If inhibition: breaking new ground in the treatment of stable coronary artery disease

oronary artery disease (CAD) is today the leading cause of mortality worldwide, and it continues to be a major burden upon public health.1 Despite falling CAD mortality rates in Western European countries, the number of CAD patients may actually be increasing as a result of aging populations and the improving prognosis for coronary patients, the latter due to more effective treatments for acute coronary syndrome and revascularization, and improved prevention.2 CAD is expected to remain the world's leading cause of disease burden (which represents aggregate mortality and morbidity) in 2020, despite considerable progress in prevention and treatment over the past 20 years.3 Despite marked advances in primary and secondary prevention, several unmet needs remain in CAD management. Current guidelines recommend a two-pronged management strategy for patients with stable CAD, who require one treatment to relieve symptoms alongside another to reduce long-term morbidity and mortality.4 Despite the progress in the field, for various reasons that include inappropriate drug dosage and patient nonadherence to treatment schedules, many patients in clinical practice do not reach therapeutic goals. In addition, the optimization of treatment can be hindered by insufficient efficacy in patients with refractory angina and by a long list of medication contraindications. Another factor is poor tolerability, which may lead to treatment discontinuation and a reduction in the efficacy of even the most rigorous management strategy. The results of the Clinical Outcomes Utilizing Revascularization and Aggressive druG Evaluation (COURAGE) trial show no extra benefit in terms of all-cause mortality, myocardial infarction, or other major cardiovascular events, with addition of percutaneous coronary intervention (PCI) in stable CAD patients receiving optimized medical therapy.5 Furthermore, interventions are not always possible, and most revascularized patients still require anti-ischemic/antianginal treatment after the procedure. Clearly, these factors indicate the importance of developing novel therapeutic approaches that can improve CAD management. Heart rate is one of the clinical parameters that is most frequently assessed in daily practice. As it is the main determinant of ischemia, heart rate reduction is an established important therapeutic strategy in the prevention of ischemia. A strong association between elevated heart rate and increased risk of total and cardiovascular mortality has been shown in the general population, as well as in patients with hypertension, diabetes, and CAD.6 Experimental data have demonstrated the involvement of heart rate in the development and progression of atherosclerosis.7 Consistent with this understanding of the important role of heart rate, ivabradine (Procoralan), the first selective and specific If inhibitor, opens up promising opportunities in the management of CAD.