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| 2. |
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| 3. |
- Cleland, J. G. F., et al.
(författare)
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Beta-blockers for heart failure with reduced, mid-range, and preserved ejection fraction: an individual patient-level analysis of double-blind randomized trials
- 2018
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 39:1, s. 26-35
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Tidskriftsartikel (refereegranskat)abstract
- Aims Recent guidelines recommend that patients with heart failure and left ventricular ejection fraction (LVEF) 40-49% should be managed similar to LVEF >= 50%. We investigated the effect of beta-blockers according to LVEF in double-blind, randomized, placebo-controlled trials. Methods and results Individual patient data meta-analysis of 11 trials, stratified by baseline LVEF and heart rhythm (Clinicaltrials.gov: NCT0083244; PROSPERO: CRD42014010012). Primary outcomes were all-cause mortality and cardiovascular death over 1.3 years median follow-up, with an intention-to-treat analysis. For 14 262 patients in sinus rhythm, median LVEF was 27% (interquartile range 21-33%), including 575 patients with LVEF 40-49% and 244 >= 50%. Beta-blockers reduced all-cause and cardiovascular mortality compared to placebo in sinus rhythm, an effect that was consistent across LVEF strata, except for those in the small subgroup with LVEF >= 50%. For LVEF 40-49%, death occurred in 21/292 [7.2%] randomized to beta-blockers compared to 35/283 [12.4%] with placebo; adjusted hazard ratio (HR) 0.59 [95% confidence interval (CI) 0.34-1.03]. Cardiovascular death occurred in 13/292 [4.5%] with beta-blockers and 26/283 [9.2%] with placebo; adjusted HR 0.48 (95% CI 0.24-0.97). Over a median of 1.0 years following randomization (n = 4601), LVEF increased with beta-blockers in all groups in sinus rhythm except LVEF >= 50%. For patients in atrial fibrillation at baseline (n = 3050), beta-blockers increased LVEF when < 50% at baseline, but did not improve prognosis. Conculations Beta-blockers improve LVEF and prognosis for patients with heart failure in sinus rhythm with a reduced LVEF. The data are most robust for LVEF < 40%, but similar benefit was observed in the subgroup of patients with LVEF 40-49%.
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| 4. |
- Rogers, J. K., et al.
(författare)
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Effect of rosuvastatin on repeat heart failure hospitalizations: The CORONA trial (controlled rosuvastatin multinational trial in heart failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier Inc.. - 2213-1787 .- 2213-1779. ; 2:3, s. 289-297
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study sought to examine the effect of statin therapy hospitalizations for heart failure (HFH) in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) trial. Background: HFH is an important, frequently recurrent event. Conventional time-to-first event analyses do not take account repeat events. We used a number of statistical approaches to examine the effect of treatment on first and repeat HFH in the CORONA trial. Methods: In the CORONA trial, 5,011 patients ≥60 years of age with chronic New York Heart Association functional classes II to IV systolic heart failure resulting from ischemia were randomized to receive rosuvastatin or placebo. Poisson, Andersen-Gill, and negative binomial methods (NB) were used to analyze the effect of rosuvastatin on HFH, and the NB and a parametric joint frailty model (JF) were used to examine this effect while accounting for the competing risk of cardiovascular (CV) death. Rosuvastatin/placebo rate ratios were calculated, both unadjusted and adjusted. Results: A total of 1,291 patients had 1 or more HFH (750 of these had a single HFH only), and there were a total of 2,408 HFHs. The hazard ratio for the conventional time-to-first event analysis for HFH was 0.91 (95% confidence interval [CI]: 0.82 to 1.02, p = 0.105). In contrast, the NB on repeat hospitalizations gave an unadjusted RR (RR) for HFH of 0.86 (95% CI: 0.75 to 0.99, p = 0.030), adjusted 0.82 (95% CI: 0.72 to 0.92, p = 0.001), and after including CV death as the last event, adjusted RR of 0.85 (95% CI: 0.77 to 0.94, p = 0.001). The JF gave an adjusted RR of 0.82 (95% CI: 0.73 to 0.92, p = 0.001). Similar results were found in analyses of all CV hospitalizations and all-cause hospitalizations. Conclusions: When repeat events were included, rosuvastatin was shown to reduce the risk of HFH by approximately 15% to 20%, equating to approximately 76 fewer admissions per 1,000 patients treated over a median 33 months of follow-up. Including repeat events could increase the ability to detect treatment effects in heart failure trials. © 2014 American College of Cardiology Foundation.
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| 5. |
- Hjamarson, A, et al.
(författare)
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Effects of controlled-release metoprolol on total mortality, hospitalizations, and well-being in patients with heart failure. The Metoprolol CR/XL randomized intervention trial in congestive heart failure
- 2000
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Ingår i: Journal of the American Medical Association. - : JAMA. - 0221-7678. ; 283:10, s. 1295-1302
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Tidskriftsartikel (refereegranskat)abstract
- Results from recent studies on the effects of beta1-blockade in patients with heart failure demonstrated a 34% reduction in total mortality. However, the effect of beta1-blockade on the frequency of hospitalizations, symptoms, and quality of life in patients with heart failure has not been fully explored. OBJECTIVE: To examine the effects of the beta1-blocker controlled-release/extended-release metoprolol succinate (metoprolol CR/XL) on mortality, hospitalization, symptoms, and quality of life in patients with heart failure. DESIGN: Randomized, double-blind controlled trial, preceded by a 2-week single-blind placebo run-in period, conducted from February 14, 1997, to October 31, 1998, with a mean follow-up of 1 year. SETTING: Three hundred thirteen sites in 14 countries. PARTICIPANTS: Patients (n = 3991) with chronic heart failure, New York Heart Association (NYHA) functional class II to IV, and ejection fraction of 0.40 or less who were stabilized with optimum standard therapy. INTERVENTIONS: Patients were randomized to metoprolol CR/XL, 25 mg once per day (NYHA class II), or 12.5 mg once per day (NYHA class III or IV), titrated for 6 to 8 weeks up to a target dosage of 200 mg once per day (n = 1990); or matching placebo (n = 2001). MAIN OUTCOME MEASURES: Total mortality or any hospitalization (time to first event), number of hospitalizations for worsening heart failure, and change in NYHA class, by intervention group; quality of life was assessed in a substudy of 741 patients. RESULTS: The incidence of all predefined end points was lower in the metoprolol CR/XL group than in the placebo group, including total mortality or all-cause hospitalizations (the prespecified second primary end point; 641 vs 767 events; risk reduction, 19%; 95% confidence interval [CI], 10%-27%; P<.001); total mortality or hospitalizations due to worsening heart failure (311 vs 439 events; risk reduction, 31%; 95% CI, 20%-40%; P<.001), number of hospitalizations due to worsening heart failure (317 vs 451; P<.001); and number of days in hospital due to worsening heart failure (3401 vs 5303 days; P<.001). NYHA functional class, assessed by physicians, and McMaster Overall Treatment Evaluation score, assessed by patients, both improved in the metoprolol CR/XL group compared with the placebo group (P = .003 and P = .009, respectively). CONCLUSIONS: In this study of patients with symptomatic heartfailure, metoprolol CR/XL improved survival, reduced the need for hospitalizations due to worsening heart failure, improved NYHA functional class, and had beneficial effects on patient well-being.
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| 6. |
- Perez, A. C., et al.
(författare)
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Thyroid-Stimulating Hormone and Clinical Outcomes: The CORONA Trial (Controlled Rosuvastatin Multinational Study in Heart Failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:1, s. 35-40
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: This study sought to examine the association between thyroid status and clinical outcomes in patients in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Hypo- and hyperthyroidism were associated with worse clinical outcomes in the SCD-HeFT (Sudden Cardiac DeathinHeart Failure Trial). Methods: In CORONA, 4,987 patients underwent baseline thyroid-stimulating hormone (TSH) measurement, 237 of which(4.8%) were receiving thyroid replacement therapy (TRT). Patients were classified as euthyroid (TSH: 0.3 to 5.0μU/ml,and no TRT), hyperthyroid (<0.3 μU/ml and no TRT), or hypothyroid (>5.0 μU/ml and no TRT). The outcome composites of cardiovascular (CV) death or hospitalization for heart failure (HF), the components of this composite, and all-cause death were compared among hyperthyroid, hypothyroid, and euthyroid states, using multivariable models adjusting for previously reported prognostic variables. Results: A total of 91.3% of patients were euthyroid, 5.0% were hypothyroid, and 3.7% were hyperthyroid. Compared with euthyroid patients, hypothyroid patients were more likely to have a history of stroke, had worse renal function andhigher N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels, were more likely to be treated with an antiarrhythmic drug (or have an implantable cardioverter defibrillator), and were less likely to smoke or be treated with a beta-blocker or angiotensin-converting enzyme inhibitor/angiotensin receptor blocker. In univariate analyses, hypothyroidism was associated with an increased risk of the composite outcome of CV death or HF hospitalization (hazard ratio: 1.29; 95% confidence interval: 1.07 to 1.57; p= 0.008), as well as all-cause death (HR: 1.36; 95% confidence interval: 1.03 to 1.76; p= 0.004). However, after adjustment for other known predictors of outcome, the associations were weakened, and when NT-proBNP was added to the models, the association between hypothyroidism and all outcomes was eliminated. Conclusions: Thyroid status is not an independent predictor of outcome in heart failure with reduced ejection fraction. (Controlled Rosuvastatin Multinational Study in Heart Failure [CORONA]; NCT00206310). © 2014 American College of Cardiology Foundation.
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| 7. |
- Perez-Moreno, A. C., et al.
(författare)
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Fatigue as a predictor of outcome in patients with heart failure. Analysis of CORONA (Controlled rosuvastatin multinational trial in heart failure)
- 2014
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Ingår i: JACC: Heart Failure. - : Elsevier BV. - 2213-1779. ; 2:2, s. 187-197
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The purpose of this study was to examine the relationship between fatigue and clinical outcomes, using dyspnea as a comparator, in patients with left ventricular ejection fraction (LVEF)≤35% enrolled in the CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure) study. Background: Although fatigue is a common symptom in heart failure (HF), little is known about its association with prognosis. Methods: At baseline in CORONA, fatigue "during the past few days" was measured using a 5-point exertion scale (0= none, 1= heavy exertion, 2= moderate exertion, 3= slight exertion, 4= rest); a 4-point scale was used for dyspnea (1to4 as for fatigue). Patients were grouped into 3 categories: a fatigue score 0 to 1 (n= 535), fatigue score 2(n=1,632), and fatigue score 3 to 4 (n= 1,663); and a dyspnea score of 1 (n= 292), dyspnea score of 2(n=1,695), and dyspnea score of 3 to 4 (n= 1,843). The association between fatigue and dyspnea and the composite outcome of cardiovascular (CV) death or HF hospital stay and each component separately was examined using Kaplan-Meier analysis and Cox proportional-hazard models. We also examined all-cause mortality. Results: In univariate analyses, symptom severity was associated with a higher risk of CV death or HF hospital stay (fatigue: group 3, 49% [n= 810], vs. group 1, 30% [n= 160]; dyspnea: group 3, 50% [n= 918], vs. group 1, 28% [n= 82]) and all-cause mortality (fatigue: group 3, 38% [n= 623], vs. group 1, 24% [n= 130]; dyspnea: group 3, 38% [n=697], vs. group 1, 23% [n= 66], log-rank p< 0.0001 for all). After adjusting for other prognostic variables, including LVEF, New York Heart Association class, and N-terminal pro-B-type natriuretic peptide level, worse fatigue remained associated with higher risk of HF hospital stay but not mortality (worse dyspnea remained associated with a higher risk of both). An increase in fatigue (or dyspnea) between baseline and 6 months was also associated with worse outcomes. Conclusions: In HF, greater fatigue is associated with worse clinical outcomes. Closer attention should be paid to this symptom in clinical practice, with more done to standardize its measurement and understand its origins, with a view to improving treatment. © 2014 American College of Cardiology Foundation.
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| 9. |
- Badar, A. A., et al.
(författare)
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Relationship between angina pectoris and outcomes in patients with heart failure and reduced ejection fraction: an analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2014
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 35:48, s. 3426-3433
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Tidskriftsartikel (refereegranskat)abstract
- Aim Angina pectoris is common in patients with heart failure and reduced ejection fraction (HF-REF) but its relationship with outcomes has not been well defined. This relationship was investigated further in a retrospective analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). Methods and results Four thousand, eight hundred and seventy-eight patients were divided into three categories: no history of angina and no chest pain at baseline (Group A; n = 1240), past history of angina but no chest pain at baseline (Group B; n = 1353) and both a history of angina and chest pain at baseline (Group C; n = 2285). Outcomes were examined using Kaplan-Meier and Cox regression survival analysis. Compared with Group A, Group C had a higher risk of non-fatal myocardial infarction or unstable angina (HR: 2.36, 1.54-3.61; P<0.001), this composite plus coronary revascularization (HR: 2.54, 1.76-3.68; P<0.001), as well as HF hospitalization (HR: 1.35, 1.13-1.63; P = 0.001), over a median follow-up period of 33 months. There was no difference in cardiovascular or all-cause mortality. Group B had a smaller increase in risk of coronary events but not of heart failure hospitalization. Conclusion Patients with HF-REF and ongoing angina are at an increased risk of acute coronary syndrome and HF hospitalization. Whether these patients would benefit from more aggressive medical therapy or percutaneous revascularization is not known and merits further investigation.
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| 10. |
- Cosmi, F., et al.
(författare)
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Treatment with insulin is associated with worse outcome in patients with chronic heart failure and diabetes
- 2018
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 20:5, s. 888-895
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Tidskriftsartikel (refereegranskat)abstract
- Aims Up to one-third of patients with diabetes mellitus and heart failure (HF) are treated with insulin. As insulin causes sodium retention and hypoglycaemia, its use might be associated with worse outcomes. Methods and results We examined two datasets: 24 012 patients with HF from four large randomized trials and an administrative database of 4 million individuals, 103 857 of whom with HF. In the former, survival was examined using Cox proportional hazards models adjusted for baseline variables and separately for propensity scores. Fine-Gray competing risk regression models were used to assess the risk of hospitalization for HF. For the latter, a case-control nested within a population-based cohort study was conducted with propensity score. Prevalence of diabetes mellitus at study entry ranged from 25.5% to 29.5% across trials. Insulin alone or in combination with oral hypoglycaemic drugs was prescribed at randomization to 24.4% to 34.5% of the patients with diabetes. The rates of death from any cause and hospitalization for HF were higher in patients with vs. without diabetes, and highest of all in patients prescribed insulin [propensity score pooled hazard ratio for all-cause mortality 1.27 (1.16-1.38), for HF hospitalization 1.23 (1.13-1.33)]. In the administrative registry, insulin prescription was associated with a higher risk of all-cause death [odds ratio (OR) 2.02, 95% confidence interval (CI) 1.87-2.19] and rehospitalization for HF (OR 1.42, 95% CI 1.32-1.53). Conclusions Whether insulin use is associated with poor outcomes in HF should be investigated further with controlled trials, as should the possibility that there may be safer alternative glucose-lowering treatments for patients with HF and type 2 diabetes mellitus.
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| 11. |
- Damman, K., et al.
(författare)
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Loop diuretics, renal function and clinical outcome in patients with heart failure and reduced ejection fraction
- 2016
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 18:3, s. 328-336
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Tidskriftsartikel (refereegranskat)abstract
- AimWe aimed to study the relationships of loop diuretic dose with renal function and clinical outcomes in patients with chronic heart failure (HF). Methods and resultsLoop diuretic dose at baseline was recorded in patients included in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA). The relationship to change in estimated glomerular filtration rate (eGFR) over time and to the first occurrence of the composite outcome of cardiovascular (CV) death or hospitalization owing to HF was examined in propensity score matched cohorts. Of the 5011 patients, 2550, 745, and 449 were receiving >80mg (high), 41-80mg (medium) and 40mg (low) of loop diuretics in furosemide equivalent daily dosages, respectively, which were used to assemble 229, 385, and 1045 pairs of propensity-matched high, medium, and low dose cohorts. Compared with matched no loop diuretic groups, eGFR declined 0.30.2, 0.3 +/- 0.3 and 1.2 +/- 0.5mL/min/1.73m(2)/year in the low-, medium-, and high-dose groups, respectively. Compared with matched no loop diuretic groups, hazard ratios (HR) (95% confidence intervals) for outcome associated with low-, medium- and high-dose groups were 1.71 (1.41-2.06), 1.99 (1.50-2.64), and 2.94 (1.95-4.41), respectively. Higher loop diuretic dose was particularly associated with increased risk for hospitalization owing to HF: HR 4.80 (2.75-8.37), P<0.001. ConclusionsThe use of loop diuretics was associated with a slightly greater rate of decline in eGFR, which did not vary significantly by diuretic dose.Loop diuretic dose was associated with higher risks of (CV) mortality and predominantly hospitalization owing to HF, which appeared to be higher among those receiving higher daily doses.
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| 12. |
- Gullestad, L., et al.
(författare)
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Galectin-3 predicts response to statin therapy in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA)
- 2012
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 33:18, s. 2290-2296
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Tidskriftsartikel (refereegranskat)abstract
- To investigate whether plasma galectin-3, a mediator of fibrogenesis, can identify patients with chronic heart failure (HF) for whom statins are effective. Patients with ischaemic systolic HF enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) were randomly assigned to 10 mg/day of rosuvastatin or placebo. Galectin-3 was measured in plasma. The primary outcome was cardiovascular death, myocardial infarction, or stroke. Of 1492 patients, 411 had a primary event during a median follow-up of 32.8 months. There was an interaction between baseline galectin-3 and rosuvastatin on the primary endpoint (P-value for interaction 0.036). Among patients with below the median plasma concentrations of galectin-3 (19.0 ng/mL), those assigned to rosuvastatin had a lower primary event rate [hazard ratio (HR) 0.65; 95 confidence interval (CI), 0.460.92; P 0.014], lower total mortality (HR 0.70; 95 CI, 0.500.98; P 0.038), and lower event rate of all-cause mortality and HF hospitalizations (HR 0.72; 95 CI, 0.540.98; P 0.017) compared with placebo, but no benefit was observed in patients with higher levels of galectin-3. The combination of concurrently low concentrations of galectin-3 and N-terminal pro-B-type natriuretic peptide (102.7 pmol/L) identified patients with a large benefit with rosuvastatin (HR 0.33; 95 CI, 0.160.67; P 0.002). Patients with systolic HF of ischaemic aetiology who have galectin-3 values 19.0 ng/mL may benefit from rosuvastatin treatment. However, the data from this post hoc analysis should be interpreted with caution since the overall results of the CORONA study did not show a significant effect on the primary endpoint.
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| 13. |
- Haver, V. G., et al.
(författare)
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Telomere length and outcomes in ischaemic heart failure: data from the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA)
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:3, s. 313-319
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Tidskriftsartikel (refereegranskat)abstract
- AimsLeucocyte telomere length is considered a marker of biological ageing and has been suggested to be shorter in patients with CAD and heart failure compared with healthy controls. The aim of this study was to determine whether telomere length is associated with clinical outcomes in patients with ischaemic heart failure and whether this association is superior to chronological age as defined by date of birth. Methods and resultsWe measured leucocyte telomere length in 3275 patients with chronic ischaemic systolic heart failure participating in the COntrolled ROsuvastatin multiNAtional Trial in Heart Failure (CORONA) study. The primary composite endpoint was cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke, which occurred in 575 patients during follow-up. We observed a significant association of leucocyte telomere lengths with the primary endpoint (hazard ratio 1.10; 95% confidence interval 1.01-1.20; P=0.03). However, this observation was not superior to age as defined by date of birth. The neutral effect of rosuvastatin treatment on clinical outcomes was not modified by baseline telomere length. ConclusionBiological age as defined by leucocyte telomere length was associated with clinical outcomes in patients with ischaemic heart failure, but this association did not add prognostic information above age as defined by date of birth.
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| 14. |
- Inglis, S. C., et al.
(författare)
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Intermittent claudication as a predictor of outcome in patients with ischaemic systolic heart failure: analysis of the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA)
- 2010
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 12:7, s. 698-705
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To examine the relationship between baseline intermittent claudication and outcomes in patients enrolled in the Controlled Rosuvastatin Multinational Trial in Heart Failure trial (CORONA). Intermittent claudication is an independent predictor of worse outcome in coronary heart disease, but its prognostic importance in heart failure (HF) is unknown. Patients aged >or=60 years with NYHA class II-IV, low ejection fraction HF of ischaemic aetiology were enrolled in CORONA. Rosuvastatin did not reduce the primary outcome or all-cause mortality. METHODS AND RESULTS: To determine whether intermittent claudication was an independent predictor of clinical outcomes, a three-step multivariable model was built: (i) demographic/clinical variables, (ii) biochemical measures added, (iii) high-sensitivity C-reactive protein and N-terminal pro B-type natriuretic-peptide added. Of the 5011 patients, 637 (12.7%) had intermittent claudication at baseline. Patients with intermittent claudication were more likely to be male (83 vs. 75%), be a current smoker (19 vs. 9%), and have diabetes mellitus (36 vs. 29%) relative to those without intermittent claudication. Over a median 33-month follow-up, 2168 patients died or were hospitalized for HF. Patients with intermittent claudication had an increased risk of death (any cause) (adjusted hazard ratio 1.36, 95% CI 1.19-1.56, P < 0.0001), death from worsening HF (1.35, 1.03-1.77, P = 0.028), sudden death (1.24, 1.00-1.54, P = 0.05), and risk of non-fatal or fatal myocardial infarction (time to first event 1.67, 1.24-2.27, P < 0.001). In the full multivariable model, intermittent claudication remained an independent predictor of most outcomes evaluated. CONCLUSION: Intermittent claudication is a relatively common symptom in ischaemic HF and an independent predictor of worse outcome. Clinical Trial Registration Information: NCT00206310-http://clinicaltrials.gov/ct2/show/NCT00206310?term=corona&ran k=2.
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| 15. |
- Kotecha, D., et al.
(författare)
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Heart Rate and Rhythm and the Benefit of Beta-Blockers in Patients With Heart Failure
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097. ; 69:24, s. 2885-2896
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The relationship between mortality and heart rate remains unclear for patients with heart failure with reduced ejection fraction in either sinus rhythm or atrial fibrillation (AF). OBJECTIVES This analysis explored the prognostic importance of heart rate in patients with heart failure with reduced ejection fraction in randomized controlled trials comparing beta-blockers and placebo. METHODS The Beta-Blockers in Heart Failure Collaborative Group performed a meta-analysis of harmonized individual patient data from 11 double-blind randomized controlled trials. The primary outcome was all-cause mortality, analyzed with Cox proportional hazard ratios (HR) modeling heart rate measured at baseline and approximately 6 months post-randomization. RESULTS A higher heart rate at baseline was associated with greater all-cause mortality for patients in sinus rhythm (n = 14,166; adjusted HR: 1.11 per 10 beats/min; 95% confidence interval [CI]: 1.07 to 1.15; p < 0.0001) but not in AF (n = 3,034; HR: 1.03 per 10 beats/min; 95% CI: 0.97 to 1.08; p = 0.38). Beta-blockers reduced ventricular rate by 12 beats/min in both sinus rhythm and AF. Mortality was lower for patients in sinus rhythm randomized to beta-blockers (HR: 0.73 vs. placebo; 95% CI: 0.67 to 0.79; p < 0.001), regardless of baseline heart rate (interaction p = 0.35). Beta-blockers had no effect on mortality in patients with AF (HR: 0.96, 95% CI: 0.81 to 1.12; p = 0.58) at any heart rate (interaction p = 0.48). A lower achieved resting heart rate, irrespective of treatment, was associated with better prognosis only for patients in sinus rhythm (HR: 1.16 per 10 beats/min increase, 95% CI: 1.11 to 1.22; p < 0.0001). CONCLUSIONS Regardless of pre-treatment heart rate, beta-blockers reduce mortality in patients with heart failure with reduced ejection fraction in sinus rhythm. Achieving a lower heart rate is associated with better prognosis, but only for those in sinus rhythm. (C) 2017 by the American College of Cardiology Foundation.
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| 16. |
- Shen, L., et al.
(författare)
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Declining Risk of Sudden Death in Heart Failure
- 2017
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Ingår i: New England Journal of Medicine. - 0028-4793. ; 377:1, s. 41-51
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND The risk of sudden death has changed over time among patients with symptomatic heart failure and reduced ejection fraction with the sequential introduction of medications including angiotensin-converting-enzyme inhibitors, angiotensin-receptor blockers, beta-blockers, and mineralocorticoid-receptor antagonists. We sought to examine this trend in detail. We analyzed data from 40,195 patients who had heart failure with reduced ejection fraction and were enrolled in any of 12 clinical trials spanning the period from 1995 through 2014. Patients who had an implantable cardioverter-defibrillator at the time of trial enrollment were excluded. Weighted multivariable regression was used to examine trends in rates of sudden death over time. Adjusted hazard ratios for sudden death in each trial group were calculated with the use of Cox regression models. The cumulative incidence rates of sudden death were assessed at different time points after randomization and according to the length of time between the diagnosis of heart failure and randomization. Sudden death was reported in 3583 patients. Such patients were older and were more often male, with an ischemic cause of heart failure and worse cardiac function, than those in whom sudden death did not occur. There was a 44% decline in the rate of sudden death across the trials (P = 0.03). The cumulative incidence of sudden death at 90 days after randomization was 2.4% in the earliest trial and 1.0% in the most recent trial. The rate of sudden death was not higher among patients with a recent diagnosis of heart failure than among those with a longer-standing diagnosis. Rates of sudden death declined substantially over time among ambulatory patients with heart failure with reduced ejection fraction who were enrolled in clinical trials, a finding that is consistent with a cumulative benefit of evidence-based medications on this cause of death. (Funded by the China Scholarship Council and the University of Glasgow.)
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| 17. |
- Batty, J. A., et al.
(författare)
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An Investigation of CYP2D6 Genotype and Response to Metoprolol CR/XL During Dose Titration in Patients With Heart Failure: A MERIT-HF Substudy
- 2014
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Ingår i: Clinical Pharmacology & Therapeutics. - : Springer Science and Business Media LLC. - 0009-9236 .- 1532-6535. ; 95:3, s. 321-330
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Tidskriftsartikel (refereegranskat)abstract
- To explore the pharmacogenetic effects of the cytochrome P450 (CYP) 2D6 genotype in patients with systolic heart failure treated using controlled/extended-release (CR/XL) metoprolol, this study assessed the CYP2D6 locus for the nonfunctional * 4 allele (1846G> A; rs3892097) in the Metoprolol CR/XL Randomised Intervention Trial in Congestive Heart Failure (MERIT-HF; n = 605). Participants were characterized as extensive, intermediate, or poor metabolizers (EMs, IMs, or PMs, respectively), based on the presence of the CYP2D6* 4 allele (EM: * 1* 1, 60.4%; IM: * 1* 4, 35.8%; and PM: * 4* 4, 3.8%). Plasma metoprolol concentrations were 2.1-/4.6-fold greater in the IM/PM groups as compared with the EM group (P < 0.0001). Metoprolol induced significantly lower heart rates and diastolic blood pressures during early titration, indicating a CYP2D6* 4 allele dose-response effect (P < 0.05). These effects were not observed at maximal dose, suggesting a saturable effect. Genotype did not adversely affect surrogate treatment efficacy. CYP2D6 genotype modulates metoprolol pharmacokinetics/pharmacodynamics during early titration; however, the MERIT-HF-defined titration schedule remains recommended for all patients, regardless of genotype.
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| 18. |
- Deedwania, P. C., et al.
(författare)
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Efficacy, safety and tolerability of metoprolol CR/XL in patients with diabetes and chronic heart failure: experiences from MERIT-HF
- 2005
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Ingår i: Am Heart J. - : Mosby, Inc.. - 1097-6744 .- 0002-8703. ; 149:1, s. 159-67
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The objective of the current study was to examine the efficacy and tolerability of the beta-blocker metoprolol succinate controlled release/extended release (CR/XL) in patients with diabetes in the Metoprolol CR/XL Randomized Intervention Trial in Chronic Heart Failure (MERIT-HF). METHODS: The Cox proportional hazards model was used to calculate hazard ratios (HR) for convenience expressed as relative risks (risk reduction = 1-HR), and 95% confidence intervals (CI). RESULTS: The risk of hospitalization for heart failure was 76% higher in diabetics compared to non-diabetics (95% CI 38% to 123%). Metoprolol CR/XL was well tolerated and reduced the risk of hospitalization for heart failure by 37% in the diabetic group (95% CI 53% to 15%), and by 35% in the non-diabetic group (95% CI 48% to 19%). Pooling of mortality data from the Cardiac Insufficiency Bisoprolol Study II (CIBIS II), MERIT-HF, and the Carvedilol Prospective Randomized Cumulative Survival Study (COPERNICUS) showed similar survival benefits in patients with diabetes (25%; 95% CI 40% to 4%) and without diabetes (36%; 95% CI 44% to 27%); test of diabetes by treatment interaction was non-significant. Adverse events were reported more often on placebo than on metoprolol CR/XL. CONCLUSIONS: Patients with heart failure and diabetes have a much higher risk of hospitalization than patients without diabetes. Regardless of diabetic status, a highly significant reduction in hospitalizations for heart failure was observed with metoprolol CR/XL therapy, which was very well tolerated also by patients with diabetes. Furthermore, the pooled data showed a statistically significant survival benefit in patients with diabetes.
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| 19. |
- Feinstein, M. J., et al.
(författare)
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Do statins reduce the risk of myocardial infarction in patients with heart failure? A pooled individual-level reanalysis of CORONA and GISSI-HF
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:4, s. 434-441
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Tidskriftsartikel (refereegranskat)abstract
- AimsCurrent guidelines do not explicitly recommend statin use in heart failure (HF). Relatively low numbers of atherothrombotic events among HF patients, in the context of their elevated competing risks for non-atherothrombotic causes of death, may have prevented previous analyses of clinical trials from detecting a benefit for statins. We pooled data from two landmark trials of HF patients not on statin therapy randomized to rosuvastatin 10mg daily vs. placebo, CORONA and GISSI-HF, in order to improve our power to detect statistically significant differences in atherothrombotic events. We also accounted for competing risks from other causes of death. Methods and resultsWe used competing risks analyses to evaluate atherothrombotic events in the context of death from other cardiovascular and non-cardiovascular causes. We also performed traditional Cox survival analyses of the same data with the intention that these statistical approaches would be complementary. CORONA participants (n=5011, median follow-up 32.8months) were older and sicker than GISSI-HF participants (n=4574, median follow-up 46.9months) by design. Rosuvastatin decreased risk for myocardial infarction (MI) among CORONA and GISSI-HF participants with ischaemic aetiology of HF (hazard ratio 0.81, 95% confidence interval 0.66-0.99, P<0.05). There were no significant differences between rosuvastatin and placebo in risks for stroke or death from other causes. ConclusionThis individual-level reanalysis of two landmark trials demonstrates a small but statistically significant decreased risk for MI among patients with ischaemic HF randomized to rosuvastatin vs. placebo. Rosuvastatin appears to be effective in preventing MI in ischaemic HF patients not already on statins.
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| 20. |
- Gravning, J., et al.
(författare)
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Prognostic Effect of High-Sensitive Troponin T Assessment in Elderly Patients With Chronic Heart Failure Results From the CORONA Trial
- 2014
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Ingår i: Circulation-Heart Failure. - : Ovid Technologies (Wolters Kluwer Health). - 1941-3289 .- 1941-3297. ; 7:1, s. 96-103
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Tidskriftsartikel (refereegranskat)abstract
- Background The incremental prognostic value of high-sensitive troponin T (hs-cTnT) in heart failure (HF) beyond that of high-sensitivity C-reactive protein and amino-terminal probrain natriuretic peptide is debated. We examined the prognostic value of hs-cTnT in a subgroup of patients from the Controlled Rosuvastatin Multinational Trial in HF (CORONA) study. Methods and Results Hs-cTnT as a risk factor for the primary end point (cardiovascular death, nonfatal myocardial infarction, and nonfatal stroke; n=356), as well as all-cause mortality (n=366), cardiovascular mortality (n=299), and the composite of cardiovascular mortality and hospitalization from worsening of HF (n=465), was investigated in 1245 patients (60 years; New York Heart Association [NYHA] class II-IV, ischemic systolic HF) randomly assigned to 10 mg rosuvastatin or placebo. In multivariable analyses, adjusting for left ventricular ejection fraction, NYHA class, age, body mass index, diabetes mellitus, sex, intermittent claudication, heart rate, estimated glomerular filtration rate, apolipoprotein B/apolipoprotein A-1 ratio, amino-terminal probrain natriuretic peptide, high-sensitivity C-reactive protein, and hs-cTnT (both dichotomized according to the 99th percentile and as a continuous variable) was associated with all end points (primary end point: hazard ratio, 1.87 and 1.51, respectively, per SD change; P<0.001; all other end points: hazard ratio, 1.39-1.70). However, improved discrimination as assessed by C-statistics was only seen for the primary end point and all-cause mortality. Conclusions Elevated hs-cTnT levels provide strong and independent prognostic information in older patients with chronic ischemic HF. Clinical Trial Registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
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| 21. |
- Kristensen, S. L., et al.
(författare)
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Comparison of outcomes after hospitalization for worsening heart failure, myocardial infarction, and stroke in patients with heart failure and reduced and preserved ejection fraction
- 2015
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Ingår i: European Journal of Heart Failure. - : Wiley. - 1388-9842. ; 17:2, s. 169-176
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Tidskriftsartikel (refereegranskat)abstract
- AimsTo investigate the prognostic significance of hospitalization for worsening heart failure (WHF), myocardial infarction (MI), and stroke in patients with chronic heart failure (HF). Methods and resultsWe studied 5011 patients with HF and reduced EF (HF-REF) in the CORONA trial and 4128 patients with HF and preserved EF (HF-PEF) in the I-Preserve trial. Adjusted hazard ratios (HRs) for death were estimated for 0-30 days and 31 days after first post-randomization WHF, MI, or stroke used as a time-dependent variable, compared with patients with none of these events. In CORONA, 1616 patients (32%) had post-randomization first events (1223 WHF, 216 MI, 177 stroke), and the adjusted HR for mortality 30 days after an event was: WHF 7.21 [95% confidence interval (CI) 2.05-25.40], MI 23.08 (95% CI 6.44-82.71), and stroke 32.15 (95% CI 8.93-115.83). The HR for mortality at >30 days was: WHF 3.62 (95% CI 3.11-4.21), MI 4.41 (95% CI 3.23-6.02), and stroke 3.19 (95% CI 2.21-4.61). In I-Preserve, 896 patients (22%) experienced a post-randomization event (638 WHF, 111 MI, 147 stroke). The HR for mortality 30 days was WHF 31.77 (95% CI 7.60-132.81), MI 154.77 (95% CI 34.21-700.17), and stroke 223.30 (95% CI 51.42-969.78); for >30 days it was WHF 3.36 (95% CI 2.79-4.05), MI 3.29 (95% CI 2.14-5.06), and stroke 5.13 (95% CI 3.61-7.29). ConclusionsIn patients with both HF-REF and HF-PEF, hospitalization for WHF was associated with high early and late mortality. The early relative risk of death was not as great as following MI or stroke, but the longer term relative risk of death was similar following all three types of event. Numerically, more deaths occurred following WHF because it was a much more common event.
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