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- Böhm, Michael, et al.
(author)
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Heart rate as a risk factor in chronic heart failure (SHIFT): the association between heart rate and outcomes in a randomised placebo-controlled trial
- 2010
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In: Lancet. - 0140-6736. ; 376:9744, s. 886-894
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Journal article (peer-reviewed)abstract
- BACKGROUND: Raised resting heart rate is a marker of cardiovascular risk. We postulated that heart rate is also a risk factor for cardiovascular events in heart failure. In the SHIFT trial, patients with chronic heart failure were treated with the selective heart-rate-lowering agent ivabradine. We aimed to test our hypothesis by investigating the association between heart rate and events in this patient population. METHODS: We analysed cardiovascular outcomes in the placebo (n=3264) and ivabradine groups (n=3241) of this randomised trial, divided by quintiles of baseline heart rate in the placebo group. The primary composite endpoint was cardiovascular death or hospital admission for worsening heart failure. In the ivabradine group, heart rate achieved at 28 days was also analysed in relation to subsequent outcomes. Analysis adjusted to change in heart rate was used to study heart-rate reduction as mechanism for risk reduction by ivabradine directly. FINDINGS: In the placebo group, patients with the highest heart rates (>or=87 beats per min [bpm], n=682, 286 events) were at more than two-fold higher risk for the primary composite endpoint than were patients with the lowest heart rates (70 to <72 bpm, n=461, 92 events; hazard ratio [HR] 2.34, 95% CI 1.84-2.98, p<0.0001). Risk of primary composite endpoint events increased by 3% with every beat increase from baseline heart rate and 16% for every 5-bpm increase. In the ivabradine group, there was a direct association between heart rate achieved at 28 days and subsequent cardiac outcomes. Patients with heart rates lower than 60 bpm at 28 days on treatment had fewer primary composite endpoint events during the study (n=1192; event rate 17.4%, 95% CI 15.3-19.6) than did patients with higher heart rates. The effect of ivabradine is accounted for by heart-rate reduction, as shown by the neutralisation of the treatment effect after adjustment for change of heart rate at 28 days (HR 0.95, 0.85-1.06, p=0.352). INTERPRETATION: Our analysis confirms that high heart rate is a risk factor in heart failure. Selective lowering of heart rates with ivabradine improves cardiovascular outcomes. Heart rate is an important target for treatment of heart failure. FUNDING: Servier, France.
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| 2. |
- Chang, S. M., et al.
(author)
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Efficacy and safety of angiotensin receptor blockade are not modified by aspirin in patients with chronic heart failure: a cohort study from the Candesartan in Heart failure--Assessment of Reduction in Mortality and morbidity (CHARM) programme
- 2010
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In: European Journal of Heart Failure. - 1388-9842. ; 12:7, s. 738-745
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Journal article (peer-reviewed)abstract
- AIMS: It is unknown whether there is an interaction between aspirin and angiotensin receptor blockers on outcomes in patients with heart failure (HF). METHODS AND RESULTS: The efficacy and safety of candesartan vs. placebo was assessed in 7599 patients with symptomatic HF and reduced or preserved left ventricular ejection fraction enrolled in the CHARM programme according to baseline aspirin use. Patients were randomized to candesartan or matching placebo and were followed for a median of 38 months. Aspirin was used in 4246 (55.9%) of patients at baseline. When compared with placebo, candesartan use was associated with lower event rates for cardiovascular (CV) death or HF hospitalization (primary outcome) in both the aspirin group (28 vs. 31.9%, HR 0.81, 95% CI 0.72-0.90) and non-aspirin group (33 vs. 38%, HR 0.81, 95% CI 0.72-0.91). Baseline aspirin use did not modify the effectiveness of candesartan in reducing the risk of CV death or HF hospitalization in CHARM overall (P = 0.64) or in the CHARM individual trials. In addition, there was no significant interaction between aspirin therapy and candesartan in terms of discontinuation of study drug due to adverse reactions (P = 0.72). CONCLUSION: There appears to be no significant modification of the benefit of candesartan on CV mortality and morbidity outcomes or safety by concomitant use of aspirin in patients with chronic HF.
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| 6. |
- Persson, H., et al.
(author)
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Improved pharmacological therapy of chronic heart failure in primary care: a randomized Study of NT-proBNP Guided Management of Heart Failure--SIGNAL-HF (Swedish Intervention study--Guidelines and NT-proBNP AnaLysis in Heart Failure)
- 2010
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In: European Journal of Heart Failure. - : Wiley. - 1388-9842 .- 1879-0844. ; 12:12, s. 1300-1308
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Journal article (peer-reviewed)abstract
- AIMS: Treatment of chronic heart failure (CHF) guided by natriuretic peptides has been studied in clinical trials with conflicting results. The aim of this study was to investigate if N-terminal pro-B-type natriuretic peptide (NT-proBNP)-guided therapy in symptomatic heart failure patients in primary care would improve clinical outcomes over and above treatment according to guidelines. METHODS AND RESULTS: SIGNAL-HF was a 9 month, randomized, single-blind, parallel group study in patients with CHF in NYHA class II-IV, ejection fraction (EF)<50% and elevated NT-proBNP levels (males>800, females>1000 ng/L). All investigators underwent a pre-study educational programme about current CHF guidelines. A control group managed by non-trained investigators was considered not possible for ethical and practical reasons. Patients were randomized to structured treatment of CHF according to guidelines with or without NT-proBNP monitoring. The choice and dose of therapy for CHF was at the investigator's discretion. The primary outcome variable was the composite endpoint of days alive, days out of hospital, and symptom score from the Kansas City Cardiomyopathy Questionnaire. In all, 252 patients were randomized. The allocation groups were well balanced with regards to age, NT-proBNP, and EF. Treatment doses of beta-blockers and blockers of the renin-angiotensin-aldosterone system were markedly increased towards target doses and to a similar degree in both groups. There were no differences between the groups concerning either the primary endpoint (P=0.28) or its components [cardiovascular (CV) death, P=0.93; CV hospitalization, P=0.88; or symptom score, P=0.28]. CONCLUSION: NT-proBNP-guided CHF treatment did not result in important improvements in clinical outcomes in patients with CHF in primary care above and beyond what could be achieved by education and structured CHF treatment according to guidelines.
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| 7. |
- Philipson, Henriette, 1953, et al.
(author)
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A pilot study of salt and water restriction in patients with chronic heart failure.
- 2010
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In: Scandinavian cardiovascular journal : SCJ. - : Informa UK Limited. - 1651-2006 .- 1401-7431. ; 44:4, s. 209-14
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Journal article (peer-reviewed)abstract
- International guidelines recommend low sodium intake and fluid restriction for patients with chronic heart failure (CHF) despite little support from scientific research. We conducted a pilot study to evaluate if dietary restriction instructions and recommendations are effective in reducing sodium and fluid intake in patients with CHF and if such reductions affect quality of life, thirst and appetite. Design. A 12-week, prospective, randomized study with an intervention and control group. The intervention group (n=17) followed a sodium-restricted diet (2-3 g/day) and fluid restriction (1.5 L/day) while the control group (n=13) received general diet information on heart failure. Urine sodium excretion was measured on three consecutive days and para-aminobenzoic acid was used to secure urine collection. Individual dietary recommendations were provided. RESULTS: Fluid intake was reduced in the intervention group compared with the control group from baseline to follow-up: 1.6(0.4)L to 1.2(0.5)L vs. 1.7(0.8)L to 1.6(0.9)L (p=0.04). Sodium excretion was reduced by > or =25% in 57% of the patients in the intervention group and in 25% in the control group (p=0.049). CONCLUSION: Patients with CHF were able to reduce sodium and fluid intake. The effects in terms of patient perceptions and clinical outcomes need to be assessed in a larger study.
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| 8. |
- Scirica, B. M., et al.
(author)
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Patients with acute coronary syndromes and elevated levels of natriuretic peptides: the results of the AVANT GARDE-TIMI 43 Trial
- 2010
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In: European Heart Journal. - 0195-668X. ; 31:16, s. 1993-2005
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Journal article (peer-reviewed)abstract
- Aims Elevated natriuretic peptides (NPs) are associated with an increased cardiovascular risk following acute coronary syndromes (ACSs). However, the therapeutic implications are still undefined. We hypothesized that early inhibition of renin-angiotensin-aldosterone system (RAAS) in patients with preserved left ventricular function but elevated NPs but following ACS would reduce haemodynamic stress as reflected by a greater reduction NP compared with placebo. Methods and results AVANT GARDE-TIMI 43 trial, a multinational, double-blind trial, randomized 1101 patients stabilized after ACS without clinical evidence of heart failure or left ventricular function
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| 10. |
- Swedberg, Karl, 1944, et al.
(author)
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Ivabradine and outcomes in chronic heart failure (SHIFT): a randomised placebo-controlled study
- 2010
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In: Lancet. - 0140-6736. ; 376:9744, s. 875-885
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Journal article (peer-reviewed)abstract
- BACKGROUND: Chronic heart failure is associated with high mortality and morbidity. Raised resting heart rate is a risk factor for adverse outcomes. We aimed to assess the effect of heart-rate reduction by the selective sinus-node inhibitor ivabradine on outcomes in heart failure. METHODS: Patients were eligible for participation in this randomised, double-blind, placebo-controlled, parallel-group study if they had symptomatic heart failure and a left-ventricular ejection fraction of 35% or lower, were in sinus rhythm with heart rate 70 beats per min or higher, had been admitted to hospital for heart failure within the previous year, and were on stable background treatment including a beta blocker if tolerated. Patients were randomly assigned by computer-generated allocation schedule to ivabradine titrated to a maximum of 7.5 mg twice daily or matching placebo. Patients and investigators were masked to treatment allocation. The primary endpoint was the composite of cardiovascular death or hospital admission for worsening heart failure. Analysis was by intention to treat. This trial is registered, number ISRCTN70429960. FINDINGS: 6558 patients were randomly assigned to treatment groups (3268 ivabradine, 3290 placebo). Data were available for analysis for 3241 patients in the ivabradine group and 3264 patients allocated placebo. Median follow-up was 22.9 (IQR 18-28) months. 793 (24%) patients in the ivabradine group and 937 (29%) of those taking placebo had a primary endpoint event (HR 0.82, 95% CI 0.75-0.90, p<0.0001). The effects were driven mainly by hospital admissions for worsening heart failure (672 [21%] placebo vs 514 [16%] ivabradine; HR 0.74, 0.66-0.83; p<0.0001) and deaths due to heart failure (151 [5%] vs 113 [3%]; HR 0.74, 0.58-0.94, p=0.014). Fewer serious adverse events occurred in the ivabradine group (3388 events) than in the placebo group (3847; p=0.025). 150 (5%) of ivabradine patients had symptomatic bradycardia compared with 32 (1%) of the placebo group (p<0.0001). Visual side-effects (phosphenes) were reported by 89 (3%) of patients on ivabradine and 17 (1%) on placebo (p<0.0001). INTERPRETATION: Our results support the importance of heart-rate reduction with ivabradine for improvement of clinical outcomes in heart failure and confirm the important role of heart rate in the pathophysiology of this disorder. FUNDING: Servier, France.
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