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      Ivabradine Treatment in a Chronic Heart Failure Patient Cohort: Symptom Reduction and Improvement in Quality of Life in Clinical Practice

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          Abstract

          Introduction

          In the prospective, open-label multicenter INTENSIFY study, the effectiveness and tolerability of ivabradine as well as its impact on quality of life (QOL) in chronic systolic heart failure (CHF) patients were evaluated over a 4-month period.

          Methods

          In CHF patients with an indication for treatment with ivabradine, resting heart rate (HR), heart failure symptoms [New York Heart Association (NYHA) class, signs of decompensation], left ventricular ejection fraction, brain natriuretic peptide (BNP) values, QOL, and concomitant medication with focus on beta-blocker therapy were documented at baseline, after 4 weeks, and after 4 months. The results were analyzed using descriptive statistical methods.

          Results

          Thousand nine hundred and fifty-six patients with CHF were included. Their mean age was 67 ± 11.7 years and 56.9% were male. 77.8% were receiving beta-blockers. Other concomitant medications included angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (83%), diuretics (61%), aldosterone antagonists (18%), and cardiac glycosides (8%). At baseline, the mean HR of patients was 85 ± 11.8 bpm, 51.1% and 37.2% of patients were classified as NYHA II and III, respectively, and 22.7% showed signs of decompensation. BNP concentrations were tracked in a subgroup, and values exceeding 400 pg/mL were noted in 53.9% of patients. The mean value of the European quality of life-5 dimensions (EQ-5D) QOL index was 0.64 ± 0.28. After 4 months of treatment with ivabradine, HR was reduced to 67 ± 8.9 bpm. Furthermore, the proportion of patients presenting with signs of decompensation decreased to 5.4% and the proportion of patients with BNP levels >400 pg/mL dropped to 26.7%, accompanied by a shift in NYHA classification towards lower grading (24.0% and 60.5% in NYHA I and II, respectively). EQ-5D index improved to 0.79 ± 0.21.

          Conclusion

          Over 4 months of treatment, ivabradine effectively reduced HR and symptoms in CHF patients in this study reflecting daily clinical practice. These benefits were accompanied by improved QOL and good general tolerability.

          Electronic supplementary material

          The online version of this article (doi:10.1007/s12325-014-0147-3) contains supplementary material, which is available to authorized users.

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          Most cited references21

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          Are hospitalized or ambulatory patients with heart failure treated in accordance with European Society of Cardiology guidelines? Evidence from 12,440 patients of the ESC Heart Failure Long-Term Registry.

          To evaluate how recommendations of European guidelines regarding pharmacological and non-pharmacological treatments for heart failure (HF) are adopted in clinical practice.
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            Efficacy of ivabradine, a new selective I(f) inhibitor, compared with atenolol in patients with chronic stable angina.

            Ivabradine, a new I(f) inhibitor which acts specifically on the pacemaker activity of the sinoatrial node, is a pure heart rate lowering agent. Ivabradine has shown anti-ischaemic and anti-anginal activity in a placebo-controlled trial. The objective of this study was to compare the anti-anginal and anti-ischaemic effects of ivabradine and the beta-blocker atenolol. In a double-blinded trial, 939 patients with stable angina were randomized to receive ivabradine 5 mg bid for 4 weeks and then either 7.5 or 10 mg bid for 12 weeks or atenolol 50 mg od for 4 weeks and then 100 mg od for 12 weeks. Patients underwent treadmill exercise tests at randomization (M(0)) and after 4 (M(1)) and 16 (M(4)) weeks of therapy. Increases in total exercise duration (TED) at trough at M(4) were 86.8+/-129.0 and 91.7+/-118.8 s with ivabradine 7.5 and 10 mg, respectively and 78.8+/-133.4 s with atenolol 100 mg. Mean differences (SE) when compared with atenolol 100 mg were 10.3 (9.4) and 15.7 (9.5) s in favour of ivabradine 7.5 and 10 mg (P<0.001 for non-inferiority). TED at M(1) improved by 64.2+/-104.0 s with ivabradine 5 mg and by 60.0+/-114.4 s with atenolol 50 mg (P<0.001 for non-inferiority). Non-inferiority of ivabradine was shown at all doses and for all criteria. The number of angina attacks was decreased by two-thirds with both ivabradine and atenolol. Ivabradine is as effective as atenolol in patients with stable angina.
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              Meta-analysis: beta-blocker dose, heart rate reduction, and death in patients with heart failure.

              Guidelines recommend that patients with heart failure receive beta-blockers in doses used in the trials that have proven their efficacy. Although the adverse effects of beta-blockade are dose-related, it is unclear whether the benefits are. To determine whether the survival benefits of beta-blockade in heart failure are associated with the magnitude of heart rate reduction or the beta-blocker dose. MEDLINE, EMBASE, CINAHL, SIGLE, Web of Science, and the Cochrane Central Register of Controlled Trials, supplemented by hand-searches of bibliographies. Randomized, placebo-controlled heart failure trials that reported all-cause mortality. Two reviewers independently extracted data on study characteristics, beta-blocker dosing and heart rate reduction, and death. The mean left ventricular ejection fraction in the 23 beta-blocker trials ranged from 0.17 to 0.36, and more than 95% of the 19 209 patients had systolic dysfunction. The overall risk ratio for death was 0.76 (95% CI, 0.68 to 0.84); however, heterogeneity testing revealed moderate heterogeneity among trials (I (2) = 30%), which was associated with the magnitude of heart rate reduction achieved within each trial (P for meta-regression = 0.006). For every heart rate reduction of 5 beats/min with beta-blocker treatment, a commensurate 18% reduction (CI, 6% to 29%) in the risk for death occurred. No significant relationship between all-cause mortality and beta-blocker dosing was observed (risk ratio for death, 0.74 [CI, 0.64 to 0.86]) in high-dose beta-blocker trials vs. 0.78 [CI, 0.63 to 0.96] in low-dose beta-blocker trials; P for meta-regression = 0.69). The analysis is based on aggregate data and resting heart rates. Few patients in these trials had bradycardia or diastolic dysfunction at baseline. The magnitude of heart rate reduction is statistically significantly associated with the survival benefit of beta-blockers in heart failure, whereas the dose of beta-blocker is not.
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                Author and article information

                Contributors
                zugck@gmx.net
                Journal
                Adv Ther
                Adv Ther
                Advances in Therapy
                Springer Healthcare (Heidelberg )
                0741-238X
                1865-8652
                27 August 2014
                27 August 2014
                2014
                : 31
                : 9
                : 961-974
                Affiliations
                [ ]Clinic/Group Practice for Internal Medicine, Steiner Thor, Straubing, Germany
                [ ]Department of Medical Affairs, Servier Deutschland GmbH, Munich, Germany
                Article
                147
                10.1007/s12325-014-0147-3
                4177104
                25160945
                a04dfe5c-4692-479c-b68b-62f4789d699c
                © The Author(s) 2014
                History
                : 10 July 2014
                Categories
                Original Research
                Custom metadata
                © Springer Healthcare 2014

                cardiology,chronic heart failure,heart rate,ivabradine,nyha class,quality of life,symptom reduction

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