Meta-Analysis: Mixed Results Seen with First-Gen DES in STEMI Patients

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First-generation drug-eluting stents (DES) achieve large reductions in target vessel revascularization (TVR) and show a trend toward less definite stent thrombosis during the first year after treatment in patients with ST-segment elevation myocardial infarction (STEMI), according to a meta-analysis published online February 23, 2012, ahead of print in the European Heart Journal. However, these advantages are offset by an increased risk of very late stent thrombosis during subsequent years.

Peter Jüni, MD, of the University of Bern (Bern, Switzerland), and colleagues performed a meta-analysis of 15 randomized controlled trials that enrolled a total of 7,867 STEMI patients and compared first-generation DES with BMS.

Outcomes Vary Over Time

Overall, the primary safety endpoint of definite stent thrombosis was reported in 151 DES patients (3.2%) and 83 BMS patients (2.7%), with the risk similar between the 2 groups (RR 1.08; 95% CI 0.82-1.43). The primary efficacy endpoint of TVR occurred less often in DES (9.0%; n = 429) than in BMS patients (14.6%; n = 452), a difference that reached significance (RR 0.51; 95% CI 0.43-0.61).

However, the influence of stent type was time dependent. DES reduced the risk of both definite and definite/probable stent thrombosis within the first year but not in subsequent years. In fact, definite stent thrombosis risk became greater with DES after 1 year. Meanwhile, the large reduction in TVR initially seen with DES was attenuated over time (table 1).

Table 1. Safety and Effectiveness of DES vs. BMS in Time

 

Definite Stent Thrombosisa

TVRb

Definite/Probable Stent Thrombosisc

RR
(95% CI)

RR
(95% CI)

RR
(95% CI)

Year 1

0.80
(0.58-1.12)

0.46
(0.38-0.55)

0.81
(0.60-1.11)

Subsequent Years

2.10
(1.20-3.69)

0.75
(0.59-0.94)

2.01
(0.79-1.31)

a P = 0.009 for interaction; b P = 0.007 for interaction; c P = 0.015 for interaction.

Analyses restricted to trials with higher methodological quality mirrored the main analysis. Exclusion of the largest trial, HORIZONS-AMI (n = 3,006), yielded similar results. The type of DES did not appear to affect how definite stent thrombosis risk changed over time, but the difference in TVR between earlier and later follow-up was greater for sirolimus-eluting stents (SES) than for paclitaxel-eluting stents (PES), though confidence intervals were wide and overlapping. Smaller trials of fewer than 300 patients indicated a greater benefit for DES patients with regard to TVR than did larger trials (P = 0.043 for interaction).

Consistent Results

This study was published within days of the recent US Food and Drug Administration (FDA) approval of the first 2 DES indicated for AMI, Ion and Taxus Liberté (Boston Scientific, Natick, MA).

In an e-mail communication with TCTMD, Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), pointed out that the meta-analysis was largely powered by HORIZONS-AMI. Because FDA approval was also based on the HORIZONS data, “physicians should not be overly concerned about the overall safety profile of PES in AMI,” he said.

Dr. Stone was not surprised by the current results. “Almost every study of DES vs. BMS in STEMI has consistently shown a reduction in TVR, and numerous meta-analyses on this topic have shown the effect estimate to be 50%,” he said, adding that no prior studies have found any significant difference in stent thrombosis between the 2 device types.

However, he noted that this study was “unique” in demonstrating not only an increase in definite stent thrombosis after 1 year with DES but also a significant decrease in TVR after 1 year.

“Most importantly, nonsignificant trends were present for a 10% reduction in all-cause death both before and after 1 year with DES compared to BMS,” he said. “These observations are consistent with our prior work demonstrating that survival with DES vs. BMS is dependent on a trade-off between much less TVR with DES (a complication which is rarely but occasionally fatal) and slightly increased late stent thrombosis with DES (a rare event which is not uncommonly fatal).”

Despite the promising results from currently available DES, “it would always be desirable to have an even safer stent without any concern for increased rates of very late stent thrombosis,” Dr. Stone said. With more and more research being done with newer generation DES in STEMI, he predicted that new options could be confirmed with larger trials.

In the paper, the authors agree that the DES landscape is shifting.

The “use of newer generation DES with durable polymers of improved biocompatibility, biodegradable polymers, which dissolve completely once the drug is eluted, or even fully bioresorbable vascular scaffolds are currently being investigated to address [the risk of very late stent thrombosis] in STEMI patients,” they note.

Study Details

Seven trials allocated patients to Cypher or Cypher Select SES (Cordis, Miami Lakes, FL) and 5 to Taxus or Taxus Express PES (Boston Scientific). Three trials used both types of DES, with the choice of DES at the discretion of the treating physician.

The duration of dual antiplatelet therapy recommended for DES patients ranged from 3 to 12 months, with identical recommended durations for DES and BMS patients in all but 1 trial.

 


Source:
Kalesan B, Pilgrim T, Heinimann K, et al. Comparison of drug-eluting stents with bare metal stents in patients with ST-segment elevation myocardial infarction. Eur Heart J. 2012;Epub ahead of print.

 

 

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Meta-Analysis: Mixed Results Seen with First-Gen DES in STEMI Patients

First generation drug eluting stents (DES) achieve large reductions in target vessel revascularization (TVR) and show a trend toward less definite stent thrombosis during the first year after treatment in patients with ST segment elevation myocardial infarction (STEMI), according to
Disclosures
  • Dr. Jüni reports serving on the steering committee and/or statistical executive committee of trials funded by Abbott Vascular, Biosensors, Medtronic, and St. Jude Medical.
  • Dr. Stone reports consulting for Abbott Vascular, Boston Scientific, and Medtronic.

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