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For patients with ST-segment elevation myocardial infarction (STEMI) who exhibit residual thrombus after aspiration thrombectomy, delaying stenting for a week—providing a type of vascular ‘cooling off’ period—and giving intensive pharmacological therapy results in improved myocardial perfusion and ventricular function compared with immediate stent implantation. The findings appear in the September 2011 issue of the Canadian Journal of Cardiology.

Investigators led by Sheng-hua Zhou, MD, PhD, of Second Xiangya Hospital of Central South University (Changsa, China), evaluated 87 STEMI patients with high thrombus burden who were scheduled for primary PCI at their institution. After thrombus aspiration, patients were divided into 2 groups:

• Immediate stenting (thrombus score of less than 2 on angiography indicating no or only possible thrombus; n = 47)
• Delayed stenting after a week of intensive pharmacologic treatment including a glycoprotein IIb/IIIa inhibitor and heparin (thrombus score of 2 or greater indicating definite thrombus; n = 40)

Giving Thrombus Time to Resolve

At baseline, there was no difference in thrombus score between the groups. In delayed stenting patients, however, thrombus burden decreased significantly between the time of aspiration and stent implantation. In the same group, the initial postprocedural TIMI flow grade was 0 in 95% and grade 1 in 5%, while 7 days later—after intensive therapy but before stenting—12.5% of patients had advanced to TIMI flow grade 2, and 87.5% had achieved flow grade 3.

Moreover, after stenting, a higher proportion of patients in the delayed than in the immediate group had achieved a TIMI flow grade of 3, while thrombus-related angiographic events such as ‘no reflow’ and distal embolization were more common in the immediate stenting group. In addition, the final corrected TIMI frame count (a quantitative measure of arterial flow) and the proportion of patients with myocardial blush grade 3 were both higher in the delayed stenting group (table 1).

Table 1. Postprocedural Angiographic Outcomes

No major bleeding occurred in either arm.

On admission, both groups had similar wall-motion function, but by 6 months, echocardiography showed a lower wall-motion score index in patients who received delayed compared with immediate stenting (1.58 vs. 2.35; P < 0.01). Moreover, the change in wall-motion score index was larger in the delayed group than in the immediate group (1.18 vs. 0.60; P < 0.01).

No MACE, including cardiac death, nonfatal infarction, recurrent ischemia, or TLR, occurred in either the immediate or delayed stenting groups during the initial hospitalization. At 6-month follow-up, 2 patients in each arm had suffered recurrent ischemia and 2 patients in the immediate stenting group and 1 in the delayed stenting group underwent TLR, but there were no overall differences in MACE.

Trend Toward Clinical Benefit

On the other hand, there was almost a fourfold lower incidence of congestive heart failure in the delayed stenting group compared with the immediate stenting group, although the difference did not reach statistical significance (5.0% vs. 19.1%; P = 0.058). 

In the setting of STEMI, stenting carries the risk of mobilizing thrombotic material, thereby causing distal embolization that jeopardizes microcirculation, the authors observe. Given the poor showing of embolic protection devices, the best strategy is to prevent embolization, they add, and offer some mechanisms that might explain why delaying stenting appears to help:

• Enables application of intensive antithrombotic therapy, which may enhance clot lysis and dissolution of residual thrombus
• Allows the lesion time to ‘cool off’ and anti-inflammatory statin treatment to take effect; with reduced platelet reactivity and inflammation, microvascular integrity may be better preserved and the culprit lesion stabilized, making stenting safer

In turn, the improvement in myocardial perfusion with delayed stenting is likely responsible for the positive effect on regional wall function, Dr. Zhou and colleagues say. They acknowledge, however, that the study was underpowered to prove clinical benefit.

Importantly, they observe, no major ischemic or bleeding events occurred during the ‘waiting’ period, probably because of the intensive medical therapy.

A Possible Treatment Revolution—But One with a Lot to Prove

In an accompanying editorial, E. Marc Jolicoeur, MD, MSc, and Jean-François Tanguay, MD, both of the Montreal Heart Institute (Montreal, Canada), write that these data and others like them “hold the promise of a possible revolution in the way we treat myocardial infarction.”

In a similar vein, Stephen G. Ellis, MD, of the Cleveland Clinic (Cleveland, OH), called the study provocative. “It’s certainly a fairly radical departure from what is presently done,” he told TCTMD in a telephone interview.

He noted that the authors zeroed in on “a bit of an unresolved issue,” namely, how to handle a patient with a fairly large thrombus burden after aspiration.

“Their approach is very interesting, although I think a modification ought to be tested further,” Dr. Ellis said. “It’s not very practical in the United States to wait 7 days before going back and intervening. And I’m not sure it’s intuitive to wait that long. You might be able to move it up to a time period that is more consistent with contemporary management in the United States—72 hours, for instance.

“Also, if this strategy is going to work, it has to be utilized selectively in people with large thrombus burdens,” he continued, adding that “whether [the researchers] picked the right cut-off [in that regard] is hard to know.”

Is Delay Worth the Cost?

Another important question is whether the increased costs associated with adjunctive anticoagulation, repeated catheterization, and extended hospital stay would be offset by the projected reduction of events by delayed stenting, the editorial notes.

In a telephone interview with TCTMD, Jeffrey W. Moses, MD, of Weill Cornell Medical College (New York, NY), strongly agreed, noting that the clinical benefit of delayed stenting would have to be clear-cut to justify the added expense.

The study and editorial authors and Drs. Moses and Ellis all concurred that the next step should be a randomized, controlled trial, including a cost-effectiveness analysis. In particular, the optimal length of delay before stent implantation and the most appropriate adjunctive therapy also require further investigation, they noted.

Drs. Moses and Ellis stressed that the study is small and far from definitive. “But all the data—the differences in embolization, myocardial perfusion, and wall motion—all hang together,” Dr. Ellis observed. “There are a lot of subsequent studies that would follow from this, and that’s often the mark of a good paper.”

Dr. Moses remained skeptical of the strategy of delay, especially in light of the possible influence of unknown confounders on the study findings. However, he said, the report at least  underscores the need for improving STEMI treatment to reduce the incidence of no reflow, whether that is ultimately achieved by mechanical or pharmacological means.

Study Details

Both immediate and delayed stenting groups were similar with regard to baseline clinical and angiographic characteristics, in particular for location of culprit artery, incidence of multivessel disease, and presence of initial TIMI flow.

 

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Sources:
1. Tang L, Zhou S-H, Hu X-Q, et al. Effect of delayed vs. immediate stent implantation on myocardial perfusion and cardiac function in patients with ST-segment elevation myocardial infarction undergoing primary percutaneous intervention with thrombus aspiration. Can J Cardiol. 2011;27:541-547.

2. Jolicoeur ME, Tanguay J-F. From primary to secondary percutaneous coronary intervention: The emerging concept of early mechanical reperfusion with delayed facilitated stenting—when earlier may not be better. Can J Cardiol. 2011;27:529-533.

 

• Dr. Moses reports serving as a consultant for Boston Scientific and Cordis.

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