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.

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.

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.

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.

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.

Systolic Blood Pressure and Outcomes in Patients With Heart Failure With Reduced Ejection Fraction.

BACKGROUND: National guidelines recommend that systolic blood pressure (SBP) in patients with heart failure with reduced ejection fraction (HFrEF) and hypertension be maintained below 130 mm Hg. OBJECTIVES: This study sought to determine associations of SBP <130 mm Hg with outcomes in patients with HFrEF. METHODS: Of the 25,345 patients in the Medicare-linked OPTIMIZE-HF registry, 10,535 had an ejection fraction (EF) ≤40%. Of these, 5,615 had stable SBP (≤20 mm Hg admission to discharge variation), and 3,805 (68%) had a discharge SBP <130 mm Hg. Propensity scores for SBP <130 mm Hg, estimated for each of the 5,615 patients, were used to assemble a matched cohort of 1,189 pairs of patients with SBP <130 versus ≥130 mm Hg, balanced on 58 baseline characteristics (mean age 76 years; mean EF 28%, 45% women, 13% African American). This process was repeated in 3,946 patients, after excluding 1,669 patients (30% of 5,615) with a discharge SBP <110 mm Hg and assembled a second matched balanced cohort of 1,099 pairs of patients with SBP 110 to 129 mm Hg versus ≥130 mm Hg. RESULTS: Thirty-day all-cause mortality occurred in 7% and 4% of matched patients with SBP <130 mm Hg versus ≥130 mm Hg, respectively (hazard ratio [HR]: 1.76; 95% confidence interval [CI]: 1.24 to 2.48; p = 0.001). HRs (95% CIs) for all-cause mortality, all-cause readmission, and HF readmission at 1 year, associated with SBP <130 mm Hg, were 1.32 (1.15 to 1.53; p < 0.001), 1.11 (1.01 to 1.23; p = 0.030), and 1.24 (1.09 to 1.42; p = 0.001), respectively. HRs (95% CIs) for 30-day and 1-year all-cause mortality associated with SBP 110 to 129 mm Hg (vs. ≥130 mm Hg) were 1.50 (1.03 to 2.19; p = 0.035), and 1.19 (1.02 to 1.39; p = 0.029), respectively. CONCLUSIONS: Among hospitalized older patients with HFrEF, SBP <130 mm Hg is associated with poor outcomes. This association persisted when the analyses were repeated after excluding patients with SBP <110 mm Hg. There is an urgent need for randomized controlled trials to evaluate optimal SBP reduction goals in patients with HFrEF.

Heart Rate and Outcomes in Hospitalized Patients With Heart Failure With Preserved Ejection Fraction.

BACKGROUND: A lower heart rate is associated with better outcomes in patients with heart failure (HF) with reduced ejection fraction (EF). Less is known about this association in patients with HF with preserved ejection fraction (HFpEF). OBJECTIVES: The aims of this study were to examine associations of discharge heart rate with outcomes in hospitalized patients with HFpEF. METHODS: Of the 8,873 hospitalized patients with HFpEF (EF ≥50%) in the Medicare-linked OPTIMIZE-HF (Organized Program to Initiate Lifesaving Treatment in Hospitalized Patients with Heart Failure) registry, 6,286 had a stable heart rate, defined as ≤20 beats/min variation between admission and discharge. Of these, 2,369 (38%) had a discharge heart rate of <70 beats/min. Propensity scores for discharge heart rate <70 beats/min, estimated for each of the 6,286 patients, were used to assemble a cohort of 2,031 pairs of patients with heart rate <70 versus ≥70 beats/min, balanced on 58 baseline characteristics. RESULTS: The 4,062 matched patients had a mean age of 79 ± 10 years, 66% were women, and 10% were African American. During 6 years (median 2.8 years) of follow-up, all-cause mortality was 65% versus 70% for matched patients with a discharge heart rate <70 versus ≥70 beats/min, respectively (hazard ratio [HR]: 0.86; 95% confidence interval [CI]: 0.80 to 0.93; p < 0.001). A heart rate <70 beats/min was also associated with a lower risk for the combined endpoint of HF readmission or all-cause mortality (HR: 0.90; 95% CI: 0.84 to 0.96; p = 0.002), but not with HF readmission (HR: 0.93; 95% CI: 0.85 to 1.01) or all-cause readmission (HR: 1.01; 95% CI: 0.95 to 1.08). Similar associations were observed regardless of heart rhythm or receipt of beta-blockers. CONCLUSIONS: Among hospitalized patients with HFpEF, a lower discharge heart rate was independently associated with a lower risk of all-cause mortality, but not readmission.

Lack of evidence of lower 30-day all-cause readmission in Medicare beneficiaries with heart failure and reduced ejection fraction discharged on spironolactone.

BACKGROUND: Therapy with evidence-based heart failure (HF) medications has been shown to be associated with lower risk of 30-day all-cause readmission in patients with HF and reduced ejection fraction (HFrEF). METHODS: We examined the association of aldosterone antagonist use with 30-day all-cause readmission in this population. Of the 2443 Medicare beneficiaries with HF and left ventricular EF ≤35% discharged home from 106 Alabama hospitals during 1998-2001, 2060 were eligible for spironolactone therapy (serum creatinine ≤2.5 for men and ≤2mg/dl for women, and serum potassium <5mEq/L). After excluding 186 patients already receiving spironolactone on admission, the inception cohort consisted of 1874 patients eligible for a new discharge prescription for spironolactone, of which 329 received one. Using propensity scores for initiation of spironolactone therapy, we assembled a matched cohort of 324 pairs of patients receiving and not receiving spironolactone balanced on 34 baseline characteristics (mean age 72years, 42% women, 33% African American). RESULTS: Thirty-day all-cause readmission occurred in 17% and 19% of matched patients receiving and not receiving spironolactone, respectively (hazard ratio [HR], 0.92; 95% confidence interval [CI], 0.64-1.32; p=0.650). Spironolactone had no association with 30-day all-cause mortality (HR, 0.84; 95% CI, 0.38-1.88; p=0.678) or HF readmission (HR, 0.74; 95% CI, 0.41 1.31; p=0.301). These associations remained unchanged during 12months of post-discharge follow-up. CONCLUSION: A discharge prescription for spironolactone had no association with 30-day all-cause readmission among older, hospitalized Medicare beneficiaries with HFrEF eligible for spironolactone therapy.

Association of 30-Day All-Cause Readmission with Long-Term Outcomes in Hospitalized Older Medicare Beneficiaries with Heart Failure.

BACKGROUND: Heart failure is the leading cause for 30-day all-cause readmission. We examined the impact of 30-day all-cause readmission on long-term outcomes and cost in a propensity score-matched study of hospitalized patients with heart failure. METHODS: Of the 7578 Medicare beneficiaries discharged with a primary diagnosis of heart failure from 106 Alabama hospitals (1998-2001) and alive at 30 days after discharge, 1519 had a 30-day all-cause readmission. Using propensity scores for 30-day all-cause readmission, we assembled a matched cohort of 1516 pairs of patients with and without a 30-day all-cause readmission, balanced on 34 baseline characteristics (mean age 75 years, 56% women, 24% African American). RESULTS: During 2-12 months of follow-up after discharge from index hospitalization, all-cause mortality occurred in 41% and 27% of matched patients with and without a 30-day all-cause readmission, respectively (hazard ratio 1.68; 95% confidence interval 1.48-1.90; P <.001). This harmful association of 30-day all-cause readmission with mortality persisted during an average follow-up of 3.1 (maximum, 8.7) years (hazard ratio 1.33; 95% confidence interval 1.22-1.45; P <.001). Patients with a 30-day all-cause readmission had higher cumulative all-cause readmission (mean, 6.9 vs 5.1; P <.001), a longer cumulative length of stay (mean, 51 vs 43 days; P <.001), and a higher cumulative cost (mean, $38,972 vs $34,025; P = .001) during 8.7 years of follow-up. CONCLUSIONS: Among Medicare beneficiaries hospitalized for heart failure, 30-day all-cause readmission was associated with a higher risk of subsequent all-cause mortality, higher number of cumulative all-cause readmission, longer cumulative length of stay, and higher cumulative cost.

Medication Errors Despite Using Electronic Health Records: The Value of a Clinical Pharmacist Service in Reducing Discharge-Related Medication Errors.

BACKGROUND: Medication errors continue to exist despite the use of electronic health records and electronic prescribing; patient-centered medication reconciliation is important to decrease errors. OBJECTIVE: To identify whether a team-based approach with a pharmacist performing medication management and discharge medication reconciliation will reduce discharge-related medication errors in an academic tertiary care hospital already using an electronic health record and computerized physician order entry. DESIGN: Prospective nonrandomized controlled trial. PATIENTS: All patients were admitted to 2 of the 6 medicine teams from August 1, 2012, through October 31, 2012. INTERVENTION: On the intervention team, a pharmacist assisted with medication management, medication reconciliation, and medication education upon discharge. Although the physicians on the control team had access to a pharmacist, they rarely collaborated with the pharmacist. The numbers of discharge-related medication discrepancies on the intervention and control teams were compared. RESULTS: Collaboration with a pharmacist reduced discharge-related medication errors. The percentage of patients without medication errors within 72 hours of discharge was 93.8% on the intervention team compared with 40.2% on the control team (P < .0001). CONCLUSION: Pharmacist's involvement in the patient care team improved patient safety by decreasing discharge medication errors caused by using electronic health records and computerized physician order entry.