|TAXUS drug-eluting stent. Source: Boston Scientific|
Three recent clinical studies rebuke the previously held belief that drug-eluting stents (DES) led to higher rates of stent thrombosis (ST). As concerns over DES have begun to dissipate, their utilization is already increasing in the first half of 2008, and many experts think this trend will continue.
Some attribute the positive outcomes changes to a natural learning curve with new technologies; however, others say that the initial negative hype was blown out of proportion because the rates of ST have always been extremely low with both bare-metal stents (BMS) and DES.
In fact, Kenneth Rosenfield, MD, director of cardiac and vascular invasive service at Massachusetts General Hospital, says that the initial acute thrombosis rate and the occurrence of acute thrombosis rate were overplayed. “It [the initial negative results] did not acknowledge the fact that there is a basal rate for acute thrombosis and recurrent occlusion in BMS. There is a basal rate of acute thrombosis in stents—whether it be bare-metal or drug-eluting. They are both very similar and very low.”
For example, a recent study published in the Journal of the American Medical Association found that the widespread use of DES is associated with a decrease in repeat procedures and does not appear to increase the risk of death, compared to BMS (2008; 299:2868-2876). Reviewing nearly 39,000 Medicare patients, David J. Malenka, MD, of Dartmouth-Hitchcock Medical Center in Lebanon, N.H., and colleagues found that that 22.8 percent of patients in the BMS group underwent a repeat revascularization (20 percent PCI; 4.2 percent CABG) compared to the 19 percent of patients in the DES group who underwent a repeat revascularization (17.1 percent PCI; 2.7 percent CABG) during a two-year follow-up.
The JAMA study is particularly important because it examines both the three-month and two-year outcomes for revascularization in a larger set of patients, says Steven Bailey, MD, president-elect of the Society for Cardiovascular Angiography and Interventions (SCAI).
Malenka and colleagues wrote that a “small but statistically significant decrease in the unadjusted rate of STEMI in the DES era cohort began to emerge at three months and increased slightly through two years of follow-up,” which they said coincided with the lower rate of repeat PCI in the DES cohort.
The JAMA researchers also found that there was no difference in unadjusted mortality risks at two years (8.4 vs. 8.4 percent), but a small decrease in STEMI existed (2.4 vs. 2 percent). The adjusted risk of death or STEMI at two years was similar.
Bailey points out that the Malenka et al trial is consistent with the later 2006-2007 SCAAR (Swedish Coronary Angiography and Angioplasty Registry) data. “SCAAR ultimately pointed out that there is an important learning curve with these new technologies,” he says.
The updated SCAAR study group analysis, presented at the 2007 European Society of Cardiology Congress, based on a one- to four-year follow-up of more than 35,000 patients who received nearly 62,000 stents, found that while ST rates clearly had increased slightly in DES by 0.5 percent over one year, it did not translate into higher deaths, as earlier believed.
SCAAR’s original negative DES results from 2003-2004 procedures reflected early use of new technologies, Bailey notes. “But when they reported their post-learning curve results in a larger population, their data repudiated their initial conclusions.”
Patient selection is important
In the real-world practice of stenting, the use of DES frequently includes off-label indications. Consequently, the incidence of ST in real-world practice is not the same as that observed in the trials. To examine DES thrombosis outside of the trial setting, José M. de la Torre-Hernández, MD, and colleagues designed the largest DES registry to date: the ESTROFA study with 20 centers in Spain.
Data from 23,500 patients treated with 34,075 stents indicate a cumulative incidence of angiographically documented stent thrombosis of 2 percent at three years—24 acute, 125 subacute and 152 late (J Am Coll Card 2008;51:986-990). Researchers found no differences between paclitaxel-eluting and sirolimus-eluting stents.
According to the researchers, they also conducted the largest subgroup analysis of 14,120 cases. They found that independent predictors for acute/subacute thrombosis were acute coronary syndrome, STEMI, renal failure, stent