Treatment of Stable Angina with a New Fixed-Dose Combination of Ivabradine and Metoprolol: Effectiveness and Tolerability in Routine Clinical Practice

Abstract

IntroductionIn this prospective, multicenter, observational cohort study, the effectiveness and tolerability of the first fixed-dose combination (FDC) formulation of the selective heart rate reducing agent ivabradine and the beta-blocker metoprolol was evaluated in stable angina pectoris (AP) patients in a clinical practice setting.MethodsStable AP outpatients received a FDC of ivabradine and metoprolol (b.i.d.) for 4 months, in addition to cardiovascular standard therapy. Resting heart rate (HR), number of angina attacks, short-acting nitrate consumption, severity of symptoms (assessed by patient judgment and documented by CCS score) and tolerability were documented. Medication adherence was assessed by a modified four-item Morisky questionnaire. Descriptive statistics were performed on all data.ResultsA total of 747 stable AP patients (mean age, 66.4 years, 62% male, 50% and 31% with previous PCI and myocardial infarction, respectively) were included. Apart from ivabradine and beta-blockers as free combination, most frequently used concomitant standard medications at baseline were aspirin (68%), statins (71%), ACEI/AT1-blockers (76%), diuretics (35%), and calcium antagonists (15%). Highly prevalent comorbidities were hypertension (86%), hyperlipidemia (65%), and diabetes (35%). After 4 months, switch to treatment with the FDC was associated with a significant reduction in mean HR by 10 bpm. Proportion of patients with ≥ 1 angina attacks/week decreased from 38 to 7%. Patients in CCS class 1 increased (25 to 63%), while they decreased in CCS class 3 (19 to 5%). Medication adherence was also significantly improved (p < 0.001 for all changes from baseline). Mostly mild adverse events were documented in 5.4% of patients.ConclusionsIn these stable AP patients in a real-life setting, treatment with a FDC of ivabradine and metoprolol was associated with reduced HR and angina symptoms, while exercise capacity (CCS score) was improved. These effects may be mainly mediated by the increased medication adherence of patients observed with use of the FDC formulation.FundingServierTrial registration numberISRCTN51906157

Effectiveness and Impact on Adherence of a New Fixed-Dose Combination of Ivabradine and Metoprolol in a Wide Range of Stable Angina Patients in Real-Life Practice

“…Data from the IMPLICOR-NOW study [20] conducted in 747 patients with stable AP were used. Baseline characteristics as well as effectiveness and tolerability in the overall population were reported previously [20].…”

“…IMPLICOR-NOW was a prospective, observational, multicenter study conducted in Germany from October 2015 to October 2016, under daily practice conditions in 260 centers [20]. Stable AP patients fulfilling criteria for treatment with the new metoprolol/ivabradine FDC (Implicor™ 5/25, 5/50, 7.5/25, 7.5/50) according to the approved EU indication were eligible for inclusion.…”

“…Patient status was clinically documented at each visit by recording HR, number of weekly angina attacks, use of short-acting nitrates (SAN), and Canadian Cardiovascular Society (CCS) class. A four-item adherence questionnaire was used to assess medication adherence at baseline compared to study end after 4 months of treatment [20]. “Complete adherence” was defined as the absence of any adherence-related problems reported in the questionnaire.…”

“…The effectiveness and safety of the first FDC formulation of metoprolol and ivabradine was assessed previously in stable AP patients in routine clinical practice [20]. Herein we report an additional analysis of the data obtained in this 4-month prospective observational study, in which the effectiveness of the metoprolol/ivabradine FDC was assessed in subgroups of patients with different clinical characteristics.…”

The Pathways to Increase the Efficacy of Drug Therapy in Patients with Ischemic Heart Disease after Coronary Artery Bypass Grafting

“…Поэтому в последнее время ведущими международными экспертными сообществами приветствуется более широкое применение фиксированных комбинаций лекарственных препаратов, что может значительно повысить готовность пациента следовать предписанному режиму медикаментозной терапии. В связи с этим обращает внимание новая фиксированная комбинация ивабрадина и метопролола тартрата (импликор), которая обеспечивает у пациентов с ИБС и сохранной фракцией выброса ЛЖ (>40 %) хороший контроль показателей гемодинамики (ЧСС, АД) и значительно снижает количество приступов стенокардии (на 37,8 %); потребность в нитратах (на 28 %); повышает качество жизни за счет увеличения числа больных со стенокардией I ФК до 63 % в течение 4 мес терапии и улучшает в 2 раза приверженность пациентов к назначенной терапии по сравнению с больными, принимающими нефиксированную комбинированную терапию β-адреноблокаторами и ивабрадином [23].…”