular Research Network represents a new paradigm in the approach to cardiovascular quality of care and outcomes research among community-based populations. Its unique ability to characterize longitudinally large, diverse populations will yield novel insights into contemporary disease and risk factor surveillance, management, outcomes, and costs. The Cardiovascular Research Network aims to become the national research partner of choice for efforts to improve the prevention, diagnosis, treatment, and outcomes of cardiovascular diseases.

Racial differences in tumor stage and survival for colorectal cancer in an insured population.

BACKGROUND: Despite declining death rates from colorectal cancer (CRC), racial disparities have continued to increase. In this study, the authors examined disparities in a racially diverse group of insured patients. METHODS: This study was conducted among patients who were diagnosed with CRC from 1993 to 1998, when they were enrolled in integrated healthcare systems. Patients were identified from tumor registries and were linked to information in administrative databases. The sample was restricted to non-Hispanic whites (n = 10,585), non-Hispanic blacks (n = 1479), Hispanics (n = 985), and Asians/Pacific Islanders (n = 909). Differences in tumor stage and survival were analyzed by using polytomous and Cox regression models, respectively. RESULTS: In multivariable regression analyses, blacks were more likely than whites to have distant or unstaged tumors. In Cox models that were adjusted for nonmutable factors, blacks had a higher risk of death from CRC (hazard ratio [HR], 1.17; 95% confidence interval [95% CI], 1.06-1.30). Hispanics had a risk of death similar to whites (HR, 1.04; 95% CI, 0.92-1.18), whereas Asians/Pacific Islanders had a lower risk of death from CRC (HR, 0.89; 95% CI, 0.78-1.02). Adjustment for tumor stage decreased the HR to 1.11 for blacks, and the addition of receipt of surgical therapy to the model decreased the HR further to 1.06. The HR among Hispanics and Asians/Pacific Islanders was stable to adjustment for tumor stage and surgical therapy. CONCLUSIONS: The relation between race and survival from CRC was complex and appeared to be related to differences in tumor stage and therapy received, even in insured populations. Targeted interventions to improve the use of effective screening and treatment among vulnerable populations may be needed to eliminate disparities in CRC.

Statin therapy and risks for death and hospitalization in chronic heart failure.

CONTEXT: Whether statin therapy has beneficial effects on clinical outcomes in patients with heart failure is unclear. OBJECTIVE: To evaluate the association between initiation of statin therapy and risks for death and hospitalization among adults with chronic heart failure. DESIGN, SETTING, AND PATIENTS: Propensity-adjusted cohort study of adults diagnosed with heart failure who were eligible for lipid-lowering therapy but had no previous known statin use, within an integrated health care delivery system in northern California between January 1, 1996, and December 31, 2004. Statin use was estimated from filled outpatient prescriptions in pharmacy databases. MAIN OUTCOME MEASURES: All-cause death and hospitalization for heart failure during a median of 2.4 years of follow-up. We examined the independent relationships between statin therapy and risks for adverse events overall and stratified by the presence or absence of coronary heart disease after multivariable adjustment for potential confounders. RESULTS: Among 24,598 adults diagnosed with heart failure who had no prior statin use, those initiating statin therapy (n = 12,648; 51.4%) were more likely to be younger, male, and have known cardiovascular disease, diabetes, and hypertension. There were 8235 patients who died. Using an intent-to-treat approach, incident statin use was associated with lower risks of death (age- and sex-adjusted rate of 14.5 per 100 person-years with statin therapy vs 25.3 per 100 person-years without statin therapy; adjusted hazard ratio, 0.76 [95% confidence interval, 0.72-0.80]) and hospitalization for heart failure (age- and sex-adjusted rate of 21.9 per 100 person-years with statin therapy vs 31.1 per 100 person-years without statin therapy; adjusted hazard ratio, 0.79 [95% confidence interval, 0.74-0.85]) even after adjustment for the propensity to take statins, cholesterol level, use of other cardiovascular medications, and other potential confounders. Incident statin use was associated with lower adjusted risks of adverse outcomes in patients with or without known coronary heart disease. CONCLUSION: Among adults diagnosed with heart failure who had no prior statin use, incident statin use was independently associated with lower risks of death and hospitalization among patients with or without coronary heart disease.

Patterns and predictors of mammography utilization among breast cancer survivors.

BACKGROUND: Improvements in cancer detection and treatment have resulted in increasing numbers of breast cancer survivors. Information regarding the use of mammography by breast cancer survivors is limited. METHODS: The use of surveillance mammography was examined over a 5-year period in a retrospective cohort of women age>or=55 years who were diagnosed with incident primary breast cancer (1996-1997) while enrolled in 1 of 4 geographically diverse integrated health systems. RESULTS: Of the 797 women included in the study, 80% (n=636) underwent mammograms during the first year after treatment for breast cancer. The percentage of women having mammograms during each yearly period decreased significantly over time. In multivariable analyses, older women with comorbid illnesses or those with late-stage disease were less likely to undergo mammograms, whereas those who underwent breast-conserving therapy (adjusted odds ratio [OR] of 1.38 [95% confidence interval (95% CI), 1.09-1.75]) were more likely to have mammograms. Women who had outpatient visits with a gynecologist (adjusted OR of 3.49 [95% CI, 2.55-4.79]), or a primary care physician (adjusted OR of 2.21 [95% CI, 1.73-2.82]) during the year were more likely to undergo mammograms in that year. CONCLUSIONS: The use of mammography among breast cancer survivors declines over time. Efforts are needed to increase awareness among healthcare providers and breast cancer survivors of the value of follow-up mammography. The current findings highlight the importance of maintaining ongoing contact with primary care physicians and gynecologists.

Baseline laboratory monitoring of cardiovascular medications in elderly health maintenance organization enrollees.

OBJECTIVES: To identify correlates of laboratory monitoring errors in elderly health maintenance organization (HMO) members at the initiation of therapy with cardiovascular medications. DESIGN: Cross-sectional study in 10 HMOs. SETTING: United States. PARTICIPANTS: From a 2 million-member sample, individuals aged 65 and older who received one of seven cardiovascular medications (angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), amiodarone, digoxin, diuretics, potassium supplements, and statins) and did not have recommended baseline monitoring performed during the 180 days before or 14 days after the index dispensing. MEASUREMENTS: The proportion of members receiving each drug for whom recommended laboratory monitoring was not performed. Laboratory monitoring error rates stratified by sex, age group, chronic disease score, and HMO site were examined, and logistic regression was used to identify predictors of laboratory monitoring errors. RESULTS: Error rates varied by medication class, ranging from 23% of patients receiving potassium supplementation without serum potassium and serum creatinine monitoring to 58% of patients receiving amiodarone who did not have recommended monitoring for thyroid and liver function. Highest error rates occurred in the youngest elderly for ACE inhibitors, ARBs, digoxin, diuretics, and potassium supplements, although in patients receiving amiodarone and statins, errors were most frequent in the oldest elderly. Errors occurred more frequently in patients with less comorbidity. CONCLUSION: Laboratory monitoring errors occurred frequently in elderly HMO members at the initiation of therapy with cardiovascular medications. Further study must examine the association between these errors and adverse outcomes.

Prescription drug use in pregnancy.

OBJECTIVE: The purpose of this study was to provide information on the prevalence of the use of prescription drugs among pregnant women in the United States. STUDY DESIGN: A retrospective study was conducted with the use of the automated databases of 8 health maintenance organizations that are involved in the Health Maintenance Research Network Center for Education and Research on Therapeutics. Women who delivered of an infant in a hospital from January 1, 1996, through December 31, 2000, were identified. Prescription drug use according to therapeutic class and the United States Food and Drug Administration risk classification system was evaluated, with the assumption of a gestational duration of 270 days, with three 90-day trimesters of pregnancy, and with a 90-day period before pregnancy. Nonprescription drug use was not assessed. RESULTS: During the period 1996 through 2000, 152,531 deliveries were identified that met the criteria for study. For 98,182 deliveries (64%), a drug other than a vitamin or mineral supplement was prescribed in the 270 days before delivery: 3595 women (2.4%) received a drug from category A; 76,292 women (50.0%) received a drug from category B; 57,604 women (37.8%) received a drug from category C; 7333 women (4.8%) received a drug from category D, and 6976 women (4.6%) received a drug from category X of the United States Food and Drug Administration risk classification system. Overall, 5157 women (3.4%) received a category D drug, and 1653 women (1.1%) received a category X drug after the initial prenatal care visit. CONCLUSION: Our finding that almost one half of all pregnant women received prescription drugs from categories C, D, or X of the United States Food and Drug Administration risk classification system highlights the importance of the need to understand the effects of these medications on the developing fetus and on the pregnant woman.