By Marie-Claude Morice
Data from large randomised trials and meta-analyses have been used to establish guidelines for the selection of invasive treatment—percutaneous coronary intervention (PCI) or coronary artery bypass grafting (CABG)—in patients with complex coronary artery disease. Marie-Claude Morice discusses these data and how newer generation drug-eluting stents may affect the future treatment of patients with coronary artery disease
The respective outcomes of the two invasive treatment modalities for patients with complex coronary artery disease, PCI and CABG, have been under close investigation over the past decade. Landmark studies such as the SYNTAX (Synergy between PCI with Taxus and cardiac surgery) and the FREEDOM (Future revascularization evaluation in patients with diabetes mellitus: optimal management of multivessel disease) trial and several meta-analyses have been conducted to assess the comparative benefits and efficiency of both strategies. The findings of these studies have helped establish guidance for the selection of the most appropriate therapeutic approach to be implemented according to the individual characteristics of the patients and to the extent, severity and location of their coronary lesions. The specific score that was initially designed for the SYNTAX trial has gained wide acceptance in routine practice in view of its effectiveness in optimising patient and treatment stratification. It has been adopted and included in guidelines.
Where do we stand today?
In patients with ST-segment elevation acute myocardial infarction (STEMI), surgery is very seldom indicated as PCI has proved to be superior to thrombolysis. In other clinical settings, patients with single-vessel disease requiring revascularisation are mostly treated by PCI with drug-eluting stent implantation, which is the default treatment recommended by European Guidelines.
For more diffusely diseased patients (ie. 3VD and left main lesions), randomised trials and meta-analyses performed with first generation drug-eluting stents have demonstrated that surgery is a more beneficial strategy in patients with triple-vessel disease and a SYNTAX score >22. However, patients with lesions in the left main coronary artery that are not associated with excessively-diffuse disease in the coronary tree and a SYNTAX score
The FREEDOM trial showed surgery to be the best option for diabetic patients with multivessel disease, but the Syntax trial, which was underpowered for the diabetic population, did not show this to be the case.
What does the future hold?
The technology applied to drug-eluting stents has evolved. The new generations of drug-eluting stents are associated with enhanced efficacy and superior clinical outcomes compared with the first-generation devices tested in the SYNTAX and FREEEDOM trials, especially in high-risk patient groups. These improved results are particularly visible in the setting of left main coronary artery disease where newer generation stents may help push the boundaries beyond the current limits for patients with a SYNTAX score higher than 32 as it is increasingly evident that the SYNTAX score is stent dependent.
A lower incidence of stent thrombosis, a much feared complication of drug-eluting stents, has also been observed in recipients of the latest generations of stents, especially those with biodegradable or a fixed but more biocompatible polymer, which may potentially translate into reduced duration of antiplatelet therapy.
Increasingly accurate individual risk-assessment methods, such as the global risk score integrating the euroSCORE and the SYNTAX score, are paving the way for a tailored approach allowing refined prognosis and optimal clinical decisions. In addition, in a cost-containment context, the use of fractional flow reserve (FFR) as a lesion-severity evaluation method should help identify lesions significant enough to benefit from revascularisation (PCI or surgery) and rationalise the use of stents.
The next generation of innovative stents, the drug-coated stent, will open up new horizons for interventional cardiology: this device is composed of a stent, a drug and no polymer. Its potential benefits are that it permits a shorter duration of dual antiplatelet treatment similar to that prescribed to bare metal stent recipients and may widen the number of patients who can be safely treated by PCI, in particular those at high risk of bleeding such as elderly patients, those on vitamin K antagonists, and patients who need rapid surgery.
Among several studies investigating this new type of stent, the multicentre, double-blinded LEADERS FREE (randomised clinical evaluation of the BioFreedom stent) trial has been designed to investigate the outcome of a high bleeding risk population assigned to receive either a bare metal stent or a polymer-free drug-coated stent with only one month of mandated dual antiplatelet therapy. Along the same line, in the SENIOR study (Short duration of dual antiplatelet therapy with Synergy everolimus-eluting stents in patients older than 75 years undergoing percutaneous coronary revascularisation). Boston Scientific will test short duration of dual antiplatelet therapy in an elderly patient population treated with the same generation of polymer-free drug-eluting stent.
If the two studies demonstrate the safety and efficacy of the drug-coated stent, they will render the use of bare metal stent obsolete and herald a new innovative breakthrough in interventional cardiology.
In summary, the first generation drug-eluting stent proved inferior to surgery in multivessel disease and to a greater extent in diabetics. The second and third generations are associated with promising outcomes in patients with left main and multivessel disease, which may increase the number of patients likely to benefit from a less-invasive approach than surgery. However, the safety and efficacy of PCI with these new devices still need to be demonstrated in diabetic and multivessel disease patients.
Tailored risk evaluation methods and the generalisation of FFR assessment should improve patient management and outcome and enhance healthcare cost-effectiveness. Finally, if proven safe and effective, the latest innovative polymer-free, drug-coated stents should replace bare metal stents.
Marie-Claude Morice is at Institut Cardiovasculaire Paris Sud (Générale de Santé), Massy, France