Canadian Registry Data Favor Drug-Eluting Stents

TORONTO, Oct. 4 -- Drug-eluting stents are associated with a lower three-year mortality rate than bare-metal devices, according to registry data here.

In 3,751 matched pairs, the three-year mortality rate was 5.5% for patients treated with drug-eluting stents versus 7.8% for patients who received bare-metal stents (P<0.001), Jack V. Tu, M.D., Ph.D., of the University of Toronto, and colleagues, reported in the Oct. 4 New England Journal of Medicine.

"We found that drug-eluting stents were most effective in reducing the need for target-vessel revascularization in patients at the highest risk for restenosis (i.e., those who had two or three risk factors-presence of diabetes, small vessels, long lesions)," they wrote. Drug-eluting stents, they added, "offer minimal benefit to patients at lower risk."

The authors also wrote that the difference in mortality favoring drug-eluting stents was not fully explained by the difference in revascularization rates. The difference could "reflect unmeasured confounding factors, and we suggest caution in concluding, on the basis of our study alone, that drug-eluting stents save lives."

In the nearly two-years since questions about the safety of drug-eluting stents first began to surface, there has been general agreement that the revascularization rate is much lower with drug-eluting stents than with bare-metal stents. That was again the case in this study-7.4% versus 10.7% (P<0.001).

Critics of drug-eluting stents downplay the significance of revascularization rates, arguing that it is an endpoint driven by angiography -- a surrogate marker that has little relevance in the real world where patients don't routinely have angiographic follow-up 90 days after implantation.

Dr. Tu and colleagues, however, reported that the 30-mortality rate for patients who needed repeat procedures was 2.5% in the bare-metal group and 2.4% in the drug-eluting stent group, demonstrating that "the need for target-vessel revascularization is a clinically significant adverse event."

The authors compared target-vessel revascularization, MI, and death rates for 3,751 propensity-score matched pairs of patients included in the Cardiac Care Network of Ontario's population-based clinical registry. All patients had index percutaneous coronary interventions from December 1, 2003 though March 31, 2005.

The average age of patients was 62 and about 70% were men. About 20% of patients had an MI one to seven days before percutaneous interventions, and 9% had MI on the day of the index percutaneous interventions. Fifty-nine percent of the patients had no history of MI for the 365 days prior to stenting.

Among the findings:

• High risk patients, i.e. those with diabetes, lesions 20 mm or longer, or vessel diameter of less than 3 mm had significantly lower rates of target-vessel revascularization (P<0.001), but the difference was not significant among low risk patients.
• During the first six months after stenting, the MI rate was 0.4 percent points lower in the drug-eluting stent group, but rates crossed at 15.6 months. At 2 years, the MI rate was 0.5% higher in the drug-eluting stent group (NS).
• The 30-mortality for patients who had MI following stenting was 6.9% irrespective of stent type.

Dr. Tu and colleagues said the crossover in MI rates in year two was also observed in other registry data, including the Swedish Coronary Angiography and Angioplasty Registry (SCAAR), and is consistent with studies that have found increased risk of late stent thrombosis with drug-eluting stents, when dual antiplatelet therapy (clopidogrel [Plavix] plus aspirin) was stopped.

If confirmed in other studies, the results suggest that aspirin and clopidogrel may need to be continued beyond the 12 months currently recommended, the authors wrote.

Last month the latest data from the SCAAR registry revealed no significant differences in mortality between bare-metal and drug-eluting devices after four years.

The SCAAR investigators said bare-metal stents were associated with a significantly higher risk of early events, while drug-eluting stents were associated with a continuous low risk of late stent thrombosis -- about 0.5% per year. (See: ESC: Increased Mortality Erased in Latest Drug-Eluting Stent Data from Swedish Registry)

Drug-eluting stents have been under increased scrutiny since March 2006 when researchers from Basel, Switzerland, reported an increase in late-stent thrombosis in a "real-world study" of stent patients. (See: Late Thrombotic Events Take Off When Stent Patients Stop Plavix)

Then in September 2006 a meta-analysis of published stent trials found a statistically significant increase in mortality with the sirolimus-eluting (Cypher) stent compared with bare-metal stents.

That report ignited a firestorm of controversy at the 2006 ESC meeting in Barcelona that has continued to make headlines over the past 12 months. The fallout from the Barcelona meeting included an FDA hearing on stent safety in December, and new guidelines on drug-eluting stent use from the American Heart Association/American College of Cardiology/Society of Cardiographic Angiography and Interventions.

Dr. Tu said the study was limited by its observational nature and by the fact that "findings may not be generalizable to countries without universal health insurance and drug-benefit plans," because dual-antiplatelet therapy is expensive.

Additionally, because the study was not a randomized trial, "there may have been unmeasured confounding factors that contribute to our findings."

The authors concluded that the "small absolute difference in mortality in favor of drug-eluting stents in our study warrants further investigation and should be confirmed or refuted, through large, randomized clinical trails with long-term follow-up."