Is the Honeymoon Over?A Commentary on the Controversy Surrounding Drug-Eluting Stents and the DES Meta-Analysis

How often have you heard that from a patient? This question has been posed to me numerous times over the course of the past twenty years. Sometimes the more you know, the harder it becomes to answer the question. Back in the early days of my cath lab career, the answer was relatively easy; with single lesion/vessel disease, go ahead, stick in a balloon. We all knew that if the disease was more complex, if it involved multiple vessels, that coronary artery bypass grafting (CABG) wasn't necessarily a four-letter word. In those early days of percutaneous transluminal coronary angioplasty (PTCA), physicians would often tell patients that the blockage may come back in about 20-25% of the patients. In later years, when the cardiology community compared devices/therapies in controlled, randomized trials, we would come to find out that restenosis with PTCA alone may have been >40%, especially in small vessels and diabetics. As technology advanced, we were able to offer more and more non-surgical options to coronary artery disease. First we tried to debulk, using directional atherectomy device. Directional coronary atherectomy (DCA) fell short of expectations; so did rotational atherectomy and lasers. Each of these devices and techniques showed early promise. DCA may not have inhibited restenosis, but excised plaque specimens from randomized trials were sent off to central core laboratories. Analysis of these plaque specimens proved extremely valuable in our understanding of the differences between de novo and restenotic atherosclerotic disease. Stents were the first new device proven through randomized clinical trials to reduce restenosis in coronary arteries. And with the permanent implantation of a stainless steel scaffold into an artery, patients now need to take an additional drug such as Ticlid or Plavix to reduce risk of thrombosis. However, with this new breakthrough came a new disease process: in-stent restenosis, a process of endothelial injury and healing within the stent. To combat this process, brachytherapy, the treatment of atherosclerotic disease with localized beta or gamma radiation, emerged on the scene like a lion and left like a lamb. Welcome to the era of drug-eluting stents. For the first time, we have a device that reduces the incidence of restenosis into the single digits. In-stent restenosis is now a relatively rare event. News of DES could be found everywhere, from newspapers to the cable news networks. The flood gates were opened. Cardiothoracic surgeons nationwide were seeing their volume of CABG (there's the four-letter word again) decrease exponentially as the use of DES soared. Patients with multi-vessel disease, severe diabetic coronary disease, and left main trunk disease were now being treated with stents in ever-increasing numbers. Now another shadow lurks on the horizon: subacute and late DES thrombosis. Concerns over the risks of subacute thrombosis in drug-eluting stents were fueled in 2006 at the European Congress of Cardiology scientific session, the American College of Cardiology scientific session, and the TCT in Washington, DC. The Cleveland Clinic meta-analysis was published just one week prior to the FDA panel meeting on December 7-8, 2006, which was called to review the DES data. A number of prominent cardiologists and industry executives were there to present data. The summary material from these sessions that I have read is inconclusive at best. While the FDA stated that the use of DES is not detrimental in approved cases, they acknowledged the data showed that DES increased the likelihood of clot formation in some patients, and the true extent of which is unknown. Dr. John McB. Hodgson, Professor of Medicine and Chief of Academic Cardiology, St. Joseph's Hospital and Medical Center, Phoenix, Arizona pointed out in the January 2007 Cath Lab Digest that inadequate stent expansion is a major contributor for both restenosis and stent thrombosis. IVUS is an important tool to insure complete strut expansion. However, as Dr. Bhatt pointed out in this issue of CLD, Renu Vermani's work in patients that have undergone autopsy showed that the rates of endothelialization were lower for DES than BMS. What this means is that DES stent struts were still bare, exposed to the blood within the vessel lumen. So, what do we know now? It is time to take a few steps back. Current DES products reduce restenosis. IVUS should be utilized regularly. Off-label use of DES increases risks. All DES patients must be on Plavix therapy long-term (12 months - indefinitely); it may be a life-and-death issue, so socio-economic issues need to be considered when deciding on a stent strategy. Lastly, we also need to realize that for some patients CABG may still be an option. The DES honeymoon is over, but divorce is not in our best interest.

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