Preface
As recalled by the recent publication of the European guidelines, the current management of patients with stable angina involves the control of anginal symptoms, the prevention of cardiovascular events—such as acute coronary syndromes, stroke, and cardiovascular death—and the control of cardiovascular risk factors. These measures contribute to preventing or slowing the progression of the disease. Achieving this goal requires prescription of multiple pharmacological agents. However, recent data have shown that, despite the use of multiple drugs, symptom control and compliance with therapy remain inadequate in many patients. Analysis of registries, for its part, indicates that drugs are often prescribed at suboptimal dosages, and that the incidence of side effects is high. A further problem resides in the fact that the choice of antianginals is often limited in patients with comorbidities, such as heart failure or asthma. Thus, in spite of undeniable advances in management, angina patients all too often remain plagued by persistent symptoms and/or side effects from treatments, which affect their quality of life.
In this context, ivabradine, the first selective and specific If inhibitor, with its novel and unique mode of action on cardiac pacemaker activity, represents a major advance in the treatment of angina patients. Ivabradine acts at the core of heart rate regulation, by binding specifically to the f-channel of the sinus node cells and selectively inhibiting the If pacemaker current. This specific and selective action ensures that ivabradine provides all the benefits of pure heart rate reduction while remaining free of the other haemodynamic effects commonly observed with the conventional agents used in stable angina. Ivabradine's clinical efficacy has been clearly established by a series of randomized trials, which have robustly documented the anti-ischaemic and antianginal efficacy of ivabradine in comparison with atenolol or amlodipine.
Over and beyond the beneficial effects of heart rate reduction in the prevention of angina, ivabradine's indications may extend even further, in view of the evidence that lower heart rate is associated with a more favourable prognosis in patients with coronary artery disease. Large-scale clinical trials will help to determine whether a broader spectrum of patients than those with angina might benefit from treatment with a pure heart rate-reducing agent such as ivabradine, and whether the clinical benefits associated with ivabradine, over and above the prevention of angina, also encompass a reduction in cardiovascular mortality and morbidity.
The present issue of the European Heart Journal Supplement is authored by a panel of experts who review the current status of angina management and the concept of If current inhibition as a new therapeutic modality in patients with ischaemic heart disease. The rationale for heart rate control is illustrated by M. Rosen who presents the role of If current inhibition as a therapeutic tool for selective and specific heart rate reduction. The exceptional opportunity for preventing angina without untoward side effects on atrioventricular conduction, repolarization, inotropism, or lusotropism thanks to the selective and specific mode of action of ivabradine is highlighted in the paper by A. J. Camm. The paper by P. G. Steg and D. Tchetche addresses the current options in the treatment of patients with stable angina, as well as the unmet needs, and emphasizes the clinical advantages of a new class of drugs, the If current inhibitors, for the existing therapeutic armamentarium.
J.-C. Tardif provides an overview of the results of the clinical development programme of ivabradine in patients with stable angina, the most extensive programme for this indication, including more than 5000 patients. Other potential clinical applications of If inhibition, such as heart failure, both due to systolic and diastolic left ventricular dysfunction, and acute coronary syndrome are also being explored.
With successful development of ivabradine, selective and specific If inhibition has entered the therapeutic armamentarium as an effective, safe, and tolerable strategy for preventing angina.
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