Randomized Trial Clouds Debate Over DES, CABG in Left Main Disease

Sirolimus-eluting stents (SES) failed to show noninferiority compared with coronary artery bypass grafting (CABG) in patients with unprotected left main disease, according to findings from a randomized trial appearing in the February 1, 2011, issue of the Journal of the American College of Cardiology.

But the results are not so clear-cut: the difference in the primary endpoint was driven solely by more repeat revascularizations with SES. Hard outcomes, meanwhile, were equivalent, while perioperative complications were increased with CABG.

Mixed Bag for Left Main

Researchers led by Enno Boudriot, MD, and Holger Thiele, MD, both of the University of Leipzig Heart Center (Leipzig, Germany), randomized 201 patients at 4 German tertiary care centers with unprotected left main disease to treatment with SES (n = 100) or CABG (n = 101). Patients were well matched in terms of baseline characteristics and median Syntax Score (24.0 in SES patients vs. 23.0 in CABG patients; P = 0.09).

There were a total of 4 periprocedural events (4%) in the SES group (3 atrial fibrillation episodes, 1 acute renal failure) compared with 30 events (30%) in the CABG group (P < 0.001). These consisted of 2 strokes (2%), 19 atrial fibrillation/flutter episodes (19%), and other complications.

At 1-year follow-up, SES failed to achieve noninferiority compared with CABG for the primary endpoint (MACE; composite of cardiac death, MI, and TVR). This outcome was solely driven by a higher rate of TVR in the SES arm, while the other individual components all achieved noninferiority (table 1).

Table 1. One-Year Outcomes

 

SES
(n = 100)

CABG
(n = 101)

P Value
(for noninferiority)

Death

2.0%

5.0%

< 0.001

MI

3.0%

3.0%

0.002

Death and MI

5.0%

7.9%

< 0.001

Repeat Revascularization

14.0%

5.9%

0.35

MACE

19.0%

13.9%

0.19


The combined rate of death, MI, and stroke was 5.0% with SES compared with 8.9% with CABG. At 36.5 months, Kaplan-Meier analysis showed equivalent rates of the primary endpoint (P = 0.13) and the composite of death and MI (P = 0.97), with repeat revascularizations still higher with SES (P = 0.03).

In addition, 71.1% of patients were angina-free following PCI, compared with 66.3% following CABG (P = 0.33). On angiographic follow-up, there were no stent thromboses in the stenting group, but in the CABG arm, 21% of grafts were totally occluded or had relevant stenosis greater than 50%, most of which were asymptomatic. Median total hospital stays were 3.0 days with stenting vs. 13.0 days with bypass surgery (P < 0.001), including a median hospital stay after revascularization of 1.0 days in the SES group vs. 8.0 days in the CABG group (P < 0.001).

“PCI with sirolimus-eluting stents is inferior to CABG at 12-month follow-up with respect to freedom from [MACE] in patients with [unprotected left main] stenosis,” the researchers conclude. “Inferiority is mainly driven by the higher repeat revascularization rate, whereas death and [MI] rates seem to be noninferior in PCI patients at lower perioperative morbidity.”

The Sneezing Analogy

According to Raj Makkar, MD, of Cedars-Sinai Medical Center (Los Angeles, CA), the current study reaffirms results of other large trials such as MAIN-COMPARE and SYNTAX, which showed that hard outcomes such as death and MI are equivalent between stenting and CABG in left main patients.

“It’s consistent,” he told TCTMD in a telephone interview. “What you’re doing is trading perioperative complications plus an increased incidence of stroke for an increase in repeat stent procedures because of the renarrowing that occurs with stents.”

The problem, he noted, is how the current trial was designed, in particular the primary endpoint. “It’s like if you could design a clinical trial for a drug such as Benadryl to see if there’s a reduction in death, MI, stroke, and sneezing,” Dr. Makkar said. “You would show that Benadryl reduces the combined endpoint, but it’s all primarily driven by sneezing.”

Breaking It Down for Patients

In an editorial accompanying the study, Robert F. Wilson, MD, and Alan K. Berger, MD, both of the University of Minnesota (Minneapolis, MN), agreed, noting that on balance, the results signal a “win” for PCI.

Nevertheless, PCI was found inferior to CABG because of the higher TVR rate, the editorialists comment. “What would knowledgeable patients conclude?” they ask. “Does an 8% reduction in repeat revascularization outweigh the increased pain and recovery time of CABG, and the higher risk of perioperative complications?”

The key, Dr. Makkar stressed, is sitting down and explaining these differences to patients, particularly the trade-off between repeat procedures and stroke risk. “If you tell patients there’s a 10% higher chance you’re going to come back for revascularization and 4 out of 5 times it can be taken care of with a repeat stent procedure vs. your recovery will be longer with bypass surgery and there’s a 1 out of 50 chance of stroke, the patient will rethink,” he said. “Stroke affects patients much more than an overnight admission for restenosis.”

Unfortunately, Dr. Makkar acknowledged, US practitioners may not be as apt to look beyond the primary endpoint in interpreting the current study. “I think America is still very conservative when it comes to left main stenting. We are way behind the curve in my opinion compared to Europe and Korea and Japan, and I think it’s primarily because of [studies] like this, where the general finding would be ‘inferior’ or ‘noninferior,’” he said. “People who are not for stenting will make their argument, and people for stenting will say there’s no difference in death and MI. Some will say the glass is half full, and some will say it’s half empty.”

Study Details

A median of 2.0 SES were implanted in the stenting arm, with a median total stent length of 36.0 mm. In the CABG arm, 46% of patients received an off-pump procedure. In all CABG patients, the left internal mammary artery (LIMA) was used to bypass the LAD, except for 1 with a nonpatent LIMA. Additionally, 54% received right internal mammary artery grafts, 37% received radial artery grafts, and 35% received saphenous vein grafts.

 


Sources:
1. Boudriot E, Thiele H, Walther T, et al. Randomized comparison of percutaneous coronary intervention with sirolimus-eluting stents versus coronary artery bypass grafting in unprotected left main stem stenosis. J Am Coll Cardiol. 2011;57:538-545.

2. Wilson RF, Berger AK. Are all end points created equal? The case for weighting. J Am Coll Cardiol. 2011;57:546-548.

 

 

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Disclosures
  • The study was supported in part by the German Heart Research Foundation.
  • Drs. Thiele, Wilson, and Berger report no relevant conflicts of interest.
  • Dr. Makkar reports serving as a consultant for Cordis and Medtronic, receiving research grants from Cordis and Edwards Lifesciences, and participating in speaker’s bureau activities for Eli Lilly.

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