AT THE ESC CONGRESS 2016
ROME (FRONTLINE MEDICAL NEWS) – There’s good news for the millions of patients living with a first-generation metallic drug-eluting stent for coronary revascularization implanted in years past: The devices perform reassuringly well a full decade after implantation, Lorenz Räber, MD, reported at the annual congress of the European Society of Cardiology.
That’s the key message of the SIRTAX VERY LATE study, the only randomized trial of first-generation drug-eluting stents (DES) that didn’t turn out the lights at a maximum of 5 years of follow-up. In fact, at the 10-year mark, SIRTAX VERY LATE shows that regardless of whether the first-generation DES was paclitaxel- or sirolimus-eluting, the risk of major adverse cardiac events due to device failure was substantially lower in the second half-decade than in the first 5 years after deployment, according to Dr. Räber of Bern (Switzerland) University Hospital.
More specifically, the cumulative risk of ischemia-driven target lesion revascularization was 14.6% at 5 years and 17.7% at 10 years, while the 5- and 10-year cumulative risks of definite stent thrombosis were 4.5% and 5.6%, respectively.
The annual risk of ischemia-driven target lesion revascularization dropped by 64%, from 1.8%/year during years 1-5 to 0.7% during years 6-10. Similarly, the annual risk of definite stent thrombosis fell from 0.67%/year to 0.23%/year after year 5, a 69% relative risk reduction. And importantly, these attenuations in risk occurred independent of age.
“The lower risk of late clinical events suggests stabilization of delayed arterial healing over time after first-generation DES implantation, with reduced chronic inflammation and neoatherosclerosis,” he said.
This is reassuring in light of the stormy history of the first-generation DES. Three years after the devices came on the U.S. market, the so-called ESC firestorm erupted. At the 2006 ESC congress, investigators presented meta-analyses suggesting the devices carried a possible late increased thrombotic risk beyond the then-recommended 3-6 months of prescribed dual-antiplatelet therapy. The use of these devices declined sharply in response, even though a Food and Drug Administration advisory panel charged with looking at the totality of evidence concluded that concerns about thrombosis didn’t outweigh the benefits of the first-generation DES over bare-metal stents.
The reductions in very late stent thrombosis and ischemia-driven target lesion revascularization beyond 5 years seen in the SIRTAX VERY LATE trial occurred despite the fact that only 15% of patients were on dual-antiplatelet therapy throughout the first 5 years and 11% were on dual-antiplatelet therapy afterwards, Dr. Räber noted.
“Our findings may have implications for secondary prevention after PCI with a first-generation DES, including the need for long-term antiplatelet therapy,” the cardiologist added.
The previously reported 5-year results of SIRTAX (the Sirolimus-Eluting Versus Paclitaxel-Eluting Stents for Coronary Revascularization trial) showed a steady increase over time in late lumen loss and an ongoing risk of very late stent thrombosis ( Circulation. 2011 Jun 21;123(24):2819-28 ). Much the same was seen at the 5-year mark in the other major trials of first-generation DES, including RAVEL , SIRIUS , and TAXUS.
However, all those studies ended at 5 years, leaving unanswered the key question of what happens later. Cardiologists have wondered if the first-generation DES they put in their patients years ago were associated with a continued steady climb in the risk of device-related adverse events, or if the risk plateaued or even dropped off. The SIRTAX VERY LATE study was conducted in order to provide answers.
SIRTAX included 1,012 Swiss patients randomized to coronary revascularization using a first-generation sirolimus- or paclitaxel-eluting stent in 2003-2004. Roughly half had stable coronary artery disease and half presented with acute coronary syndromes. The 10-year follow-up conducted in the SIRTAX VERY LATE study captured 895 (88%) of the original 1,012 subjects.
The cumulative incidence of major cardiac adverse events – a composite of cardiac death, MI, and ischemia-driven target lesion revascularization – was 20.8% at 5 years and 33.8% at 10 years. The rate was similar between years 1-5 and 6-10.
The cumulative all-cause mortality rate was 10.4% at 5 years and 24.2% at 10 years. The rate was 2.0%/year during years 1-5 and accelerated significantly to 3.1%/year in years 6-10. However, this increase appears to be largely due to the background impact of advancing age rather than to any effect of having a first-generation DES. The 5- and 10-year all-cause mortality rates in the age- and sex-matched general Swiss population are similar to those seen in SIRTAX VERY LATE, at 9.6% and 22.1%, respectively, the cardiologist observed.
The cumulative incidence of MI in the study population was 7% at 5 years and 9.7% at 10 years. Between years 1-5 the rate was 0.9%/year, dropping to 0.6%/year during years 6-10.
One of the useful potential purposes for the new SIRTAX VERY LATE follow-up data beyond 5 years is that the results could serve as a benchmark in evaluating the long-term safety and efficacy of the much newer drug-eluting fully bioresorbable vascular scaffolds, since the potential benefits of these new devices may not appear until relatively late, after the devices themselves have disappeared. SIRTAX VERY LATE sets the bar for stent-related adverse events 5 years or more after device implantation at an annual risk of less than 0.3%/year for stent thrombosis and less than 1%/year for ischemia-driven target lesion revascularization.
Session co-chair Hector Bueno, MD, drew attention to the fact that no significant differences in clinical outcomes were seen at either 5 or 10 years between the sirolimus- and paclitaxel-eluting stent recipients. That’s noteworthy because more than a decade ago when the primary endpoint of SIRTAX was reported, much was made of the finding that the 9-month rate of major adverse cardiac events was significantly lower in the sirolimus-eluting stent group ( N Engl J Med. 2005 Aug 18;353[7]:653-62 ). Over time, any outcome differences between the two devices were erased, observed Dr. Bueno of Complutense University of Madrid.
The SIRTAX VERY LATE study was funded by grants from Bern University Hospital. Dr. Räber reported having no relevant financial interests.
Simultaneously with his presentation in Rome at ESC 2016, the study results were published online (Eur Heart J. 2016 Aug 30. doi: 10.1093/eurheartj/ehw343 ).
