Percutaneous coronary intervention (PCI) with sirolimus-eluting stents (SES) is feasible in patients on chronic dialysis, but the condition confers substantially increased risk for death and repeat revascularization, according to a registry study published online December 31, 2010, ahead of print in the European Heart Journal.

Investigators led by Yoritaka Otsuka, MD, of the National Cardiovascular Center (Osaka, Japan), analyzed outcomes for 2,050 consecutive patients who underwent PCI with SES at 50 Japanese centers between September 2004 and September 2005, dividing them into those who were on chronic dialysis (n = 106) and those who were not (n = 1,944).

Higher Restenosis at 8 Months

On mandatory angiographic follow-up at 8 months, treated vessels in the dialysis group had significantly smaller minimal lumen diameter and larger percent diameter stenosis, leading to higher mean late loss (0.49 ± 0.89 mm vs. 0.14 ± 0.56 mm; P = 0.002) and binary restenosis rate (26.4% vs. 8.2%; P < 0.001) than those in the nondialysis group.

At 3 years, the primary endpoint of cardiac death was a remarkable 7-fold higher among dialysis patients, while the other primary endpoint of TLR was about 3-fold higher compared with the nondialysis group. All-cause mortality and MACE (all-cause death, MI, emergency CABG, or TLR) were also greater in the dialysis group. In addition, although the incidence of Academic Research Consortium-defined definite or probable stent thrombosis among dialysis patients was doubled, the number of events was small and the difference was not significant (table 1).

Table 1. Outcomes at 3 Years

 

Even after propensity score matching, dialysis was strongly associated with risk of cardiac death (HR 5.51; 95% CI 2.58-11.78; P < 0.0001) and TLR (HR 2.83; 95% CI 1.62-4.93; P = 0.0003).

In multivariate analysis, dialysis was the strongest predictor of increased risk for cardiac death to 3 years (HR 7.23; 95% CI 3.47-15.06). Dialysis also headed the list of independent risk factors for TLR to 3 years (HR 4.67; 95% CI 2.85-7.66).

PCI Difficult But Feasible

PCI was more complex and difficult to perform in dialysis patients due to their tendency toward moderate to severe calcified lesions, eccentric lesions, and need for high-pressure dilatation and rotational atherectomy, the authors say. Nonetheless, they add, “our study showed that PCI with SES in [dialysis patients] is highly feasible with a delivery success rate of 99.8%.”

Results of 2 small, observational studies comparing SES with BMS in dialysis patients have been inconsistent, the authors observe, but the TLR rates of 15.8% for the first year and 19.4% over 3 years seen in the current study are “acceptable and lower than those for BMS in previous studies in [dialysis] patients.”

Although this registry was not designed to evaluate the mechanism of restenosis, the investigators suggest 4 possibilities:

• Sirolimus is not effective or the dose in SES is insufficient for calcified lesions
• There is decreased efficacy due to a defect in the polymer
• Stent fracture
• Stent underexpansion

Randomized Trial Outcasts

In a telephone interview with TCTMD, Khaled M. Ziada, MD, of the University of Kentucky (Lexington, KY), said that observational studies on dialysis patients are of interest because this population has been systematically excluded from randomized trials comparing treatment strategies.

Although the risk conferred by dialysis is difficult to tease out considering the high rates of comorbidities such as diabetes and hypertension, the study does confirm 2 main findings, he said: “Patients on dialysis are much sicker [than others], and they die at a dramatic rate.”

Overall, the current study shows that stenting is feasible and safe in dialysis patients, Dr. Ziada said, although it is a bit more complicated and may require more-experienced operators and additional work.

PCI a Better Option Than Bypass Surgery?

“In fact, PCI is a very good option for these patients,” he continued. Bypass surgery typically offers higher upfront risk in return for greater longevity, but with such high 3-year mortality [in dialysis patients]—which is often unrelated to cardiovascular events—that advantage is lost, he suggested. “In our center, we exhaust all PCI options before sending patients to surgery,” he noted. “Of course, some have anatomy that is not amenable. But if we can do multivessel PCI, we do that rather than bypass surgery—something we don’t do in any other patient group.”

Michael E. Farkouh, MD, MSc, of Mount Sinai Medical Center (New York, NY), told TCTMD in a telephone interview that the results of the current study would not be surprising to clinicians because it is well documented that dialysis patients are at far greater risk for future events after PCI “The issue is that some literature—mostly short-term studies—suggest that DES may help attenuate some of the risk,” he said. “But this study suggests that if you follow patients out long enough, the outcomes are comparable to what we see with BMS. The outcomes are still poor.”

For dialysis patients, it is especially important to explain the risks and benefits of a proposed intervention, Dr. Farkouh advised. “In [non-urgent] dialysis patients, I would take a step back and try to optimize their antianginal regimen. If a patient is highly symptomatic, it might be reasonable to go ahead and revascularize with DES. It’s questionable whether bypass surgery is a treatment option.”

Reducing Symptoms Is the Primary Goal

By the time most patients need dialysis, they are typically end-stage and the therapeutic goal is not to extend life but to reduce symptoms and maintain quality of life, Dr. Farkouh observed. He suggested that it would be more fruitful for future trials to address patients who have reduced renal function but are not yet on dialysis. In that population, there may be a role for PCI on top of optimal medical therapy, with the dual goals of reducing cardiovascular events and sparing patients from dialysis.

Acknowledging the challenges, Dr. Ziada asserted that greater efforts should be made to include dialysis patients in future randomized trials, at least in subgroup analyses. The bottom line, he noted, is that despite much progress in therapies, the one-third mortality rate in these patients has not budged over the past decade. “It’s pathetic—we really have to do better,” he concluded.

Study Details

There were no differences in mean age, gender distribution, or previous MI or PCI between the 2 groups. However, the dialysis group had a higher prevalence of LVEF less than 30%, previous CABG, diabetes, multivessel disease, and PAD, while patients in the nondialysis group had a higher prevalence of obesity and hyperlipidemia.

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Source:
Otsuka Y, Ishiwata S, Inada T, et al. Comparison of hemodialysis patients and nonhemodialysis patients with respect to clinical characteristics and 3 year clinical outcomes after sirolimus-eluting stent implantation: Insights from the Japan multicenter postmarketing surveillance registry. Eur Heart J. 2010;Epub ahead of print.

 

 

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