Meta-Analysis: First-Gen DES Show Long-term Safety, Efficacy in STEMI Setting

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At 5-year follow-up, patients with ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PCI) with first-generation drug-eluting stents (DES) experience a substantial reduction in repeat revascularization compared with bare-metal stents (BMS), according to a large meta-analysis published in the April 23, 2012, issue of Archives of Internal Medicine. Death, reinfarction, and stent thrombosis, meanwhile, were statistically similar between the 2 groups.

Researchers led by Giuseppe De Luca, MD, PhD, of Eastern Piedmont University (Novara, Italy), pooled patient-level data from 11 randomized controlled trials involving 3,980 primary PCI patients assigned to DES and 2,318 assigned to BMS. The vast majority of DES used were sirolimus-eluting Cypher stents (Cordis, Miami Lakes, FL) and paclitaxel-eluting Taxus stents (Boston Scientific, Natick, MA).

No Difference in Mortality

At long-term follow-up (mean, 1,201 days), a total of 432 patients had died, with similar mortality (the primary endpoint) and cardiac mortality rates observed between the DES and BMS arms. DES implantation reduced the occurrence of TVR. Academic Research Consortium-defined definite or probable stent thrombosis was not significantly different between the 2 groups nor was the rate of reinfarction (table 1).

Table 1. Outcomes at 5 Years

But because the assumption of proportionality of hazards for stent thrombosis was not met (P = 0.04), the researchers also used a Cox model with time-varying regression coefficients. This method changed the hazard ratio such that over the long term (2 years from the beginning of the study) the risk of stent thrombosis was actually higher after DES than after BMS (HR 2.81; 95% CI 1.28-6.19; P = 0.04).

Similarly, the assumption of proportionality of hazards was not met for reinfarction (P = 0.01), which also changed over time, increasing significantly for the DES group compared with the BMS group (HR 2.06; 95% CI 1.22-3.49; P = 0.03).

Expectations Better for Current DES

In an e-mail communication with TCTMD, study coauthor Gregg W. Stone, MD, of Columbia University Medical Center (New York, NY), said the heightened risks do not appear to translate into increases in mortality.

“Mortality tended to be lower with DES than BMS at all time periods, although the differences did not reach statistical significance,” he said.

Dr. Stone added that he would expect recently available DES to outperform the first-generation devices. In fact, a recent network meta-analysis published online ahead of print in the Lancet that he coauthored strongly suggests that newer DES, especially fluoropolymer-based everolimus-eluting stents, have lower rates of definite stent thrombosis not only compared to first-generation DES but also to BMS.

“However, all meta-analyses are hypothesis-generating and require testing in adequately powered randomized trials before being accepted as definitive,” he cautioned. “Clinical equipoise continues to be present in the clinical community regarding the utility of DES vs. BMS in STEMI.”

Further light is expected to be shed on this subject when the HORIZONS-AMI II trial begins later this year. Dr. Stone reported that 7,000 to 10,000 patients with STEMI will be randomized to everolimus-eluting Promus Element stents (Boston Scientific) or BMS, with the study powered to determine whether there are not only improved clinical outcomes but a reduction in stent thrombosis with DES compared with BMS.

“If positive, this demonstration will truly be paradigm shifting,” Dr. Stone said. “The HORIZONS-AMI II trial should write the final chapter on DES vs. BMS in STEMI.”

For Some, Uncertainty Remains

But not everyone is convinced that the benefits of DES in STEMI patients warrant the potential risks. In an invited commentary accompanying the study, James M. Brophy, MD, PhD, of Royal Victoria Hospital (Montreal, Canada), questions the generalizability of the results to real-world populations, suggesting that “the effectiveness of DES over BMS implantation in reducing target vessel revascularizations may be artificially inflated by protocol-mandated, rather than clinically driven, repeated angiograms.”

He also raises the issue of incomplete information about specific patient groups (those with diabetes, long coronary lesions, or smaller vessel disease) or particular stent models, saying these variations would be important for clinicians to know when weighing benefits or risks of DES.

Dr. Stone responded that the study authors agree and will be performing such analyses in the future.

But Dr. Brophy counters in his editorial that patients with STEMI should be informed “that substituting DES for BMS in 100 patients likely results in no mortality differences but approximately 5 fewer repeat revascularizations at the cost of 1 additional late reinfarction with a possibility that this risk may be substantially higher.”

Furthermore, depending on the costs of repeat revascularization, the choice of DES “may be seen as a pricey dessert whose exact caloric and nutritional value remains uncertain,” Dr. Brophy writes.

Note: Dr. Stone is a faculty member of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Sources:
1. De Luca G, Dirksen MT, Spaulding C, et al. Drug-eluting vs. bare-metal stents in primary angioplasty: A pooled patient-level meta-analysis of randomized trials. Arch Intern Med. 2012;172:611-621.

2. Brophy JM. Drug-eluting stents in ST-segment elevation myocardial infarction: Looking for just deserts. Arch Intern Med. 2012;172:621-622.

 

 

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• Meta-Analysis: Mixed Results Seen with First-Gen DES in STEMI Patients
• DES Noninferior for Survival Compared with BMS in STEMI
• DES, BMS Equally Effective for STEMI, Revascularization Edge Goes to DES

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