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Almost 1 in 5 patients with unprotected left main disease implanted with drug-eluting stents (DES) will experience in-stent restenosis. However, their long-term prognosis appears to be benign if they receive timely, optimal treatment, according to results of a single-center study published in the March 22, 2011, issue of the Journal of the American College of Cardiology.

Investigators led by Seung-Jung Park, MD, PhD, of Asan Medical Center (Seoul, South Korea), analyzed 509 consecutive patients with unprotected left main disease who underwent DES implantation at their center between February 2003 and November 2007.

Over a median follow-up of 3.4 years, 5.6% of patients died (2.3% of cardiovascular disease), 10% had an acute MI, and 10% had repeat TLR. Nine patients suffered Academic Research Consortium-defined definite or probable stent thrombosis, but none of these events occurred in patients with in-stent restenosis.

Of the 502 patients who survived for at least 6 months, 80.1% underwent routine or clinically driven angiographic follow-up. Restenosis was identified in 17.7%—more than two-thirds within the first year. The disease was focal in 80.3% and diffuse in 19.7%. The prevalence of restenosis varied by lesion type, amounting to 9.7% of nonbifurcation lesions and 22.1% of bifurcation lesions. Among restenosis patients, 15.5% had silent ischemia, while 59.2% presented with stable angina, 23.9% with unstable angina, and 1.4% with nonfatal MI.

Restenosis Predictors

In multivariate analysis, male sex reduced the likelihood of experiencing in-stent restenosis (HR 0.41; 95% CI 0.24-0.69; P = 0.007), while restenosis was positively predicted by:

• Previous restenotic lesion (HR 4.59; 95% CI 2.40-8.77; P < 0.001)
• Bifurcation involvement (HR 2.56; 95% CI 1.27-5.19; P = 0.009)
• Complex stenting with 2 or more stents in bifurcation lesions (HR 2.50; 95% CI 1.28-4.76; P = 0.007)
• Total number of stents (HR 4.76; 95% CI 2.94-7.67; P < 0.001)

Among patients with in-stent restenosis, 56.3% were treated with repeat PCI (of whom a little fewer than half received another DES), 14.1% underwent bypass surgery, and 29.6% received medical therapy only.

The median follow-up after restenosis treatment was 31.7 months (IQR, 22.4-46.6 months). No deaths were reported. One patient experienced an MI, and 6 required repeat TLR. The rate of survival free from MACE (composite of death, MI, or TLR) was 86.6% overall and did not differ among the treatment groups: 85.6% for medical therapy, 86.4% for PCI, and 90.0% for CABG (P = 0.91).

No Mortality Impact

Importantly, Cox regression analysis demonstrated that in-stent restenosis did not affect the risk of hard clinical endpoints of death, MI, or the composite of death or MI (table 1).

Table 1. Effect of In-Stent Restenosis on Death, MI

“The choice of treatment strategy for [in-stent restenosis] depends primarily on several clinical and angiographic factors, making optimal patient selection crucial in the appropriate treatment of these lesions and achievement of favorable long-term outcomes,” the authors write. These include:

• Lesion characteristics
• Procedural complexities
• Extent of extra-left main disease
• Patient clinical characteristics such as age, diabetes, and ejection fraction
• Patient and/or physician preference

The authors acknowledge some important limitations to their study. Not only was the choice of therapy for in-stent restenosis at physician discretion but the treatment groups were small and dissimilar, making any comparison of the different therapies vulnerable to hidden confounders.

In a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Weill Cornell Medical College (New York, NY), noted that the study’s 17.6% restenosis rate, though considerably higher than what was seen in the SYNTAX trial, is probably more realistic. But the main finding—that restenosis does not affect survival—is “a big message,” he said.

Issue of Angiographic Surveillance Reopened

Dr. Moses agreed with the authors that it remains unsettled whether angiographic surveillance is advisable. “There did seem to be a marginal advantage in the long term for angiographic follow-up,” he observed, citing the 4.4% absolute difference in mortality favoring patients who had such follow-up over those who did not (3.6% vs. 8.0%; log-rank P = 0.004).

When the investigators state that the long-term prognosis of restenosis may be benign, “what they are really saying is, with a high level of detection, restenosis is benign,” Dr. Moses stressed. “Maybe it was their aggressive surveillance that made it benign. The current recommendations say no [angiographic follow-up], but this paper may reopen that question, especially given the good results.”

Dr. Moses expressed confidence in the ability of PCI to treat most restenoses. “Every once in a while you get a really nasty restenosis, and you send [that patient] to surgery,” he noted. “But in this whole cohort followed for over 3 years, only 10 [subjects] went to CABG. That’s pretty remarkable.”

In general, lesion characteristics guide decisions about how to handle restenosis, he added. “If it’s a focal area, it can be managed fine with PCI,” Dr. Moses said. On the other hand, “aggressive restenosis has a poor prognosis, so for those patients you would lean toward bypass.” The same holds true for complex bifurcation restenosis or a procedure requiring another set of double stents, he added. “But if the restenosis is mild and maybe you did FFR and [the obstruction] was stable over time, maybe you would just treat it medically.

“It takes a lot of experience to understand what’s feasible and safe and what’s not,” he commented.

Study Details

About 82% of patients had additional vessel involvement beyond the left main lesions, and 61% showed distal left main involvement. Most DES were sirolimus-eluting stents. After each procedure, patients were maintained on aspirin indefinitely and clopidogrel (75 mg daily) for at least 12 months.

Source:

Lee J-Y, Park D-W, Kim Y-H, et al. Incidence, predictors, treatment, and long-term prognosis of patients with restenosis after drug-eluting stent implantation for unprotected left main coronary artery disease. J Am Coll Cardiol. 2011;57:1349-1358.

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