| 1. |
- Cleland, John G F, et al.
(författare)
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Plasma concentration of amino-terminal pro-brain natriuretic peptide in chronic heart failure: prediction of cardiovascular events and interaction with the effects of rosuvastatin: a report from CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure).
- 2009
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 1558-3597 .- 0735-1097. ; 54:20, s. 1850-9
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: We investigated whether plasma amino-terminal pro-brain natriuretic peptide (NT-proBNP), a marker of cardiac dysfunction and prognosis measured in CORONA (Controlled Rosuvastatin Multinational Trial in Heart Failure), could be used to identify the severity of heart failure at which statins become ineffective. BACKGROUND: Statins reduce cardiovascular morbidity and mortality in many patients with ischemic heart disease but not, overall, those with heart failure. There must be a transition point at which treatment with a statin becomes futile. METHODS: In CORONA, patients with heart failure, reduced left ventricular ejection fraction, and ischemic heart disease were randomly assigned to 10 mg/day rosuvastatin or placebo. The primary composite outcome was cardiovascular death, nonfatal myocardial infarction, or stroke. RESULTS: Of 5,011 patients enrolled, NT-proBNP was measured in 3,664 (73%). The midtertile included values between 103 pmol/l (868 pg/ml) and 277 pmol/l (2,348 pg/ml). Log NT-proBNP was the strongest predictor (per log unit) of every outcome assessed but was strongest for death from worsening heart failure (hazard ratio [HR]: 1.99; 95% confidence interval [CI]: 1.71 to 2.30), was weaker for sudden death (HR: 1.69; 95% CI: 1.52 to 1.88), and was weakest for atherothrombotic events (HR: 1.24; 95% CI: 1.10 to 1.40). Patients in the lowest tertile of NT-proBNP had the best prognosis and, if assigned to rosuvastatin rather than placebo, had a greater reduction in the primary end point (HR: 0.65; 95% CI: 0.47 to 0.88) than patients in the other tertiles (heterogeneity test, p = 0.0192). This reflected fewer atherothrombotic events and sudden deaths with rosuvastatin. CONCLUSIONS: Patients with heart failure due to ischemic heart disease who have NT-proBNP values <103 pmol/l (868 pg/ml) may benefit from rosuvastatin.
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| 2. |
- Kjekshus, John, et al.
(författare)
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Rosuvastatin in older patients with systolic heart failure.
- 2007
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Ingår i: The New England journal of medicine. - 1533-4406. ; 357:22, s. 2248-61
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with systolic heart failure have generally been excluded from statin trials. Acute coronary events are uncommon in this population, and statins have theoretical risks in these patients. METHODS: A total of 5011 patients at least 60 years of age with New York Heart Association class II, III, or IV ischemic, systolic heart failure were randomly assigned to receive 10 mg of rosuvastatin or placebo per day. The primary composite outcome was death from cardiovascular causes, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included death from any cause, any coronary event, death from cardiovascular causes, and the number of hospitalizations. RESULTS: As compared with the placebo group, patients in the rosuvastatin group had decreased levels of low-density lipoprotein cholesterol (difference between groups, 45.0%; P<0.001) and of high-sensitivity C-reactive protein (difference between groups, 37.1%; P<0.001). During a median follow-up of 32.8 months, the primary outcome occurred in 692 patients in the rosuvastatin group and 732 in the placebo group (hazard ratio, 0.92; 95% confidence interval [CI], 0.83 to 1.02; P=0.12), and 728 patients and 759 patients, respectively, died (hazard ratio, 0.95; 95% CI, 0.86 to 1.05; P=0.31). There were no significant differences between the two groups in the coronary outcome or death from cardiovascular causes. In a prespecified secondary analysis, there were fewer hospitalizations for cardiovascular causes in the rosuvastatin group (2193) than in the placebo group (2564) (P<0.001). No excessive episodes of muscle-related or other adverse events occurred in the rosuvastatin group. CONCLUSIONS: Rosuvastatin did not reduce the primary outcome or the number of deaths from any cause in older patients with systolic heart failure, although the drug did reduce the number of cardiovascular hospitalizations. The drug did not cause safety problems. (ClinicalTrials.gov number, NCT00206310.)
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| 3. |
- McMurray, John J V, et al.
(författare)
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Effects of statin therapy according to plasma high-sensitivity C-reactive protein concentration in the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA): a retrospective analysis.
- 2009
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Ingår i: Circulation. - 1524-4539. ; 120:22, s. 2188-96
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: We examined whether the antiinflammatory action of statins may be of benefit in heart failure, a state characterized by inflammation in which low cholesterol is associated with worse outcomes. METHODS AND RESULTS: We compared 10 mg rosuvastatin daily with placebo in patients with ischemic systolic heart failure according to baseline high sensitivity-C reactive protein (hs-CRP) <2.0 mg/L (placebo, n=779; rosuvastatin, n=777) or > or = 2.0 mg/L (placebo, n=1694; rosuvastatin, n=1711). The primary outcome was cardiovascular death, myocardial infarction, or stroke. Baseline low-density lipoprotein was the same, and rosuvastatin reduced low-density lipoprotein by 47% in both hs-CRP groups. Median hs-CRP was 1.10 mg/L in the lower and 5.60 mg/L in the higher hs-CRP group, with higher hs-CRP associated with worse outcomes. The change in hs-CRP with rosuvastatin from baseline to 3 months was -6% in the low hs-CRP group (27% with placebo) and -33.3% in the high hs-CRP group (-11.1% with placebo). In the high hs-CRP group, 548 placebo-treated (14.0 per 100 patient-years of follow-up) and 498 rosuvastatin-treated (12.2 per 100 patient-years of follow-up) patients had a primary end point (hazard ratio of placebo to rosuvastatin, 0.87; 95% confidence interval, 0.77 to 0.98; P=0.024). In the low hs-CRP group, 175 placebo-treated (8.9 per 100 patient-years of follow-up) and 188 rosuvastatin-treated (9.8 per 100 patient-years of follow-up) patients experienced this outcome (hazard ratio, 1.09; 95% confidence interval, 0.89 to 1.34; P>0.2; P for interaction=0.062). The numbers of deaths were as follows: 581 placebo-treated (14.1 per 100 patient-years of follow-up) and 532 rosuvastatin-treated (12.6 per 100 patient-years) patients in the high hs-CRP group (hazard ratio, 0.89; 95% confidence interval, 0.79 to 1.00; P=0.050) and 170 placebo-treated (8.3 per 100 patient-years) and 192 rosuvastatin-treated (9.7 per 100 patient-years) patients in the low hs-CRP group (hazard ratio, 1.17; 95% confidence interval, 0.95 to 1.43; P=0.14; P for interaction=0.026). CONCLUSIONS: In this retrospective hypothesis-generating study, we found a significant interaction between hs-CRP and the effect of rosuvastatin for most end points whereby rosuvastatin treatment was associated with better outcomes in patients with hs-CRP > or = 2.0 mg/L. CLINICAL TRIAL REGISTRATION INFORMATION: URL: http://www.clinicaltrials.gov. Unique identifier: NCT00206310.
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| 4. |
- 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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| 5. |
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| 6. |
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| 7. |
- Kjekshus, J., et al.
(författare)
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A statin in the treatment of heart failure? Controlled rosuvastatin multinational study in heart failure (CORONA): study design and baseline characteristics
- 2005
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Ingår i: Eur J Heart Fail. - 1388-9842. ; 7:6, s. 1059-69
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Previous prospective outcome studies of statins have not provided any guidance on benefit-risk in patients with heart failure. AIM: The primary objective is to determine whether rosuvastatin (10 mg) reduces the combined endpoint of cardiovascular mortality, non-fatal myocardial infarction or non-fatal stroke (time to first event). The first secondary endpoint is all-cause mortality. METHODS: CORONA is a randomized, double-blind, placebo-controlled trial. Briefly, men and women, aged > or =60 years with chronic symptomatic systolic heart failure of ischemic aetiology and ejection fraction < or =0.40 (NYHA class III and IV) or < or =0.35 (NYHA class II) were eligible if they were not using or in need of cholesterol lowering drugs. RESULTS: Mean age was 73 years (n=5016; 24% women), with 37% in NYHA II and 62% in NYHA III, ejection fraction 0.31, total cholesterol 5.2 mmol/L. Sixty percent have a history of myocardial infarction, 63% hypertension, and 30% diabetes. Patients are well treated for heart failure with 90% on loop or thiazide diuretics, 42% aldosterone antagonists, 91% ACE inhibitor or AT-I blocker, 75% beta-blockers, and 32% digitalis. CONCLUSION: CORONA is important for three main reasons: (1) A positive result is very important because of the high risk of the population studied, the increasing prevalence of elderly patients with chronic symptomatic systolic heart failure in our society, and the health economic issues involved. (2) If negative, new mechanistic questions about heart failure have to be raised. (3) If neutral we can avoid unnecessary polypharmacy.
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| 8. |
- Remme, Willem J, et al.
(författare)
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Awareness and perception of heart failure among European cardiologists, internists, geriatricians, and primary care physicians.
- 2008
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 29:14, s. 1739-52
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To assess awareness of heart failure (HF) management recommendations in Europe among cardiologists (C), internists and geriatricians (I/G), and primary care physicians (PCPs). METHODS AND RESULTS: The Study group on HF Awareness and Perception in Europe (SHAPE) surveyed randomly selected C (2041), I/G (1881), and PCP (2965) in France, Germany, Italy, the Netherlands, Poland, Romania, Spain, Sweden, and the UK. Each physician completed a 32-item questionnaire about the diagnosis and treatment of HF (left ventricular ejection fraction <40%). This report provides an analysis of HF awareness among C, I/G, and PCP. Seventy-one per cent I/G and 92% C use echocardiography, and 43% I/G and 82% C use echo-Doppler as a routine diagnostic test (both P < 0.0001). In contrast, 75% PCP use signs and symptoms to diagnose HF. Fewer I/G would use an angiotensin-converting enzyme (ACE)-inhibitor in >90% of their patients (64 vs. 82% C, P < 0.0001), whereas only 47% PCP would routinely prescribe an ACE-inhibitor. Worsening HF was considered a risk of ACE-inhibitor therapy by 35% PCP. I/G and PCP consistently do not prescribe target ACE-inhibitor doses (P < 0.0001 vs. C). Only 39% I/G would use a beta-blocker in >50% of their patients (vs. 73% C, P < 0.0001). Also, only 5% PCP would always, and 35% often, prescribe a beta-blocker and reach target doses in only 7-29%. Moreover, 34% PCP and 26% I/G vs. 11% C (P < 0.0001) do not start a beta-blocker in patients with mild HF, who are already on an ACE-inhibitor and are on diuretic. In mild, stable HF, 39% PCP and 18% I/G would only prescribe diuretics, vs. 7% C (P < 0.0001). In patients with worsening HF in sinus rhythm and on an optimal ACE-inhibitor, beta-blockade and diuretics, significantly more C would add spironolactone, but I/G would more often add digoxin. CONCLUSION: Although each physician group lacks complete adherence to guideline-recommended management strategies, these are used significantly less well by I, G, and PCPs, indicating the need for education of these essential healthcare providers.
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| 9. |
- Køber, Lars, et al.
(författare)
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Increased mortality after dronedarone therapy for severe heart failure
- 2008
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Ingår i: The New England journal of medicine. - 1533-4406. ; 358:25, s. 2678-2687
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Dronedarone is a novel antiarrhythmic drug with electrophysiological properties that are similar to those of amiodarone, but it does not contain iodine and thus does not cause iodine-related adverse reactions. Therefore, it may be of value in the treatment of patients with heart failure. METHODS: In a multicenter study with a double-blind design, we planned to randomly assign 1000 patients who were hospitalized with symptomatic heart failure and severe left ventricular systolic dysfunction to receive 400 mg of dronedarone twice a day or placebo. The primary end point was the composite of death from any cause or hospitalization for heart failure. RESULTS: After inclusion of 627 patients (310 in the dronedarone group and 317 in the placebo group), the trial was prematurely terminated for safety reasons, at the recommendation of the data and safety monitoring board, in accordance with the board's predefined rules for termination of the study. During a median follow-up of 2 months, 25 patients in the dronedarone group (8.1%) and 12 patients in the placebo group (3.8%) died (hazard ratio in the dronedarone group, 2.13; 95% confidence interval [CI], 1.07 to 4.25; P=0.03). The excess mortality was predominantly related to worsening of heart failure--10 deaths in the dronedarone group and 2 in the placebo group. The primary end point did not differ significantly between the two groups; there were 53 events in the dronedarone group (17.1%) and 40 events in the placebo group (12.6%) (hazard ratio, 1.38; 95% CI, 0.92 to 2.09; P=0.12). More increases in the creatinine concentration were reported as serious adverse events in the dronedarone group than in the placebo group. CONCLUSIONS: In patients with severe heart failure and left ventricular systolic dysfunction, treatment with dronedarone was associated with increased early mortality related to the worsening of heart failure. (ClinicalTrials.gov number, NCT00543699.)
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| 10. |
- Metra, Marco, et al.
(författare)
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Advanced chronic heart failure: A position statement from the Study Group on Advanced Heart Failure of the Heart Failure Association of the European Society of Cardiology.
- 2007
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Ingår i: European journal of heart failure : journal of the Working Group on Heart Failure of the European Society of Cardiology. - : Wiley. - 1388-9842 .- 1879-0844. ; 9:6-7, s. 684-94
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Forskningsöversikt (refereegranskat)abstract
- Therapy has improved the survival of heart failure (HF) patients. However, many patients progress to advanced chronic HF (ACHF). We propose a practical clinical definition and describe the characteristics of this condition. Patients that are generally recognised as ACHF often exhibit the following characteristics: 1) severe symptoms (NYHA class III to IV); 2) episodes with clinical signs of fluid retention and/or peripheral hypoperfusion; 3) objective evidence of severe cardiac dysfunction, shown by at least one of the following: left ventricular ejection fraction<30%, pseudonormal or restrictive mitral inflow pattern at Doppler-echocardiography; high left and/or right ventricular filling pressures; elevated B-type natriuretic peptides; 4) severe impairment of functional capacity demonstrated by either inability to exercise, a 6-minute walk test distance<300 m or a peak oxygen uptake<12-14 ml/kg/min; 5) history of >1 HF hospitalisation in the past 6 months; 6) presence of all the previous features despite optimal therapy. This definition identifies a group of patients with compromised quality of life, poor prognosis, and a high risk of clinical events. These patients deserve effective therapeutic options and should be potential targets for future clinical research initiatives.
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