ESC Congress 2014: Positive, Negative Findings Come on Background of Improving Outcomes Overall

BARCELONA, Spain—The recent European Society of Cardiology (ESC) Congress, held August 30 through September 3, 2014, offered many studies of interest to the interventional cardiologist, from trials looking at ways to improve how patients fare following percutaneous coronary intervention (PCI) to investigations of transcatheter aortic valve replacement (TAVR).

Although there were some negative results, they have to be seen in the context of outcomes that are improving overall, according to Kim Allan Williams Sr., MD, of Rush University Medical Center (Chicago, IL).

“I think the demands go up as success goes up, and… whether we’re talking about interventions or medications, we expect people to live longer and to have a better outcome. And we’re constantly setting a higher bar for ourselves,” Dr. Williams, who is president-elect of the American College of Cardiology, told TCTMD in an interview.

“That really was a good theme at this meeting—yes there were some negative trials with some particular drugs, but there were a lot of positive messages,” he said. “We can do much better with older patients and more interventions than we were able to do in the past.”

PCI Studies Tackle Complete Revascularization, FFR Guidance

The CvLPRIT trial—which drew comparisons to the PRAMI trial that was presented at last year’s meeting—showed that opening all blocked arteries during primary PCI for STEMI rather than the culprit artery only reduced the risk of MACE by a relative 55%.

Current US guidelines give a class III recommendation—indicating harm—against revascularizing a noninfarct artery at the time of primary PCI for STEMI patients without hemodynamic compromise.

Even with the CvLPRIT and PRAMI results pointing in the same direction, Roxana Mehran, MD, of Mount Sinai Medical Center (New York, NY), indicated that the guidelines were not yet ready to be changed, noting that both trials were underpowered and that the overall body of evidence links complete revascularization to greater mortality risk.

“But when you see these 2 studies going the other way, I wonder if the class III should be lifted…,” she said. “So that, perhaps, should be visited, but I still think it doesn’t really change practice. I think that we need to have large randomized studies.” She noted that the 4,000-patient COMPLETE trial is ongoing.

Dr. Williams agreed that that the evidence is not yet definitive but said it seems to be headed in favor of complete revascularization: “I think we’re getting to the point where we may have enough data to convince our guideline committees that things should change.”

Among the other PCI studies presented at the meeting were 2 evaluating the use of fractional flow reserve to improve outcomes, FAME 2 in patients with stable CAD and FAMOUS-NSTEMI. In the former, FFR-guided PCI continued to show a benefit compared with medical therapy alone for the primary endpoint of all-cause death, MI, or urgent revascularization at 2 years of follow-up. In the latter trial, FFR guidance increased the percentage of patients who were initially treated with medical therapy rather than PCI or CABG without altering 1-year outcomes.

Negative Findings for Acute STEMI Therapies

In the ATLANTIC trial, administration of ticagrelor in the ambulance—instead of upon hospital arrival—was shown to be safe for STEMI patients but without any improvement in outcomes.

Dr. Mehran called it “a very important study” that set a high bar with its primary endpoints— the proportion of patients who did not have 70% or greater ST-segment resolution before or after PCI and the proportion of patients who did not have TIMI flow of grade 3 in the infarct-related artery at initial angiography or after PCI—that could not be reached, perhaps because the investigators were able to shorten the time from the ambulance to the hospital to the point that the drug did not have enough time to work.

Still, the finding could have implications for treatment in the United States, where physicians do not ride in ambulances to diagnose and treat STEMI. “It’s good clinicians don’t have to think about … dealing with that in the ambulance,” Dr. Mehran said.

Two other trials explored therapies administered during PCI to improve STEMI outcomes. The NOMI trial randomized patients to receive placebo or inhaled nitric oxide before PCI and for up to 4 hours after the start of reperfusion. The treatment did not reduce infarct size in the overall cohort, although it was beneficial in the subgroup of patients who did not receive nitroglycerin.

And in the MITOCARE trial, administration of a novel drug called TRO40303—which was shown to reduce infarct size in animal studies—after coronary angiography but before balloon inflation during primary PCI for STEMI did not limit reperfusion injury after the procedure.

Several Studies Provide Insight Into TAVR

TAVR again was a hot topic at this year’s meeting, with studies exploring outcomes with different devices and access approaches and in high-risk patients.

One retrospective single-center study with 142 patients showed that CoreValve (Medtronic; Minneapolis, MN) was associated with more 30-day complications and higher 2-year mortality compared with Sapien (Edwards Lifesciences; Irvine, CA) in patients with mixed aortic stenosis. Dr. Mehran noted, however, that the retrospective design could not account for differences in patient selection, particularly the effect of the larger aortic annulus in the CoreValve group.

Another study showed that the real-world outcomes following TAVR with the repositionable Direct Flow Medical valve (Direct Flow Medical; Santa Rosa, CA) are similar to those seen in the DISCOVER CE Mark trial at 30 days.

Other studies found that transapical TAVR carries a higher risk of 1-year mortality compared with transvascular procedures, that TAVR outcomes appear to be better in high-risk diabetic patients compared with their nondiabetic counterparts, and that postprocedural mitral regurgitation is associated with lower survival.

Stents Getting Better

Long-term results from the PROTECT trial showed that Endeavor zotarolimus-eluting stents (ZES; Medtronic; Minneapolis, MN) continued to reduce the risk of stent thrombosis and the composite of death or MI compared with Cypher sirolimus-eluting stents (SES; Cordis/Johnson & Johnson; Warren, NJ) through 5 years.

Dr. Mehran pointed out that neither stent is used anymore, saying, “Our field moves faster than the data… And so we have to keep striving and be creative about how to continue on this important path” of designing trials to evaluate outcomes.

In the BIOSCIENCE trial, outcomes were similar for an SES with a biodegradable polymer (Orsiro; Biotronik AG; Bülach, Switzerland) and an everolimus-eluting stent with a durable polymer (Xience Prime/Xpedition; Abbott Vascular; Abbott Park, IL). An accompanying editorial in the Lancet questioned how much the already excellent outcomes from newer DES can be improved and whether it is worth the effort of continued development.

Dr. Williams said that companies should continue to try to improve outcomes from DES implantation. “Good enough to me would mean that there’d be zero restenosis, zero thrombosis, and that you could take the dual antiplatelet therapy down fairly quickly when you really needed to with a fairly low risk,” he said.

An analysis of the SCAAR registry confirmed the low very late stent thrombosis risk with newer DES.

Medication in the Nonacute Setting After ACS

In the SOLID-TIMI 52 trial, the investigational lipoprotein-associated phospholipase A₂ inhibitor darapladib failed to reduce the rate of coronary heart disease death, MI, or urgent revascularization (primary endpoint) in the 3 years after ACS, with no differences for other clinical outcomes either.

Another trial—IBIS-4—suggested that high-dose rosuvastatin might reverse atherosclerosis in STEMI patients who have undergone successful revascularization, although the treatment did not seem to have any effect on plaque composition.

Two observational studies—one based in the United States and one in France—explored the importance of medication adherence after MI. The former showed that greater adherence to guideline-based medications in the first year was associated with improved outcomes, whereas the latter suggested that patients with preserved LV function can stop taking beta-blockers without a negative effect on survival.

Additional studies presented at the meeting included:

• TRAPID-AMI: Evaluated an algorithm that helps identify MI within 1 hour in patients with acute chest pain.
• APOLLO: Showed worse long-term outcomes in American vs European survivors of acute MI.
• FAST-MI: Found that post-acute MI survival is improving for elderly patients in France.
• SYMPLICITY HTN-3: Renal denervation safe up to 1 year after the procedure, but still not effective.
• ACCOAST: A substudy showed that prasugrel pretreatment is associated with increased bleeding in NSTEMI patients.
• RITA-3: The advantage of a routine invasive strategy for NSTE-ACS disappears by 10 years.
• TASTE: Any hint of benefit of performing manual thrombus aspiration before PCI in patients with STEMI is gone by 1 year of follow-up.

Source:
Presentations at: European Society of Cardiology Congress; August 29-September 3, 2014; Barcelona, Spain.

Related Stories:

• ESC Congress 2013: Mix of Trials with Potential to Reshape Practice
• ESC Congress 2012: Diverse Lineup of Practice-Changing Presentations
• ESC Congress 2011: Drugs, Devices Work Together