Efficacy Profile of Ivabradine in Patients with Heart Failure plus Angina Pectoris

Borer, Jeffrey S.; Swedberg, Karl; Komajda, Michel; Ford, Ian; Tavazzi, Luigi; Böhm, Michael; Depré, Christophe; Wu, Yanyu; Maya, Juan; Dominjon, Fabienne

doi:10.1159/000449243

Cited by 16 publications

(12 citation statements)

References 17 publications

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“…51 Ivabradine also reduced the composite endpoint of CV death and heart failure hospitalisation by 15%, 20% and 18% in the respective subgroups (P for interaction=0.52). 56 …”

Section: Ivabradine In Treatment Of Stable Angina Pectorismentioning

confidence: 99%

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

et al. 2018

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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 f 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.

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“…51 Ivabradine also reduced the composite endpoint of CV death and heart failure hospitalisation by 15%, 20% and 18% in the respective subgroups (P for interaction=0.52). 56 …”

Section: Ivabradine In Treatment Of Stable Angina Pectorismentioning

confidence: 99%

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

et al. 2018

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“…Ivabradine in patients with severe HF, often not included or underrepresented in trials, was associated with nominally, non‐significant risk reductions for the primary composite endpoint (16%), all‐cause death (22%), cardiovascular death (22%), HF death (37%), and hospitalizations for worsening HF (17%) . This post hoc analysis underscores that HR reduction is beneficial irrespective of disease severity without safety concerns in severe HF and can improve outcomes in patients with severe HF extending to those with sinus tachycardia after heart transplantation and ongoing angina . In agreement, the beneficial effect of beta‐blockers appears to largely depend on their HR risk of properties rather than their dose or the blood pressure achieved on treatment …”

Section: Role Of Heart Rate As a Risk Indicatormentioning

confidence: 78%

Heart rate and its reduction in chronic heart failure and beyond

Vukadinović

Borer

et al. 2017

European J of Heart Fail

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Heart rate (HR) is associated with cardiovascular outcomes in all the stages of the cardiovascular continuum as well as in patients with pulmonary, cerebrovascular, and renal disease, sepsis, cancer, and erectile dysfunction. In patients with cardiovascular disease, but also in the general population, increased HR represents an important indicator of mortality with each acceleration of HR over 70 b.p.m. increasing the risk. In patients in sinus rhythm with chronic heart failure with reduced ejection fraction (HFrEF), a HR >70 b.p.m. increased the risk of hospitalization, and >75 b.p.m. the risk of cardiovascular death as shown in the Systolic Heart Failure Treatment with the I Inhibitor Ivabradine Trial (SHIFT). Reducing HR with ivabradine by 11 b.p.m. (placebo-controlled) reduced the primary composite endpoint (cardiovascular death and hospitalization for worsening heart failure). Ivabradine was well tolerated showing benefit irrespective of age or diabetes status, and also in the presence of low systolic blood pressure and severe heart failure (SHIFT trial). Therefore, HR qualifies as a modifiable risk factor in heart failure. In patients with stable coronary disease, HR is a risk marker but HR reduction with ivabradine does not improve outcomes. The role of selective HR lowering remains unclear in patients with pulmonary, renal, cerebrovascular, and other diseases, as the potential benefit of interventions on HR has not been explored in these conditions. Future studies should scrutinize if HR reduction improves outcomes, defining HR as a potential risk factor and therapeutic target in other conditions beyond heart failure.

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“…It should be noted that ivabradine, nicorandil, and trimetazidine are not mentioned in the American and Canadian guidelines as these drugs are not available in the USA or Canada. This is partially true for ivabradine which is actually marketed in the USA for the treatment of heart failure and, as shown by a subanalysis of the SHIFT trial, patients with angina and heart failure might benefit from the concomitant use of ivabradine [79]. Ranolazine is also not mentioned in the Canadian guidelines.…”

Section: Pharmacological Treatment Of Anginamentioning

confidence: 99%

“…A recent analysis of patients with ischaemic heart disease and angina enrolled in SHIFT showed that the outcome benefits of ivabradine were maintained [79]. The “morbidity mortality evaluation of the l f inhibitor ivabradine in patients with CAD and left ventricular dysfunction” (BEAUTIFUL) trial, involving 10,917 patients with stable CAD and left ventricular dysfunction, assessed the effects of ivabradine on patient outcomes [89].…”

Section: Drugs That Reduce Heart Ratementioning

confidence: 99%

Treatment of Angina: Where Are We?

Balla

Pavasini

Ferrari³

2018

Cardiology

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Ischaemic heart disease is a major cause of death and disability worldwide, while angina represents its most common symptom. It is estimated that approximately 9 million patients in the USA suffer from angina and its treatment is challenging, thus the strategy to improve the management of chronic stable angina is a priority. Angina might be the result of different pathologies, ranging from the “classical” obstruction of a large coronary artery to alteration of the microcirculation or coronary artery spasm. Current clinical guidelines recommend antianginal therapy to control symptoms, before considering coronary artery revascularization. In the current guidelines, drugs are classified as being first-choice (beta-blockers, calcium channel blockers, and short-acting nitrates) or second-choice (ivabradine, nicorandil, ranolazine, trimetazidine) treatment, with the recommendation to reserve second-line modifications for patients who have contraindications to first-choice agents, do not tolerate them, or remain symptomatic. However, such a categorical approach is currently questioned. In addition, current guidelines provide few suggestions to guide the choice of drugs more suitable according to the underlying pathology or the patient comorbidities. Several other questions have recently emerged, such as: is there evidence-based data between first- and second-line treatments in terms of prognosis or symptom relief? Actually, it seems that newer antianginal drugs, which are classified as second choice, have more evidence-based clinical data that are more contemporary to support their use than what is available for the first-choice drugs. It follows that actual guidelines are based more on tradition than on evidence and there is a need for new algorithms that are more individualized to patients, their comorbidities, and pathophysiological mechanism of chronic stable angina.

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Efficacy Profile of Ivabradine in Patients with Heart Failure plus Angina Pectoris

Cited by 16 publications

References 17 publications

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

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

Heart rate and its reduction in chronic heart failure and beyond

Treatment of Angina: Where Are We?

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