Treatment of stable angina pectoris by ivabradine in every day practice: The REDUCTION Study
Section snippets
Design
This trial was performed as a multicenter, prospective, open-label, noninterventional study. A total of 4,954 patients treated with ivabradine were included and prospectively followed by 1,503 general practitioners, internal medicine physicians, and cardiologists in private practice in Germany. All participating physicians filled out standardized questionnaires during the patient's course of treatment.
The study complies with the Declaration of Helsinki. It was conducted in accordance with the
Study population
Of the 4,954 patients, 59% were men and 41% were women. Mean age was 65.1 ± 10.4 years. A total of 3,964 (80%) patients had arterial hypertension; 3,806 (77%) had hypercholesterolemia; 2,170 (44%) were overweight; 1,422 (29%) were smokers or exsmokers; and 1,421 (29%) had diabetes mellitus.
The mean duration of coronary artery disease in the group was 5.2 ± 4.9 years. The duration of the history of angina pectoris was 3.6 ± 3.9 years. In 19% of the patients, the duration of angina pectoris was<6
Discussion
Because of strict patient selection criteria, there may be a discrepancy between the results of highly controlled clinical trials and everyday clinical practice.22 Observational databases can be useful adjuncts to randomized, controlled trials to see whether efficacy under controlled conditions in specialist clinics translates into effective treatment in routine practice. Therefore, in this study, the efficacy, safety, and tolerance of ivabradine were evaluated deliberately under everyday
Conclusions
Ivabradine reduces heart rate in everyday practice in a broad population of patients. It is highly effective in the treatment of stable angina pectoris and reduces the attacks and nitrate consumption in combination with a standard medical therapy.
Ivabradine was well tolerated by most patients and has a lower rate of reported ADR in everyday practice compared with available reports from controlled trials.
The results confirm the findings from randomized controlled trials for the routine use of
Disclosures
T.M.'s and R.K.'s participation at scientific congresses has been supported by Servier Deutschland. T.M. is member of the advisory board. J.K. has no conflict of interest.
Acknowledgements
We thank Dieter Schremmer from the ‘Gesellschaft für Therapieforschung’ and all investigators for their contributions to the study. The investigators who participated were J. Taggeselle, L. Feβ, R. Aubele, N. Hassler, K. Hofmann, V. Adelberger, T. Arnold, B. Holz, M. Hwaidi, H.-D. Kombächer, R. Meysing, S. Appel, J. Bazowski, R. Bernauer, H. Böneke, M. Braun, E. Daelmann, M. Deiβner, S. Duddy, M.-A. Eisenbarth, H. Fissan, C. Freese, G. Gölz, M. Gutting, K. Hallbaum, M. Hilgedieck, J.-A. Hintze,
References (29)
- et al.
Heart rate and cardiovascular mortality: the Framingham Study
Am Heart J
(1987) - et al.
Resting heart rate in cardiovascular disease
J Am Coll Cardiol
(2007) - et al.
Heart rate as a prognostic risk factor in patients with coronary artery disease and left-ventricular systolic dysfunction (BEAUTIFUL): a subgroup analysis of a randomised controlled trial
Lancet
(2008) Funny channels in the control of cardiac rhythm and mode of action of selective blockers
Pharmacol Res
(2006)- et al.
Anti-ischaemic effect of ivabradine
Pharmacol Res
(2006) - et al.
The natural history of atrial fibrillation: incidence, risk factors, and prognosis in the Manitoba Follow-Up Study
Am J Med
(1995) - et al.
Relations between heart rate, ischemia, and drug therapy during daily life in patients with coronary artery disease
Circulation
(1991) - et al.
Subsets of ambulatory myocardial ischemia based on heart rate activity. Circadian distribution and response to anti-ischemic medication. The Angina and Silent Ischemia Study Group (ASIS)
Circulation
(1993) - et al.
The role of heart rate and the benefits of heart rate reduction in acute myocardial ischemia
Eur Heart J
(2007) - et al.
2007 Chronic Angina Focused Update of the ACC/AHA 2002 guidelines for the management of patients with chronic stable angina
Circulation
(2007)
Guidelines on the management of stable angina pectoris
Eur Heart J
Nationale Versorgungsleitlinie Chronische KHK. Version 2008
Heart rate as a prognostic factor for coronary heart disease and mortality: findings in three Chicago epidemiologic studies
Am J Epidemiol
Long-term prognostic value of resting heart rate in patients with suspected or proven coronary artery disease
Eur Heart J
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2019, Pharmacological ResearchCitation Excerpt :The REDUCTION was a multicenter, prospective, open-label, non-interventional study which evaluated the efficacy, safety and tolerability of ivabradine in 4,954 patients with CAD and stable angina. The follow up was performed by physicians in private practice, with the intend to reproduce «real life» conditions rather than the controlled environment of a randomized clinical trial [43]. Of note, only 344 (6.9%) patients received ivabradine on top of beta-blocker, and the rest 2350 (54.4%) who were treated with a beta-blocker at the beginning of the study discontinued.
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2017, Chronic Coronary Artery Disease: A Companion to Braunwald's Heart DiseaseIvabradine in combination with beta-blocker reduces symptoms and improves quality of life in elderly patients with stable angina pectoris: Age-related results from the ADDITIONS study
2014, Experimental GerontologyCitation Excerpt :Overall, these findings suggest a good tolerance of the drug under everyday conditions in elderly patients. The results for the combination of ivabradine and beta-blocker are in good agreement with controlled studies with predominantly younger patients (Fox et al., 2008a; Swedberg et al., 2010; Tardif et al., 2009) and two open-label studies (Köster et al., 2009; Werdan et al., 2012). Most notably, the encouraging safety data mirror the results from the octogenarian subset of patients in the REDUCTION trial (Köster et al., 2010).
Angina pectoris in women: Focus on microvascular disease
2013, International Journal of CardiologyCitation Excerpt :However, presence of women in these trials was low (10–15%) [100–102], nor was subgroup analysis for gender performed. A large observational study showed effective treatment of stable angina by ivabradine in patients mainly not taking beta-blockers due to contraindications or intolerance [104]; of 4954 patients, 41% were women, and therefore those findings could be translated to a female population; however, because of its open-label design and absence of a placebo-controlled group, those data are not definitive. Very little information is available with respect to the effects of “classical” antianginal drugs on long term outcomes.