Drug for a while, polymer for life: Is it a good solution?

Ruef and colleagues report on the results of a retrospective study comparing not only two different drug-eluting stents but also two different concepts of drug-eluting stent technology: one represented by the polymer-free, microporous surface rapamycin-eluting stent and the other by the polymer-based, paclitaxeleluting stent. Three major limitations, two of them already acknowledged by the authors, should be taken into account before drawing conclusions from this study. First, the study is nonrandomized, which limits its ability to reliably compare two different devices. Second, the follow-up period was of only six-month length, which is not sufficient to assess the advantages or the weaknesses of the two drug-eluting stent technologies evaluated in this study. Third, the primary end point was a composite of target-lesion and nontarget-lesion related events, which may dilute differences in outcomes induced by the devices themselves. The latter limitation becomes less relevant knowing that the authors provided detailed information on the individual components of the end point including target-lesion revascularization and stent thrombosis. The major strength of the work of Ruef and colleagues is that these investigators included ‘‘all-comers’’ or a ‘‘real-life’’ cohort of patients. Included in this cohort were patients with acute myocardial infarction, patients with left main disease and patients with vein graft lesions. All of these situations are commonly associated with an increased risk of adverse outcomes and constitute the so-called ‘‘off-label’’ use of drug-eluting stents. We know that differences in performance between drugeluting stent types can become more evident in high-risk patient or lesion subsets [1], and that these groups might serve as a ‘stress test,’ challenging devices of inferior quality. The risk profile of the patient population can determine the power of the trial to detect differences between two drug-eluting stents and not surprisingly, trials that have failed to include subsets of patients or lesions at high-risk have also failed to demonstrate differences between unequal devices. The main results of the study can be summarized as follows. The 2 drug-eluting stent technologies evaluated were highly effective with an overall incidence of target-lesion revascularization of only 5% at 6 months. They also were sufficiently safe as shown by the very low incidence of stent thrombosis, cardiac death and myocardial infarction. Polymer-free rapamycin-eluting stents and polymer-based paclitaxel-eluting stents were associated with outcomes that were not significantly different confirming the results of a previous randomized trial on the same drug-eluting stents [2]. Drug-eluting stents are an important advance in the prevention of restenosis. They are increasingly being used in challenging patient and lesion subsets, where, in the past, the risk of restenosis associated with baremetal stents would have been prohibitive. Although these groups are known for their increased risk of major adverse cardiac events after surgical or percutaneous coronary interventions, drug-eluting stents have been demonstrated to be safe even in these ‘‘off-label’’ situations [3]. This is also confirmed by the very low rates of adverse events observed with drug-eluting stents in the cohort of nonselected patients in the study of Ruef and colleagues. The performance of currently available drug-eluting stents is thought to be most affected by the antiproliferative drug and the polymer that controls its release kinetics [4]. Optimal pattern and duration of drugrelease to achieve maximal efficacy and safety are not known. Although these parameters may be drug-specific, it is believed that a few-week period of inhibition of events that lead to restenosis is sufficiently long to achieve durable efficacy. For this reason, drugs are fully released within a few weeks from the majority of current drug-eluting stents. However, most of the drugeluting stents use permanent polymers, which continue to remain in the vessel wall even after accomplishing their drug-release mission. Their permanent presence