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Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study

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Abstract

Aim

Several clinical trials have demonstrated the antianginal and anti-ischemic efficacy of ivabradine in combination with beta-blocker in patients with stable angina pectoris. The ADDITIONS (PrActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) study evaluated the efficacy, safety, and tolerability of ivabradine added to beta-blocker, and its effect on angina symptoms and quality of life in routine clinical practice.

Methods

This non-interventional, multicenter, prospective study included 2,330 patients with stable angina pectoris treated with a flexible dose of ivabradine twice daily in addition to beta-blocker for 4 months. The parameters recorded included heart rate, number of angina attacks, nitrate consumption, tolerance, and quality of life.

Results

After 4 months ivabradine (mean dose 12.37 ± 2.95 mg/day) reduced heart rate by 19.4 ± 11.4 to 65.6 ± 8.2 bpm (p < 0.0001). The number of angina attacks was reduced by 1.4 ± 1.9 per week (p < 0.0001), and nitrate consumption by 1.9 ± 2.9 U per week (p < 0.0001). At baseline (i.e., on beta-blocker), half of the patients (51%) were classified as Canadian Cardiovascular Society (CCS) grade II; 29% were CCS grade I. After 4 months’ treatment with ivabradine, most of the patients were CCS grade I (68%). The EQ-5D index improved by 0.17 ± 0.23 (p < 0.0001). The overall efficacy of ivabradine was considered by the physicians as “very good” (61%) or “good” (36%) in most patients. Suspected adverse drug reactions were documented in 14 patients; none were severe.

Conclusion

In daily clinical practice, combining ivabradine with beta-blocker not only reduces heart rate, number of angina attacks, and nitrate consumption, but also improves the quality of life in patients with stable angina pectoris.

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Acknowledgments

The authors thank METRONOMIA Clinical Research GmbH, Munich, for their substantive support of the statistical analysis, and all investigators for their contributions to the study. The investigators participated were M. Abdel- Quader, R. Antar, R. Aubele, S. Bock, P. Borchert, M.C. Brunke, J. Busaker, S. Djatschuk, M. Durak, M. Erdmann, D. Götze, P. Hammerl, S. Jasinski, N. Jung, T. Jung, O. Kahn, F. König, M. Köstering, T. Kornadt, K. Kreye, R. Kubbutat, R. Lange, R. Leischik, H. Littwitz, S. Mittnacht, P.Papachrysanthou, M. Patten, S. Pohl- Wegener, P. Pyriki, G.J. Qagisch, H. Reifenberg, I. Richter, F. Richter, E. Schaubert, O. Scheuermann, T. Scholl, D. Schulz, A. Sobejko, J. Steindorf, R. Stroh, H.J. Stühn- Pfeiffer, S. Vogel, T. Walter, H. G. Weber, A. Wilke, M. Zeydabadinejad. The list of further investigators is available from the corresponding author. The study was supported by funding from Servier Deutschland GmbH, Munich.

Conflict of interest statement

KW, HE, and SN are engaged in RCTs with ivabradine fully or partly supported by Servier (BEAUTIFUL, SHIFT, SIGNIFY, MODIFY and others). KW received honoraria for lectures from Servier, is a member of the German Procoralan advisory board of Servier and receives research grants for experimental and clinical ivabradine research from Servier. GH is an employee of Servier.

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Correspondence to Karl Werdan.

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Werdan, K., Ebelt, H., Nuding, S. et al. Ivabradine in combination with beta-blocker improves symptoms and quality of life in patients with stable angina pectoris: results from the ADDITIONS study. Clin Res Cardiol 101, 365–373 (2012). https://doi.org/10.1007/s00392-011-0402-4

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