Meta-analysis Confirms Late Safety of Second-Generation DES
Abundant evidence on second-generation
DES should allay longstanding concerns about the potential for late stent
thrombosis and other long-term events seen with earlier stent designs,
according to a meta-analysis of randomized trials published in the June 16, 2015,
issue of the Journal of the American
College of Cardiology.
“We now have enough data
to look long-term at whether the improvements that have been made to DES have
resulted in better outcomes compared with first-generation stents or bare-metal
stents,” said lead investigator Gregg W. Stone, MD, of Columbia University
Medical Center (New York, NY), in a telephone interview with TCTMD.
Evidence is “quite robust,” he said, “that contemporary DES provide not only an efficacy advantage but also [seem] more safe than first-generation DES and— perhaps surprisingly—than BMS, with a suggestion of reductions in stent thrombosis, MI, and death.”
For the network meta-analysis, Dr. Stone and colleagues assessed data from 51 randomized trials comprising a total of 52,158 patients that compared BMS vs DES or different DES to each other. Follow-up durations ranged from 3 to 5 years (median, 3.8 years).
First-generation DES included:
- Cypher sirolimus-eluting stents (SES; Cordis)
- Taxus Express and Liberté paclitaxel-eluting stents (PES; Boston Scientific)
Second-generation DES included:
- Cobalt-chromium everolimus-eluting stents (EES; Abbott Vascular)
- Platinum-chromium EES (Boston Scientific)
- Phosphorylcholine-based zotarolimus-eluting stents (ZES)
- Resolute ZES (Medtronic)
- Biomatrix and Nobori bioabsorbable-polymer biolimus-eluting stents (BES; Biosensors and Terumo, respectively)
In pooled analysis, the second-generation DES outperformed first-generation DES and BMS for a variety of measures (table 1). All DES were associated with lower rates of TVR than BMS.
.JPG "Table 1. Late Clinical Outcomesa")
BES had lower rates of definite/probable stent thrombosis than BMS, PES, and SES but did not offer extra protection against definite stent thrombosis. Cobalt-chromium EES slightly reduced the odds of definite stent thrombosis vs BES, however. Additionally, TVR was less common with BES vs BMS or PES.
Legacy of a ‘Firestorm’
Safety concerns with first-generation DES first burst onto the scene in 2006 when several scientific presentations at the European Society of Cardiology Congress ignited a “firestorm” by showing increased risk of late stent thrombosis and related clinical events compared with BMS. Included were 4-year results from 2 registries.
According to Dr. Stone, the results of the network meta-analysis are reassuring in general for second-generation DES and suggest that “there is less stent thrombosis with contemporary DES compared to not only first-generation DES but also BMS.”
The meta-analysis also concurs with other recent studies suggesting that cobalt-chromium EES have “hit the sweet spot of being the most safe and most effective, although it should be pointed out that there [are] also more data on that stent than other devices,” he observed. “More data [are] required before we simply declare that, but certainly the results at this point would suggest that it is the front-runner in terms of safety, in particular.”
Biodegradable-polymer BES may surpass BMS and first-generation DES, but they do “not appear to offer any advantages compared to the best-in-class durable-polymer contemporary DES. In fact, the EES look to be safer,” Dr. Stone added. “Now, there are newer-generation, more-advanced designs out there, namely the Synergy EES [Boston Scientific]…so it is not fair to lump all [bioabsorbable stents] into 1 category at this point.”
Validity of COURAGE, SYNTAX Challenged
Stéphane Rinfret, MD, SM, of the Quebec Heart and Lung Institute (Quebec, Canada), and colleagues write in an accompanying editorial: “This well-executed analysis summarizes an enormous quantity of aggregated data and thus provides substantial reassurance about the safety and efficacy [of] current-generation DES that are in common clinical use.”
Furthermore, the editorialists say, the surprising finding that second-generation DES may be associated with lower mortality compared with BMS and first-generation DES “has profound implications.” It calls into question results of the COURAGE and SYNTAX trials, which generally found no mortality benefit for PCI vs medical therapy or CABG, respectively, and raises the question of “whether these historic trials need to be repeated, now with the use of another current-generation DES.”
The ongoing EXCEL trial is 1 such attempt to gain more insight on this issue, Dr. Stone said.
But before leaping to conclusions, Dr. Rinfret and colleagues say, it is important to consider possible explanations for the mortality difference apart from improvements in DES. For example, treatment of recurrent restenosis, which is more frequent with BMS, may eventually take a toll on the patient “in the form of complications from repeated hospitalizations and procedure, thereby leading to increased mortality with BMS.”
Additionally, a “subtle form of confounding” may still exist within the randomized trials used in the meta-analysis. The editorialists point out that “variation in DAPT duration prescribed with newer-generation DES might explain this long-term difference, rather than the stent itself.
“Regardless of the underlying mechanism, the results of this meta-analysis provide considerable reassurance to the practicing clinician that current-generation DES have largely eliminated the risk of late, catastrophic, stent-related events,” Dr. Rinfret and colleagues say. “As a result, we now have reached a major milestone in the maturation of PCI as a treatment for obstructive coronary artery disease.”
Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.
Sources:
1. Palmerini T, Benedetto
U, Biondi-Zoccai G, et al. Long-term safety of drug-eluting and bare-metal
stents: evidence from a comprehensive network meta-analysis. J Am Coll Cardiol. 2015;65;2496-2507.
2. Rinfret S, Baron SJ,
Cohen DJ. Percutaneous coronary intervention: finally mature enough
[editorial]. J Am Coll Cardiol. 2015;65;2508-2510.
Disclosures:
- Dr. Stone reports having served as a consultant to Boston Scientific..
- Dr. Rinfret reports serving as a consultant for Boston Scientific and Terumo.
Related Stories:
L.A. McKeown is a Senior Medical Journalist for TCTMD, the Section Editor of CV Team Forum, and Senior Medical…
Read Full Bio
Comments