EXPERT ANALYSIS FROM THE CARDIOVASCULAR CONFERENCE AT SNOWMASS

SNOWMASS, COLO. (FRONTLINE MEDICAL NEWS) – The tide appears to have turned regarding the merits of percutaneous coronary intervention in non-infarct-related arteries in conjunction with primary PCI for ST-elevation MI in patients with multivessel disease, Douglas E. Drachman, MD, said at the Annual Cardiovascular Conference at Snowmass.

Previously, multivessel PCI in STEMI patients who are hemodynamically stable was believed harmful and was given a Class IIIb recommendation – meaning don’t do it – in the 2013 American College of Cardiology/American Heart Association STEMI guidelines. Just 2 years later, however, new evidence in the form of three randomized trials prompted a focused update of the joint guidelines in which the practice was upgraded to Class IIb status, meaning it could be considered and may be beneficial.

The findings from three randomized trials demonstrated that multivessel PCI in STEMI patients is safe and may result in better outcomes.

Roughly 50% of STEMI patients have significant lesions in non-infarct-related arteries (non-IRA). The question of how best to treat such patients is an important one because multivessel coronary disease in STEMI is associated with increased risks of both reinfarction and mortality, noted Dr. Drachman, an interventional cardiologist at Massachusetts General Hospital in Boston.

He offered several reasons why the findings of the three influential randomized trials differed from earlier negative retrospective observational studies: “I would argue there’s been significant improvement in our technique in doing PCI. We’re primarily doing transradial interventions now for our patients, so the risk associated with multiple accesses is reduced. Our ability to use more potent antithrombotic strategies is enhanced by our concern about bleeding risk. And the stent platforms that we use in our interventional strategies have improved to the point that we are tackling ever more challenging lesions with greater aplomb and less concern that we may cause harm. I think all these factors have enhanced the ability of the interventionalist to select and treat non-IRAs in a staged fashion and be less parsimonious at the point of care.”

The remaining questions are which non-IRA lesions should be treated, in whom, when relative to primary PCI, and what are the cost implications? These issues are being tackled in at least eight active randomized controlled trials. Depending upon the answers to come, multivessel PCI in STEMI patients could receive a further upgrade in the guidelines.

Since release of the 2015 focused guideline update, several large studies have provided further backing for multivessel PCI in STEMI patients with significant multivessel disease, although these weren’t randomized prospective studies and hence must be considered hypothesis-generating.

One of these major pieces of evidence was a meta-analysis of observational studies led by Eric R. Bates, MD, professor of internal medicine at the University of Michigan in Ann Arbor. He and his coinvestigators analyzed studies comparing culprit vessel-only primary PCI for STEMI patients with multivessel disease versus staged PCI in which primary PCI was done first, followed by PCI of a non-infarct-related vessel later during the same hospitalization or soon after. Staged PCI was the clear winner, with a 2.2-fold greater likelihood of freedom from mortality ( J Am Coll Cardiol. 2016 Sep 6;68(10):1066-81 ).

When the investigators compared studies of staged PCI versus multivessel PCI in the same session as primary PCI, staged PCI was again the clear winner, with a 4-fold greater freedom from mortality.

Among the possible risks of performing PCI of a non-IRA in the same session as primary PCI are increased risks of thrombosis, contrast-induced nephropathy, stent undersizing due to vasospasm, and unintended jeopardy of distant viable myocardium due to microembolization or side branch occlusion, Dr. Drachman said.

“Maybe in certain circumstances it’s best to let the dust settle after the urgent vessel intervention. Wait a couple of days and then make your plan,” the cardiologist advised.

Another informative recent piece of evidence was provided by a Canadian retrospective observational study which compared revascularization strategies in 6,503 consecutive STEMI patients with multivessel disease. Staged multivessel PCI during the index hospitalization was performed in 658 patients, multivessel PCI during the primary PCI session in 1,325, and PCI limited to the infarct-related artery in 4,520. The study endpoints were 2-year all-cause mortality and repeat revascularization.

Staged multivessel PCI had the lowest mortality and repeat revascularization rates. The 2-year mortality rate associated with this strategy was 45% less than with multivessel intervention at the time of primary PCI and 35% lower than for culprit vessel-only PCI, which unsurprisingly had the highest repeat revascularization rate ( JACC Cardiovasc Interv. 2017 Jan 9;10(1):11-23 ).

The first of the three randomized trials that led to a change in the guidelines was the UK PRAMI study (Preventive Angioplasty in Acute Myocardial Infarction). It showed at a mean 23-months followup that STEMI patients with multivessel disease had a 65% reduction in the relative risk of a composite endoint of cardiovascular death, MI, or refractory angina if they received non-IRA PCI at the same time as primary PCI compared with PCI limited to the IRA ( N Engl J Med. 2013 Sep 19;369(12):1115-23 ).

Next came another UK trial: CvLPRIT (Complete vs. Culprit-Lesion Only Primary PCI) demonstrated a 65% reduction in the composite 12-month outcome of all-cause mortality, MI, heart failure, or ischemia-driven PCI with staged PCI during the index hospitalization compared with culprit vessel-only PCI ( J Am Coll Cardiol. 2015 Mar 17;65(10):963-72 ).

Finally, DANAMI-3-PRIMULTI (the Third Danish Study of Optimal Acute Treatment of Patients with STEMI: Primary PCI in Multivessel Disease) showed a dramatic reduction in the risk of ischemia-driven PCI during a median 27 months of followup in patients who underwent staged multivessel PCI guided by the findings of fractional flow reserve measurement compared with primary PCI limited to the IRA ( Lancet. 2015 Aug 15;386(9994):665-71 ). However, fractional flow reserve-guided multivessel PCI didn’t decrease the risk of death or nonfatal recurrent MI, leaving its role unsettled pending the results of ongoing clinical trials.

Dr. Drachman said it’s clear certain STEMI patients should not undergo non-IRA PCI. These include anyone in whom the procedure would be lengthy due to vessel tortuosity or chronic total occlusion, as well as patients with stable saphenous vein graft disease or heavily calcified lesions requiring atherectomy, since multivessel PCI in those settings would pose a high risk for additional left ventricular dysfunction.

“Be thoughtful about patients who have renal dysfunction,” he added.

Dr. Drachman reported having no financial conflicts of interest.

bjancin@frontlinemedcom.com

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