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[24]: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 in left anterior descending artery (LAD), stent length, and diabetes. For late thrombosis, independent predictors were STEMI, stent in LAD, and stent length. Additionally, early discontinuation of antiplatelet therapy was a relatively common finding in patients with late ST.


Second-generation stents

De la Torre-Hernández says that they are currently continuing with the ESTROFA for second-generation DES, including Abbott’s XIENCE V and Medtronic’s Endeavor and they continue to find fewer cases of ST. He attributes the decrease to a better selection of those candidates who should receive DES.

“We are more aware of patients who may have problems with antiplatelet therapy. We are learning to use more IVUS [intravascular ultrasound] during the stenting procedures, more over-dilation of the stents. We have learned how to properly manage patients with DES now, and we are likely to see less stent thrombosis in the coming years,” de la Torre-Hernández explains.

If the patient is properly chosen, the rates for stent thrombosis will be very low—below 1.2 percent a year, according de la Torre-Hernández.

In a separate retrospective cohort study that also appeared in JACC, Peter W. Groeneveld, MD, from the Philadelphia Veterans Affairs Medical Center, and colleagues found that DES receipt was associated with fewer subsequent revascularization procedures, lower rates of hospitalization for acute MI (AMI) and improved survival among elderly Medicare beneficiaries (2008; 51:2017-2024).

Groeneveld et al found that the receipt of a DES was associated with a significant survival benefit, with an adjusted mortality hazard ratio of 0.83 compared with contemporary controls, and a hazard ratio of 0.79 compared with historical controls. Patients with DES had significantly lower adjusted rates of revascularization procedures within the first two years after PCI and lower hospitalization rates for subsequent AMI.

The study implies, the researchers wrote, “that DES have previously unrecognized clinical value in reducing mortality, although this effect may be confined to, or substantially more pronounced among, elderly patients.”

Based on the positive DES findings of these studies, many experts think it will lead to an increase in utilization, despite the drop-off in PCI procedures in the past several years.

“The studies comparing bare-metals with DES, the studies done with XIENCE V and Endeavor are all very positive. I think their use will increase, not maybe reaching the 90 percent rate in 2004-2005, but maybe reaching 80 percent usage,” de la Torre-Hernández says.
 

Between the last quarter of 2007 and the first quarter of 2008, the stent industry saw four consecutive months of increased drug-eluting stent use in the U.S. Source: CRT