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The greater incidence of myocardial infarction (MI) seen when using 2 drug-eluting stents (DES) to treat bifurcation lesions compared with provisional DES stenting is at least partly due to a greater rate of stent thrombosis, according to a meta-analysis published online June 12, 2013, ahead of print in JACC: Cardiovascular Interventions. According to the authors, the finding suggests the use of more aggressive antiplatelet therapy in the setting of double DES stenting.

Investigators led by Marco Zimarino, MD, PhD, of the Institute of Cardiology and Center of Excellence on Aging (Chieti, Italy), looked at data from 6,961 patients enrolled in 5 randomized trials and 7 observational studies that compared single-DES (n = 5,093) vs. double-DES (n = 1,868) strategies in bifurcation lesions between January 2001 and December 2011.

Overall, there was a more than twofold increased risk of definite stent thrombosis, the primary endpoint, with double vs. single stenting, although in subanalyses the increase reached significance only among observational studies. MI was also more common after double stenting, while all-cause mortality and TVR occurred at similar rates between the 2 strategies (table 1).

Table 1. Relative Risk of Double vs. Single Bifurcation Stenting

In addition, meta-regression analysis showed an association between the relative risk of stent thrombosis and MI (P = 0.040).

The authors noted a number of study limitations, including:

• Inclusion of both RCTs and observational studies
• Differing techniques for double stenting used in the trials
• Exclusive use of first-generation DES

Two Culprits Behind MI

In an e-mail communication with TCTMD, Dr. Zimarino identified 2 temporally separated sources of increased MI risk with a double-DES strategy. “The periprocedural risk is related to the technique itself, which is more complex than single DES, while, in the follow-up, the increased ‘spontaneous’ MI is likely DES thrombosis-related,” he said.

However, Somjot S. Brar, MD, MPH, of Kaiser Permanente (Los Angeles, CA), put the emphasis on periprocedural MI. “I think that the stent thrombosis probably accounts for a minority of the MIs,” he told TCTMD in a telephone interview, pointing to a disconnect between the rates of DES thrombosis and MI seen in the study. “A 2% stent thrombosis rate does not explain that 8% MI rate,” he emphasized, adding that periprocedural MIs may be much more important.

Sometimes Double Stenting Is Necessary

“One of the things that gets lost in all of this literature about 1 vs. 2 stents is that there are definitely patients for whom a 2-stent strategy needs to be done from the outset,” Dr. Brar added. “Just because the body of literature pretty consistently shows an increased event rate with 2 stents does not mean that 2 stents will never be required.”

In a telephone interview with TCTMD, Samin Sharma, MD, of Mount Sinai Medical Center (New York, NY), agreed, noting that stent thrombosis is a plausible, but still only “hypothesis-generating,” explanation for the excess MIs.

The main issue for clinicians is deciding which patients will need a side branch stent beforehand, he emphasized. “We know that you will have a worse outcome in cases where you should use 2 stents, but you try to do 1 stent and then do a bailout [stent if necessary]. The goal should be to identify cases with a large, angulated side branch and effusive disease and go straight to a 2-stent approach in maybe 30% to 35% of bifurcation lesions,” he said.

Overall, it is important to distinguish the cases where you can help, he stressed, and leave alone smaller, less angulated side branches with less disease, where you probably will do no good.

The Way Forward Depends on the Mechanism

To try to forestall the adverse effects of double stenting, the study authors suggest more aggressive antiplatelet therapy. Dr. Sharma endorsed this approach, suggesting use of prasugrel or ticagrelor, and possibly a IIb/IIIa inhibitor such as abciximab or eptifibatide to prevent thrombosis and periprocedural MI—although whether this additional treatment is necessary with second—generation DES is debatable.

Dr. Brar, on the other hand, contended that stent thrombosis is not driving the occurrence of MIs and thus aggressive antiplatelet therapy is unlikely to be of much benefit. He believes instead that it may be the technical complexity of the 2-stent strategy with the extra manipulations required that leads to more periprocedural MIs. “The opportunity there lies in dedicated bifurcation systems that may allow the procedure to be done in a more simplified, systematic way,” he said. Understanding the mechanism is important, Dr. Brar added, because definitive trials in a small population like this are unlikely.

 

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Source:
Zimarino M, Corazzini A, Ricci F, et al. Late thrombosis after double versus single drug-eluting stent in the treatment of coronary bifurcations: A meta-analysis of randomized and observational studies. J Am Coll Cardiol Intv. 2013; Epub ahead of print.

 

 

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