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In patients with multivessel coronary disease and chronic kidney disease (CKD), a new-generation drug-eluting stent reduces the need for revascularization over 1 year compared with an identical bare-metal stent (BMS), according to a study published online December 19, 2013, ahead of print in Circulation. Moreover, the advantage holds true even for those with severe renal dysfunction.

Investigators led by Fabrizio Tomai, MD, of the European Hospital (Rome, Italy), randomized 252 ischemic patients with CKD (eGFR < 60 mL/min) and at least 2 significant lesions in at least 2 major epicardial vessels to implantation with the Xience V everolimus-eluting stent (Abbott Vascular, Redwood City, CA) in 1 or more vessels in each individual (total 257) and its bare-metal counterpart, Multi-link Vision (Abbott Vascular), in another vessel or vessels (total 255).

Twenty patients (9.3%) underwent angiography before 12-month follow-up due to symptom recurrence, while 195 (90.7%) had scheduled SPECT imaging 9 to 12 months after the index PCI. Among the latter, 16 patients underwent angiography for signs of ischemia in the treated regions, with significant stent restenosis detected in 87.5%.

Ischemia-Driven TVR Reduced More Than Fourfold

At 12 months, TVR was performed in 14.8% of patients: 13% of BMS-treated lesions and 4.3% of DES-treated lesions (P = 0.001). The incidence of ischemia-driven TVR (the primary endpoint) was higher in the BMS group than the EES group (11.4%; 95% CI 7.8-16% vs. 2.7%; 95% CI 1.1-5.6%; P < 0.001). The EES advantage was maintained among patients with only 2 treated vessels and among diabetics (both P < 0.001). EES were also superior to BMS in both moderate (2.6% vs. 7.3%; P = 0.03) and severe CKD (3.1% vs. 24.2%; P = 0.005).

At 12-month clinical follow-up, 8 patients had died, 3 for cardiac reasons. There were 3 MIs and 1 possible case of subacute thrombosis. One patient required dialysis. No cases of late stent thrombosis were seen.

In multivariate analysis, BMS implantation predicted an almost fivefold higher risk of ischemia-driven TVR compared with EES (OR 4.95; 95% CI 2.1-11.6; P < 0.001), while a larger reference vessel diameter was associated with a reduced risk of revascularization (OR 0.32; 95% CI 0.1-0.7; P = 0.006).

The clear advantages of DES over BMS in all CKD patients despite the strong performance of the latter devices “confirm and extend [the findings] obtained in previous investigations with first-generation DES in patients with mild to moderate CKD,” the authors write. Moreover, the fact that low rates of clinical restenosis were preserved in patients with severe CKD—“arguably … one of the highest-risk groups in terms of efficacy of coronary revascularization”—is reinforced by use of intraindividual comparison, which obviates “the multiple and unpredictable baseline differences in high-risk populations.”

However, the study design precludes comparison of the different stents in terms of patient-centered major clinical endpoints, the investigators acknowledge. And the impact of lesion-specific factors on outcome could not be completely assessed since the lesions were not routinely characterized by intravascular imaging. Moreover, operators were not blinded to the type of randomized stent.

Finally, Dr. Tomai and colleagues caution, the findings refer to the approximately half of study patients in whom complete revascularization could be achieved and therefore cannot be applied to all CKD patients with multivessel disease. 

Clever Trial Design 

The trial is largely a response to a number of prior observations that in patients with severe CKD, especially those on dialysis, the type of stent implanted makes little difference, Sorin J. Brener, MD, of Weill Cornell Medical College (New York, NY), told TCTMD in a telephone interview, adding, “In that sense, it’s an important contribution.”

Moreover, he noted, the trial design, using patients as their own controls, is clever in that it “excludes the possibility that certain patient-specific characteristics affect their overall predisposition toward restenosis.”

Interestingly, he continued, outcomes for the entire cohort were very good. “This tells us that even if you put in a BMS, it’s not the end of the world by any stretch of the imagination [since] 85% to 90% of the patients don’t have any problems,” he commented

One possible study limitation, Dr. Brener noted, is the 12-month follow-up, since DES may tend to develop stenosis later than BMS do, and that may explain the “remarkably low” rate of restenosis. In fact, the overall results are “a little too good to be true,” he observed, adding that the tip-off is the 1-year mortality rate of 1%.

Dr. Brener also noted that three quarters of the study patients had moderate CKD while only one-quarter had severe disease. The case for DES superiority would have been stronger had the proportions been reversed, he suggested, adding that in the future not only should CKD patients not be excluded from randomized trials but perhaps they should be aggressively recruited since they are likely to reap a greater absolute benefit from DES.

Nonetheless, the overall finding that EES--and very likely all second-generation and newer DES--perform at least as well in patients with CKD as in those without the comorbidity is “an important message,” Dr. Brener concluded.

Study Details 

The mean age of the study population was 73 years. A high proportion of patients presented with 3-vessel disease (42%), ACS (57%), and diabetes (44%). The mean eGFR was 46.8 mL/min, and 10% of patients were on dialysis. Lesion type, reference vessel diameter, pre- and post-procedural MLD, and percent diameter stenosis at angiography were similar between the groups. Stent postdilation, total stent length, and number of stents per treated vessel were higher in the EES group, while the rate of direct stenting and final stent diameter were higher in the BMS group. 

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