Long-Term Outcomes with Bare Metal Stents

Abstract & Commentary

By Andrew Boyle, MBBS, PhD Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco Dr. Boyle reports no financial relationships relevant to this field of study.

Source: Doyle B, et al. Outcomes of stent thrombosis and restenosis during extended follow-up of patients treated with bare-metal stents. Circulation. 2007;116:2391-2398.

Recently, there has been considerable concern regarding the long-term safety of drug-eluting stents. Reports of late (> 30 days post implantation), and very late (> 1 year post implantation), stent thrombosis have raised concern over these devices, and there has been a corresponding resurgence in the use of bare metal stents. Bare metal stents (BMS) are known to have a low rate of subacute stent thrombosis (< 30 days post implantation), less than 1% on dual anti-platelet therapy, both in clinical trials and in years of clinical experience. In-stent restenosis (ISR) is the major Achilles' heel of BMS, and ISR has been considered "benign" compared to stent thrombosis. Therefore, despite scant long-term follow-up data, BMS have been considered a safe option in the long term.

Doyle and colleagues performed a retrospective study of a large cohort of patients undergoing PCI at the Mayo Clinic from 1994 to 2000, to determine the long-term outcomes of BMS, with a focus on stent thrombosis and ISR. The follow-up period was up to 10 years. They included all patients who had PCI with BMS, performed in the standard manner followed by 2-4 weeks of dual anti-platelet therapy. All patients received intra-procedural heparin via the same protocol, and the use of platelet glycoprotein IIb/IIIa inhibitors was at the operator's discretion. Exclusion criteria were: cardiogenic shock; intra-procedural complications; brachytherapy; inability to receive dual anti-platelet therapy for any reason; patient refusal to participate; and the use of investigational stents. During the study period, 4855 patients underwent PCI and 4503 were eligible for the study; 93% of these had follow-up data available. Baseline demographics of this cohort showed 71% were male, mean age of 65 years, and 21% were diabetic, which is similar to many large cohort studies of real-world patients. Of the study participants, 68% presented with unstable angina, 10% with acute myocardial infarction (MI), and 14% presented within a week of acute MI, representing a relatively high-risk population. The procedural characteristics of this cohort also showed they were not at low risk: 41% of patients had 2 or more stents placed; 45% of lesions were type C; 13% were bifurcation lesions; 31% had visible thrombus; and 8% were in saphenous vein grafts.

The cumulative incidence of stent thrombosis was 0.5% at 30 days, 0.8% at 1 year, and 2.0% at 10 years. Stent thrombosis at any time after implantation is associated with an increased mortality. Doyle et al used the Academic Research Consortium (ARC) definition of definite and probable stent thrombosis, but did not include possible stent thrombosis. Late, or very late, stent thrombosis presented with ST elevation MI in 44% and with non-ST elevation MI in 56%. Doyle et al subdivided the cohort based on "on-label" use, a single stent in a native coronary artery for a de novo lesion, versus "off-label" use, including all other cases. At 10-years post-implantation, the incidence of stent thrombosis was slightly higher in off-label uses (2.5% vs 1.4%, P = 0.024 vs on-label), but there was no significant difference at earlier time-points. However, when saphenous vein graft PCI were excluded, there was no difference in stent thrombosis between "on-label" and "off-label" uses at any time-point. The factors that correlated with increased risk of late, or very late, stent thrombosis were a mix of lesion- and patient-specific factors: ulcerated lesions; vein graft PCI; prior MI; prior stroke; prior bypass surgery; heart failure; and peripheral arterial disease. This suggests that a large burden of atherosclerotic disease in a patient may predispose them to late events. Doyle et al point out that this may reflect progression of disease, rather than the stent itself, but further studies are needed to confirm this.

ISR was found in at least one stent in 9.6% of patients at 1 year, 13.9% at 5 years, and 18.1% at 10 years. Interestingly, although ISR is often considered benign, the presentation of ISR over 10 years with stable angina in 9%, unstable angina in 7.4%, MI in 2.1%, and other unstable presentations like decompensated heart failure or ventricular arrhythmias in 0.4%. Doyle et al focused on the 2.1% of patients whose ISR presented with MI. These patients had increased mortality, with a hazard ratio of 2.4, compared to those whose ISR did not present with MI. Patients with ISR who did not present with MI had the same mortality as those with no ISR at all. Doyle et al caution that BMS are associated with a 2.1% rate of ISR presenting with MI over 10 years, and that this is associated with an increased mortality. Therefore, choosing a BMS because restenosis is considered "benign", compared to the risk of stent thrombosis caused by drug-eluting stents,may not necessarily be appropriate. Furthermore, although BMS have lower rates of stent thrombosis than drug-eluting stents, the rates of death and MI appear similar. Doyle et al suggest that the 2.1% rate of MI presentation of ISR, and the corresponding increase in mortality, may explain this discrepancy.

Commentary

This study is limited by its retrospective design and the small numbers of events. Also, no data regarding duration of, or compliance with, dual anti-platelet therapy are presented. Another limitation is that the BMS used during the study period may not reflect the outcomes of newer BMS technologies that have reached the market since then. Finally, no comparisons can be drawn with other methods of treating coronary disease, such as medical therapy, drug-eluting stents, or bypass surgery. Notably, most of the patients in this study presented with acute coronary syndromes, so patients with stable coronary artery disease treated with BMS may not have the same outcomes. However, this study provides excellent long-term follow-up in a large cohort of patients reflecting current real-world clinical practice. Furthermore, using contemporary definitions of stent thrombosis, rather than old trial definitions, provides important new information that may help guide clinicians in decision-making in the cardiac catheterization lab.

In summary, use of BMS is associated with a significant risk of both stent thrombosis (2.0%) and ISR presenting with acute MI (2.1%) over a 10-year follow-up associated with increased mortality. The current tendency to use BMS over drug-eluting stents, for reasons of safety, may not be justified. Clinical decision-making should weigh the relative risks of restenosis and thrombosis on the basis of lesion- and patient-specific variables.