Jingrong Yang

Comparative effectiveness of different beta-adrenergic antagonists on mortality among adults with heart failure in clinical practice.

BACKGROUND Randomized trials have demonstrated the efficacy of selected beta-blockers in systolic heart failure, but the comparative effectiveness of different beta-blockers in practice is poorly understood. METHODS We compared mortality associated with different beta-blockers following hospitalization for heart failure between 2001 and 2003. Longitudinal exposure to beta-blockers was ascertained from pharmacy databases. Patient characteristics and other medication use were identified from administrative, hospitalization, outpatient, and pharmacy databases. Death was identified from administrative, state mortality, and Social Security Administration databases. Multivariate Cox regression was used to examine the association between different beta-blockers and death. RESULTS Among 11 326 adults surviving a hospitalization for heart failure, 7976 received beta-blockers (atenolol, 38.5%; metoprolol tartrate, 43.2%; carvedilol, 11.6%; and other, 6.7%) during follow-up. The rate (per 100 person-years) of death during the 12 months after discharge varied by exposure and type of beta-blocker (atenolol, 20.1; metoprolol tartrate, 22.8; carvedilol, 17.7; and no beta-blockers, 37.0). After adjustment for confounders and the propensity to receive carvedilol, the risk of death compared with atenolol was higher for metoprolol tartrate (adjusted hazard ratio [HR], 1.16; 95% confidence interval [CI], 1.01-1.34) and no beta-blockers (HR, 1.63; 95% CI, 1.44-1.84) but was not significantly different for carvedilol (HR, 1.16; 95% CI, 0.92-1.44). CONCLUSIONS Compared with atenolol, the adjusted risks of death were slightly higher with shorter-acting metoprolol tartrate but did not significantly differ for carvedilol in adults with heart failure. Our results should be interpreted cautiously and they suggest the need for randomized trials within real-world settings comparing a broader spectrum of beta-blockers for heart failure.

Effectiveness and Safety of Digoxin Among Contemporary Adults With Incident Systolic Heart Failure

Background—Clinical guidelines recommend digoxin for patients with symptomatic systolic heart failure (HF) receiving optimal medical therapy, but this recommendation is based on limited, older trial data. We evaluated the effectiveness and safety of digoxin in a contemporary cohort of patients with incident systolic HF. Methods and Results—We identified adults with incident systolic HF between 2006 and 2008 within Kaiser Permanente Northern California who had no prior digoxin use. We used multivariable extended Cox regression to examine the association between new digoxin use and risks of death and HF hospitalization, controlling for medical history, laboratory results, medications, HF disease severity, and the propensity for digoxin use. We also conducted analyses stratified by sex and concurrent &bgr;-blocker use. Among 2891 newly diagnosed patients with systolic HF, 529 (18%) received digoxin. During a median 2.5 years of follow-up, incident digoxin use was associated with higher rates of death (14.2 versus 11.3 per 100 person-years) and HF hospitalization (28.2 versus 24.4 per 100 person-years). In multivariable analysis, incident digoxin use was associated with higher mortality (hazard ratio, 1.72; 95% confidence interval, 1.25–2.36) but no significant difference in the risk of HF hospitalization (hazard ratio, 1.05; 95% confidence interval, 0.82–1.34). Results were similar in analyses stratified by sex and &bgr;-blocker use. Conclusions—Digoxin use in patients with incident systolic HF was independently associated with a higher risk of death but no difference in HF hospitalization.

Post-discharge Follow-up Characteristics Associated With 30-Day Readmission After Heart Failure Hospitalization.

Background:Readmission within 30 days after hospitalization for heart failure (HF) is a major public health problem. Objective:To examine whether timing and type of post-discharge follow-up impacts risk of 30-day readmission in adults hospitalized for HF. Design:Nested matched case-control study (January 1, 2006–June 30, 2013). Setting:A large, integrated health care delivery system in Northern California. Participants:Hospitalized adults with a primary diagnosis of HF discharged to home without hospice care. Measurements:Outpatient visits and telephone calls with cardiology and general medicine providers in non-emergency department and non-urgent care settings were counted as follow-up care. Statistical adjustments were made for differences in patient sociodemographic and clinical characteristics, acute severity of illness, hospitalization characteristics, and post-discharge medication changes and laboratory testing. Results:Among 11,985 eligible adults, early initial outpatient contact within 7 days after discharge was associated with lower odds of readmission [adjusted odds ratio (OR)=0.81; 95% CI, 0.70–0.94], whereas later outpatient contact between 8 and 30 days after hospital discharge was not significantly associated with readmission (adjusted OR=0.99; 95% CI, 0.82–1.19). Initial contact by telephone was associated with lower adjusted odds of 30-day readmission (adjusted OR=0.85; 95% CI, 0.69–1.06) but was not statistically significant. Conclusions:In adults discharged to home after hospitalization for HF, outpatient follow-up with a cardiology or general medicine provider within 7 days was associated with a lower chance of 30-day readmission.

Effectiveness and safety of spironolactone for systolic heart failure.

Aldosterone receptor antagonists have been shown in randomized trials to reduce morbidity and mortality in adults with symptomatic systolic heart failure. We studied the effectiveness and safety of spironolactone in adults with newly diagnosed systolic heart failure in clinical practice. We identified all adults with newly diagnosed heart failure, left ventricular ejection fraction of <40%, and no previous spironolactone use from 2006 to 2008 in Kaiser Permanente Northern California. We excluded patients with baseline serum creatinine level of >2.5 mg/dl or a serum potassium level of >5.0 mEq/L. We used Cox regression with time-varying covariates to evaluate the independent association between spironolactone use and death, hospitalization, severe hyperkalemia, and acute kidney injury. Among 2,538 eligible patients with a median follow-up of 2.5 years, 521 patients (22%) initiated spironolactone, which was not associated with risk of hospitalization (adjusted hazard ratio 0.91, 95% confidence interval 0.77 to 1.08) or death (adjusted hazard ratio 0.93, confidence interval 0.60 to 1.44). Crude rates of severe hyperkalemia and acute kidney injury during spironolactone use were similar to that seen in clinical trials. Spironolactone was independently associated with a 3.5-fold increased risk of hyperkalemia but not with acute kidney injury. Within a diverse community-based cohort with incident systolic heart failure, use of spironolactone was not independently associated with risks of hospitalization or death. Our findings suggest that the benefits of spironolactone in clinical practice may be reduced compared with other guideline-recommended medications.

Effectiveness of β-Blockers in Heart Failure With Left Ventricular Systolic Dysfunction and Chronic Kidney Disease

BACKGROUND Establishing medication effectiveness outside of a randomized trial requires careful study design to mitigate selection bias. Previous observational studies of β-blockers in patients with chronic kidney disease and heart failure have had methodologic limitations that may have introduced bias. We examined whether initiation of β-blocker therapy was associated with better outcomes among patients with chronic kidney disease and newly diagnosed heart failure with left ventricular systolic dysfunction. METHODS AND RESULTS We identified 668 adults in the Kaiser Permanente Northern California system from 2006 to 2008 with chronic kidney disease, incident heart failure, left ventricular systolic dysfunction, and no previous β-blocker use. We defined chronic kidney disease as estimated glomerular filtration rate <60 mL min(-1) 1.73 m(-2) or proteinuria, and we excluded patients receiving dialysis. We used extended Cox regression to assess the association of treatment with death and the combined end point of death or heart failure hospitalization. Initiation of β-blocker therapy was associated with a significantly lower crude risk of death (hazard ratio [HR] 0.47, 95% confidence interval [CI] 0.35-0.63), but this association was attenuated and no longer significant after multivariable adjustment (HR 0.75, CI 0.51-1.12). β-Blocker therapy was significantly associated with a lower risk of death or heart failure hospitalization even after adjustment for potential confounders (HR 0.67, CI 0.51-0.88). CONCLUSIONS β-Blocker therapy is associated with lower risk of death or heart failure hospitalization among patients with chronic kidney disease, incident heart failure, and left ventricular systolic dysfunction.

Association of Burden of Atrial Fibrillation With Risk of Ischemic Stroke in Adults With Paroxysmal Atrial Fibrillation: The KP-RHYTHM Study

Importance Atrial fibrillation is a potent risk factor for stroke, but whether the burden of atrial fibrillation in patients with paroxysmal atrial fibrillation independently influences the risk of thromboembolism remains controversial. Objective To determine if the burden of atrial fibrillation characterized using noninvasive, continuous ambulatory monitoring is associated with the risk of ischemic stroke or arterial thromboembolism in adults with paroxysmal atrial fibrillation. Design, Setting, and Participants This retrospective cohort study conducted from October 2011 and October 2016 at 2 large integrated health care delivery systems used an extended continuous cardiac monitoring system to identify adults who were found to have paroxysmal atrial fibrillation on 14-day continuous ambulatory electrocardiographic monitoring. Exposures The burden of atrial fibrillation was defined as the percentage of analyzable wear time in atrial fibrillation or flutter during the up to 14-day monitoring period. Main Outcomes and Measures Ischemic stroke and other arterial thromboembolic events occurring while patients were not taking anticoagulation were identified through November 2016 using electronic medical records and were validated by manual review. We evaluated the association of the burden of atrial fibrillation with thromboembolism while not taking anticoagulation after adjusting for the Anticoagulation and Risk Factors in Atrial Fibrillation (ATRIA) or CHA2DS2-VASc stroke risk scores. Results Among 1965 adults with paroxysmal atrial fibrillation, the mean (SD) age was 69 (11.8) years, 880 (45%) were women, 496 (25%) were persons of color, the median ATRIA stroke risk score was 4 (interquartile range [IQR], 2-7), and the median CHA2DS2-VASc score was 3 (IQR, 1-4). The median burden of atrial fibrillation was 4.4% (IQR ,1.1%-17.23%). Patients with a higher burden of atrial fibrillation were less likely to be women or of Hispanic ethnicity, but had more prior cardioversion attempts compared with those who had a lower burden. After adjusting for either ATRIA or CHA2DS2-VASc stroke risk scores, the highest tertile of atrial fibrillation burden (≥11.4%) was associated with a more than 3-fold higher adjusted rate of thromboembolism while not taking anticoagulants (adjusted hazard ratios, 3.13 [95% CI, 1.50-6.56] and 3.16 [95% CI, 1.51-6.62], respectively) compared with the combined lower 2 tertiles of atrial fibrillation burden. Results were consistent across demographic and clinical subgroups. Conclusions and Relevance A greater burden of atrial fibrillation is associated with a higher risk of ischemic stroke independent of known stroke risk factors in adults with paroxysmal atrial fibrillation.

Research LetterAcute Kidney Injury Ascertainment Is Affected by the Use of First Inpatient Versus Outpatient Baseline Serum Creatinine

To the Editor: An important methodological issue concerning acute kidney injury (AKI) definitions is the choice of “baseline” serum creatinine (SCr). The most recent consensus definition proposes a rolling 48-hour window for AKI ascertainment during hospitalization, or the use of a baseline value that is “known or presumed to have occurred in the past 7 days.” However, significant misclassification in assigning AKI status can occur when admission or nadir inpatient SCr (as has been done in a number of studies) is used rather than a preadmission outpatient baseline. A wellrecognized concern with the use of admission SCr to define baseline kidney function is that it will be higher than a patient’s true baseline if communityacquired AKI is present, and therefore communityacquired AKI will be missed if the admission SCr is used to define baseline. However, animal and