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Role of ivabradine in management of stable angina in patients with different clinical profiles.

ABSTRACT: In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the If current, decreases myocardial oxygen consumption while increasing diastolic time, without affecting myocardial contractility or coronary vasomotor tone. Ivabradine is indicated for treatment of stable angina and chronic heart failure (HF). This review examines available evidence regarding the efficacy and safety of ivabradine in stable angina, when used as monotherapy or in combination with beta-blockers, in particular angina subgroups and in patients with stable angina with left ventricular systolic dysfunction (LVSD) or HF. Trials involving more than 45 000 patients receiving treatment with ivabradine have shown that this agent has antianginal and anti-ischaemic effects, regardless of age, sex, severity of angina, revascularisation status or comorbidities. This heart rate-lowering agent might also improve prognosis, reduce hospitalisation rates and improve QOL in angina patients with chronic HF and LVSD.

SUBMITTER: Kaski JC

PROVIDER: S-EPMC5888443 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Role of ivabradine in management of stable angina in patients with different clinical profiles.

Kaski Juan Carlos JC Gloekler Steffen S Ferrari Roberto R Fox Kim K Lévy Bernard I BI Komajda Michel M Vardas Panos P Camici Paolo G PG

Open heart 20180309 1

In chronic stable angina, elevated heart rate contributes to the development of symptoms and signs of myocardial ischaemia by increasing myocardial oxygen demand and reducing diastolic perfusion time. Accordingly, heart rate reduction is a well-known strategy for improving both symptoms of myocardial ischaemia and quality of life (QOL). The heart rate-reducing agent ivabradine, a direct and selective inhibitor of the <i>I</i><sub>f</sub> current, decreases myocardial oxygen consumption while inc ...[more]

PMID: 29632676

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Project description: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).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.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.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.

Project description:IntroductionIn the prospective, open-label, non-interventional, multicenter RESPONSIfVE study, the effectiveness, response rates and tolerability of ivabradine with or without beta blocker (BB) were evaluated in patients with chronic stable angina pectoris (AP) in daily clinical practice.MethodsIn patients with AP, ivabradine was given twice daily in flexible doses for 4 months. Resting heart rate (HR), number of angina attacks, short-acting nitrate use, severity of symptoms [by Canadian Cardiovascular Society (CCS) score] and tolerability with or without existing BB therapy were documented and analyzed using descriptive statistical methods.ResultsIn total, 1250 patients with AP (mean age 66.0 ± 10.9 years, 59.6% male, 31.9% previous myocardial infarction) and an indication for ivabradine were included. Sixty-five percent of all patients received BB. Further concomitant standard medication included aspirin (74.2%), statins (69.3%), angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (84.2%), diuretics (40.0%), long-acting nitrates (15.7%), and calcium antagonists (21.4%). After 4 months of ivabradine treatment (mean daily dose 11.0 ± 2.7 mg), mean HR was reduced from 82.4 ± 11.8 beats per minute (bpm) to 67.1 ± 8.4 bpm. The average number of angina attacks/week decreased from 1.2 ± 1.9 to 0.1 ± 0.6 and the average use of short-acting nitrates/week from 1.5 ± 2.8 units to 0.2 ± 1.0 units. CCS classification of patients improved from 76% classified in CCS grades II or III and 24% in CCS grade I to 66% classified in CCS grade I and only 35% remaining in CCS grades II or III at study end. Response rate to ivabradine (defined as HR <70 bpm or HR reduction ≥10 bpm) reached 87%. HR reduction, symptomatic improvement and response rates were comparable in patients with or without BB. Adverse drug reactions were reported for 2.2% of patients.ConclusionIn this prospective study over a four-month period in clinical practice, ivabradine effectively reduced HR, angina attacks, and nitrate consumption in patients with AP with or without concomitant BB therapy. Ivabradine improved CCS scores and achieved a high treatment response rate with good general tolerability.FundingServier.Trial registrationControlled-trials.com identifier, ISRCTN73861224.

Project description: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.

Project description:IntroductionTrimetazidine (TMZ) has been shown to be efficacious for angina treatment. The TMZ 80-mg formulation allows one-daily (od) dosage, which could improve symptom control and adherence.MethodsThe 3-month, observational, multicenter, prospective ODA (antianginal effectiveness and tolerability of trimetazidine modified release 80 mg Once Daily in stable Angina patients in real-world practice) study assessed TMZ 80 mg od effectiveness in stable angina patients with persistent symptoms despite therapy. Two clinical situations were compared: patients who initiated treatment with TMZ 80 mg od (initiation group) and patients who were previously treated with TMZ 20 mg thrice daily (tid) or TMZ 35 mg MR twice daily (bid) and switched to TMZ 80 mg od (switch group). Number of angina attacks, short-acting nitrate (SAN) consumption, self-reported patient daily activity, Canadian Cardiovascular Society (CCS) class, adherence to antianginal therapy, overall efficacy and tolerability were assessed.ResultsA significant decrease in weekly number of angina attacks was observed for both the initiation group (n = 1841 patients) from 4.8 ± 3.5 at baseline to 0.9 ± 1.4 at 3 months (M3) (P < 0.001), and the switch group (n = 1216 patients) from 4.4 ± 1.3 at baseline to 0.9 ± 1.3 at M3 (P < 0.001). Significant reduction in SAN consumption and improvement in CCS class were observed for both groups. Adherence to antianginal therapy improved in both groups at 1 month (M1) and M3. Overall effectiveness of TMZ 80 mg od was rated by physicians as "very good" (68% initiation group, 70% switch group), "good" (31% initiation group, 29% switch group), "moderate" (1%, both groups) or "poor" (< 1%, both groups). Overall tolerability of TMZ 80 mg od was rated by physicians as "very good" (75%), "good" (25%) or "moderate" (< 1%) in both groups.ConclusionsTMZ 80 mg od, in association with other antianginal therapy, effectively reduced angina attacks and SAN consumption and improved physical activity and adherence to antianginal therapy both in patients initiating TMZ treatment and those switching from a bid or tid formulation.Trial registrationISRCTN registry Identifier, ISRCTN97780949.FundingServier. Plain language summary available for this article.

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Role of ivabradine in management of stable angina in patients with different clinical profiles.

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Role of ivabradine in management of stable angina in patients with different clinical profiles.

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