By Jeffrey Zimmet, MD, PhD
Associate Professor of Medicine, University of California, San Francisco; Director, Cardiac Catheterization Laboratory, San Francisco VA Medical Center
Dr. Zimmet reports no financial relationships relevant to this field of study.
SYNOPSIS: This randomized trial showed no difference between contemporary drug-eluting stents and bare-metal stents with regard to death and myocardial infarction, while drug-eluting stents demonstrated an advantage in both repeat revascularization and stent thrombosis at six years of follow-up.
SOURCE: Bønaa KH, Mannsverk J, Wiseth R, et al. Drug-eluting or bare-metal stents for coronary artery disease. N Engl J Med 2016 Aug 29. [Epub ahead of print].
Advances in percutaneous coronary intervention (PCI) devices continue improving the safety and efficacy of this procedure, which clinicians use each year to treat millions of patients. Compared with first-generation drug-eluting stents (DES), second-generation devices not only are more deliverable and easier to use, but also are considered to be safer and more effective, with faster healing and lower rates of stent thrombosis. This has led to wide-ranging speculation about whether these benefits would lead to reductions in hard events, including mortality and non-fatal myocardial infarction (MI). Often lost in the conversation comparing first-generation DES, which no longer are in use, with more modern devices is the fact that its counterpart, the bare-metal stent (BMS), also has improved substantially over time.
The NORSTENT trial was designed as a real-world comparison of long-term outcomes with contemporary DES and BMS. All patients undergoing PCI in Norway between Sept. 15, 2008, and Feb. 14, 2011, were evaluated for enrollment in the trial. Patients were excluded from the trial primarily if they previously had been treated with coronary stents, if they were undergoing treatment of a bifurcation requiring a two-stent technique, or if they had known comorbidities limiting life expectancy to less than five years. Patients with a contraindication to long-term dual antiplatelet therapy (in the case of this trial, nine months of dual antiplatelet therapy) or an ongoing indication for warfarin also were excluded. During this period, out of a total of 20,663 patients undergoing PCI, 12,425 were eligible to participate, and 9,013 actually were randomized. The majority of BMS patients received modern thin-strut stents, while among DES patients, 82.9% received everolimus-eluting stents and 13.1% zotarolimus-eluting stents. In the DES group, 5.1% received older, first-generation stents.
At six years of follow-up, there was no significant difference in the primary composite outcome of all-cause mortality and nonfatal MI between the DES and BMS groups (16.6% vs. 17.1%; P = 0.66). Unsurprisingly, rates of target-lesion revascularization were lower in the DES group (5.3 vs. 10.3%; P < 0.001), as were rates of all revascularization (16.5 vs. 19.8%; hazard ratio, 0.76; P < 0.001). This translates to a number needed to treat of 30 to prevent one revascularization with DES over BMS. The six-year rates of definite stent thrombosis were low in both groups, but were significantly lower in the DES group (0.8% vs. 1.2%; P = 0.0498).
The authors concluded that there was no significant difference in death or non-fatal MI between DES and BMS at six years of follow-up, while both restenosis and stent thrombosis were significantly lower with DES.
In many ways, conclusions from this trial are in the eye of the beholder; however, several points are worth highlighting. First, the lack of a difference between contemporary DES and BMS in all-cause death and MI is unsurprising based on past data, but serves as a useful reminder. The reason to choose DES in the average case is clearly not to prevent these outcomes.
Contrary to the perceptions of many, but in agreement with multiple recent studies, including the EXAMINATION trial and the SCAAR registry, DES as compared with BMS actually showed reduced rates of definite stent thrombosis. This is quite a turnaround from the early days of first-generation DES, which carried higher rates of late ST. That this difference persists out to six years of follow-up provides very solid reassurance about the safety of current DES devices. The observation that this difference did not translate to lower rates of MI or mortality simply reflects the low overall frequency of stent thrombosis.
What about repeat revascularization? Again, there is no surprise in the revelation that DES leads to lower rates of clinical restenosis and repeat procedures. What might surprise some is that the magnitude of the difference is relatively low (approximately a 5% absolute risk reduction in target lesion revascularization), and that restenosis of the target lesion with BMS was only approximately 10% at six years. Two points are worth mentioning here. First, clinical restenosis requiring repeat intervention is an important outcome, both with regard to healthcare costs and to quality of life. That the NORSTENT study did not demonstrate a coincident improvement in subjective health status most likely reflects, as noted by one editorialist, a failure of the measurement tool rather than a lack of true benefit. On the other hand, the relatively low event rates with BMS means there still is a role for these devices in current practice.
Although the improved safety and efficacy of DES means that these stents will remain the scaffolds of choice in the majority of clinical situations — especially in the context of higher restenosis risk, such as in diabetics, multiple stents, smaller vessels, and chronic total occlusions — BMS remain an attractive option for patients who require noncardiac surgery, who cannot tolerate or adhere to longer-term dual antiplatelet therapy, or for whom cost is an issue.