EuroPCR 2012: Biodegradable Devices, Imaging Take Center Stage
PARIS, France—Findings on novel devices and imaging techniques, as well as other practice-changing results, were presented at last week's EuroPCR 2012, held May 15-18.
Biodegradable, Permanent Polymers Neck and Neck
In an interview at the conference’s conclusion, EuroPCR course director William Wijns, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium), told TCTMD that a pressing question for interventional cardiology right now is if there is any advantage to having a DES polymer that, over a relatively short period of time, would disappear into the body and leave what is essentially a BMS behind.
The difference in ischemic risk will be “incremental,” he said, noting that as such, “I’m not surprised at all that a single trial probably would not be powered to address this.” Long-term follow-up in high-risk subgroups might provide evidence backing biodegradable polymers, Dr. Wijns suggested.
But at EuroPCR, results for devices employing this technology were mixed.
The 30-center EVOLUTION trial assessed 2 sirolimus-eluting stents (SES): the biodegradable-polymer Excel (JW Medical Systems, Weihai, China) and the permanent-polymer Cypher Select (Cordis, Miami Lakes, FL). In nearly 2,000 patients with de novo coronary artery lesions and clinical presentations ranging from silent ischemia to ACS, Excel was noninferior to Cypher at 12 months for the primary endpoint of target lesion failure (TLF; cardiac death, MI, and ischemia-driven TLR). Cases of Academic Research Consortium-defined definite/probable stent thrombosis were rare and evenly distributed.
In the STEMI setting, COMFORTABLE-AMI indicated that the biolimus A9-eluting BioMatrix stent (Biosensors, Singapore) was superior to an equivalent BMS in terms of MACE (cardiac death, target-vessel reinfarction, and ischemia-driven TLR) as well as several of the component endpoints.
COMPARE II, meanwhile, found similar results between the biolimus A9-eluting, biodegradable-polymer Nobori stent (Terumo, Tokyo, Japan) and the Xience V/Promus everolimus-eluting stent (Abbott Vascular, Boston Scientific) in a “real-world” cohort of unselected patients.
But when SORT OUT V pitted Nobori against Cypher Select Plus (Cordis) in an all-comers population, the novel stent did not meet noninferiority criteria for the primary endpoint of 9-month MACE (combined cardiac death, MI, definite stent thrombosis, and clinically driven TVR).
The disappointment offers a chance to reflect on what noninferiority trials really mean, Dr. Wijns noted, because event rates were so low that it took only a handful to swing the results. “They’re really flirting with the border of meeting or not meeting the primary endpoint,” he said.
Asked why comparisons with Cypher still matter now that the stent is no longer being manufactured, Dr. Wijns emphasized: “Who cares about Cypher? Patients. . . . Of course, we’ve moved on to the next generation. That doesn’t mean we should forget the millions of patients who have been treated with this device and of course care about long-term outcomes.”
Two trials used optical coherence tomography (OCT) to document similarly good vessel healing between next-generation biodegradable-polymer stents and a second-generation DES equipped with a permanent polymer.
STACCATO randomized 64 ACS patients—21 STEMI, 21 NSTEMI, and 22 stable/unstable angina—with de novo lesions to receive Xience V/Promus stents or Biomatrix stents. The prevalence of malapposed struts was similar between the 2 devices immediately after implantation, but by 9 months, the everolimus-eluting stent had fewer uncovered struts (primary endpoint) and higher mean neointimal thickness.
The randomized ISAR-TEST-6 OCT trial pitted Nobori against Xience V/Promus. By 6- to 8-month follow-up, lack of coverage and malapposition were both numerically more common with the biolimus-A9-eluting stent, while median neointimal thickness was higher with the everolimus-eluting stent, but the disparities did not reach statistical significance. However, the proportion of lesions with at least 30% uncovered stent struts was numerically lower with BES than with EES.
One Step Further: Bioabsorbable Scaffolds
Two novel DES with bioresorbable scaffolds made promising debuts in separate first-in-man studies. Both devices documented early evidence of safety and efficacy. They are next in line after the PLLA-based BVS stent (Abbott Vascular, Santa Clara, CA), currently the fully bioabsorbable DES that is farthest along in clinical studies.
In the DESOLVE trial, a myolimus-eluting stent employing the DESolve bioresorbable coronary scaffold (Elixir, Sunnyvale, CA) was tested in 16 patients with single de novo coronary lesions. At 6 months, the primary endpoint of late lumen loss was 0.19 ± 0.19 mm, with no binary restenosis. Other angiographic, OCT, and clinical outcomes also were positive.
Dr. Wijns seemed quite taken with the DESOLVE device, noting “as far as I know, it's the first [bioabsorbable and also self-expanding scaffold]. If you think of it, that’s really in line with the ultimate objective of [this concept], because you want to respect the integrity of the vessel. . . . [I]f at the time of delivery, you have to use very high pressure, we know about some of the difficulties that brings with it in terms of sizing and also [the stent risks being] brittle if you over expand it. This is a device that’s going to adapt [and not put] continuous pressure on the wall.”
Longer-term results for a different fully bioresorbable DES—the DREAMS (Drug-Eluting Absorbable Metal Scaffold) stent (Biotronik, Berlin, Germany)—were provided by the BIOSOLVE-I trial. The device not only includes a bioabsorbable magnesium-alloy scaffold but also delivers paclitaxel via a bioresorbable PLGA polymer. In 46 patients with de novo coronary lesions, the primary endpoint of 6-month TLF (cardiac death, target-vessel MI, and clinically driven TLR) was 4.3%, driven by 2 cases of TLR. There was no cardiac death, MI, or stent thrombosis. By 12 months, 1 MI occurred (2.3%) outside of the scaffolded area but within the treated vessel, bringing the TLF rate to 7.0%. Late lumen loss remained stable over time.
Imaging Makes an Appearance
New iterations of imaging technology also represented highlights at EuroPCR, according to Dr. Wijns.
Though noninvasive fractional flow reserve (FFR) still seems promising after last year's DISCOVER FLOW trial, he cautioned that results are yet to come from the larger trial currently testing the technique, which is slated to be presented at the European Society of Cardiology Congress 2012 in Munich, Germany. “So far the data have come from a limited number of sites. This will be the first test of its application on a more widespread platform,” Dr. Wijns noted.
But at this meeting, he continued, the biggest advance was from data showing how FFR measurements could be used to plan treatment. “I think it is spectacular,” Dr. Wijns commented. “Of course, there is the immediate impact of being able to anticipate what the functional outcome will be of the planned anatomic intervention, because again the story here is the synergy between anatomy and function. That’s the Holy Grail.”
Such information could be useful throughout patient management from the referring physician to post-procedural evaluation, he said. “It changes the triage of the therapy between interventional medical treatment and surgery [as well as details of the PCI. For example, m]any patients have diffuse disease and just implanting a stent, which is focal per definition, may leave them with improved FFR but not quite within the normal range or the highest normal range values. We know today that those patients need to receive more aggressive lifestyle change management and secondary prevention.”
FAME II, for example, demonstrated how FFR measurements can help identify which patients with stable CAD should not rely solely on optimal medical therapy (OMT) and should also undergo PCI. The advantage offered by FFR in terms of reducing repeat revascularization was so striking, in fact, that the trial stopped recruiting patients ahead of schedule.
All subjects were slated for DES implantation in up to 3 vessels at the time of enrollment. Based on their FFR results, patients were stratified to different treatment strategies:
- Those with FFR > 0.80 received OMT alone, with half randomly assigned to follow-up in a registry (n = 131)
- Those who had at least 1 stenosis with FFR ≤ 0.80, indicating hemodynamic significance, entered into a randomized comparison of OMT with (n = 352) or without PCI (n = 339)
Within the randomized cohort, the need for urgent or any revascularization was higher at 1 year in patients assigned to OMT alone, showing the value of FFR in identifying patients in need of revascularization. Importantly, outcomes were equivalent between the registry patients—who were given OMT alone after being cleared of having hemodynamically significant lesions—and those randomized to OMT plus PCI.
Another study demonstrated how using CT imaging to calculate FFR enables accurate 3-D modeling of coronary stenosis and “virtual stenting.” The technique can be used to predict the success of PCI, and it yields high diagnostic accuracy comparable to the gold standard of invasive FFR. CT-derived FFR had an overall sensitivity of 100% and specificity of 96% in predicting ischemia after stenting. Negative- and positive-predictive values were 100% and 50%, respectively, with a total accuracy rate of 96%.
The CLI-OPCI registry illustrated how using OCT to guide routine PCI can reveal procedural issues not caught by angiography alone, leading to corrective intervention in up to one-third of cases and better outcomes. Researchers looked at 335 consecutive patients undergoing PCI at 3 high-OCT-volume Italian centers between 2009 and 2011. Patients were matched with 335 randomly selected subjects undergoing PCI during the same month with angiographic guidance alone.
OCT was only used after an optimal angiographic result based on the operator’s judgment and did not lead to any major complications. Meanwhile, OCT disclosed numerous issues missed on angiography including malapposition and thrombus. These findings led to additional interventions in 34.7% of cases, and the OCT group had better outcomes both in-hospital and at 1 year.
According to Dr. Wijns, “OCT really unravels with exquisite detail the interaction between the device and the disease. If you interpret it properly there is the potential for having an impact on outcomes and improving early stent thrombosis rates [in complex or high-risk subsets].”
But, he added, “the caveat is that this was done by very expert OCT users who know when and when not to react to what they see. Overreaction would cause side effects . . . and drive costs.”
Two additional studies showed conflicting results on the accuracy of a new intracoronary resistance measurement that obviates the need for drug administration in estimating coronary stenosis severity.
Still Working to Optimize PCI
Several trials looked at how to improve PCI outcomes.
TROFI found that thrombectomy does little to improve flow area and often fails to completely remove thrombus when used in conjunction with primary PCI in treating STEMI.
But results from the SMART trial confirm that when such therapy is used, rheolytic thrombectomy outperforms manual aspiration. The study randomized 80 STEMI patients to primary PCI plus either rheolytic thrombectomy or manual aspiration. Following treatment, TIMI flow grade was improved with the patients receiving rheolytic thrombectomy instead of manual aspiration, as was TIMI thrombus grade. Early ST-segment resolution was also numerically superior with rheolytic thrombectomy, though the difference just missed statistical significance. The primary endpoint of number of quadrants containing thrombus on OCT was improved with rheolytic thrombectomy, but not to a significant extent.
Two observational studies presented evidence consistent with a growing body of literature demonstrating improved outcomes after transradial PCI for acute MI.
Results from the Scottish Coronary Revascularization Register showed that procedural success was higher with transradial PCI while complications such as vascular access issues and major bleeding were lower with radial access. At 1 year, hard outcomes were improved with transradial PCI including MI, stroke, and death, associations that remained significant on multivariable analysis.
A single-center study from Spain of more than 600 patients found that procedural characteristics such as overall time, fluoroscopy time, and contrast volume were similar for PCI using radial and femoral access in STEMI patients. Procedural success, meanwhile, was higher with transradial PCI, as were deferments of PCI for significant noninfarct-related lesions. This, however, did not alter the shorter length of hospital stay that occurred with transradial patients. In-hospital complications were lower with transradial PCI, including death, major bleeding, and vascular access site issues.
Statins also made an appearance at EuroPCR, with ROMA II Reload showing that a loading dose of rosuvastatin or atorvastatin prior to PCI in stable patients already on chronic statin therapy improves clinical outcomes out to 12 months. Investigators randomized 350 patients undergoing elective PCI to a loading dose of 40-mg rosuvastatin or 80-mg atorvastatin (Lipitor, Pfizer, New York, NY) within 24 hours prior to the procedure. A control group of 100 registry patients received standard therapy (aspirin and clopidogrel the day before PCI). All had already been receiving statin therapy.
Both rosuvastatin and atorvastatin showed similar levels of myonecrosis (CK-MB > 3 times ULN) at 12 hours post-procedure. This was also true at 24 hours. Importantly, both statin groups lowered the endpoint compared with the control group. At 30 days, cumulative MACCE rates were equivalent between the rosuvastatin and atorvastatin groups, both showing improved outcomes compared with controls. This was sustained at 6 and 12 months.
Another study, CIBELES, found that the second-generation Xience V/Promus stent performs as well as Cypher in treating chronic total occlusions (CTOs). In nearly 200 patients, the newer device proved noninferior at preventing in-stent late loss at 9 months. By 1 year, clinical outcomes were numerically higher with Cypher but statistically similar for the 2 stent designs.
TAVR at 10 Years
Marking the tenth anniversary of transcatheter aortic valve replacement (TAVR), the conference offered new information about the procedure.
The SOURCE XT registry is designed to capture outcomes with the Sapien XT valve (Edwards Lifesciences, Irvine, CA), a second-generation TAVR device. According to researchers, it achieves the highest survival yet seen at 30 days with transfemoral access (4.3%). In a comparison between transfemoral and transapical access, procedural complications as well as 30-day mortality and major bleeding rates were higher with the latter technique. Both access routes, however, saw improvements in ejection fraction at 30 days compared with baseline.
The Global Valve-in-Valve Registry revealed that treating a failed bioprosthesis via TAVR is feasible and often effective, albeit technically demanding. Investigators culled data from 54 centers in Europe, North America, Australia, New Zealand, and the Middle East on 416 high-risk patients at a median of 8 to 10 years after initial treatment. Procedures were complicated, but at 30 days, valve-in-valve therapy had improved functional capacity.
Another study on TAVR attempted to tease out biomarkers that might predict results of aortic intervention during the first year after treatment. More than a dozen biomarkers were collected, including those involved in renal function, nitric oxide production, oxidative stress, and metabolism of the extracellular matrix.
Presentations at: EuroPCR; May 15-18, 2012; Paris, France.
- Dr. Wijns reports receiving research funding and honoraria from multiple drug and device companies as well as holding stock in Cardio3 Biosciences.