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Use of intravascular ultrasound (IVUS) rather than angiography to guide drug-eluting stent (DES) implantation results in lower rates of stent thrombosis, myocardial infarction (MI), and major adverse cardiac events (MACE) at 1 year, according to a substudy of the ADAPT-DES trial published online November 26, 2013, ahead of print in Circulation. The benefit is strongest in patients with acute coronary syndromes (ACS) or complex lesions.

The main trial involving 8,665 ‘all-comers’ patients correlated high on-treatment platelet reactivity following DES implantation with ischemic events such as stent thrombosis and MI as well as bleeding.  

For the prespecified substudy, Gregg W. Stone, MD of Columbia University Medical Center (New York, NY), and colleagues compared outcomes for patients in whom stenting was guided by IVUS  (n=3,349) or angiography (n = 5,234) between July 2008 and September 2010.

At 1 year, the rate of Academic Research Consortium-defined definite or probable stent thrombosis (primary endpoint) was  lower in the IVUS-guided group than the angiography guided group, as were the rates of MI, MACE (cardiac death, MI, or definite/probable stent thrombosis), and ischemia-driven TLR (table 1).

Table 1. Clinical Outcomes at 1 Year

The difference in stent thrombosis rates emerged within 1 month of stenting and increased up to  1 year.

While IVUS was associated with a lower rate of target-vessel MI (1.7% vs. 2.9%; P = 0.0004), the type of guidance did not affect non-target vessel MI.  

Although IVUS lowered MACE rates in both complex and noncomplex patients, the greater benefit was seen in complex patients. Moreover, there was a gradient of benefit among those with STEMI, NSTEMI/unstable angina, and stable angina, with the largest absolute benefit in STEMI patients. 

Study Confirms Bias in Favor of IVUS 

Overall, this study is likely to make interventionalists more confident about using IVUS rather than angiography alone after DES implantation coauthor Akiko Maehara, MD, of NewYork-Presbyterian/Columbia University Medical Center (New York, NY) told TCTMD in a telephone interview.

“We know that in this cohort of patients, IVUS was very well done,” Dr. Maehara said. In some previously published studies, whether the procedure was performed correctly was unclear, and incorrectly performed IVUS could explain some of the discrepancies in outcome, she explained.

The current study  confirms a bias of  many interventional cardiologists, especially in Europe,  that angiography alone does not optimize stent results, commented Lloyd W Klein, MD, of Rush Medical College (Chicago, IL) in a telephone interview with TCTMD. Moreover, the data indicate a clinical benefit for adjunctive IVUS use, he added.

Confounding Cannot Be Ruled Out

However, the study is not randomized and does not make clear when and how operators decided to use IVUS, leaving the results open to possible selection bias, said Dr. Klein. “More information is needed on how IVUS imaging was utilized in patients and how it changed treatment strategy,” he said. “What did the interventionists do differently? Did they put in another stent? Did they expand it more by postdilating?” Perhaps certain findings and treatments were more beneficial than others, he added.

Additionally, the angiography-guided group included more patients with multivessel disease and ACS, and a tendency to perform IVUS in patients with less extensive disease, nonacute lesions, or larger blood vessels may have simply been a marker for less illness in these patients, said Dr. Klein.  “If this is correct, it’s possible that IVUS imaging didn’t really impact outcomes,” he said.

Selection bias is possible, Dr. Maehara acknowledged.. However, she noted, “in terms of stent thrombosis, MI, and MACE, our findings were very robust, and we performed statistical adjustment for confounding factors and found that these clinical outcomes were still significantly reduced.”

In an editorial accompanying the study, Lorenz Räber, MD, and Stephan Windecker, MD, of Bern University Hospital (Bern, Switzerland), were skeptical. “[D]espite using propensity-adjusted multivariable analyses, residual confounding factors cannot be excluded beyond reasonable doubt,” they write. “Along this line, important differences in clinical endpoints unrelated to IVUS-guidance versus angiography-guidance such as major bleeding emerged.” 

Event-free Survival Pattern Questioned

Dr. Klein also noted that the event-free survival curve in this study separates early and continues to diverge out to 1 year. “If you think this is due to stent thrombosis, it’s hard to explain why the curves separate right away in the hospital,” he said.  “Stent thrombosis might explain the late divergence, but the early divergence if the angiogram was truly perfect may be due to some other factor.”

Stent thrombosis usually occurs within 1 month of stenting, which explains the separation of [the] curve right after discharge, Dr. Maehara countered. “Stent underexpansion and/or residual disease at the stent edge, which are known as predictors of early stent thrombosis, may be missed by angiography alone,” she explained.

The next step is a randomized trial comparing the imaging modalities, Dr. Maehara, said, noting that such research should better define optimal stenting and how operators decide to use IVUS.  

Dr. Klein agreed, saying that future protocols “need to better define how an interventional cardiologist should decide to treat.”

Study Details

Patients in the IVUS group were younger ( P < 0.0001) and were less likely to have undergone prior CABG and have 3-vessel disease, but were more likely to have STEMI. Larger and longer stents and everolimus-eluting devices were more likely to be used in the IVUS group. While heparin was administered more often in patients who received IVUS guidance, bivalirudin was used less frequently.

Note: Drs Stone, Maehara, and several other coauthors are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

 

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Sources:
1. Witzenbichler B, Maehara A, Weisz G, et al.  Relationship between intravascular ultrasound guidance and clinical outcomes after drug-eluting stents: The ADAPT-DES study.  Circulation. 2013;Epub ahead of print. 

2. Räber L, Windecker S. IVUS-guided percutaneous coronary interventions: An ongoing odyssey? Circulation. 2013;Epub ahead of print. 

 

 

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