Ivabradine In Combination Research Articles

Efficacy and Safety of Ivabradine in Combination with Beta-Blockers in Patients with Stable Angina Pectoris: A Systematic Review and Meta-analysis.

IntroductionBeta-blockers are recommended by the European Society of Cardiology as first-line antianginal therapy for reducing heart rate (HR) and symptoms in patients with chronic coronary syndrome, despite a lack of data showing superiority to other antianginal agents. Most patients with angina pectoris require combination therapy to manage symptoms, with a second-line agent chosen to manage the predominant cardiovascular problem. Ivabradine, a selective sinus node If channel inhibitor shown to reduce HR and protect against anginal symptoms, has previously demonstrated noninferior anti-ischaemic and antianginal efficacy to beta-blockers.MethodsThis systematic review and meta-analysis assessed the efficacy and safety of ivabradine in patients with stable angina pectoris who remained symptomatic despite receiving beta-blockers. Keyword searches of PubMed, The Cochrane Central Library Register, ClinicalTrials.gov, The World Health Organization International Clinical Trials Registry Platform (ICTRP) and Google Scholar identified studies comparing ivabradine plus beta-blockers with placebo or other first- or second-line antianginal agents in patients with stable angina pectoris. No date limits or language restrictions were applied. Outcomes were evaluated after 1 and 4 months of treatment, including changes in HR, angina attacks, use of short-acting nitrates, quality of life and safety. Risk of bias was evaluated on the basis of recommendations of the Cochrane Handbook for Systematic Reviews of Interventions.ResultsSeven relevant studies were identified (N = 6821). Ivabradine plus a beta-blocker consistently reduced HR, anginal symptoms and short-acting nitrate consumption within 1 month of initiating therapy, with continued reductions for up to 4 months. Furthermore, ivabradine plus beta-blocker therapy was well tolerated, with bradycardia rarely reported (0.1% of patients overall). This study is limited by the inclusion of only two randomised studies, which may lead to result interpretation bias.ConclusionsIvabradine may be valuable for tailoring early antianginal treatment when used in combination with beta-blockers for chronic stable angina inadequately controlled by beta-blockers.Supplementary InformationThe online version contains supplementary material available at 10.1007/s12325-022-02222-1.

Efficacy of Ivabradine in Combination with Beta-Blockers Versus Uptitration of Beta-Blockers in Patients with Stable Angina (CONTROL-2 Study).

IntroductionHeart rate (HR) reduction is an integral part of antianginal therapy, but many patients do not reach the guideline-recommended target of less than 60 bpm despite high use of beta-blockers (BB). Failure to uptitrate BB doses may be partly to blame. To explore other options for lowering HR and improving angina control, CONTROL-2 was initiated to compare the efficacy and tolerability of the combination of BBs with ivabradine versus uptitration of BBs to maximal tolerated dose, in patients with stable angina.MethodsThis multicenter, open, randomized study included 1104 patients with Canadian Cardiovascular Society (CCS) class II or III stable angina, in sinus rhythm, and on background stable treatment with non-maximal recommended doses of BBs. Consecutive patients were allocated to ivabradine + BB or BB uptitration in a 4:1 ratio.ResultsAt the end of the study (week 16), addition of ivabradine to BB treatment and BB uptitration resulted in reduction in HR (61 ± 6 vs. 63 ± 8 bpm; p = 0.001). At week 16, significantly more patients on ivabradine + BB were in CCS class I than with BB uptitration (37.1% vs. 28%; p = 0.017) and significantly more patients were angina-free (50.6% vs. 34.2%; p < 0.001). Patient health status based on the visual analogue scale (VAS) was also better in the ivabradine + BB group. Adverse events (AEs) were significantly more common with BB uptitration than with the ivabradine + BB combination (18.4% vs. 9.4%, p < 0.001).ConclusionIn patients with stable angina, combination therapy with ivabradine + BB demonstrated good tolerability, safety, and more pronounced clinical improvement, compared to BB uptitration.Trial RegistrationISRCTN30654443.FundingServier.

Variations on a Precision Medicine Theme: One Size Fits Some.

Precision medicine, or personalized medicine, refers to the tailoring of therapy to the individual characteristics of patients. It can be applicable to patients with advanced disease and to preventative interventions as well. The impetus for this approach came from sequencing of the human genome and the anticipation that an individual’s sequence would inform treatment, aided perhaps by Big Data algorithms. In heart failure, advances in omics have occurred alongside other disciplines but from a practical standpoint, our ability to provide precision medicine remains more or less in the neutral position. In this article, we maintain that despite significant limitations on our ability to use genotyping or Big Data to impact real-world heart failure care in real time, we are in fact practicing a significant degree of precision medicine and can continue to do more of the same with relatively modest changes in approach to practice. The advent of angiotensin-converting enzyme inhibitors and β-blockers impacted heart failure therapeutics1,2 in a truly revolutionary way. They are recommended across all New York Heart Association classes for the management of patients with heart failure with reduced ejection fraction (EF).3 Although β-blockers have not been critically examined in patients with class I symptoms, we accept the notion that for these 2 classes of drugs, one size truly does fit all. We argue about dose, not whether we should use the drugs.4,5 We can also debate the duration of treatment in patients who have normalized their EF and the likelihood of recurrence of heart failure if those medications are stopped. Fundamentally, the importance of blockade of the renin–angiotensin system and adrenergic stimulation are fully accepted concepts that apply in young and old, symptomatic and asymptomatic, borderline low and very low EF, left ventricular failure and biventricular failure, in the …

Adjunctive ivabradine in combination with amiodarone: A novel therapy for pediatric congenital junctional ectopic tachycardia

Treatment of congenital junctional ectopic tachycardia (JET) is often challenging. In the majority of patients affected, a combination of ≥2 antiarrhythmic drugs is required for JET control. The purpose of this study was to assess the efficacy and safety of adjunctive ivabradine therapy for pediatric congenital JET. Since January 2015, 5 consecutive patients aged 10 days to 3.5 years (median 8 weeks) were treated with adjunctive ivabradine for congenital JET. All patients had previously undergone antiarrhythmic therapy with unsatisfactory control of JET. Ivabradine was administered orally at an initial dosage of 0.05-0.1 mg/kg/d divided into 2 single doses and was increased up to 0.28 mg/kg/d if necessary. In all 5 patients, ivabradine proved to be successful in controlling JET. Complete suppression of JET and conversion into sinus rhythm were achieved in 4 of 5 patients. The remaining patient had effective heart rate control with persistent slow JET. Mean heart rate was reduced by 31% compared to pre-ivabradine (P = .03) as assessed by 24-hour Holter monitoring. Echocardiography revealed improvement of left ventricular function in all 3 patients with previously impaired left ventricular function. No significant side effects of ivabradine were encountered during median follow-up of 135 days (range 37-203 days). In our group of patients with congenital JET, adjunctive treatment with ivabradine resulted in effective and safe rhythm/heart rate control and therefore may be recommended early in the course of this rare inborn tachyarrhythmia.

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.

Cardiac and Hemodynamic Benefits: Mode of Action of Ivabradine in Heart Failure.

Heart failure has seen a number of therapeutic advances in recent years. Despite this, heart failure is still related to increasing rates of morbidity, repeated hospitalizations, and mortality. Ivabradine is a recent treatment option for heart failure. It has a mode of action that includes reduction in heart rate, and leads to improvement in outcomes related to heart failure mortality and morbidity, as demonstrated by the results of the SHIFT trial in patients with systolic heart failure, functional classes II and III on the New York Heart Association classification, and left ventricular ejection fraction ≤ 35%. These results are intriguing since many heart failure drugs reduce heart rate without such benefits, or with quite different effects, making it more difficult to understand the novelty of ivabradine in this setting. Many of the drugs used in heart failure modify heart rate, but most have other pathophysiological effects beyond their chronotropic action, which affect their efficacy in preventing morbidity and mortality outcomes. For instance, heart rate reduction at rest or exercise with ivabradine prolongs diastolic perfusion time, improves coronary blood flow, and increases exercise capacity. Another major difference is the increase in stroke volume observed with ivabradine, which may underlie its beneficial cardiac effects. Finally, there is mounting evidence from both preclinical and clinical studies that ivabradine has an anti-remodeling effect, improving left ventricular structures and functions. All together, these mechanisms have a positive impact on the prognosis of ivabradine-treated patients with heart failure, making a compelling argument for use of ivabradine in combination with other treatments.

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Objective: To investigate the effects of Ivabradine in combination with Perindopril on exercise tolerance test (ETT), and heart rate variability (HRV) in patients with coronary artery disease (CAD) and arterial hypertension (AH). Design and method: 90 subjects with mild to moderate AH and CAD were randomized into 2 groups: Group 1 - 48 patients (mean age 56,1 ± 0,8 years) received Ivabradine (mean 10,7 ± 0,4 mg) and Perindopril (mean dose 4,8 ± 0,6 mg). Group 2 - 42 patients (mean age 54,2 ± 1,3 years) – Metoprolol (mean dose 47,5 ± 5,3 mg). Groups were matched for age, sex, office blood pressure, cardiovascular risk factors. ETT, 24-hour monitoring of blood pressure and electrocardiography with HRV program were evaluated initially and after 8 weeks of therapy. Results: At 8-week follow-up both groups showed a comparable decrease in blood pressure. In group 1 more significant decrease of heart rate especially at night time was revealed. The exercise time did not change in both groups. In group 1 revealed a decrease in the number of patients with low exercise tolerance by 9.7% and the increase in the number of patients with a high tolerance exercise by 8.6%. In group 2 increased the number of patients with a high tolerance exercise by 12.6 %. In both groups there was noted that dynamic vagosympathetic interaction in heart rate regulation increased high-frequency component and time domain PNN50% as well as SDNNind and RMSSD in group 2. Conclusions: Combination therapy with Ivabradine and Perindopril has a positive effect on ETT and HRV (like Metoprolol) however its influence on heart rate is more significant in patients with CAD and AH.

POTS following traumatic stress: Interacting central and intracardiac neural control?

Cardiovascular autonomic dysfunction is one of the most overlooked complications in patients with diabetes. We report the case of a 19-year-old woman with a 4-year history of diabetes referred due to palpitations and light-headedness following traumatic stress. Rise of heart rate and blood pressure during tilt table testing indicated hyperadrenergic postural orthstatic tachycardia syndrome (POTS). Elevated blood pressure variability, an indirect parameter of increased sympathetic activity, remained almost stable during orthostatic stress. Short-term treatment with ivabradine in combination with psychosocial support alleviated POTS-related symptoms. Our findings suggest that traumatic stress in patients with type 1 diabetes mellitus might translate into disturbed neural heart rate control due to a central, ephemeral alteration in autonomic balance.

Ivabradine in Combination with Beta-Blockers in Patients with Chronic Stable Angina After Percutaneous Coronary Intervention

IntroductionThe 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).MethodsADDITIONS 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.ResultsData 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.ConclusionIvabradine 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.Electronic supplementary materialThe online version of this article (doi:10.1007/s12325-015-0182-8) contains supplementary material, which is available to authorized users.

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

BackgroundClinical 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 ≥75years in everyday practice. MethodsIn 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 4months. 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%) ≥75years. ResultsIn these 479 patients ≥75years ivabradine (mean dose 11.61±3.18mg per day) after 4months of treatment reduced HR by 19.2±11.6bpm to 65.4±8.3bpm. 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±1.8units (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. ConclusionsIn daily clinical practice, addition of ivabradine to beta-blockers was effective in reducing HR, angina attacks and nitrate consumption in elderly patients (≥75years) with stable angina pectoris. In addition, a marked improvement of CCS symptom scores and QoL was demonstrated. Treatment was generally well tolerated.

Long-term therapy with ivabradine in combination with beta-blockers in patients with stable angina pectoris and effect of beta-blocker background dose: results from the ADDITIONS 1-year follow-up

Objectives: The non-interventional multicenter ADDITIONS study follow-up evaluated the effectiveness, safety, and effect on quality of life (QoL) of ivabradine (iva) in combination with betablockers over one year. Methods: Resting heart rate (HR), the number of angina attacks, nitrate consumption, and concomitant medications were documented in 901 patients with chronic stable angina treated with iva twice daily in flexible doses in combination with betablockers for one year. QoL was evaluated by the EQ-5D patient questionnaire at each visit. A descriptive statistical analysis was performed. Results: 901 patients (intention to treat, mean age 65.4±10.6 years, 58% male) with chronic stable angina were analyzed. 53% of the patients had undergone a PCI or CABG before and 35% had a history of myocardial infarction. All patients received betablockers (e.g. Metoprolol 41%, mean daily dose (mdd) 109.6 mg; Bisoprolol 39%, mdd 6.9 mg; Nebivolol 13%, mdd 4.9 mg; Carvedilol 7%, mdd 28.9 mg) and concomitant standard medication. At baseline, most patients (49%) were classified CCS grade II, mean HR was 86.1±12.6 bpm, a mean of 1.7±2.2 angina attacks per week were reported, consumption of short-acting nitrates was 2.3±3.2 units per week, and the EQ-5D index was 0.66±0.28. After one year, iva (mean dose 12.53±2.84 mg per day) had reduced HR by 20.7±14.0 bpm to 65.4±8.8 bpm, the number of angina attacks by 1.4±2.5 per week (p<0.0001, Wilcoxon signed rank test), and nitrate consumption by 1.9±3.1 units per week (p<0.0001), had improved EQ-5D index by 0.18±0.27 (p<0.0001), and most patients (63%) were classified CCS grade I. HR reduction and improvement of angina symptoms by iva was similar in three subgroups defined by betablocker background dose (<50%, 50% to 99%, and ≥100% of recommended target dose): see table. View this table: Table 1 Conclusion: Over one year the combination of iva with betablockers in clinical practice not only effectively reduced HR, number of angina attacks, and nitrate consumption, but also improved QoL and CCS class in patients with stable angina. Moreover, the treatment effect of iva on HR and angina symptoms was independent of background betablocker dose.

Ivabradine in combination with beta-blockers improves ejection fraction and symptom score in patients with stable angina pectoris and left ventricular dysfunction: 1-year follow-up of ADDITIONS study

P4016 | BEDSIDE Ivabradine in combination with beta-blockers improves ejection fraction and symptom score in patients with stable angina pectoris and left ventricular dysfunction: 1-year follow-up of ADDITIONS study K. Werdan1, H. Ebelt1, G. Stoeckl2, S. Nuding1, F. Hoepfner1, U. MuellerWerdan1. 1Martin Luther University of Halle-Wittenberg, Department of Cardiology, Halle, Germany; 2Servier Deutschland GmbH, Munich, Germany

GW24-e2957 Efficacy of ivabradine in combination with metoprolol versus uptitration of metoprolol in patients after Q-wave myocardial infarction with early left ventricular systolic dysfunction

ObjectivesThe purpose of the study was to evaluate the effect of combination of ivabradine with metoprolol tartrate versus uptitration of metoprolol tartrate on left ventricular (LV) systolic function and plasma...

Ivabradine in Combination With Metoprolol Succinate in the Treatment of Inappropriate Sinus Tachycardia

Inappropriate sinus tachycardia (IST) is a clinical syndrome characterized by excessive resting heart rate (HR) or a disproportional increase in HR during exercise. β-blocker or calcium channel-blocker therapy is often noneffective or not well tolerated. The HR reduction on ivabradine is similar to β-blockers but in some patients its efficacy to resolve all IST-related symptoms is limited. The aim of the study was to assess the efficacy and safety of combining ivabradine with metoprolol succinate in patients with refractory highly symptomatic IST. Twenty patients (36 ± 10 years; 16 women) with IST were enrolled. All patients received metoprolol succinate 95 mg single dose during the first month of the study. After 4 weeks of treatment with metoprolol, ivabradine was administered as adjuvant therapy up to 7.5 mg twice daily. Holter monitoring and treadmill stress test were performed at baseline, after 4, and 8 weeks of the study, respectively. We observed significant and similar reduction in resting HR both for metoprolol and for combined therapy compared to the baseline. The mean HR during daily activity was significantly lower on ivabradine and metoprolol compared to monotherapy with β-blocker. The combined treatment yielded a significant increase in exercise capacity as assessed by treadmill stress test. After 4 weeks of combined therapy a significant reduction in IST-related symptoms, measured by means of the European Heart Rhythm Association score, was observed. Combining ivabradine with metoprolol is an effective and well-tolerated treatment option for IST in patients with refractory to monotherapy.

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

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. 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 4months. The parameters recorded included heart rate, number of angina attacks, nitrate consumption, tolerance, and quality of life. After 4months ivabradine (mean dose 12.37±2.95mg/day) reduced heart rate by 19.4±11.4 to 65.6±8.2bpm (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±2.9U 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 4months' 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. 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.

Effects of ivabradine in combination with metoprolol on left ventricle remodeling after Q-wave myocardial infarction with early moderate left ventricle systolic dysfunction

Effects of ivabradine in combination with metoprolol on left ventricle remodeling after Q-wave myocardial infarction with early moderate left ventricle systolic dysfunction

Efficacy of Ivabradine in Combination with Beta-Blocker Versus Uptitration of Beta-Blocker in Patients with Stable Angina

The antianginal and anti-ischemic efficacy of the selective I (f) inhibitor ivabradine is established in patients with stable angina in monotherapy and in combination with other antianginals, including beta-blocker. This pilot study compared the antianginal and anti-ischemic efficacy and hemodynamic profile of ivabradine plus 5mg bisoprolol versus those of 10mg bisoprolol in patients with stable angina. Twenty-nine patients with stable angina and moderate left ventricular systolic dysfunction already on bisoprolol 5mg od were randomized into 2 groups. Group 1 (n = 17) received ivabradine (5-7.5mg bid) in addition to bisoprolol 5mg od, while in group 2 (n = 12) bisoprolol was uptitrated first to 7.5mg and then 10mg od. Patients underwent a treadmill test, 6-minute walking test, and echocardiography at baseline and after 2months. Mean resting heart rate decreased in both groups, from 76.6 ± 4.6bpm to 59.3 ± 2.5bpm (P < 0.001) in group 1 and from 75.9 ± 3.0bpm to 60.5 ± 2.3bpm (P = 0.002) in group 2. The effect on resting heart rate did not differ significantly between the two groups. However, more patients became asymptomatic in group 1 than in group 2. Addition of ivabradine also improved exercise capacity, as shown by the results of the 6-minute walking and exercise tolerance tests, whereas in group 2 neither parameter was significantly affected. Chronotropic reserve significantly improved with ivabradine, but not with bisoprolol 10mg. These results suggest that combining ivabradine with low dose bisoprolol in stable angina patients produces additional antianginal and anti-ischemic benefits and improves chronotropic reserve.

Ivabradine in combination with beta-blocker therapy for the treatment of stable angina pectoris in every day clinical practice

The anti-anginal efficacy of the selective I(f) inhibitor ivabradine has been demonstrated in controlled clinical trials. However, there is limited information about the safety and efficacy of a combined treatment of ivabradine with beta-blockers, particularly outside of clinical trials in every day practice. This analysis from the REDUCTION study evaluated the safety and efficacy of a combined therapy of beta-blockers and ivabradine in every day practice. In this multi-center study 4,954 patients with stable angina pectoris were treated with ivabradine in every day routine practice and underwent a clinical follow-up for 4 months. 344 of these patients received a co-medication with beta-blockers. Heart rate (HR), angina pectoris episodes, nitrate consumption, overall efficacy and tolerance were analyzed. After 4 months of treatment with ivabradine HR was reduced by 12.4 ± 11.6 bpm from 84.3 ± 14.6 to 72.0 ± 9.9 bpm, p < 0.0001. Angina pectoris episodes were reduced from 2.8 ± 3.3 to 0.5 ± 1.3 per week, p < 0.0001. Consumption of short-acting nitrates was reduced from 3.7 ± 5.6 to 0.7 ± 1.7 units per week, p < 0.0001. Five patients (1.5%) reported adverse drug reactions (ADR). The most common ADR were nausea and dizziness (<0.6% each). There was no clinically relevant bradycardia. Efficacy and tolerance were graded as 'very good/good' for 96 and 99% of the patients treated. Ivabradine effectively reduces heart rate and angina pectoris in combination with beta-blockers and is well tolerated by patients in every day practice.

Efficacy of the If current inhibitor ivabradine in patients with chronic stable angina receiving beta-blocker therapy: a 4-month, randomized, placebo-controlled trial

AimsTo evaluate the anti-anginal and anti-ischaemic efficacy of the selective If current inhibitor ivabradine in patients with chronic stable angina pectoris receiving beta-blocker therapy.Methods and resultsIn this double-blinded trial, 889 patients with stable angina receiving atenolol 50 mg/day were randomized to receive ivabradine 5 mg b.i.d. for 2 months, increased to 7.5 mg b.i.d. for a further 2 months, or placebo. Patients underwent treadmill exercise tests at the trough of drug activity using the standard Bruce protocol for randomization and at 2 and 4 months. Total exercise duration at 4 months increased by 24.3 ± 65.3 s in the ivabradine group, compared with 7.7 ± 63.8 s with placebo (P < 0.001). Ivabradine was superior to placebo for all exercise test criteria at 4 months (P < 0.001 for all) and 2 months (P-values between <0.001 and 0.018). Ivabradine in combination with atenolol was well tolerated. Only 1.1% of patients withdrew owing to sinus bradycardia in the ivabradine group.ConclusionThe combination of ivabradine 7.5 mg b.i.d. and atenolol at the commonly used dosage in clinical practice in patients with chronic stable angina pectoris produced additional efficacy with no untoward effect on safety or tolerability.