Ivabradine in Combination with Metoprolol Improves Symptoms and Quality of Life in Patients with Stable Angina Pectoris: A post hoc Analysis from the ADDITIONS Trial.

OBJECTIVES: Elevated heart rate can increase myocardial oxygen demand and reduce myocardial perfusion, provoking myocardial ischemia and angina symptoms. We evaluated adding ivabradine to the therapy of patients on metoprolol. METHODS: ADDITIONS (prActical Daily efficacy anD safety of Procoralan® In combinaTION with betablockerS) was a multicenter, 4-month, noninterventional, prospective, open-label trial that involved stable-angina patients. Along with metoprolol, patients received ivabradine (5 or 7.5 mg, b.i.d.). We investigated the effect of ivabradine on heart rate, angina attacks, nitrate consumption, quality of life (QoL) and tolerability as well as the influence of baseline heart rate. RESULTS: Heart rate fell by 19.7 ± 11.2 bpm, with an 8-fold decrease in weekly angina attacks (1.7 ± 2.2 to 0.2 ± 0.7) and nitrate consumption (2.4 ± 3.4 to 0.3 ± 0.9). Patient numbers in Canadian Cardiovascular Society class I more than doubled (i.e. from 29 to 65%) and QoL improved (the EQ-5D index and visual analog scale scores rose from 0.68 ± 0.27 to 0.84 ± 0.20 and 58.1 ± 18.4 to 72.2 ± 15.5 mm, respectively). The effect of ivabradine was greater in patients with a baseline heart rate ≥70 bpm (mean reduction in heart rate -21.2 ± 10.4 bpm, with a relative reduction in angina attacks and short-acting nitrate consumption of 87.1 and 87.2%, respectively). CONCLUSIONS: Ivabradine combined with metoprolol safely and effectively reduces heart rate, angina attacks and nitrate use, and improves QoL in stable-angina patients.

Automated fall risk assessment of elderly using wearable devices.

INTRODUCTION: Falls cause major expenses in the healthcare sector. We investigate the ability of supporting a fall risk assessment by introducing algorithms for automated assessments of standardized fall risk-related tests via wearable devices. METHODS: In a study, 13 participants conducted the standardized 6-Minutes Walk Test, the Timed-Up-and-Go Test, the 30-Second Sit-to-Stand Test, and the 4-Stage Balance Test repeatedly, producing 226 tests in total. Automatedalgorithms computed by wearable devices, as well as a visual analysis of the recorded data streams, were compared to the observational results conducted by physiotherapists. RESULTS: There was a high congruence between automated assessments and the ground truth for all four test types (ranging from 78.15% to 96.55%), with deviations ranging all well within one standard deviation of the ground truth. Fall risk (assessed by questionnaire) correlated with the individual tests. CONCLUSIONS: The automated fall risk assessment using wearable devices and algorithms matches the validity of the ground truth, thus providing a resourceful alternative to the effortful observational assessment, while minimizing the risk of human error. No single test can predict overall fall risk; instead, a much more complex model with additional input parameters (e.g., fall history, medication etc.) is needed.

Subgroups of monocytes predict cardiovascular events in patients with coronary heart disease. The PHAMOS trial (Prospective Halle Monocytes Study).

BACKGROUND: Monocytes can be differentiated by the presence of CD14 and CD16 (CD14++CD16-, classical; CD14++CD16+, intermediate and CD14 + CD16++, non-classical monocytes). Recent studies have reported conflicting results regarding an association between subtypes of monocytes as defined by the expression of these two surface markers in atherosclerosis. METHODS: We investigated subtypes of monocytes in n = 994 patients with angiographically documented coronary artery disease (CAD). We compared total numbers of monocyte subgroups stratified by tertiles with the occurrence of the pre-defined combined endpoint (non-fatal myocardial infarction, cardiovascular death and non-haemorrhagic cerebral insult). Patients were followed up for a minimum of 52 weeks. Classical risk factors of coronary heart disease were included in multivariate analysis. RESULTS: The primary endpoint occurred 134 times at a median time of 34.5 weeks (IR 10.6/59.6). Intermediate (p = 0.813), non-classical (p = 0.725) and the number of total monocytes (p = 0.626) stratified by tertiles showed no significant association with the combined endpoint. However, a higher absolute number of classical monocytes divided in tertiles was associated with incidence of the combined endpoint {T1 = 8.9% vs T2 = 14.2% vs T3 = 16.0% (p = 0.021)}. When comparing the third with the first tertile of Mo1 population, multivariate analysis showed a hazard ratio of 1.646 (CI: 1.005-2.699, p = 0.048). CONCLUSIONS: The absolute counts of classical monocytes divided in tertiles are predictive of major adverse cardiac events in patients with CAD. A tremendous shift from classical to intermediate monocytes was also confirmed in patients with CAD. These data highlight the importance of CD14++ monocytes in cardiovascular diseases.

Ivabradine in combination with Beta-blockers in patients with chronic stable angina after percutaneous coronary intervention.

INTRODUCTION: The anti-anginal efficacy of ivabradine is well established. We describe a post hoc analysis in the ADDITIONS database to investigate effectiveness and tolerability of ivabradine in combination with beta-blocker in patients with angina who have had a percutaneous coronary intervention (PCI). METHODS: ADDITIONS was a non-interventional, multicenter prospective study including 2,330 patients with stable angina. In addition to beta-blocker, patients were treated with ivabradine in approved dosages for 4 months. We divided the population according to whether they had previously had a PCI or not, and explored the effect of ivabradine on heart rate, number of weekly angina attacks, frequency of nitrate consumption, as well as quality of life (QoL) and tolerability. RESULTS: Data were available for 2,319 patients, of whom 51.4% had previously had a PCI. There was no difference in the effect of ivabradine on mean heart rate between patients with a previous PCI [64.4 ± 7.6 beats per minute (bpm)] than those without (66.8 ± 8.5 bpm) at 4 months (both P < 0.0001). Similarly, the number of angina attacks decreased from 1.9 ± 2.4 to 0.5 ± 1.5 per week in patients with a previous PCI and 1.5 ± 2.0 to 0.3 ± 1.0 per week in patients without a previous PCI (both P < 0.0001). The frequency of nitrate consumption fell from 2.7 ± 3.7 to 1.0 ± 1.9 per week and 1.8 ± 2.8 to 0.6 ± 1.5 per week (both P < 0.0001) in patients with and without a previous PCI, respectively. There was no difference in the improvements in Canadian Cardiovascular Society class of angina, QoL, and physicians' assessment of effectiveness and tolerability between patients with a previous PCI and those without. CONCLUSION: Ivabradine is an effective and well-tolerated anti-anginal treatment in patients with stable angina after PCI. Ivabradine reduced the frequency of weekly angina attacks and nitrate consumption, led to an improvement in Canadian Cardiovascular Society class and a substantial improvement in the QoL of stable angina patients.

Ivabradine 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.

BACKGROUND: Clinical trials have proven the anti-anginal and anti-ischemic efficacy of the pacemaker current inhibitor ivabradine in combination with beta-blockers in patients with stable angina pectoris (AP). This retrospective subgroup analysis of the ADDITIONS study evaluated the effectiveness and tolerability of ivabradine combined with beta-blockers, and its effects on angina symptoms and quality of life in elderly patients ≥ 75 years in everyday practice. METHODS: In the non-interventional, multicenter, prospective, open-label ADDITIONS study 2330 patients with stable AP of different age groups were treated with a flexible dose of ivabradine twice daily in addition to beta-blockers for 4 months. Heart rate (HR), number of angina attacks, nitrate consumption, tolerance, and quality of life (QoL) were evaluated. A subgroup analysis was performed, focusing on 479 patients (21%) ≥ 75 years. RESULTS: In these 479 patients ≥ 75 years ivabradine (mean dose 11.61 ± 3.18 mg per day) after 4 months of treatment reduced HR by 19.2 ± 11.6 bpm to 65.4 ± 8.3 bpm. The average number of angina attacks per week was decreased by 1.6 ± 1.8 to 0.4 ± 1.3 and the average consumption of short-acting nitrates per week was reduced by 2.2 ± 3.2 to 0.6 ± 1.8 units (both p < 0.0001). There was a marked shift in Canadian Cardiovascular Society (CCS) grade distribution with most patients (57%) now classified as CCS grade I, and 42% as CCS grades II and III. This was accompanied by an improvement in EQ-5D QoL index to 0.75 ± 0.22 (p < 0.0001). Tolerability of ivabradine treatment was rated by the physicians as "very good/good" for 72%/28% of elderly patients. CONCLUSIONS: In daily clinical practice, addition of ivabradine to beta-blockers was effective in reducing HR, angina attacks and nitrate consumption in elderly patients (≥ 75 years) with stable angina pectoris. In addition, a marked improvement of CCS symptom scores and QoL was demonstrated. Treatment was generally well tolerated.

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

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.