| 51. |
- Monzo, Luca, et al.
(författare)
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Visit-to-visit blood pressure variation and outcomes in heart failure with reduced ejection fraction: findings from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial.
- 2020
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Ingår i: Journal of hypertension. - 1473-5598. ; 38:3, s. 420-425
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Tidskriftsartikel (refereegranskat)abstract
- Visit-to-visit office blood pressure (BP) variability (BPV) has been associated with morbidity and mortality outcomes in several cardiovascular conditions. The aim of this study was to evaluate the association between BPV and outcomes in patients with heart failure and reduced ejection fraction and the effect of eplerenone on BPV.We evaluated the associations between BPV, calculated as SBP coefficient of variation (SBP-CoV = SD/mean × 100%), and the primary composite endpoint of cardiovascular mortality or heart failure hospitalization (HFH), and its components, in 2549 patients from the Eplerenone in Patients with Systolic Heart Failure and Mild Symptoms trial. Lower SBP-CoV was independently associated with a higher risk of all the studied outcomes, while higher as well as lower SBP-CoV were associated with a higher risk of cardiovascular death. After a median follow-up period of 21 months the risk of the composite outcome of cardiovascular death or HFH was almost double in the lower SBP-CoV tertile as compared with the intermediate tertile [adjusted hazard ratio: 2.01, 95% confidence interval (1.62-2.51), P < 0.001]. The relationship between SBP-CoV and outcomes was not modified by eplerenone (P value for interaction = 0.48). An interaction was detected between mean SBP and SBP-CoV for the primary outcome (P = 0.048) and for HFH (P = 0.018). The effect modification was slight, but lower SBP-CoV was associated with worse outcomes in patients with both low and high SBP, while this interaction was less clear for patients with SBP in the 'normal' range.In our patients with heart failure and reduced ejection fraction and mild symptoms, both a lower and higher SBP-CoV were associated with worse outcomes. SBP-CoV did not modify the benefit of eplerenone. Further studies are warranted to clarify the role of BPV in heart failure. CLINICALTRIALS.NCT00232180.
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| 52. |
- Nymo, S. H., et al.
(författare)
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The association between neutrophil gelatinase-associated lipocalin and clinical outcome in chronic heart failure: Results from CORONA
- 2012
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Ingår i: Journal of Internal Medicine. - : Wiley. - 0954-6820 .- 1365-2796. ; 271, s. 436-443
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Tidskriftsartikel (refereegranskat)abstract
- Objective. To study the prognostic value of neutrophil gelatinase-associated lipocalin (NGAL) in chronic heart failure (HF) of ischaemic aetiology. Background. Neutrophil gelatinase-associated lipocalin is a marker of kidney injury as well as matrix degradation and inflammation and has previously been shown to be increased in HF. We investigated whether serum NGAL levels could provide prognostic information in chronic HF. Methods. We assessed NGAL as a predictor of primary outcomes (cardiovascular death, nonfatal stroke and nonfatal myocardial infarction, n=307) and all-cause mortality (n=321), cardiovascular mortality (n=259) and hospitalization (n=647) as well as the number of hospitalizations during follow-up for all (n=1934) and CV causes (n=1204) in 1415 patients with chronic HF (≥60years, New York Heart Association class II-IV, ischaemic systolic HF) in the CORONA population, randomly assigned to 10mg rosuvastatin or placebo. Results. Multivariate analysis revealed that NGAL added significant information when adjusting for clinical variables, but was no longer significant when further adjusting for apolipoprotein A-1 (ApoA-1), glomerular filtration rate (GFR), C-reactive protein (CRP) and N-terminal pro-brain natriuretic peptide (NT-proBNP). However, belonging to the highest NGAL tertile was associated with more frequent hospitalization, even after adjusting for clinical variables, GFR and ApoA-1, but not after adjusting for CRP and NT-proBNP. There was no interaction between rosuvastatin treatment and NGAL. Conclusion. Neutrophil gelatinase-associated lipocalin added no significant information to NT-proBNP and GFR in a multivariate model for primary and secondary end-points. © 2012 The Association for the Publication of the Journal of Internal Medicine.
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| 53. |
- Rossignol, Patrick, et al.
(författare)
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Impact of eplerenone on cardiovascular outcomes in heart failure patients with hypokalaemia
- 2017
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 19:6, s. 792-799
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Tidskriftsartikel (refereegranskat)abstract
- © 2016 The Authors. European Journal of Heart Failure © 2016 European Society of Cardiology Aims: Although hypokalaemia is common among patients with heart failure (HF), the prognostic significance of baseline hypokalaemia and hypokalaemia during follow-up in HF patients receiving a mineralocorticoid receptor antagonist (MRA) remains uncertain. Methods and results: Results of the EMPHASIS-HF trial in patients (n = 2737) with HF and reduced EF with mild symptoms, randomized to eplerenone or placebo, were analysed with regard to the presence or occurrence of hypokalaemia (serum K + < 4.0 mmol/L) and the risk of cardiovascular death or hospitalization for HF (primary endpoint). Median follow-up was 21 months. Baseline hypokalaemia and hypokalaemia during follow-up were common occurrences (19.6% and 40.6%, respectively). Hypokalaemia during follow-up was associated with worse outcomes in multivariable analyses [hazard ratio (HR) 1.26, 95% confidence interval (CI) 1.05–1.52, P = 0.01] without evidence of interaction with eplerenone. In contrast, baseline hypokalaemia was associated with outcomes in the placebo group (HR 1.37, 95% CI 1.05–1.79, P = 0.02) but not in the eplerenone group (HR 0.87, 95% CI 0.62–1.23, P = 0.44; P for interaction = 0.04). Concurrently, eplerenone was found to be more protective in patients with baseline hypokalaemia vs. patients without baseline hypokalaemia compared with placebo (HR 0.44, 95% 0.30–0.64, P < 0.0001 vs. 0.69, 95% CI 0.57–0.83, P = 0.0001; P for interaction = 0.04). In patients without baseline hypokalaemia, eplerenone use decreased the rate of hypokalaemia during follow-up (HR 0.69, 95% CI 0.59–0.80, P < 0.001). A potassium level > 4.0 mmol/L at 1 month after randomization mediated 26.0% (0.6–51.4%) of the eplerenone treatment effect (P = 0.04). Conclusion: In HF patients receiving optimal therapy but not treated with eplerenone, baseline hypokalaemia was associated with worse outcomes. Conversely, hypokalaemia amplified the treatment effect of eplerenone.
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| 54. |
- Schwartz, Gregory G, et al.
(författare)
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Effects of Dalcetrapib in Patients with a Recent Acute Coronary Syndrome
- 2012
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Ingår i: New England Journal of Medicine. - : Massachusetts Medical Society. - 0028-4793 .- 1533-4406. ; 367:22, s. 2089-2099
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND less thanbrgreater than less thanbrgreater thanIn observational analyses, higher levels of high-density lipoprotein (HDL) cholesterol have been associated with a lower risk of coronary heart disease events. However, whether raising HDL cholesterol levels therapeutically reduces cardiovascular risk remains uncertain. Inhibition of cholesteryl ester transfer protein (CETP) raises HDL cholesterol levels and might therefore improve cardiovascular outcomes. less thanbrgreater than less thanbrgreater thanMETHODS less thanbrgreater than less thanbrgreater thanWe randomly assigned 15,871 patients who had had a recent acute coronary syndrome to receive the CETP inhibitor dalcetrapib, at a dose of 600 mg daily, or placebo, in addition to the best available evidence-based care. The primary efficacy end point was a composite of death from coronary heart disease, nonfatal myocardial infarction, ischemic stroke, unstable angina, or cardiac arrest with resuscitation. less thanbrgreater than less thanbrgreater thanRESULTS less thanbrgreater than less thanbrgreater thanAt the time of randomization, the mean HDL cholesterol level was 42 mg per deciliter (1.1 mmol per liter), and the mean low-density lipoprotein (LDL) cholesterol level was 76 mg per deciliter (2.0 mmol per liter). Over the course of the trial, HDL cholesterol levels increased from baseline by 4 to 11% in the placebo group and by 31 to 40% in the dalcetrapib group. Dalcetrapib had a minimal effect on LDL cholesterol levels. Patients were followed for a median of 31 months. At a prespecified interim analysis that included 1135 primary end-point events (71% of the projected total number), the independent data and safety monitoring board recommended termination of the trial for futility. As compared with placebo, dalcetrapib did not alter the risk of the primary end point (cumulative event rate, 8.0% and 8.3%, respectively; hazard ratio with dalcetrapib, 1.04; 95% confidence interval, 0.93 to 1.16; P = 0.52) and did not have a significant effect on any component of the primary end point or total mortality. The median C-reactive protein level was 0.2 mg per liter higher and the mean systolic blood pressure was 0.6 mm Hg higher with dalcetrapib as compared with placebo (Pandlt;0.001 for both comparisons). less thanbrgreater than less thanbrgreater thanCONCLUSIONS less thanbrgreater than less thanbrgreater thanIn patients who had had a recent acute coronary syndrome, dalcetrapib increased HDL cholesterol levels but did not reduce the risk of recurrent cardiovascular events. (Funded by F. Hoffmann-La Roche; dal-OUTCOMES ClinicalTrials.gov number, NCT00658515.)
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| 55. |
- Schwartz, Gregory G, et al.
(författare)
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Rationale and design of the dal-OUTCOMES trial: Efficacy and safety of dalcetrapib in patients with recent acute coronary syndrome
- 2009
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 158:6, s. 896-U34
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Tidskriftsartikel (refereegranskat)abstract
- Background Despite contemporary therapies for acute coronary syndrome (ACS), morbidity and mortality remain high. Low levels of high-density lipoprotein (HDL) cholesterol are common among patients with ACS and may contribute to ongoing risk. Strategies that raise levels of HDL cholesterol, such as inhibition of cholesterol ester transfer protein (CETP), might reduce risk after ACS. Dal-OUTCOMES is a multicenter, randomized, double-blind, placebo-controlled trial designed to test the hypothesis that CETP inhibition with dalcetrapib reduces cardiovascular morbidity and mortality in patients with recent ACS. Design The study will randomize approximately 15,600 patients to receive daily doses of dalcetrapib 600 mg or matching placebo, beginning 4 to 12 weeks after an index ACS event. There are no prespecified boundaries for HDL cholesterol levels at entry. Other elements of care, including management of low-density lipoprotein cholesterol, are to follow best evidence-based practice. The primary efficacy measure is time to first occurrence of coronary heart disease death, nonfatal acute myocardial infarction, unstable angina requiring hospital admission, resuscitated cardiac arrest, or atherothrombotic stroke. The trial will continue until 1,600 primary end point events have occurred, all evaluable subjects have been followed for at least 2 years, and 80% of evaluable subjects have been followed for at least 2.5 years. Summary Dal-OUTCOMES will determine whether CETP inhibition with dalcetrapib, added to current evidence-based care, reduces cardiovascular morbidity and mortality after ACS.
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| 56. |
- 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. - 2213-1787 .- 2213-1779. ; 11:3, s. 291-304
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Tidskriftsartikel (refereegranskat)abstract
- 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.The authors addressed this question in a post hoc analysis of the DAPA-HF (Dapagliflozin and Prevention of Adverse Outcomes in Heart Failure) trial.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.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).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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| 57. |
- 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. - 1879-0844 .- 1388-9842. ; 24:10, s. 1856-68
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Tidskriftsartikel (refereegranskat)abstract
- 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.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.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.ClinicalTrials.gov NCT03036124.
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| 58. |
- Alexander, John H., et al.
(författare)
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Apixaban vs. warfarin with concomitant aspirin in patients with atrial fibrillation : insights from the ARISTOTLE trial
- 2014
-
Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:4, s. 224-232
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Tidskriftsartikel (refereegranskat)abstract
- Aims We assessed the effect of concomitant aspirin use on the efficacy and safety of apixaban compared with warfarin in patients with atrial fibrillation (AF). Methods and results In ARISTOTLE, 18 201 patients were randomized to apixaban 5 mg twice daily or warfarin. Concomitant aspirin use was left to the discretion of the treating physician. In this predefined analysis, simple and marginal structured models were used to adjust for baseline and time-dependent confounders associated with aspirin use. Outcome measures included stroke or systemic embolism, ischaemic stroke, myocardial infarction, mortality, major bleeding, haemorrhagic stroke, major or clinically relevant non-major bleeding, and any bleeding. On Day 1, 4434 (24%) patients were taking aspirin. Irrespective of concomitant aspirin use, apixaban reduced stroke or systemic embolism [with aspirin: apixaban 1.12% vs. warfarin 1.91, hazard ratio (HR) 0.58, 95% confidence interval (CI) 0.39-0.85 vs. without aspirin: apixaban 1.11% vs. warfarin 1.32%, HR 0.84, 95% CI 0.66-1.07; P interaction = 0.10] and caused less major bleeding than warfarin (with aspirin: apixaban 3.10 vs. warfarin 3.92%, HR 0.77, 95% CI 0.60-0.99 vs. without aspirin: apixaban 1.82% vs. warfarin 2.78, HR without aspirin 0.65, 95% CI 0.55-0.78; P interaction = 0.29). Similar results were seen in the subgroups of patients with and without arterial vascular disease. Conclusion Apixaban had similar beneficial effects on stroke or systemic embolism and major bleeding compared with warfarin, irrespective of concomitant aspirin use.
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| 59. |
- Bello, Natalie A, et al.
(författare)
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Increased risk of stroke with darbepoetin alfa in anaemic heart failure patients with diabetes and chronic kidney disease.
- 2015
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Ingår i: European journal of heart failure. - : Wiley. - 1879-0844 .- 1388-9842. ; 17:11
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Tidskriftsartikel (refereegranskat)abstract
- The use of an erythropoesis-stimulating agent, darbepoetin alfa (DA), to treat anaemia in patients with diabetes mellitus and chronic kidney disease was associated with a heightened risk of stroke and neutral efficacy in the Trial to Reduce Cardiovascular Events with Aranesp Therapy (TREAT), despite epidemiological data suggesting the contrary. However, this association has not been evaluated in another randomized, placebo-controlled trial.
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| 60. |
- Brum, Wagner S., et al.
(författare)
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Effect of Neprilysin Inhibition on Alzheimer Disease Plasma Biomarkers : A Secondary Analysis of a Randomized Clinical Trial
- 2023
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Ingår i: JAMA Neurology. - 2168-6149 .- 2168-6157.
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Tidskriftsartikel (refereegranskat)abstract
- Amyloid-β (Aβ) accumulation is critical in Alzheimer disease (AD), and neprilysin is involved in physiologically clearing Aβ. Concerns exist regarding long-term use of sacubitril/valsartan, a neprilysin inhibitor and angiotensin receptor blocker used for heart failure, and its potential to increase AD risk. We evaluated neprilysin inhibition’s effect on AD blood biomarkers in patients with coronary heart disease.
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