Renin-Angiotensin Inhibition and Outcomes in HFrEF and Advanced Kidney Disease.

BACKGROUND: Renin-angiotensin system inhibitors improve outcomes in patients with heart failure with reduced ejection fraction (HFrEF). However, less is known about their effectiveness in patients with HFrEF and advanced kidney disease. METHODS: In the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF), 1582 patients with HFrEF (ejection fraction ≤40%) had advanced kidney disease (estimated glomerular filtration rate <30 mL/min/1.73 m2). Of these, 829 were not receiving angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs) prior to admission, of whom 214 were initiated on these drugs prior to discharge. We calculated propensity scores for receipt of these drugs for each of the 829 patients and assembled a matched cohort of 388 patients, balanced on 47 baseline characteristics (mean age 78 years; 52% women; 10% African American; 73% receiving beta-blockers). Hazard ratios (HR) and 95% confidence intervals (CI) were estimated comparing 2-year outcomes in 194 patients initiated on ACE inhibitors or ARBs to 194 patients not initiated on those drugs. RESULTS: The combined endpoint of heart failure readmission or all-cause mortality occurred in 79% and 84% of patients initiated and not initiated on ACE inhibitors or ARBs, respectively (HR associated with initiation, 0.79; 95% CI, 0.63-0.98). Respective HRs (95% CI) for the individual endpoints of - Respective HRs (95% CI) for the individual endpoints of all-cause mortality and heart failure readmission were 0.81 (0.63-1.03) and 0.63 (0.47-0.85). CONCLUSIONS: The findings from our study add new information to the body of cumulative evidence that suggest that renin-angiotensin system inhibitors may improve clinical outcomes in patients with HFrEF and advanced kidney disease. These hypothesis-generating findings need to be replicated in contemporary patients.

Risk of Stroke in Older Adults With Heart Failure.

Heart failure (HF) is a risk factor for incident stroke. However, less is known about the independent nature of this association and to what extent various baseline characteristics may mediate this risk. Of the 5,795 community-dwelling adults aged ≥65 years in the Cardiovascular Health Study, 5,448 were free of baseline stroke, of whom 229 had baseline HF. We used a multivariable-adjusted Cox regression model to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for centrally adjudicated incident stroke associated with HF. Participants had a mean age of 73 years, 58% were women, and 15% were African-American. During 23 years of follow-up, incident stroke occurred in 18.8% and 19.3% of those with and without HF, respectively, but the time to first stroke was shorter in those with HF (age-gender-race-adjusted HR 1.64, 95% CI 1.21 to 2.25). The association remained essentially unchanged after adjustments for tobacco, alcohol, and physical activity (HR 1.63, 95% CI 1.21 to 2.24), attenuated after adjustment for hypertension, atrial fibrillation, myocardial infarction, and diabetes mellitus (HR 1.26, 95% CI 0.92 to 1.72), and further attenuated after additional adjustment for 10 baseline functional and subclinical variables (HR 1.05, 95% CI 0.76 to 1.46). In conclusion, despite a similar 23-year stroke incidence, time to first stroke was shorter in older adults with HF than without. However, this extra risk appears to be mediated primarily by 4 cardiovascular diseases that are also risk factors for HF. These findings highlight the importance of the primary prevention of these HF risk factors to reduce the extra risk of stroke in HF.

Assessment of Lung Cancer Risk Among Smokers for Whom Annual Screening Is Not Recommended.

Importance: The US Preventive Services Task Force does not recommend annual lung cancer screening with low-dose computed tomography (LDCT) for adults aged 50 to 80 years who are former smokers with 20 or more pack-years of smoking who quit 15 or more years ago or current smokers with less than 20 pack-years of smoking. Objective: To determine the risk of lung cancer in older smokers for whom LDCT screening is not recommended. Design, Settings, and Participants: This cohort study used the Cardiovascular Health Study (CHS) data sets obtained from the National Heart, Lung and Blood Institute, which also sponsored the study. The CHS enrolled 5888 community-dwelling individuals aged 65 years and older in the US from June 1989 to June 1993 and collected extensive baseline data on smoking history. The current analysis was restricted to 4279 individuals free of cancer who had baseline data on pack-year smoking history and duration of smoking cessation. The current analysis was conducted from January 7, 2022, to May 25, 2022. Exposures: Current and prior tobacco use. Main Outcomes and Measures: Incident lung cancer during a median (IQR) of 13.3 (7.9-18.8) years of follow-up (range, 0 to 22.6) through December 31, 2011. A Fine-Gray subdistribution hazard model was used to estimate incidence of lung cancer in the presence of competing risk of death. Cox cause-specific hazard regression models were used to estimate hazard ratios (HRs) and 95% CIs for incident lung cancer. Results: There were 4279 CHS participants (mean [SD] age, 72.8 [5.6] years; 2450 [57.3%] women; 663 [15.5%] African American, 3585 [83.8%] White, and 31 [0.7%] of other race or ethnicity) included in the current analysis. Among the 861 nonheavy smokers (<20 pack-years), the median (IQR) pack-year smoking history was 7.6 (3.3-13.5) pack-years for the 615 former smokers with 15 or more years of smoking cessation, 10.0 (5.3-14.9) pack-years for the 146 former smokers with less than 15 years of smoking cessation, and 11.4 (7.3-14.4) pack-years for the 100 current smokers. Among the 1445 heavy smokers (20 or more pack-years), the median (IQR) pack-year smoking history was 34.8 (26.3-48.0) pack-years for the 516 former smokers with 15 or more years of smoking cessation, 48.0 (35.0-70.0) pack-years for the 497 former smokers with less than 15 years of smoking cessation, and 48.8 (31.6-57.0) pack-years for the 432 current smokers. Incident lung cancer occurred in 10 of 1973 never smokers (0.5%), 5 of 100 current smokers with less than 20 pack-years of smoking (5.0%), and 26 of 516 former smokers with 20 or more pack-years of smoking with 15 or more years of smoking cessation (5.0%). Compared with never smokers, cause-specific HRs for incident lung cancer in the 2 groups for whom LDCT is not recommended were 10.54 (95% CI, 3.60-30.83) for the current nonheavy smokers and 11.19 (95% CI, 5.40-23.21) for the former smokers with 15 or more years of smoking cessation; age, sex, and race-adjusted HRs were 10.06 (95% CI, 3.41-29.70) for the current nonheavy smokers and 10.22 (4.86-21.50) for the former smokers with 15 or more years of smoking cessation compared with never smokers. Conclusions and Relevance: The findings of this cohort study suggest that there is a high risk of lung cancer among smokers for whom LDCT screening is not recommended, suggesting that prediction models are needed to identify high-risk subsets of these smokers for screening.

Initiation of anti-hypertensive drugs and outcomes in patients with heart failure with preserved ejection fraction and persistent hypertension.

BACKGROUND: National heart failure (HF) guidelines recommend that in patients with HF with preserved ejection fraction (EF;HFpEF) and hypertension, systolic blood pressure (SBP) should be maintained below 130 mmHg. The objective of the study is to examine the association between initiation of anti-hypertensive drugs and outcomes in patients with HFpEF with persistent hypertension. METHODS: Of the 8873 hospitalized patients with HFpEF (EF ≥50%) with a history of hypertension without renal failure in Medicare-linked OPTIMIZE-HF, 3315 had a discharge SBP ≥130 mmHg, of whom 1971 were not receiving anti-hypertensive drugs, thiazides and calcium channel blockers, before hospitalization. Of these, 366 received discharge prescriptions for those drugs. We assembled a propensity score-matched cohort of 365 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 37 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 730) had a mean age of 78 years; 67% were women and 17% African Americans. During 6 (median 2.5) years of follow-up, 66% of the patients died and 45% had HF readmission. HRs (95% CIs) for all-cause mortality at 30 days, 12 months and 6 years associated with anti-hypertensive drug initiation were 0.64 (0.30-1.36), 0.70 (0.51-0.97), and 0.95 (0.79-1.13), respectively. Respective HRs (95% CIs) for HF readmission were 1.65 (0.97-2.80), 1.18 (0.90-1.56) and 1.09 (0.88-1.35). CONCLUSIONS: Among hospitalized older patients with HFpEF with uncontrolled hypertension, the initiation of therapy with anti-hypertensive drugs was not associated with all-cause mortality or hospital readmission.

In-Hospital Weight Loss and Outcomes in Patients With Heart Failure.

BACKGROUND: Acute decompensation of heart failure (HF) is often marked by fluid retention, and weight loss is a marker of successful diuresis. We examined the relationship between in-hospital weight loss and post-discharge outcomes in patients with HF. METHODS: We conducted a propensity score-matched study of 8830 patients hospitalized for decompensated HF in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, in which 4415 patients in the weight-loss group and 4415 patients in the no-weight-loss group were balanced on 75 baseline characteristics. We defined weight loss as an admission-to-discharge weight loss of 1-30 kilograms, and we defined no weight loss as a weight gain or loss of < 1 kilogram. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with weight loss were estimated. RESULTS: Patients had a mean age of 78 years, 57% were women, and 11% were African American. The median weight loss in the weight-loss group was 3.6 (interquartile range, 2.0-6.0) kilograms. HRs and 95% CIs for 30-day all-cause mortality, all-cause readmission and HF readmission associated with weight loss were 0.75 (0.63-0.90), 0.90 (0.83-0.99) and 0.83 (0.72-0.96), respectively. Respective 60-day HRs (95% CIs) were 0.80 (0.70-0.92), 0.91 (0.85-0.98) and 0.88 (0.79-0.98). These associations were attenuated and lost significance during 6 months of follow-up. CONCLUSIONS: Among older patients hospitalized for decompensated HF, in-hospital weight loss was associated with a lower risk of mortality and hospital readmission. These findings suggest that in-hospital weight loss, a marker of successful diuresis and decongestion, is also a marker of improved clinical outcomes.

Beta-Blocker Use and Outcomes in Nursing Home Residents with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: Beta-blockers improve clinical outcomes in patients with heart failure with reduced ejection fraction (HFrEF). Less is known about their role in older nursing home residents with HFrEF. METHODS: From the combined OPTIMIZE-HF and Alabama Heart Failure Project data sets, we assembled a propensity score-matched balanced cohort of 6494 hospitalized patients ≥65 years with HFrEF (ejection fraction ≤40%). In our primary approach, hazard ratios (HRs) and 95% confidence intervals (CI)s for outcomes associated with discharge prescriptions for beta- blockers were estimated, examining for heterogeneity by admission from nursing homes. In our sensitivity approach, we examined these associations in a separately assembled propensity score-matched cohort of 122 patients admitted from nursing homes. RESULTS: In the matched primary cohort of 6494 patients, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.80 (0.74-0.87) and 0.94 (0.86-1.02), respectively. Respective HRs (95% CIs) in the nursing home and non-nursing home subgroups were 0.77 (0.51-1.16) and 0.81 (0.74-0.87) for all-cause mortality (interaction P: 0.653) and 1.06 (0.53-2.12) and 0.89 (0.82-0.96) for heart failure readmission (interaction P: 0.753). In the matched sensitivity cohort of 122 patients admitted from nursing homes, HRs (95% CIs) for 12-month all-cause mortality and heart failure readmission were 0.86 (0.55-1.35) and 1.07 (0.52-2.22), respectively. Similar associations were observed for 30-day outcomes. CONCLUSIONS: Beta-blocker use was associated with a lower risk of all-cause mortality but not of heart failure readmission in older patients with HFrEF, which were similar for patients admitted and not admitted from nursing homes.

Initiation of Anti-Hypertensive Drugs and Outcomes in Patients with Heart Failure with Reduced Ejection Fraction.

BACKGROUND: In patients with heart failure with reduced ejection fraction (HFrEF) and hypertension, systolic blood pressure is recommended to be maintained below 130 mmHg, although this has not been shown to be associated with improved outcomes. We examined the association between anti-hypertensive drug initiation and outcomes in patients with HFrEF. METHODS: In the Medicare-linked OPTIMIZE-HF, 7966 patients with HFrEF (ejection fraction ≤40%) without renal failure were not receiving anti-hypertensive drugs before hospitalization, of whom 692 received discharge prescriptions for those drugs (thiazides and calcium channel blockers). We assembled a propensity score-matched cohort of 687 pairs of patients initiated and not initiated on anti-hypertensive drugs, balanced on 38 baseline characteristics. Hazard ratios (HR) and 95% confidence intervals (CIs) for outcomes associated with anti-hypertensive drug initiation were estimated in the matched cohort. RESULTS: Matched patients (n = 1374) had a mean age of 74 years, 41% were female, 17% were African-American, 66% were discharged on renin-angiotensin system inhibitors and beta blockers, and 10% on aldosterone antagonists. During 6 (median 2.5) years of follow-up, 70% of the patients died and 53% had heart failure readmission. Anti-hypertensive drug initiation was not significantly associated with all-cause mortality (HR, 0.95; 95% CI, 0.83-1.07) or heart failure readmission (HR, 0.93; 95% CI, 0.80-1.07). Similar associations were observed during 30 days and 12 months of follow-up. CONCLUSIONS: Among hospitalized older patients with HFrEF receiving contemporary treatments for heart failure, initiation of an anti-hypertensive drug was not associated with a lower risk of all-cause mortality or hospital readmission.

Income disparity and incident cardiovascular disease in older Americans.

OBJECTIVE: To examine the association between income and cardiovascular disease (CVD) in community-dwelling older adults. METHODS: Of the 5795 Medicare-eligible community-dwelling older Americans aged 65-100 years in the Cardiovascular Health Study (CHS), 4518 (78%) were free of baseline CVD, defined as heart failure, acute myocardial infarction, stroke, or peripheral arterial disease. Of them, 1846 (41%) had lower income, defined as a total annual household income <$16,000. Using propensity scores for lower income, estimated for each of the 4518 participants, we assembled a matched cohort of 1078 pairs balanced on 42 baseline characteristics. Outcomes included centrally adjudicated incident CVD and mortality. RESULTS: Matched participants (n = 2156) had a mean age of 73 years, 63% were women, and 13% African American. During an overall follow-up of 23 years, incident CVD, all-cause mortality and the combined endpoint of incident CVD or mortality occurred in 1094 (51%), 1726 (80%) and 1867 (87%) individuals, respectively. Compared with the higher income group, hazard ratio (HR) for time to the first occurrence of incident CVD in the lower income group was 1.16 with a 95% confidence interval (CI) of 1.03 to 1.31. A lower income was also associated with a significantly higher risk of all-cause mortality (HR, 1.19; 95% CI, 1.08-1.30), and consequently a higher risk of the combined endpoint of incident CVD or death (HR, 1.20; 95% CI, 1.09-1.31). CONCLUSION: Among community-dwelling older Americans free of baseline CVD, an annual household income <$16,000 is independently associated with significantly higher risks of new-onset CVD and death.

Length of stay and readmission in older adults hospitalized for heart failure.

INTRODUCTION: Hospital length of stay (LoS) and hospital readmissions are metrics of healthcare performance. We examined the association between these two metrics in older patients hospitalized with decompensated heart failure (HF). MATERIAL AND METHODS: Eight thousand and forty-nine patients hospitalized for HF in 106 U.S. hospitals had a median LoS of 5 days; among them, 3777 had a LoS > 5 days. Using propensity scores for LoS > 5 days, we assembled 2723 pairs of patients with LoS 1-5 vs. > 5 days. The matched cohort of 5446 patients was balanced on 40 baseline characteristics. We repeated the above process in 7045 patients after excluding those with LoS > 10 days, thus assembling a second matched cohort of 2399 pairs of patients with LoS 1-5 vs. 6-10 days. Hazard ratios (HR) and 95% confidence intervals (CI) for outcomes associated with longer LoS were estimated in matched cohorts. RESULTS: In the primary matched cohort (n = 5446), LoS > 5 days was associated with a higher risk of all-cause readmission at 30 days (HR = 1.16; 95% CI: 1.04-1.31; p = 0.010), but not during longer follow-up. A longer LoS was also associated with a higher risk of mortality during 8.8 years of follow-up (HR = 1.13; 95% CI: 1.06-1.21; p < 0.001). LoS had no association with HF readmission. Similar associations were observed among the matched sensitivity cohort (n = 4798) that excluded patients with LoS > 10 days. CONCLUSIONS: In propensity score-matched balanced cohorts of patients with HF, a longer LoS was independently associated with poor outcomes, which persisted when LoS > 10 days were excluded.

Development and evolution of a two-day intensive resident experience in geriatric medicine.

As the older adult population increases, the need to enhance medical education and training in Geriatric Medicine (GM) is essential. To enhance resident training, faculty at two southeastern universities developed a Resident Award Summit, a two-day active learning experience, designed to expose family and internal medicine residents to GM principles and the various career options available in GM.Over 10 years, 353 residents from 108 residency programs participated. Resident feedback indicated that attending the event had a positive impact on future practice (M = 4.65, SD = .58) and showed that the amount of GM training received was limited, with 83.5% and 70.2% ranking adequacy of medical student and resident training as limited, respectively.To impact practice, long-term change must occur. Experiences such as the Resident Award Summit allow GM faculty to educate and prepare residents though positive teaching experiences, providing residents with the skills needed to care for older adults in their communities.

Systolic Blood Pressure and Outcomes in Older Patients with HFpEF and Hypertension.

BACKGROUND: New hypertension and heart failure guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with preserved ejection fraction (HFpEF) and hypertension be lowered to <130 mm Hg. METHODS: Of the 6778 hospitalized patients with HFpEF and a history of hypertension in the Medicare-linked OPTIMIZE-HF registry, 3111 had a discharge SBP <130 mm Hg. Using propensity scores for SBP <130 mm Hg, we assembled a matched cohort of 1979 pairs with SBP <130 versus ≥130 mm Hg, balanced on 66 baseline characteristics (mean age, 79 years; 69% women; 12% African American). We then assembled a second matched cohort of 1326 pairs with SBP <120 versus ≥130 mm Hg. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with SBP <130 and <120 mm Hg were separately estimated in the matched cohorts using SBP ≥130 mm Hg as the reference. RESULTS: HRs (95% CIs) for 30-day, 12-month, and 6-year all-cause mortality associated with SBP <130 mm Hg were 1.20 (0.91-1.59; P = 0.200), 1.11 (0.99-1.26; P = 0.080), and 1.05 (0.98-1.14; P = 0.186), respectively. Respective HRs (95% CIs) associated with SBP <120 mm Hg were 1.68 (1.21-2.34; P = 0.002), 1.28 (1.11-1.48; P = 0.001), and 1.11 (1.02-1.22; P = 0.022). There was no association with readmission. CONCLUSIONS: Among older patients with HFpEF and hypertension, compared with SBP ≥130 mm Hg, the new target SBP <130 mm Hg had no association with outcomes but SBP <120 mm Hg was associated with a higher risk of death but not of readmission. Future prospective studies need to evaluate optimal SBP treatment goals in these patients.

Loop Diuretic Prescription and Long-Term Outcomes in Heart Failure: Association Modification by Congestion.

BACKGROUND: The effect of loop diuretics on clinical outcomes in heart failure has not been evaluated in randomized controlled trials. In hospitalized patients with heart failure, a discharge loop diuretic prescription has been shown to be associated with improved 30-day outcomes, which appears to be more pronounced in subgroups with congestion. In the current study, we examined these associations and association modifications during longer follow-up. METHODS: We assembled a propensity score-matched cohort of 2191 pairs of hospitalized heart failure patients discharged with, vs without, a prescription for loop diuretics, balanced on 74 baseline characteristics (mean age 78 years; 54% women; 11% African American). RESULTS: Hazard ratio (HR) and 95% confidence interval (CI) for 6-year combined endpoint of heart failure readmission or all-cause mortality was 1.02 (0.96-1.09). HRs and 95% CIs for this combined endpoint in patients with no, mild-to-moderate, and severe pulmonary rales were 1.19 (1.07-1.33), 0.95 (0.86-1.04), and 0.77 (0.63-0.94), respectively (P for interaction, < .001). Respective HRs (95% CIs) for no, mild-to-moderate, and severe lower extremity edema were 1.16 (1.06-1.28), 0.94 (0.85-1.04), and 0.71 (0.56-0.89; interaction P < .001). CONCLUSIONS: The association between a discharge loop diuretic prescription and long-term clinical outcomes in hospitalized patients with heart failure is modified by admission congestion with worse, neutral, and better outcomes in patients with no, mild-to-moderate, and severe congestion, respectively. If these findings can be replicated, congestion may be used to risk-stratify patients with heart failure for potential optimization of loop diuretic prescription and outcomes.

Loop Diuretic Prescription and 30-Day Outcomes in Older Patients With Heart Failure.

BACKGROUND: Heart failure (HF) is a major source of morbidity and mortality. Fluid retention and shortness of breath are its cardinal manifestations for which loop diuretics are used. Although their usefulness is well accepted, less is known about their role in improving clinical outcomes. OBJECTIVES: The purpose of this study was to determine the relationship between loop diuretics and clinical outcomes in patients with HF. METHODS: Of the 25,345 older patients hospitalized for HF in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 9,866 (39%) received no pre-admission diuretics. The study excluded 1,083 patients receiving dialysis and 847 discharged on thiazide diuretics. Of the remaining 7,936 patients, 5,568 (70%) were prescribed loop diuretics at discharge. Using propensity scores for receipt of loop diuretics estimated for each of the 7,936 patients, a matched cohort of 2,191 pairs of patients was assembled balanced on 74 baseline characteristics. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated in the matched cohort. RESULTS: Matched patients (n = 4,382) had a mean age of 78 years, 54% were women, and 11% were African American. The 30-day all-cause mortality occurred in 4.9% (107 of 2,191) and 6.6% (144 of 2,191) of patients in the loop diuretic and no loop diuretic groups, respectively (HR when the use of loop diuretics was compared with nonuse: 0.73; 95% CI: 0.57 to 0.94; p = 0.016). Patients in the loop diuretic group had a significantly lower risk of 30-day HF readmission (HR: 0.79; 95% CI: 0.63 to 0.99; p = 0.037) but not of 30-day all-cause readmission (HR: 0.89; 95% CI: 0.79 to 1.01; p = 0.081). None of the associations was statistically significant during 60 days of follow-up. CONCLUSIONS: Hospitalized older patients not taking diuretics prior to hospitalization for HF decompensation who received a discharge prescription for loop diuretics had significantly better 30-day clinical outcomes than those not discharged on loop diuretics. These findings provide new information about short-term clinical benefits associated with loop diuretic use in HF.

Digoxin Initiation and Outcomes in Patients with Heart Failure (HFrEF and HFpEF) and Atrial Fibrillation.

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization but has no effect on mortality in patients with heart failure without atrial fibrillation in the randomized controlled trial setting. Observational studies of digoxin use in patients with atrial fibrillation have suggested a higher risk for poor outcomes. Less is known about this association in patients with heart failure and atrial fibrillation, the examination of which was the objective of the current study. METHODS: We conducted an observational propensity score-matched study of predischarge digoxin initiation in 1768 hospitalized patients with heart failure and atrial fibrillation in the Medicare-linked Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure (OPTIMIZE-HF) registry, balanced on 56 baseline characteristics (mean age, 79 years; 55% women; 7% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes were estimated for the 884 patients initiated on digoxin compared with 884 not initiated on digoxin. RESULTS: HRs (95% CIs) for 30-day, 2-year, and 4-year all-cause mortality were 0.80 (0.55-1.18; P = .261), 0.94 (0.87-1.16; P = .936), and 1.01 (0.90-1.14; P = .729), respectively. Respective HRs (95% CIs) for heart failure readmission were 0.67 (0.49-0.92; P = .014), 0.81 (0.69-0.94; P = .005), and 0.85 (0.74-0.97; P = .022), and those for all-cause readmission were 0.78 (0.64-0.96; P = .016), 0.90 (0.81-1.00; P = .057), and 0.91 (0.83-1.01; P = .603). These associations were homogeneous between patients with left ventricular ejection fraction ≤45% vs >45%. CONCLUSIONS: Among hospitalized older patients with heart failure (HFrEF and HFpEF) and atrial fibrillation, initiation of digoxin was associated with a lower risk of heart failure readmission but had no association with mortality.

Hypokalaemia and outcomes in older patients hospitalized for heart failure.

AIMS: Hypokalaemia is a risk factor for ventricular arrhythmias and sudden death in ambulatory patients with chronic heart failure (HF). The objective of this study was to examine the association between hypokalaemia and outcomes in hospitalized patients with decompensated HF in whom sudden death is less common. METHODS AND RESULTS: Of the 5881 hospitalized patients with HF, 1052 had consistent hypokalaemia (both admission and discharge serum potassium <4.0 mmol/L), and 2538 had consistent normokalaemia (both admission and discharge serum potassium 4.0-5.0 mmol/L). Propensity scores for consistent hypokalaemia, estimated for each of 3590 (1052 + 2538) patients, were used to assemble a matched cohort of 971 pairs of patients with consistent hypokalaemia vs. consistent normokalaemia, balanced on 54 baseline characteristics (mean age, 75 years; 60% women; 28% African American). We repeated the above process to assemble 2327 pairs of patients with discharge potassium <4.0 vs. 4.0-5.0 mmol/L and 449 pairs of patients with discharge serum potassium <3.5 vs. 4.0-5.0 mmol/L. Hazard ratios (HR) and 95% confidence intervals (CIs) associated with hypokalaemia were estimated in matched cohorts. 30 day all-cause mortality occurred in 5% and 4% of patients with consistent normokalaemia vs. consistent hypokalaemia, respectively (HR, 0.78; 95% CI, 0.52-1.18; P = 0.241). HRs (95% CI) for 30 day mortality associated with discharge serum potassium <4.0 and <3.5 mmol/L were 0.90 (0.70-1.16; P = 0.419) and 1.69 (0.94-3.04; P = 0.078), respectively. Hypokalaemia (<4.0 or <3.5 mmol/L) had no association with long-term mortality or other outcomes. CONCLUSIONS: In hospitalized older patients with HF, compared with normokalaemia (serum potassium 4.0-5.0 mmol/L), hypokalaemia (<4.0 or <3.5 mmol/L) had no significant associations with outcomes.

Digoxin Initiation and Outcomes in Patients with Heart Failure with Preserved Ejection Fraction.

BACKGROUND: Digoxin reduces the risk of heart failure hospitalization in patients with heart failure with reduced ejection fraction. Less is known about this association in patients with heart failure with preserved ejection fraction (HFpEF), the examination of which was the objective of the current study. METHODS: In the Medicare-linked OPTIMIZE-HF registry, 7374 patients hospitalized for HF had ejection fraction ≥50% and were not receiving digoxin prior to admission. Of these, 5675 had a heart rate ≥50 beats per minute, an estimated glomerular filtration rate ≥30 mL/min/1.73 m2 or did not receive inpatient dialysis, and digoxin was initiated in 524 of these patients. Using propensity scores for digoxin initiation, calculated for each of the 5675 patients, we assembled a matched cohort of 513 pairs of patients initiated and not initiated on digoxin, balanced on 58 baseline characteristics (mean age, 80 years; 66% women; 8% African American). Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with digoxin initiation were estimated in the matched cohort. RESULTS: Among the 1026 matched patients with HFpEF, 30-day heart failure readmission occurred in 6% and 9% of patients initiated and not initiated on digoxin, respectively (HR 0.70; 95% CI, 0.45-1.10; P = .124). HRs (95% CIs) for 30-day all-cause readmission and all-cause mortality associated with digoxin initiation were 0.95 (0.73-1.23; P = .689) and 0.93 (0.55-1.56; P = .773), respectively. Digoxin initiation had no association with 6-year outcomes. CONCLUSION: Digoxin initiation prior to hospital discharge was not associated with 30-day or 6-year outcomes in older hospitalized patients with HFpEF.

Prior Heart Failure Hospitalization and Outcomes in Patients with Heart Failure with Preserved and Reduced Ejection Fraction.

BACKGROUND: A prior hospitalization resulting from heart failure is associated with poor outcomes in ambulatory patients with heart failure. Less is known about this association in hospitalized patients with heart failure and whether it varies by ejection fraction. METHODS: Of the 25,345 hospitalized patients in the Medicare-linked OPTIMIZE-HF registry, 22,491 had known heart failure, of whom 7648 and 9558 had heart failure with preserved (≥50%) and reduced (≤40%) ejection fraction (HFpEF and HFrEF), respectively. Overall, 927 and 1862 patients with HFpEF and HFrEF had hospitalizations for heart failure during the 6 months before the index hospitalization, respectively. Using propensity scores for prior heart failure hospitalization, we assembled two matched cohorts of 924 pairs and 1844 pairs of patients with HFpEF and HFrEF, respectively, each balanced for 58 baseline characteristics. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes during 6 years of follow-up. RESULTS: Among 1848 matched patients with HFpEF, HRs (95% CIs) for all-cause mortality, all-cause readmission, and heart failure readmission were 1.35 (1.21-1.50; P <0.001), 1.34 (1.21-1.47; P <0.001), and 1.90 (1.67-2.16; P <0.001), respectively. Respective HRs (95% CIs) in 3688 matched patients with HFrEF were 1.17 (1.09-1.26; P <0.001), 1.32 (1.23-1.41; P <0.001), and 1.48 (1.37-1.61; P <0.001). CONCLUSIONS: Among hospitalized patients with heart failure, a previous hospitalization for heart failure is associated with higher risks of mortality and readmission in both HFpEF and HFrEF. The relative risks of death and heart failure readmission appear to be higher in HFpEF than in HFrEF.

Opioid Use and Outcomes in Hospitalized Older Patients With Heart Failure Receiving and Not Receiving Hospice Referrals.

BACKGROUND: The use of opioids is associated with poor outcomes. Less is known about this association in patients with heart failure (HF) and whether it varies by the receipt of hospice care. METHODS: Of the 7467 patients hospitalized for HF without previous opioid use, 124 received discharge opioids. We matched 123 of these patients with 123 not receiving opioids based on their propensity scores for opioid use, thus assembling a matched cohort of 246 patients balanced on 30 baseline characteristics (mean age, 76 years, 60% women, and 11% African American). We repeated the process in hospice (n = 155; 20 received opioids) and nonhospice (n = 7298; 104 received opioids) subgroups, thus assembling 2 matched cohorts of 22 and 208 patients, respectively. Hazard ratios (HRs) and 95% confidence intervals (CIs) associated with opioid use were estimated from matched cohorts. RESULTS: During 8.6 (median, 1.4) years of follow-up, all-cause mortality occurred in 80% and 68% of matched patients in the opioid and nonopioid groups, respectively (HR, 1.49; 95% CI, 1.11-1.99; P = 0.008). There was evidence of heterogeneity in this association between hospice and nonhospice patients (P for interaction, 0.027). Among matched hospice and nonhospice patients, HRs (95% CIs) for mortality were 6.37 (2.06-19.69; P = 0.001) and 1.42 (1.03-1.96; P = 0.035), respectively. HRs (95% CIs) for 30-day and 1-year mortality were 1.98 (1.06-3.70; P = 0.033) and 1.72 (1.18-2.49; P = 0.004), respectively. HRs (95% CIs) for all-cause, HF, and non-HF readmissions were 1.31 (0.97-1.76; P = 0.079), 1.03 (0.71-1.49; P = 0.866), and 1.75 (1.05-2.91; P = 0.031), respectively. Readmission associations were similar among matched nonhospice patients. There was no readmission among matched hospice patients receiving opioids. CONCLUSIONS: In older patients with HF, opioid use is associated with a higher risk of mortality, which is greater in the hospice subgroup, and a higher risk of non-HF readmission in the nonhospice subgroup.

Early Effects of Starting Doses of Enalapril in Patients with Chronic Heart Failure in the SOLVD Treatment Trial.

BACKGROUND: In the Studies of Left Ventricular Dysfunction (SOLVD) treatment trial, similar clinical benefits were observed between starting doses of enalapril and the target dose achieved by postrandomization up-titration. In our current analysis, protecting the randomization, we examined the early effects of starting doses of enalapril. METHODS: There were 2569 patients with mild-to-moderate chronic heart failure with reduced ejection fraction (ejection fraction ≤35%) randomized to receive starting doses (5-10 mg/day) of placebo (n = 1284) or enalapril (n = 1285). At day 14, both study drugs were blindly up-titrated to the target dose (20 mg/day). Overall, 96% (2458/2569) of the patients returned for dose up-titration, which was achieved in 59% (1444/2458), 48% (696/1444) of whom were in the enalapril group. Hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes in the enalapril group were estimated. RESULTS: HRs (95% CIs) for all-cause mortality, heart failure hospitalization, and the combined endpoint of heart failure hospitalization or all-cause mortality at 14 days after randomization were 0.80 (0.32-2.03), 0.63 (0.35-1.12), and 0.65 (0.39-1.06), respectively. Corresponding HRs (95% CIs) at 30 days were 0.82 (0.41-1.67), 0.43 (0.27-0.68), and 0.43 (0.27-0.68), respectively. The magnitude of these early effects of starting doses of enalapril is similar to its previously reported long-term effects at the target dose. CONCLUSION: These data suggest that in stable ambulatory patients with heart failure with reduced ejection fraction, the magnitude of the early effect of starting doses of enalapril is similar to that observed during longer-term therapy with the target doses of the drug.

Renin-Angiotensin Inhibition and Outcomes in Nursing Home Residents With Heart Failure.

BACKGROUND: Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs-ARBs) improve outcomes in heart failure (HF). Less is known about this association in nursing home (NH) residents. METHODS: Of the 8024 hospitalized HF patients, 542 were NH residents, of whom 250 received ACEIs-ARBs. We assembled a propensity score-matched cohort of 157 pairs of NH residents receiving and not receiving ACEIs-ARBs balanced on 29 baseline characteristics (mean age, 83 years, 74% women, 17% African American), in which we estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for outcomes associated with ACEI-ARB use. We then checked for interaction in a matched cohort of 5130 patients (378 were NH residents) assembled from the 8024 patients. RESULTS: Among 314 matched NH residents, HRs (95% CIs) for 30-day all-cause readmission, HF readmission, and all-cause mortality were 0.78 (0.47-1.28), 0.68 (0.29-1.60), and 1.26 (0.70-2.27), respectively. Respective HRs (95% CIs) at 1 year were 0.76 (0.56-1.02), 0.68 (0.42-1.09), and 1.04 (0.78-1.38). Among 5130 matched patients, ACEI-ARB use was associated with a significantly lower risk of all outcomes at both times, with no significant interactions, except for 1-year mortality, which was only significant in the non-NH subgroup (P for interaction, 0.026). CONCLUSIONS: We found no evidence that the use of ACEIs or ARBs is associated with improved outcomes in patients with HF in the NH setting. However, we also found no evidence that this association is different in NH residents with HF versus non-NH patients with HF. Future larger studies are needed to demonstrate effectiveness of these drugs in the NH setting.