ACC/i2 2013: Controversy, Late Breaking Trial News Dominate Busy Meeting

SAN FRANCISCO, CA—Interventionalists at this year’s annual American College of Cardiology (ACC)/i2 Scientific Session, held March 9-11, 2013, found a panoply of useful information to take home to their busy practices. Beyond the data, however, the meeting held some surprises.

Embargo Break Shadows PREVAIL

The first day of ACC/i2 kicked off with controversy when the PREVAIL study was pulled from the official program due to early release of data from the Watchman device’s manufacturer, Boston Scientific.

PREVAIL randomized 407 patients at 41 institutions to either left atrial appendage (LAA) closure with Watchman or warfarin treatment. The trial involved 3 co-primary endpoints.

The first primary endpoint (acute occurrence of death, ischemic stroke, systemic embolism, and procedure or device related complications requiring major cardiovascular or endovascular intervention) was met with only 6 total events (2.2%) in the device group through 7 days. While LAA closure did not show improvement in the second primary endpoint (composite of stroke, systemic embolism, and cardiovascular/unexplained death at 18 months), there were similar, low event rates in both the control and study arms. However, Watchman did show a benefit with regard to the third primary endpoint (ischemic stroke or systemic embolism after 7 days and up to 18 months).

In an interview with TCTMD, Annual Scientific Session Program Committee Co-Chair Neal S. Kleiman, MD, of Methodist DeBakey Heart and Vascular Center (Houston, TX), said the debacle is unlikely to affect how PREVAIL is perceived “because information like this on the LAA is important to clinical practice and people are going to want to see the data regardless of what type of ‘buzz’ has occurred.”

Thinking ‘Outside the Box’

Also not without controversy was DEFER-STEMI, which according to Dr. Kleiman, “gives people a tremendous kick in the pants.”

The single-center all-comers trial included 101 STEMI patients who underwent initial reperfusion with aspiration thrombectomy and/or balloon angioplasty such that TIMI 3 flow was established. Patients were then randomized to immediate or deferred stenting, with a median delay to stenting of 9 hours in the latter group. Overall, the incidence of no reflow or slow flow was significantly lower in the deferred stenting group compared with those who underwent usual care with immediate stenting (6% vs. 29%; P = 0.003).

“This study is about as outside the box as I have ever seen recently,” Dr. Kleiman said. “Whether it is practical and whether the results will be concordant if replicated on a larger scale, I don’t know, but I love it when people make us question things that we accept as gospel because that’s how you make significant changes in practice.”

Another study to offer a new twist on the old way of doing things was the PRATO-ACS trial of early, high-dose rosuvastatin for prevention of contrast-induced nephropathy (CIN) in patients with NSTE-ACS scheduled for intervention. Development of CIN was lower in patients randomized to rosuvastatin on top of standard therapy (6.7% vs. 15.1%; P = 0.001). The number-needed-to-treat to prevent 1 case of CIN was 12.

 

CHAMPION PHOENIX offered good news for the novel intravenous ADP-receptor inhibitor cangrelor. Nearly 11,000 patients undergoing either urgent or elective PCI were randomized to receive cangrelor or clopidogrel. The rate of the primary composite efficacy endpoint (all-cause death, MI, ischemia-driven revascularization, or stent thrombosis at 48 hours), the secondary efficacy endpoint of stent thrombosis at 48 hours, and MI all were lower in the cangrelor group compared with the clopidogrel group. These results were maintained at 30 days and were consistent across multiple prespecified subgroups.

“It’s nice to see that giving a potent antagonist of P2Y12 early produces some meaningful outcomes,” Dr. Kleiman said, adding that it was a “favorable surprise” and “I think this one’s a winner.”

New Stent Data

In the NEXT trial, the Nobori biodegradable-polymer, biolimus A9-eluting stent (BES) went head-to-head against the current-generation Xience V/Promus everolimus-eluting stent (EES). With a 1-year TLR rate of 4.2% in each arm and angiographic in-segment late loss of 0.03 mm with BES vs. 0.06 mm with EES, Nobori proved noninferior to Xience V/Promus (P for noninferiority < 0.0001 for each comparison).

For the all-comers HOST-ASSURE trial, the Promus Element EES proved noninferior to the Endeavor Resolute zotarolimus-eluting stent. All individual clinical outcomes were similar between the study arms. The results were maintained in all prespecified subgroups, with the exception of vessel diameter; smaller vessels favored Promus Element and larger vessels favored Resolute (P for interaction = 0.030).

In APPOSITION III, a new self-expanding stent showed promise in STEMI patients. Researchers examined 965 STEMI patients implanted with the bare-metal or paclitaxel-eluting version of the self-expanding nitinol Stentys device. The rate of MACE (cardiac death, target vessel MI, and clinically-driven TLR) at 12 months was low (9.3%; n = 86), with a trend toward fewer events in patients who received post-dilatation vs. those who did not. More specifically, post-dilatation resulted in less cardiac death or target vessel MI (2.4% vs. 5.0%; P = 0.03) and definite stent thrombosis (1.9% vs. 5.0%; P = 0.01).

Another study, DES LATE, suggested that aspirin monotherapy results in similar rates of ischemic outcomes while decreasing bleeding compared with dual antiplatelet therapy beyond 12 months in stable patients who receive DES. At 2 years, the primary endpoint of cardiac death, MI, and stroke was similar between both groups, as were all secondary endpoints.

Stent technique was a focus of the randomized DKCRUSH-III trial, which demonstrated in more than 400 patients that the double-kissing crush procedure—involving side stenting and 2 kissing balloon inflations—produced fewer MACE and repeat procedures than the culotte technique.

“This trial tells us that in a complex situation, if you can keep it simple, you should,” Dr. Kleiman commented.

Aortic Valve Updates

New data from PARTNER II Cohort B, meanwhile, showed that the lower profile Sapien XT is at least as safe and effective as its predecessor, the Edwards Sapien valve. A total of 560 patients from 28 US centers who were judged unsuitable candidates for surgery were randomized in the study.

At 30 days, all-cause death was numerically lower in the Sapien XT group. Disabling stroke, rehospitalization, and the composite endpoint all were similar between groups (table 1).

Table 1. PARTNER II Cohort B: Primary Endpoint Events at 30 Days

 

In other news from PARTNER, 3-year results from the nearly 700-patient high-risk Cohort A showed similar all-cause mortality (primary endpoint) and stroke for TAVR and surgical valve repair. Although major vascular complications were increased with TAVR vs. surgery (12.5% vs. 3.8%; P < 0.001), this difference was balanced by decreases in major bleeding and MI. No instances of structural valve deterioration were reported. Moderate or severe paravalvular regurgitation was more frequent after TAVR than after surgery at 1, 2, and 3 years (P < 0.001 for all).

Data on 13,595 patients followed for 1 year in the multicenter GARY registry indicated that in patients at highest risk, TAVR and surgery are associated with similar outcomes. However, in patients at low and intermediate risk, surgery appears to reduce mortality more than TAVR.

“Given that the uptake of TAVR in Germany has been must faster than in the United States, I think the kind of results like what we are seeing in GARY are going to shape how we create policy [here],” Dr. Kleiman added.

Off-Pump Trifecta

A trio of studies showed conflicting results between CABG procedures performed on- or off-pump.

In both CORONARY and GOPCABE, no clear benefit was evident for off-pump despite suggestions that it offers better neurocognitive outcomes and avoidance of ‘pump-head.’

However, 30-day results from the single-center PRAGUE-6 trial, suggested an advantage of off-pump CABG in those at highest operative risk. All 206 patients enrolled in the trial had a EuroScore of 6 or greater. For the primary combined 30-day endpoint of death, MI, stroke and new renal failure requiring hemodialysis, patients in the off-pump group had significantly better outcomes compared with the on-pump group (9.2% vs. 20.6%; P = 0.028), driven primarily by reductions in acute MI.

The MASS COMM trial added more data to a growing body of evidence indicating favorable outcomes in patients undergoing elective PCI at hospitals without on-site cardiac surgery. More than 3,500 patients at Massachusetts centers without on-site surgery capabilities were randomized to undergo PCI at the initial hospital, or be transferred to another that had surgical back-up. At 30 days, rates of MACE (death, MI, repeat coronary revascularization, or stroke) were equivalent between the onsite and no-onsite surgery groups (9.4% vs. 9.5%), meeting the criteria for noninferiority (P < 0.001).

“This is going to generate a lot of discussion,” Dr. Kleiman predicted. “If there’s one take-home message, it’s that there should be absolutely no room for sloppiness [when setting up] these kinds of programs. PCI has come a long way—we can do a good job with minimal risk in most patients, but we don’t want to take a step backward.”

Other studies from ACC/i2 2013 of interest to the interventional community included:

• ACRIN PA: In patients who presented with chest pain and were randomized to cardiac CTA in the ED or traditional screening tools, 1-year safety outcomes were low and similar in both cohorts
• ULTIMA: In this international, multicenter trial an ultrasound-accelerated strategy was superior to anticoagulation with heparin alone in reversing right ventricular dilatation and dysfunction at 24 hours in patients with submassive pulmonary embolism
• STREAM: Prehospital fibrinolysis with timely coronary angiography resulted in equally effective reperfusion compared with primary PCI in patients presenting early after STEMI who are unable to undergo prompt primary PCI after first medical contact
• ORBIT II: A novel atherectomy system that “sands away” hard plaque components exceeded its safety and efficacy goals in patients with severely calcified coronary lesions
• ARMYDA-9 CAROTID: Doubling the clopidogrel dose and reloading with atorvastatin both proved effective in reducing stroke and new cerebral ischemic lesions in patients undergoing carotid stenting
• SELECT-ACS: Infusion of the drug inclacumab at least 1 hour prior to PCI was found to reduce markers of myocardial damage in patients with non-STEMI
• BMC2 PCI registry: Despite guideline recommendations to the contrary, a substantial segment of patients undergoing PCI fail to receive preprocedural aspirin

 

 

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Source:Presentations at: American College of Cardiology 62nd Annual Scientific Session; March 9-11, 2013; San Francisco, CA.

 

 

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