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For most patients with multivessel disease undergoing primary percutaneous coronary intervention (PCI), a strategy of staged PCI—revascularization of the infarct-related vessel followed by deferred treatment of nonculprit lesions—provides better short- and long-term outcomes than PCI of all lesions during a single procedure.

The common conclusion, reached by both a large meta-analysis and an observational study published in the August 9, 2011, issue of the Journal of the American College of Cardiology, supports current STEMI guidelines. However, according to several experts, the nonrandomized nature of the studies makes their findings far from definitive.

Large Meta-analysis Compares Strategies

In the meta-analysis, a team led by Pieter J. Vlaar, MD, PhD, of the University Medical Center Groningen (Groningen, The Netherlands), identified 4 prospective and 14 retrospective studies published between 1985 and August 2010 in which 40,280 STEMI patients with multivessel disease underwent primary PCI.

The trials included 3 different strategies:

• Culprit PCI, or PCI confined to culprit vessel lesions
• Multivessel PCI, or PCI of the culprit vessel plus at least 1 nonculprit lesion
• Staged PCI, or PCI of the culprit vessel, after which at least 1 nonculprit lesion was treated during a staged procedure

Five studies compared all 3 strategies, while 10 compared culprit PCI with multivessel PCI; 2 compared culprit PCI with staged PCI; and 1 compared multivessel PCI with staged PCI.

Among studies of culprit vs. multivessel PCI, patients treated with the former were older and had higher rates of 3-vessel disease but were similar to multivessel PCI patients with regard to the proportion of men vs. women and the frequency of diabetes and cardiogenic shock.

In pooled analysis of short-term mortality (in-hospital or within 30 days), the primary outcome, staged PCI proved superior to both culprit and multivessel PCI. Moreover, culprit PCI appeared to be safer than multivessel PCI (table 1).

Table 1. Short-term Mortality in Pairwise Comparisons of PCI Strategies

However, heterogeneity emerged among trials comparing culprit vs. multivessel PCI, with prospective studies overall showing a trend favoring multivessel PCI (OR 1.98; 95% CI 0.57-6.85; P = 0.28) and retrospective trials favoring culprit PCI (OR 0.62; 95% CI 0.45-0.84; P = 0.007).

Two studies investigated culprit PCI vs. multivessel PCI in patients presenting with cardiogenic shock (n = 3,248). Even in this high-risk cohort, those who underwent PCI of the culprit vessel alone had lower short-term mortality (total effect OR 0.68; 95% CI 0.56-0.84; P = 0.0003).

In addition, in pooled analysis, staged PCI was associated with lower long-term mortality compared with both culprit PCI (OR 1.74; 95% CI 1.06-2.85; P = 0.03) and multivessel PCI (OR 2.28; 95% CI 1.39-3.72; P = 0.001). No significant heterogeneity was seen across the trials. Moreover, in a network analysis, there was no significant inconsistency among the trials for either short- or long-term mortality.

Staged PCI Advantage Reinforced by Observational Study

In the second study, investigators led by Ran Kornowski, MD, of Rabin Medical Center (Petah Tiqwaa, Israel), looked at the 668 patients from the 3,602-patient STEMI cohort of the HORIZONS-AMI (Harmonizing Outcomes with RevasculariZatiON and Stents in Acute Myocardial Infarction) trial who underwent PCI for multivessel disease. In this subgroup, patients were divided into those who received “one-time” PCI of both culprit and nonculprit lesions (n = 275) or a staged strategy (n = 393).

At 1 year, patients who underwent staged PCI had lower rates of all-cause mortality, Academic Research Consortium-defined definite stent thrombosis, and TIMI major bleeding as well as a trend toward less MACE (composite of death, reinfarction, ischemia-driven TVR, and stroke). The 2 PCI strategies were similar with regard to rates of reinfarction and ischemia-driven TVR (table 2).

Table 2. One-Year Outcomes

Even when the analysis was restricted to ‘truly elective’ nonculprit procedures (excluding lesions in vessels with TIMI flow grade 0 to 2), staged PCI yielded lower rates of all-cause mortality (1.3% vs. 8.0%; P = 0.04) and cardiac mortality (0% vs. 4.9%; P = 0.05) compared with one-time multivessel PCI.

Moreover, in multivariable analysis adjusted for propensity score, staged vs. single PCI was the only predictor of 1-year mortality (HR 0.30; 95% CI 0.12-0.73; P = 0.0083).

Why Multivessel PCI Persists

According to Dr. Vlaar and colleagues, some reasons why immediate multivessel PCI appears more harmful than beneficial include the fact that it takes place in the enhanced thrombogenic environment of STEMI, increases the complexity and duration of the procedure, and is performed in the absence of objective evidence that the nonculprit lesions are in fact causing ischemia.

Yet despite unfavorable outcomes reported in retrospective studies and discouragement by US guidelines, multivessel PCI is still performed in 10% to 20% of STEMI cases, observes John A. Bittl, MD, of the Ocala Heart Institute (Ocala, FL), in an accompanying editorial.

One possible reason, he suggests, is that identification of a single culprit lesion is sometimes challenging, or more than one culprit lesion may be suspected. In addition, Dr. Bittl notes, STEMI patients with multivessel disease are known to be at higher risk than those with single-vessel disease, and patients who receive ‘all-in-one’ PCI typically have lower ejection fractions.

But another reason for the variability in practice, he suggests, is that much of the evidence against multivessel PCI is indirect or retrospective. Retrospective cohort studies may be confounded by an inability to take into account all the clinical and patient variables that prompt operators to choose one strategy over another. For example, he points out, in the meta-analysis “the results of the large cohort studies seem to disagree with the results of smaller prospective studies.”

Guidelines, Not Commandments

“Practice guidelines define a standard, but they are not commandments,” Dr. Bittl emphasizes. “No single approach is applicable to the myriad presentations of STEMI.” One step to aid clinical decision making is performing angiography that assesses the entire coronary anatomy before targeting a lesion for PCI, he suggests. Another is using fractional flow reserve, if possible, to support the choice of staged PCI.

In a telephone interview with TCTMD, Stephen G. Ellis, MD, of the Cleveland Clinic (Cleveland, OH), called the studies highly flawed, noting that “most readers overestimate the capacity of propensity analysis and other statistical methods to correct for unmeasured confounders.” STEMI patients who undergo multivessel PCI are different from, and likely to be sicker than, those who undergo culprit PCI, he added.

Dr. Ellis acknowledged that the preponderance of evidence probably favors staged PCI, except in the setting of cardiogenic shock. “But that [approach] is not scientifically well grounded” and physicians will continue to do multivessel PCI “whenever they believe their patients are in trouble,” he observed.

Unmeasured Confounders Likely Driving Secondary Interventions

Jeffrey W. Moses, MD, of Weill Cornell Medical College (New York, NY), said that in general multivessel PCI should be discouraged. “In the throes of an MI, unless it is absolutely necessary, it just makes sense not to introduce transient ischemia [via angioplasty] in another zone of the heart, to leave the myocardium alone and let it recover before dealing with [nonculprit] lesions,” he told TCTMD in a telephone interview.

On the other hand, he noted, it seems unlikely that the high excess mortality reported for multivessel PCI can be attributed to performing angioplasty in nonculprit arteries. “My strong feeling is that there is some unmeasured confounder driving the secondary interventions at the time of the procedure that we’re just not capturing,” Dr. Moses said. “In the absence of randomized data, all these conclusions [about staged vs. multivessel PCI] are very tentative.”

However, Dr. Moses pointed to 2 scenarios in which acute multivessel PCI should be considered:

• When angiography identifies several possible infarct-related arteries
• When patients are in cardiogenic shock and have severe flow-restricting lesions in nonculprit vessels that are not being compensated for

Dr. Moses added that it is important that what he called “the flip side of the message” not be neglected, that multivessel disease should be addressed at some point. In his practice, he said, unless nonculprit lesions are critical, staging is scheduled for 6 weeks after the index MI to allow the myocardium time to recover.

Dr. Ellis concluded that although the current studies are far from definitive, they at least “stir the pot” and promote discussion. Only an adequately powered randomized trial can settle the issue of how to manage multivessel disease in STEMI patients, he said, adding that the odds of that happening are low because potential industry sponsors have little at stake in the results.

Note: Several coauthors of the HORIZONS-AMI substudy are faculty members of the Cardiovascular Research Foundation, which owns and operates TCTMD.

2. Kornowski R, Mehran R, Dangas G, et al. Prognostic impact of staged versus “one-time”

multivessel percutaneous intervention in acute myocardial infarction: Analysis from the HORIZONS-AMI (Harmonizing Outcomes with Revascularization and Stents in Acute Myocardial Infarction) trial. J Am Coll Cardiol. 2011;58:704-711.

3. Bittl JA. Interventional strategies for ST-segment elevation myocardial infarction and multivessel coronary artery disease. J Am Coll Cardiol. 2011;58:712-714.

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