Preoperative use of angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers and diuretics increases the risk of dehydration after ileostomy formation: population-based cohort study.

BACKGROUND: Readmission rates following ileostomy formation are high. Dehydration and consecutive renal failure are common causes of readmission, potentially pronounced by drugs affecting the homeostasis. The aim of the study was to assess the risk of dehydration after ileostomy formation in patients treated with angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor blockers (ARB) or diuretics. METHOD: This nationwide population-based cohort study used data derived from the Colorectal Cancer Data Base of several Swedish healthcare registers. The study included all patients operated on with elective anterior resection and temporary ileostomy for rectal cancer clinically staged I-III in Sweden in 2007-2016. Exposure was at least two dispensations of ACEI, ARB or diuretics within 1 year prior to surgery. Outcome was 90-day readmission due to dehydration including acute renal failure. RESULTS: In total, 3252 patients were included with 1173 (36.1%) exposed to ACEI, ARB or diuretics. The cumulative incidence for 90-day readmission due to dehydration was 29.0% (151 of 520) for exposed versus 13.8% (98 of 712) for unexposed. The proportion of readmissions due to any reason was 44.3% (520 of 1173) for exposed compared to 34.2% (712 of 2079) for unexposed. The incidence rate ratio for readmission due to dehydration was 2.83 (95% c.i. 2.21 to 3.63, P < 0.001). The hazard rate ratio was 2.45 (95% c.i. 1.83 to 3.27, P < 0.001) after adjusting for age, gender and comorbidity. CONCLUSION: Medication with ACEI, ARB or diuretics defines a vulnerable patient group with increased risk of readmission due to dehydration after ileostomy formation.

Comparison of preventive effects of combined furosemide and mannitol versus single diuretics, furosemide or mannitol, on cisplatin-induced nephrotoxicity.

Cisplatin (CDDP)-induced nephrotoxicity is a common dose-limiting toxicity, and diuretics are often administered to prevent nephrotoxicity. However, the efficacy and optimal administration of diuretics in preventing CDDP-induced nephrotoxicity remain to be established. This study aimed to evaluate the efficacy of combining furosemide and mannitol to prevent CDDP-induced nephrotoxicity. This was a post-hoc analysis of pooled data from a multicenter, retrospective, observational study, including 396 patients who received one or two diuretics for CDDP-based chemotherapy, compared using propensity score matching. Multivariate logistic regression analyses were used to identify risk factors for nephrotoxicity. There was no significant difference in the incidence of nephrotoxicity between the two groups (22.2% vs. 28.3%, P = 0.416). Hypertension, CDDP dose ≥ 75 mg/m2, and no magnesium supplementation were identified as risk factors for nephrotoxicity, whereas the use of diuretics was not found to be a risk factor. The combination of furosemide and mannitol showed no advantage over a single diuretic in preventing CDDP-induced nephrotoxicity. The renal function of patients receiving CDDP-based chemotherapy (≥ 75 mg/m2) and that of those with hypertension should be carefully monitored. Magnesium supplementation is important for these patients.

Incident Diuretic Use and Subsequent Risk of Bone Fractures: A Large Nationwide Observational Study of US Veterans.

OBJECTIVE: To investigate the association of incident use of diuretics with subsequent risk of incident bone fractures. PATIENTS AND METHODS: In a nationwide cohort of 863,339 US veterans receiving care from the VA health care system between October 1, 2004, and September 30, 2006, with follow-up through June 30, 2018, we examined the association of incident diuretic use (overall, and separately by thiazide, loop, and potassium-sparing diuretics) with subsequent risk of incident bone fractures using multivariable Cox regression models while minimizing confounding by indication using a target trial emulation approach. RESULTS: Patients were 63.3±12.9 years old; 93.5% (n=807,180) were male; and 27.1% (n=233,996) were diabetic. Their baseline estimated glomerular filtration rate was 84.4±16.5 mL/min per 1.73 m2. Among 863,339 patients, 424,386 (49.2%) newly initiated diuretics, of which 77.4% (n=328,524), 22.5% (n=95,457), and 0.1% (n=405) were thiazide, loop, and potassium-sparing diuretic users, respectively. After multivariable adjustments, incident diuretic use (vs non-use) was significantly associated with higher risk of incident fracture (adjusted HR [aHR], 1.14; 95% CI, 1.11 to 1.16). The association was most pronounced for loop diuretics (aHR, 1.39; 95% CI, 1.35 to 1.44) but less evident for thiazide diuretics (aHR, 1.08; 95% CI, 1.06 to 1.10) and was not significant for potassium-sparing diuretics (aHR, 0.97; 95% CI, 0.62 to 1.52). The diuretic-fracture association was more evident in younger (vs older) patients, those with (vs without) corticosteroid use, and those with lower (vs higher) serum sodium levels. CONCLUSION: Incident use of diuretics, particularly loop diuretics, was independently associated with higher risk of incident bone fractures. Our findings suggest distinct pathophysiologic contributions of diuretics to bone metabolism and the need for careful attention to skeletal outcomes when initiating diuretics.

Comparative safety and effectiveness of angiotensin converting enzyme inhibitors and thiazides and thiazide-like diuretics under strict monotherapy.

Previous work comparing safety and effectiveness outcomes for new initiators of angiotensin converting-enzyme inhibitors (ACEi) and thiazides demonstrated more favorable outcomes for thiazides, although cohort definitions allowed for addition of a second antihypertensive medication after a week of monotherapy. Here, we modify the monotherapy definition, imposing exit from cohorts upon addition of another antihypertensive medication. We determine hazard ratios (HR) for 55 safety and effectiveness outcomes over six databases and compare results to earlier findings. We find, for all primary outcomes, statistically significant differences in effectiveness between ACEi and thiazides were not replicated (HRs: 1.11, 1.06, 1.12 for acute myocardial infarction, hospitalization with heart failure and stroke, respectively). While statistical significance is similarly lost for several safety outcomes, the safety profile of thiazides remains more favorable. Our results indicate a less striking difference in effectiveness of thiazides compared to ACEi and reflect some sensitivity to the monotherapy cohort definition modification.

Non-steroidal anti-inflammatory drugs, renin-angiotensin system blockade or diuretics and risk of acute kidney injury: A case-crossover study.

BACKGROUND: Aging-related physiological changes, such as decline in renal function, not only exacerbates pre-existing comorbidities but also escalate the susceptibility to adverse events. Previous studies have shown that non-steroidal anti-inflammatory drugs (NSAIDs) are associated with an increased risk of acute kidney injury (AKI), and the concomitant use of renin-angiotensin system blockade or diuretics may further potentiate the risk. However, studies evaluating the risk of AKI associated with NSAIDs (including routes, concomitant use of different NSAIDs, categories (traditional NSAIDs or COX-2 inhibitors), and cumulative doses of NSAIDs) are limited, particularly the risk of AKI associated with the dual or triple combination of NSAIDs with renin-angiotensin system blockade (RAS blockades) and/or diuretics. METHODS: A case-crossover study utilized two sets of longitudinal data from Taiwan's National Health Insurance Research Database (NHIRD). Newly admitted patients with a primary AKI diagnosis were included, with the index date defined as the first admission date. The 1-7 days and 181-187 days prior to the index date served as the case and control periods. Exposure to NSAIDs and co-exposures of RAS blockade and/or diuretics were assessed in both periods. Multivariable conditional logistic regression models, adjusting for potential confounders, estimated adjusted odds ratios (aORs) and 95 % confidence intervals (CIs) for AKI associated with NSAIDs, dual, or triple combinations. Sensitivity analyses explored result robustness by varying case and control period lengths. RESULTS: The study included 1,284 newly diagnosed AKI patients. NSAIDs showed a 3.55-fold increased risk of AKI (aOR: 3.55; 95 % CI 2.70-4.65), with similar risks for traditional NSAIDs and COX-2 inhibitors. Use of multiple NSAIDs, parenteral dosage forms, and higher cumulative doses increased AKI risk. Dual combination with either RAS blockade or diuretics resulted in a 2.90-fold (aOR: 2.90; 95 %CI 1.47-5.70) and 12.68-fold (aOR: 12.68; 95 %CI 6.15-26.12) risk, respectively. The highest risk occurred with triple combination (aOR: 29.22; 95 %CI 12.82-66.64). CONCLUSIONS: NSAIDs, including both non-selective NSAIDs and COX2 inhibitors, elevate the risk of AKI. Increased AKI risk is linked to using multiple NSAIDs, the parenteral dosage form, and higher cumulative doses. Dual combination of RAS blockade with NSAIDs or diuretics with NSAIDs, as well as triple therapy, heightens the risk, with the latter associated with the highest risk of AKI.

The Role of Sodium-Glucose Co-Transporter-2 Inhibitors on Diuretic Resistance in Heart Failure.

Heart failure (HF) remains a major cause of morbidity and mortality worldwide. Recently, significant advances have been made in its treatment; however, diuretics remain the cornerstone in managing congestion in HF. Although diuretic resistance poses a significant challenge in the management of HF and is associated with poor outcomes, only limited alternative pharmaceutical options are available in clinical practice. The objective of this narrative review is to provide a comprehensive analysis of the current evidence on the effects of sodium-glucose co-transporter-2 (SGLT-2) inhibitors on diuretic resistance in HF patients. The primary emphasis is placed on clinical data that assess the impact of SGLT-2 inhibitors on fluid balance, symptom improvement, and clinical outcomes and secondarily on safety profile and potential adverse effects associated with SGLT-2 inhibitor use in acute decompensated HF. The current evidence on the efficacy of SGLT-2 on diuretic resistance remains controversial. Findings from observational and randomized studies are quite heterogenous; however, they converge on the notion that although SGLT-2 inhibitors show promise for mitigating diuretic resistance in HF, their diuretic effect may not be potent enough to be widely used to relieve objective signs of congestion in patients with HF. Importantly, the introduction of SGLT-2 inhibitors in HF treatment appears to be generally well tolerated, with manageable adverse effects. Further research is needed to investigate the underlying mechanisms and the possible beneficial impact of SGLT-2 inhibitors on diuretic resistance in HF.

Risk of CKD among patients with DM taking diuretics or SGLT2i: a retrospective cohort study in Taiwan.

BACKGROUND: This study aimed to evaluate the long-term risk of CKD and renal function declines using a combination of diuretics and SGLT2i. METHODS: We selected the data of subjects who had at least two outpatient records or at least one inpatient record for DM treatment as the DM group from the National Health Insurance Research Database (NHIRD). Patients receiving versus not receiving SGLT2i were defined as the SGLT2i and non-SGLT2i cohorts, respectively. The patients in the two groups were matched 1:1 through propensity score matching based on age, sex, year of index date, and comorbidities. RESULTS: The diuretics-only group had a higher risk of CKD (aHR, 2.46; 95% CI, 1.68-3.61) compared to the neither SGLT2i nor diuretics group, while the both SGLT2i and diuretics group and the SGLT2i only group had lower risks (aHR, 0.45, 95% CI, 0.32-0.63; aHR, 0.26, 95% CI, 0.17-0.40) than the diuretics-only group. The SGLT2i-only group had a lower risk (aHR, 0.58, 95% CI, 0.36-0.94) than the both SGLT2i and diuretics group. CONCLUSION: This study indicates that diuretics could raise the risk of CKD in diabetic patients, but when used in combination with SGLT2i, they continue to offer protection against CKD.

Could admission level of uric acid predict total diuretic dose in acute heart failure?

BACKGROUND: Recent studies have shown that increases in serum UA levels are associated with adverse clinical outcomes in patients with chronic heart failure (CHF); the aim of this study was to determine the relationship between serum uric acid and total diuretic dose received during hospitalization in hospitalized patients with acute exacerbation of heart failure. The main purpose of this study is to determine the role of uric acid as a biomarker that can be a substitute for pro-BNP in clinical evaluation and the need for diuretics in hospitalized patients with acute heart failure. METHODS: After approving the plan in the Research Council of the Heart Department and obtaining an ethical code from the Regional Committee on Research Ethics (Human Subjects Studies), the researcher referred to the archives of our center, the case of 100 patients diagnosed with acute heart failure. Cardiac patients were selected, and the information required for the study was collected using a pre-prepared data collection form, and the information was entered into SPSS software after categorization and appropriate analysis and statistical tests were performed on it. Were performed and in all statistical tests the statistical significance level was considered 0.05: RESULTS: 100 patients with acute heart failure were included in this study with a mean age of 63.43 ± 14.78 years. 66% of them were men. The mean dose of furosemide in these patients was 680.92 ± 377.47 mg and the mean serum uric acid level in these patients was 8.55 ± 2.50 mg / dL. In the study of the relationship between the variables, there was a significant relationship between the dose of furosemide received with the serum level of serum uric acid (P = 0.017, r = 0.248 and P = 0.009, r = -0.267, respectively). There is also a significant relationship between serum uric acid level and patient mortality (P = 0.013, r = 0.247). However this relationship lost its significance after multivariate analysis. CONCLUSION: There is a significant relationship between serum uric acid level and diuretic use. However, in-hospital mortality is not related to uric acid levels at admission.

Severe methotrexate toxicity in elderly patients under diuretics.

OBJECTIVES: To explore the toxicity of low-dose methotrexate (MTX), an uncommon, but life-threatening event. METHODS: We analysed the presentation, course and risk factors of all patients admitted to the rheumatology ward with severe low-dose MTX toxicity. These patients were compared with patients without signs of relevant MTX toxicity. RESULTS: The 12 patients admitted for MTX toxicity included 7 patients with rheumatoid arthritis, 2 with psoriatic arthritis or psoriasis, 2 patients with giant cell arteritis and 1 with myositis. 1 patient died from infections, while 11 survived under folinic acid administration. All patients suffering from severe MTX toxicity were older than 70 years and were therefore compared with 400 patients who were also older than 70 years, but without MTX toxicity. Of these 400 control patients, the group of patients not on MTX (n=232) had more renal impairment than the group of patients on MTX (n=168). Compared with the 168 MTX-treated patients without toxicity, the 12 patients with life-threatening toxic events had a lower median estimated glomerular filtration rate (eGFR) at the routine visit preceding the acute event (64 (range 32-77) vs 69 (range 8 to >90) mL/min x 1.73, p=0.0251). A multivariate analysis found that patients with toxicity were more frequently treated with diuretics (6/12 vs 24/168), proton pump inhibitors (PPIs; 10/12 vs 70/168) and levetiracetam (2/12 vs 1/168). CONCLUSIONS: Patients older than 70 years with lower eGFR and being on diuretics, but also on PPIs and levetiracetam, have a significantly higher risk for MTX toxicity.

Diuretic Use in Post-Kidney Transplant Patients: A Retrospective Chart Review.

BACKGROUND: The occurrence of delayed graft function (DGF) significantly enhances the possibility of both acute and chronic rejection of the transplanted organ, thereby reducing patient quality of life and survival rates. To prevent and manage oliguria in renal transplant patients, loop diuretics are presently commonly used. In our study, we assessed the possible impact of furosemide on the incidence of DGF among kidney transplant recipients. METHODS: A review of medical records was conducted to examine demographic characteristics and kidney transplant outcomes in an adult (older than 18 years old) population. The primary objective was to determine the incidence of delayed graft function (DGF), whereas the secondary objective was to compare the creatinine levels and estimated glomerular filtration rate (eGFR) at day 30 and day 90 post-transplantation in patients who were administered furosemide vs those who were not. RESULTS: This study included 330 patients who underwent kidney transplantation. Furosemide was administered to 169 (51.3%), whereas 161(48.7%) patients did not receive continued dose of diuretic postoperatively. The rate of DGF was significantly higher in patients who received furosemide than in those who did not (furosemide 44% vs 4%; P < .001). The eGFR was lower in the furosemide group compared to the no furosemide group at day 30 (56 ± 24 vs 71 ± 24 mL/min/1.73 m2, P < .001) and day 90 (66 ± 27 vs 78 ± 25 mL/min/1.73 m2, P < .001). CONCLUSIONS: Our results show that there is no benefit in treating an oliguric AKI with furosemide. Administration of furosemide, especially in high doses, may increase the risk of toxicity, delay dialysis, and increase the length of stay.

Thiazide Diuretics and Risk of Colorectal Cancer: A Population-Based Cohort Study.

Evidence from clinical trials and observational studies on the association between thiazide diuretics and colorectal cancer risk is conflicting. We aimed to determine whether thiazide diuretics are associated with an increased colorectal cancer risk compared with dihydropyridine calcium channel blockers (dCCBs). A population-based, new-user cohort was assembled using the UK Clinical Practice Research Datalink. Between 1990-2018, we compared thiazide diuretic initiators with dCCB initiators and estimated hazard ratios (HR) with 95% confidence intervals (CIs) of colorectal cancer using Cox proportional hazard models. Models were weighted using standardized morbidity ratio weights generated from calendar time-specific propensity scores. The cohort included 377,760 thiazide diuretic initiators and 364,300 dCCB initiators, generating 3,619,883 person-years of follow-up. Compared with dCCBs, thiazide diuretics were not associated with colorectal cancer (weighted HR = 0.97, 95% CI: 0.90, 1.04). Secondary analyses yielded similar results, although an increased risk was observed among patients with inflammatory bowel disease (weighted HR = 2.45, 95% CI: 1.13, 5.35) and potentially polyps (weighted HR = 1.46, 95% CI: 0.93, 2.30). Compared with dCCBs, thiazide diuretics were not associated with an overall increased colorectal cancer risk. While these findings provide some reassurance, research is needed to corroborate the elevated risks observed among patients with inflammatory bowel disease and history of polyps.

Use of furosemide in preterm neonates with acute kidney injury is associated with increased mortality: results from the TINKER registry.

BACKGROUND: Diuretics are commonly used in neonatal AKI with the rationale to decrease positive fluid balance in critically sick neonates. The patterns of furosemide use vary among hospitals, which necessitates the need for a well-designed study. METHODS: The TINKER (The Indian Iconic Neonatal Kidney Educational Registry) study provides a database, spanning 14 centres across India since August 2018. Admitted neonates (≤ 28 days) receiving intravenous fluids for at least 48 h were included. Neonatal KDIGO criteria were used for the AKI diagnosis. Detailed clinical and laboratory parameters were collected, including the indications of furosemide use, detailed dosing, and the duration of furosemide use (in days). RESULTS: A total of 600 neonates with AKI were included. Furosemide was used in 8.8% of the neonates (53/600). Common indications of furosemide use were significant cardiac disease, fluid overload, oliguria, BPD, RDS, hypertension, and hyperkalemia. The odds of mortality was higher in neonates < 37 weeks gestational age with AKI who received furosemide compared to those who did not receive furosemide 3.78 [(1.60-8.94); p = 0.003; univariate analysis] and [3.30 (1.11-9.82); p = 0.03]; multivariate logistic regression]. CONCLUSIONS: In preterm neonates with AKI, mortality was independently associated with furosemide treatment. The furosemide usage rates were higher in neonates with associated co-morbidities, i.e. significant cardiac diseases or surgical interventions. Sicker babies needed more resuscitation at birth, and died early, and hence needed shorter furosemide courses. Thus, survival probability was higher in neonates treated with long furosemide courses vs. short courses.

Association of a calcium channel blocker and diuretic prescribing cascade with adverse events: A population-based cohort study.

BACKGROUND: Prescribing cascades occur when a drug adverse event is misinterpreted as a new medical condition and a second, potentially unnecessary drug, is prescribed to treat the adverse event. The population-level consequences of prescribing cascades remain unknown. METHODS: This population-based cohort study used linked health administrative databases in Ontario, Canada. The study included community-dwelling adults, 66 years of age or older with hypertension and no history of heart failure (HF) or diuretic use in the prior year, newly dispensed a calcium channel blocker (CCB). Individuals subsequently dispensed a diuretic within 90 days of incident CCB dispensing were classified as the prescribing cascade group, and compared to those not dispensed a diuretic, classified as the non-prescribing cascade group. Those with and without a prescribing cascade were matched one-to-one on the propensity score and sex. The primary outcome was a serious adverse event (SAE), which was the composite of emergency room visits and hospitalizations in the 90-day follow-up period. We estimated hazard ratios (HRs) with 95% confidence intervals (CI) for SAE using an Andersen-Gill recurrent events regression model. RESULTS: Among 39,347 older adults with hypertension and no history of HF who were newly dispensed a CCB, 1881 (4.8%) had a new diuretic dispensed within 90 days after CCB initiation. Compared to the non-prescribing cascade group, those in the prescribing cascade group had higher rates of SAEs (HR: 1.21, 95% CI: 1.02-1.43). CONCLUSIONS: The CCB-diuretic prescribing cascade was associated with an increased rate of SAEs, suggesting harm beyond prescribing a second drug therapy. Our study raises awareness of the downstream impact of the CCB-diuretic prescribing cascade at a population level and provides an opportunity for clinicians who identify this prescribing cascade to review their patients' medications to determine if they can be optimized.

Levels of Albumin and Impact on Loop Diuretic and Albumin Co-administration in Heart Failure.

ABSTRACT: Management of heart failure (HF) requires the use of loop diuretics to relieve congestion and improve symptoms. When loop diuretics alone fail to induce adequate diuresis, albumin has been proposed to enhance loop diuretic delivery and promote redistribution of fluid for excretion by the kidneys. Despite the theoretical benefits of albumin, studies suggesting its benefit in HF are scarce and the co-administration of loop diuretics and albumin remains controversial. This retrospective, observational study evaluated patients with HF 18 years or older who received concomitant intravenous loop diuretic and albumin administration. The primary objective was to evaluate the association of serum albumin level with urine output (UOP) in hospitalized patients with HF who received concomitant albumin and loop diuretic therapy. Secondary endpoints included total weight loss after 72 hours, and ICU and hospital lengths of stay. In total, 276 patients were included for analysis. There was no association between initial serum albumin level and 72-hour UOP (coefficient -623.1, 95% confidence interval -1558.6 to 312.4; P = 0.191) or weight difference at 72 hours (coefficient -1.0, 95% confidence interval -2.4 to 0.3; P = 0.131). Lower albumin levels were associated with longer ICU ( P = 0.034) and hospital ( P = 0.039) lengths of stay. Concomitant thiazide diuretic use and increasing loop diuretic doses were associated with increased 72-hour UOP. The results of our study suggests that providers should avoid using baseline albumin levels as guidance for albumin dosing in HF. Given the lack of comparator groups, larger randomized controlled trials should be done to provide a definitive role for albumin to enhance diuresis in patients with HF on intravenous loop diuretics.

Influence of vasopressin receptor antagonists on triple-whammy acute kidney injury: A VigiBase analysis.

Although diuretics play an important role in triple-whammy acute kidney injury (AKI), it is unclear whether the type of diuretic influences the risk of triple-whammy AKI. The aim of this study was to evaluate whether vasopressin receptor antagonists affect triple-whammy AKI. This cross-sectional study used disproportionality analysis of VigiBase data to assess the risk of AKI with various diuretics. Although multiple logistic regression analysis showed that aldosterone antagonists (odds ratio [OR] 2.19, 95% CI 2.01-2.37), loop diuretics (OR 4.40, 95% CI 4.07-4.76) and thiazide diuretics (OR 1.98, 95% CI 1.83-2.15) increased the risk of AKI in patients who received non-steroidal anti-inflammatory drugs (NSAIDs) and renin-angiotensin system inhibitors (RASi), vasopressin receptor antagonists did not increase the risk of AKI in those patients. Vasopressin receptor antagonists might not influence the development of triple-whammy AKI.

Timing of Worsening Renal Function in Patients Hospitalized for Heart Failure Exacerbation Who Were Being Treated With Intravenous Diuretic Therapy.

BACKGROUND: This retrospective observational study investigated the incidence of worsening renal function (WRF) in patients hospitalized for heart failure (HF) and treated with intravenous diuretics in Japan.Methods and Results: Associations between WRF at any point and HF treatments, and the effects of WRF on outcomes were evaluated (Diagnosis Procedure Combination database). Of 1,788 patients analyzed (mean [±SD] age 80.5±10.2 years; 54.4% male), 641 (35.9%) had WRF during a course of hospitalization for worsening HF: 208 (32.4%) presented with WRF before admission (BA-WRF; estimated glomerular filtration rate decreased by ≥25% from baseline at least once between 30 days prior to admission and admission); 44 (6.9%) had WRF that persisted before and after admission (P-WRF); and 389 (60.7%) had WRF develop after admission (AA-WRF). Delayed initial diuretic administration, higher maximum doses of intravenous diuretics during hospitalization, and diuretic readministration during hospitalization were associated with a significantly higher incidence of AA-WRF. Patients with WRF at any time point were at higher risk of death during hospitalization compared with patients without WRF, with adjusted hazard ratios of 3.56 (95% confidence interval [CI] 2.23-5.69) for BA-WRF, 3.23 (95% CI 2.21-4.71) for AA-WRF, and 13.16 (95% CI 8.19-21.15) for P-WRF (all P<0.0001). CONCLUSIONS: Forty percent of WRF occurred before admission for acute HF; there was no difference in mortality between patients with BA-WRF and AA-WRF.