LAUSR

In the last decades, the widespread use of percutaneous coronary intervention (PCI) with drug-eluting stent (DES) implantation and the introduction of novel anti-ischemic drugs represented major steps forward for the treatment of coronary artery disease (CAD). However, despite these improvements refractory angina remains an important healthy problem [1]. Indeed, it has been estimated that there are >500,000 Canadians and up to 1.8 million Americans living with refractory angina [1]. Moreover, clinical trials and registries clearly demonstrated that 20–30% of patients undergoing percutaneous or surgical revascularization might continue to experience persistence of angina despite a successful revascularization [2]. Thus, each year, as many as 525,000 patients develop refractory angina in continental Europe and in the USA [3], and an additional 500,000 who undergo either PCI or coronary bypass surgery continue to suffer from angina, which means that an additional 1 million patients could benefit annually from new targeted therapies [4]. According to the 2013 ESC Guidelines on Stable coronary artery disease (CAD), refractory angina is defined as a ‘chronic condition caused by clinically established reversible myocardial ischemia in the presence of CAD, which cannot be adequately controlled by a combination of medical therapy, angioplasty and coronary artery bypass graft’ [3]. Refractory angina represents a very disabling condition, which determines a very poor quality of life. It has also an important clinical impact on public health resources determining a large number of hospitalizations and exceeding instrumental examinations. Current guidelines recommend the introduction of an optimized medical therapy with ß-blockers, calcium-channel blockers or nitrates as first-line approach, and ivabradine, ranolazine, nicorandil or trimetazidine as second-line [3]. In addition, in case of failure of medical therapy alone, the use of non-pharmacological approaches, such as enhanced external balloon counterpulsation (EECP), spinal-cord stimulation (SCS) and transcutaneous electric nerve stimulation (TENS) [3] may be considered. However none of these devices has become a standard of care, and despite their initial promise, many trials demonstrated only modest improvements in exercise capacity and in angina relief [5]. Thus, new treatments for refractory angina are needed.