| 1. |
- Adamson, Carly, et al.
(författare)
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Efficacy of Dapagliflozin in Heart Failure with Reduced Ejection Fraction According to Body Mass Index.
- 2021
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 23:10, s. 1662-1672
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: In heart failure with reduced ejection fraction (HFrEF), there is an ’obesity paradox’, where survival is better in patients with a higher body mass index (BMI) and weight loss is associated with worse outcomes. We examined the effect of a sodium-glucose co-transporter 2 inhibitor according to baseline BMI in the Dapagliflozin And Prevention of Adverse- outcomes in Heart Failure trial (DAPA-HF). METHODS AND RESULTS: Body mass index was examined using standard categories, i.e. underweight ($<$18.5 kg/m(2) ); normal weight (18.5-24.9 kg/m(2) ); overweight (25.0-29.9 kg/m(2) ); obesity class I (30.0-34.9 kg/m(2) ); obesity class II (35.0-39.9 kg/m(2) ); and obesity class III ($>$/=40 kg/m(2) ). The primary outcome in DAPA-HF was the composite of worsening heart failure or cardiovascular death. Overall, 1348 patients (28.4%) were under/normal- weight, 1722 (36.3%) overweight, 1013 (21.4%) obesity class I and 659 (13.9%) obesity class II/III. The unadjusted hazard ratio (95% confidence interval) for the primary outcome with obesity class 1, the lowest risk group, as reference was: under/normal-weight 1.41 (1.16-1.71), overweight 1.18 (0.97-1.42), obesity class II/III 1.37 (1.10-1.72). Patients with class I obesity were also at lowest risk of death. The effect of dapagliflozin on the primary outcome and other outcomes did not vary by baseline BMI, e.g. hazard ratio for primary outcome: under/normal-weight 0.74 (0.58-0.94), overweight 0.81 (0.65-1.02), obesity class I 0.68 (0.50-0.92), obesity class II/III 0.71 (0.51-1.00) (P-value for interaction = 0.79). The mean decrease in weight at 8 months with dapagliflozin was 0.9 (0.7-1.1) kg (P $<$ 0.001). CONCLUSION: We confirmed an ’obesity survival paradox’ in HFrEF. We showed that dapagliflozin was beneficial across the wide range of BMI studied. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 2. |
- Adamson, Carly, et al.
(författare)
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IGFBP-7 and Outcomes in Heart Failure With Reduced Ejection Fraction : Findings From DAPA-HF.
- 2023
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Ingår i: JACC. Heart failure. - : Elsevier BV. - 2213-1779 .- 2213-1787. ; 11:3, s. 291-304
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Insulin-like growth factor-binding protein-7 (IGFBP-7) has been proposed as a potential prognostic biomarker in heart failure (HF), but the association between elevation in IGFBP-7 and HF outcomes in ambulant patients with heart failure with reduced ejection fraction (HFrEF) is unknown. OBJECTIVES: The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial. METHODS: The primary outcome was a composite of cardiovascular death or a worsening HF event. The risk of adverse outcome was compared across tertiles of IGFBP-7 concentration by means of Cox proportional hazard models adjusted for N-terminal pro-B- type natriuretic peptide (NT-proBNP) and high-sensitivity troponin T (hsTnT). The efficacy of randomized treatment across IGFBP-7 tertiles was assessed. Change in IGFBP-7 at 12 months was compared with the use of geometric means. RESULTS: A total of 3,158 patients had IGFBP-7 measured at baseline, and 2,493 had a repeated measure at 12 months. Patients in the highest tertile of IGFBP-7 had evidence of more advanced HFrEF. The adjusted HR for the primary endpoint in tertile 3, compared with tertile 1, was 1.48 (95% CI: 1.17-1.88). There was no modification of the benefit of dapagliflozin by baseline IGFBP-7 (P interaction = 0.34). Dapagliflozin did not change IGFBP-7 levels over 1 year (P = 0.34). CONCLUSIONS: Higher IGFBP-7 in patients with HFrEF was associated with worse clinical profile and an increased risk of adverse clinical outcomes. IGFBP-7 provided prognostic information incremental to clinical variables, NT-proBNP, and hsTnT. The benefit of dapagliflozin was not modulated by IGFBP-7 level. (Study to Evaluate the Effect of Dapagliflozin on the Incidence of Worsening Heart Failure or Cardiovascular Death in Patients With Chronic Heart Failure [DAPA-HF]; NCT03036124).
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| 3. |
- Adamson, Carly, et al.
(författare)
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Liver Tests and Outcomes in Heart Failure with Reduced Ejection Fraction : Findings from DAPA-HF.
- 2022
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Ingår i: European journal of heart failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 24:10, s. 1856-1868
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Reflecting both increased venous pressure and reduced cardiac output, abnormal liver tests are common in patients with severe heart failure and are associated with adverse clinical outcomes. We aimed to investigate the prognostic significance of abnormal liver tests in ambulatory patients with heart failure with reduced ejection fraction (HFrEF), explore any treatment interaction between bilirubin and sodium- glucose cotransporter 2 (SGLT2) inhibitors and examine change in liver tests with SGLT2 inhibitor treatment. METHODS AND RESULTS: We explored these objectives in the Dapagliflozin And Prevention of Adverse outcomes in Heart Failure (DAPA-HF) trial, with focus on bilirubin. We calculated the incidence of cardiovascular death or worsening heart failure by bilirubin tertile. Secondary cardiovascular outcomes were examined, along with the change in liver tests at the end-of-study visit. Baseline bilirubin was available in 4720 patients (99.5%). Participants in the highest bilirubin tertile (T3) have more severe HFrEF (lower left ventricular ejection fraction, higher N-terminal pro-B-type natriuretic peptide [NT-proBNP] and worse New York Heart Association class), had a greater burden of atrial fibrillation but less diabetes. Higher bilirubin (T3 vs. T1) was associated with worse outcomes even after adjustment for other predictive variables, including NT-proBNP and troponin T (adjusted hazard ratio for the primary outcome 1.73 [95% confidence interval 1.37-2.17], p $<$ 0.001; and 1.52 [1.12-2.07], p = 0.01 for cardiovascular death). Baseline bilirubin did not modify the benefits of dapagliflozin. During follow-up, dapagliflozin had no effect on liver tests. CONCLUSION: Bilirubin concentration was an independent predictor of worse outcomes but did not modify the benefits of dapagliflozin in HFrEF. Dapagliflozin was not associated with change in liver tests. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov NCT03036124.
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| 4. |
- Andersson, Charlotte, et al.
(författare)
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A risk score for predicting 30-day mortality in heart failure patients undergoing non-cardiac surgery
- 2014
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 16:12, s. 1310-1316
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundHeart failure is an established risk factor for poor outcomes in patients undergoing non-cardiac surgery, yet risk stratification remains a clinical challenge. We developed an index for 30-day mortality risk prediction in this particular group. Methods and resultsAll individuals with heart failure undergoing non-cardiac surgery between October 23 2004 and October 31 2011 were included from Danish administrative registers (n=16827). In total, 1787 (10.6%) died within 30days. In a simple risk score based on the variables from the revised cardiac risk index, plus age, gender, acute surgery, and body mass index category the following variables predicted mortality (points): male gender (1), age 56-65years (2), age 66-75years (4), age 76-85years (5), or age >85years (7), being underweight (4), normal weight (3), or overweight (1), undergoing acute surgery (5), undergoing high-risk procedures (intra-thoracic, intra-abdominal, or suprainguinal aortic) (3), having renal disease (1), cerebrovascular disease (1), and use of insulin (1). The c-statistic was 0.79 and calibration was good. Mortality risk ranged from <2% for a score <5 to >50% for a score 20. Internal validation by bootstrapping (1000 re-samples) provided c-statistic of 0.79. A more complex risk score based on stepwise logistic regression including 24 variables at P<0.05 performed only slightly better, c-statistic=0.81, but was limited in use by its complexity. ConclusionsFor patients with heart failure, this simple index can accurately identify those at low risk for perioperative mortality.
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| 5. |
- Andersson, Charlotte, et al.
(författare)
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Noncardiac Surgery in Patients With Aortic Stenosis: A Contemporary Study on Outcomes in a Matched Sample From the Danish Health Care System
- 2014
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Ingår i: Clinical Cardiology. - : Wiley. - 1932-8737 .- 0160-9289. ; 37:11, s. 680-686
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundPast research has identified aortic stenosis (AS) as a major risk factor for adverse outcomes in noncardiac surgery; however, more contemporary studies have questioned the grave prognosis. To further our understanding of this, the risks of a 30-day major adverse cardiovascular event (MACE) and all-cause mortality were investigated in a contemporary Danish cohort. HypothesisAS is not an independent risk factor for adverse outcomes in noncardiac surgery. MethodsAll patients with and without diagnosed AS who underwent noncardiac surgery in 2005 to 2011 were identified through nationwide administrative registers. AS patients (n=2823; mean age, 75.5years, 53% female) were matched with patients without AS (n=2823) on propensity score for AS and surgery type. ResultsIn elective surgery, MACE (ie, nonfatal myocardial infarction, ischemic stroke, or cardiovascular death) occurred in 66/1772 (3.7%) of patients with AS and 52/1772 (2.9%) of controls (P=0.19), whereas mortality occurred in 67/1772 (3.8%) AS patients and 51/1772 (2.9%) controls (P=0.13). In emergency surgery, 163/1051 (15.5%) AS patients and 120/1051 (11.4%) controls had a MACE (P=0.006), whereas 225/1051 (21.4%) vs 179/1051 (17.0%) AS patients and controls died, respectively (P=0.01). Event rates were higher for those with symptoms (defined as use of nitrates, congestive heart failure, or use of loop diuretics), compared with those without symptoms (P<0.0001). ConclusionsAS is associated with high perioperative rates of MACE and mortality, but perhaps prognosis is, in practice, not much worse for patients with AS than for matched controls. Symptomatic patients and patients undergoing emergency surgery are at considerable risks of a MACE and mortality.
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| 6. |
- Bang, Casper N., et al.
(författare)
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Effect of lipid lowering on new-onset atrial fibrillation in patients with asymptomatic aortic stenosis : The Simvastatin and Ezetimibe in Aortic Stenosis (SEAS) study
- 2012
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 163:4, s. 690-696
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Tidskriftsartikel (refereegranskat)abstract
- Background Lipid-lowering drugs, particularly statins, have anti-inflammatory and antioxidant properties that may prevent atrial fibrillation (AF). This effect has not been investigated on new-onset AF in asymptomatic patients with aortic stenosis (AS). Methods Asymptomatic patients with mild-to-moderate AS (n = 1,421) were randomized (1: 1) to double-blind simvastatin 40 mg and ezetimibe 10 mg combination or placebo and followed up for a mean of 4.3 years. The primary end point was the time to new-onset AF adjudicated by 12-lead electrocardiogram at a core laboratory reading center. Secondary outcomes were the correlates of new-onset AF with nonfatal nonhemorrhagic stroke and a combined end point of AS-related events. Results During the course of the study, new-onset AF was detected in 85 (6%) patients (14.2/1,000 person-years of follow-up). At baseline, patients who developed AF were, compared with those remaining in sinus rhythm, older and had a higher left ventricular mass index a smaller aortic valve area index. Treatment with simvastatin and ezetimibe was not associated with less new-onset AF (odds ratio 0.89 [95% CI 0.57-1.97], P = .717). In contrast, age (hazard ratio [HR] 1.07 [95% CI 1.05-1.10], P < .001) and left ventricular mass index (HR 1.01 [95% CI 1.01-1.02], P < .001) were independent predictors of new-onset AF. The occurrence of new-onset AF was independently associated with 2-fold higher risk of AS-related outcomes (HR 1.65 [95% CI 1.02-2.66], P = .04) and 4-fold higher risk of nonfatal nonhemorrhagic stroke (HR 4.04 [95% CI 1.18-13.82], P = .03). Conclusions Simvastatin and ezetimibe were not associated with less new-onset AF. Older age and greater left ventricular mass index were independent predictors of AF development. New-onset AF was associated with a worsening of prognosis. (Am Heart J 2012;163:690-6.)
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| 7. |
- Bang, Casper N., et al.
(författare)
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Four-Group Classification of Left Ventricular Hypertrophy Based on Ventricular Concentricity and Dilatation Identifies a Low-Risk Subset of Eccentric Hypertrophy in Hypertensive Patients
- 2014
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Ingår i: Circulation Cardiovascular Imaging. - 1941-9651 .- 1942-0080. ; 7:3, s. 422-429
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Tidskriftsartikel (refereegranskat)abstract
- Background-Left ventricular hypertrophy (LVH; high LV mass [LVM]) is traditionally classified as concentric or eccentric based on LV relative wall thickness. We evaluated the prediction of subsequent adverse events in a new 4-group LVH classification based on LV dilatation (high LV end-diastolic volume [EDV] index) and concentricity (mass/end-diastolic volume [M/EDV](2/3)) in hypertensive patients. Methods and Results-In the Losartan Intervention for Endpoint Reduction (LIFE) echocardiography substudy, 939 hypertensive patients with measurable LVM at baseline were randomized to a mean of 4.8 years of losartan- or atenolol-based treatment. Patients with LVH (LVM/body surface area >= 116 and >= 96 g/m(2) in men and woman, respectively) were divided into 4 groups-concentric nondilated (increased M/EDV, normal EDV), eccentric dilated (increased EDV, normal M/EDV), concentric dilated (increased M/EDV and EDV), and eccentric nondilated (normal M/EDV and EDV)-and compared with patients with normal LVM. Time-varying LVH classes were tested for association with all-cause and cardiovascular mortality and a composite end point of myocardial infarction, stroke, heart failure, and cardiovascular death in multivariable Cox analyses. At baseline, the LVs were categorized as eccentric nondilated in 12%, eccentric dilated in 20%, concentric nondilated in 29%, concentric dilated in 14%, and normal LVM in 25%. Treatment changed the prevalence of 4 LVH groups to 23%, 4%, 5%, and 7%; 62% had normal LVM after 4 years. In time-varying Cox analyses, compared with normal LVM, those with eccentric dilated and both concentric nondilated and dilated LVH had increased risks of all-cause or cardiovascular mortality or the composite end point, whereas the eccentric nondilated group did not. Conclusions-Hypertensive patients with relatively mild LVH without either increased LV volume or concentricity have similar risk of all-cause mortality or cardiovascular events because hypertensive patients with normal LVM seem to be a low-risk group.
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| 8. |
- Bang, Casper N., et al.
(författare)
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Renin-angiotensin system inhibition is not associated with increased sudden cardiac death, cardiovascular mortality or all-cause mortality in patients with aortic stenosis
- 2014
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Ingår i: International Journal of Cardiology. - : Elsevier BV. - 0167-5273 .- 1874-1754. ; 175:3, s. 492-498
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Tidskriftsartikel (refereegranskat)abstract
- Background: Renin-angiotensin system inhibition (RASI) is frequently avoided in aortic stenosis (AS) patients because of fear of hypotension. We evaluated if RASI with angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) increased mortality in patients with mild to moderate AS. Methods: All patients (n = 1873) from the Simvastatin and Ezetimibe in Aortic Stenosis study: asymptomatic patients with AS and preserved left ventricular (LV) ejection fraction were included. Risks of sudden cardiac death (SCD), cardiovascular death and all-cause mortality according to RASI treatment were analyzed by multivariable time-varying Cox models and propensity score matched analyses. Results: 769 (41%) patients received RASI. During a median follow-up of 4.3 +/- 0.9 years, 678 patients were categorized as having severe AS, 545 underwent aortic valve replacement, 40 SCDs, 103 cardiovascular and 205 all-cause deaths occurred. RASI was not associated with SCD (HR: 1.19 [95% CI: 0.50-2.83], p = 0.694), cardiovascular (HR: 1.05 [95% CI: 0.62-1.77], p = 0.854) or all-cause mortality (HR: 0.81 [95% CI: 0.55-1.20], p = 0.281). This was confirmed in propensity matched analysis (all p > 0.05). In separate analyses, RASI was associated with larger reduction in systolic blood pressure (p = 0.001) and less progression of LV mass (p = 0.040). Conclusions: RASI was not associated with SCD, cardiovascular or all-cause mortality in asymptomatic AS patients. However, RASI was associated with a potentially beneficial decrease in blood pressure and reduced LV mass progression. (C) 2014 Elsevier Ireland Ltd. All rights reserved.
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| 9. |
- Bang, Casper N., et al.
(författare)
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Systolic left ventricular function according to left ventricular concentricity and dilatation in hypertensive patients : the Losartan Intervention For Endpoint reduction in hypertension study
- 2013
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Ingår i: Journal of Hypertension. - : Lippincott Williams & Wilkins. - 0263-6352 .- 1473-5598. ; 31:10, s. 2060-2068
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Tidskriftsartikel (refereegranskat)abstract
- Background:Left ventricular hypertrophy [LVH, high left ventricular mass (LVM)] is traditionally classified as concentric or eccentric based on left ventricular relative wall thickness. We evaluated left ventricular systolic function in a new four-group LVH classification based on left ventricular dilatation [high left ventricular end-diastolic volume (EDV) index and concentricity (LVM/EDV(2/3))] in hypertensive patients.Methods and results:Nine hundred thirty-nine participants in the Losartan Intervention For Endpoint reduction in hypertension (LIFE) echocardiography substudy had measurable LVM at enrolment. Patients with LVH (LVM/body surface area 116g/m(2) in men and 96g/m(2) in women) were divided into four groups; eccentric nondilated' (normal LVM/EDV and EDV), eccentric dilated' (increased EDV, normal LVM/EDV), concentric nondilated' (increased LVM/EDV with normal EDV), and concentric dilated' (increased LVM/EDV and EDV) and compared to patients with normal LVM. At baseline, 12% had eccentric nondilated, 20% eccentric dilated, 29% concentric nondilated, and 14% concentric dilated LVH, with normal LVM in 25%. Compared with the concentric nondilated LVH group, those with concentric dilated LVH had significantly lower pulse pressure/stroke index and ejection fraction; higher LVM index, stroke volume, cardiac output, left ventricular midwall shortening, left atrial volume and isovolumic relaxation time; and more had segmental wall motion abnormalities (all P<0.05). Similar differences existed between patients with eccentric dilated and those with eccentric nondilated LVH (all P<0.05). Compared with patients with normal LVM, the eccentric nondilated had higher LV stroke volume, pulse pressure/stroke index, Cornell voltage product and SBP, and lower heart rate and fewer were African-American (all P<0.05).Conclusion:The new four-group classification of LVH identifies dilated subgroups with reduced left ventricular function among patients currently classified with eccentric or concentric LVH.
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| 10. |
- Butt, Jawad H., et al.
(författare)
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Efficacy and Safety of Dapagliflozin According to Frailty in Heart Failure With Reduced Ejection Fraction : A Post Hoc Analysis of the DAPA- HF Trial.
- 2022
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Ingår i: Annals of internal medicine. ; 175:6, s. 820-830
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Frailty may modify the risk-benefit profile of certain treatments, and frail patients may have reduced tolerance to treatments. OBJECTIVE: To investigate the efficacy of dapagliflozin according to frailty status, using the Rockwood cumulative deficit approach, in DAPA- HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure). DESIGN: Post hoc analysis of a phase 3 randomized clinical trial. (ClinicalTrials.gov: NCT03036124). SETTING: 410 sites in 20 countries. PATIENTS: Patients with symptomatic heart failure (HF) with a left ventricular ejection fraction of 40% or less and elevated natriuretic peptide. INTERVENTION: Addition of once-daily 10 mg of dapagliflozin or placebo to guideline-recommended therapy. MEASUREMENTS: The primary outcome was worsening HF or cardiovascular death. RESULTS: Of the 4744 patients randomly assigned in DAPA-HF, a frailty index (FI) was calculable in 4742. In total, 2392 patients (50.4%) were in FI class 1 (FI $<$/=0.210; not frail), 1606 (33.9%) in FI class 2 (FI 0.211 to 0.310; more frail), and 744 (15.7%) in FI class 3 (FI $>$/=0.311; most frail). The median follow-up time was 18.2 months. Dapagliflozin reduced the risk for worsening HF or cardiovascular death, regardless of FI class. The differences in event rate per 100 person-years for dapagliflozin versus placebo from lowest to highest FI class were -3.5 (95% CI, -5.7 to -1.2), -3.6 (CI, -6.6 to -0.5), and -7.9 (CI, -13.9 to -1.9). Consistent benefits were observed for other clinical events and health status, but the absolute reductions were generally larger in the most frail patients. Study drug discontinuation and serious adverse events were not more frequent with dapagliflozin than placebo, regardless of FI class. LIMITATION: Enrollment criteria precluded the inclusion of very high-risk patients. CONCLUSION: Dapagliflozin improved all outcomes examined, regardless of frailty status. However, the absolute reductions were larger in more frail patients. PRIMARY FUNDING SOURCE: AstraZeneca.
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