CAD Complexity Does Not Affect Dominance of Newer vs Older DES

New-generation DES improve 2-year outcomes compared with early-generation stents regardless of the complexity of CAD, although the advantage might be greater in patients with higher Syntax scores, according to pooled results from 4 all-comers trials.

The findings may have implications for the choice of revascularization method, suggest Stephan Windecker, MD, of Bern University Hospital (Bern, Switzerland), and colleagues.

“New-generation DES have the potential to reduce the existing gap between percutaneous and surgical myocardial revascularization in patients with advanced CAD,” they write in the November issue of JACC: Cardiovascular Interventions.

In past trials, including SYNTAX and FREEDOM, PCI with early-generation DES was inferior to CABG for patients with multivessel disease.

Newer stents have addressed some of the problems with earlier devices by introducing thinner struts, more biocompatible or biodegradable polymer coatings, different antiproliferative agents, and lower drug loads and thereby have improved outcomes, according to Windecker and colleagues. But it remains unclear whether the complexity of CAD influences the relative safety and effectiveness of newer vs older DES.

“This is important, as the treatment effect of new-generation DES may be camouflaged by the overriding effect of the underlying CAD,” the authors write.

To explore the issue, the researchers looked at pooled data from 6,081 patients treated with DES in 4 contemporary all-comers trials conducted in Europe between 2004 and 2013: SIRTAX, LEADERS, RESOLUTE, and BIOSCIENCE.

About three-quarters (74.8%) of patients received new-generation DES, including everolimus-eluting Xience V or Prime or Xpedition (Abbott Vascular), zotarolimus-eluting Resolute (Medtronic), biodegradable polymer biolimus-eluting BioMatrix Flex (Biosensors), and biodegradable polymer sirolimus-eluting Orsiro (Biotronik AG). The rest received early-generation sirolimus-eluting Cypher or Cypher Select (Cordis) or paclitaxel-eluting Taxus (Boston Scientific).

At 2 years of follow-up, new-generation DES were associated with lower rates of the composite of cardiac death, MI, or ischemia-driven TLR (primary device-oriented clinical endpoint); TLR (primary effectiveness endpoint); and definite stent thrombosis (primary safety endpoint) compared with early-generation stents.

The investigators then stratified the results according to CAD complexity based on Syntax score, grouping patients who had a score ≤ 11 (median score for the overall cohort) or higher.

Findings related to the device-oriented clinical endpoint were not modified by CAD complexity (P = .219 for interaction). However, for ischemia-driven TLR, the advantage for new-generation DES tended to be greater in patients with more complex disease (P = .059 for interaction). For definite stent thrombosis, newer stents had significantly more benefit in patients with higher Syntax scores (P = .013 for interaction).

New-generation devices were associated with a reduced risk of cardiac mortality in patients with a Syntax score > 11 (HR 0.46; 95% CI 0.31-0.70) but not in those with lower scores (P = .042 for interaction), a finding that “may be interpreted as the result of improved safety and effectiveness with new-generation DES in patients with more advanced CAD severity,” Windecker and colleagues write.

Better Against CABG?

American and European guidelines agree that CABG is preferred over PCI in patients with advanced CAD, the researchers note. Because the data forming the basis for those recommendations came from studies involving early-generation DES, they say, “it is tempting to speculate whether the use of new-generation DES may alleviate the existing gap between CABG and early-generation DES in patients with severe multivessel disease.”

Still, the findings of the current study, which did not include a CABG arm, should be considered hypothesis-generating only, they add. They point out that there are ongoing trials comparing new-generation DES with CABG, including EXCEL and FAME 3.

In an accompanying editorial, David Holmes Jr, MD, of the Mayo Clinic (Rochester, MN), and Michael Mack, MD, of Heart Hospital Baylor Plano (Dallas, TX), say that, because of how CAD complexity was defined, the study does not inform whether new-generation stents may perform better than early-generation stents when compared with CABG in patients with complex disease.

Splitting patients into 2 groups based on the median Syntax score in the current analysis differs from how patients were divided in the SYNTAX trial, which had tertiles of low (0-22), intermediate (23-32), and high (33 and higher) scores.

“In this analysis, in the ‘high CAD complexity group,’ some patients may have been considered in the lowest tertile in the SYNTAX trial, making any potential comparisons difficult,” Holmes and Mack write. Using the SYNTAX divisions would have made it easier to interpret the results, they say.

“It would have been particularly valuable to know the performance of a new-generation DES in the highest risk tertile of the patients using the cutoff of ≥ 33,” they write.

But despite that shortcoming, the study provides important information, they say, pointing to the apparently enhanced benefits of new-generation DES as Syntax scores increase in patients with clinically moderate disease.

The study shows that “Moore’s law in integrated electronics, where important advances occur with each new generation, is also true in interventional cardiology, and new DES stents perform better in terms of safety and effectiveness than older versions do,” the editorialists conclude.

However, the results of previous trials of PCI vs CABG in the most complex patients remain untested, they add. “We can look forward to the results of the [EXCEL trial]… for validation of the progress that this meta-analysis appears to demonstrate.”

Sources: 
1. Piccolo R, Pilgrim T, Heg D, et al. Comparative effectiveness and safety of new-generation versus early-generation drug-eluting stents according to complexity of coronary artery disease: a patient-level pooled analysis of 6,081 patients. JACC Cardiovasc Interv. 2015;8:1657-1666.
2. Holmes DR Jr, Mack MJ. Moore’s law: apples and oranges [editorial]. 2015;8:1667-1669.

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