EuroPCR 2011: Novel Technologies with Transformative Potential Stand Out
PARIS, France—At last week’s EuroPCR 2011, held May 17-20, late breaking trials reported incremental improvements in outcomes using new stents, procedural techniques, and adjunctive drugs—as well as some disappointments. But beneath the standard trial fare ran an undercurrent of excitement about some novel technologies that showed the potential for shaking up the field of interventional cardiology.
That was the assessment of co-chair William Wijns, MD, PhD, of Cardiovascular Center Aalst (Aalst, Belgium). “These technologies are not all at the same stage of development,” he told TCTMD in an interview, “but [the idea that] they are far way and of interest only to a minority of academically oriented colleagues [no longer holds],” he said. “Practicing physicians have these technologies on their radar, and they are watching them move closer and closer to the time when they can put them to use to help their patients.”
As examples of potentially practice-shifting technologies, Dr. Wijns cited past EuroPCR innovation awardees: bioabsorbable stents (2007), OCT imaging (2008), TAVI (2009), and renal sympathetic denervation (2009). This year that honor went to CT-based fractional flow reserve (FFR). Each of these technologies adds significant value to interventional therapy, he said.
Novel CT Technology Brings Functional Power to Noninvasive Diagnosis
Coronary CT angiography supplemented by sophisticated computation appears to accurately diagnose significant CAD by combining the anatomic imaging of conventional CT with a simulated version of the hemodynamic assessment provided by invasive FFR. In the first-in-man DISCOVER-FLOW study, in which 103 patients underwent both CT angiography and conventional FFR, CT-derived FFR results correlated well with those yielded by invasive FFR (R = 0.72; P < 0.01), improving the weak positive predictive value of conventional CT.
The noninvasive combination of anatomic and functional features represents the holy grail of CAD assessment, commented Dr. Wijns. “[This new technology] involves lots of assumptions and sophisticated computing, but we think that the scientists behind the approach are [solid] and the initial data are promising.” If the technology proves itself in more robust trials, Dr. Wijns predicted it will have far-reaching impact on practice. “You could envisage that in elective cases the patient no longer comes to the cath lab for diagnosis but only for treatment,” he said.
A related trial demonstrated an additional benefit of functional assessment of stenoses. In a cost-effectiveness analysis based on patient level data from the FAME trial, use of FFR to guide stenting in multivessel disease not only improved patient outcomes but saved money, at least in several European countries.
Maximizing Primary PCI’s Benefit
A number of trials centered on adjunctive treatment for acute MI. According to Dr. Wijns, clinicians have increasingly realized that the clear benefit of primary PCI is compromised by so-called reperfusion injury. Thus, efforts to supplement mechanical revascularization stem from an important unmet need, he emphasized, and they underline that improvement in STEMI outcomes is likely to come in part from a synergy between stenting and pharmacology.
As one example, in a small single-center substudy of the HEBE III trial, STEMI patients undergoing primary PCI with a novel stent designed to capture circulating endothelial progenitor cells, who also received a single bolus of erythropoietin (EPO), had lower levels of late loss at 9 months than those who received a placebo (0.43 mm vs. 0.79 mm; P = 0.004). The EPO group also had less need for repeat revascularization at 1 year (7% vs. 18%; P = 0.013). Previous research has shown that EPO mobilizes progenitor cells from bone marrow.
On the other hand, an approach thought to promising for minimizing reperfusion injury, postconditioning, failed to be cardioprotective and even appeared to be harmful. In the POST-AMI trial, 78 STEMI patients who underwent primary PCI with abciximab were randomized to receive 4 cycles of balloon inflation/deflation during the first minutes after reperfusion or no postconditioning. Compared with controls, the postconditioning group not only had a slightly higher infarct size at 30 days, the primary endpoint (20.2 ± 11.9% vs. 14.3 ± 9.9%; P = 0.056) but also more microvascular obstruction and MACE at 30 and 60 days.
Demonstrating that technique matters, in an observational study of STEMI patients from the SCAAR registry, primary PCI performed via transradial access reduced adjusted mortality at 30 days (especially in those over 70 years of age) and 1 year, bleeding complications, and length of hospital stay compared with transfemoral access. Because of multiple confounders, however, a prospective study is required to confirm these benefits.
In addition, a pair of adjunctive therapies showed promise in preserving myocardium during intervention. In the ROMA trial of patients undergoing elective PCI, those randomized to a 40-mg loading dose of rosuvastatin 24 hours before the procedure suffered less myonecrosis and in new 12-month Kaplan-Meier results had lower MACCE rates than patients who received standard therapy. Another agent, the glucogen-like-peptide-1 analog exenatide, improved myocardial salvage in STEMI patients compared with placebo in the randomized POSTCON II trial.
Drug-Eluting Balloons, Bioabsorbable Polymer Stent Advance
In a registry study of 105 patients with moderate to severe claudication of the femoropopliteal artery, a paclitaxel-eluting balloon featuring a hydrophilic coating that facilitates drug absorption (IN PACT Admiral, Medtronic/Invatec, Roncadelle, Italy) reduced the need for provisional stenting and improved Rutherford class (P < 0.001 vs. baseline) at 12 months.
In 5-year follow-up of a pooled cohort from the Paccocath ISR I and II randomized trials, treatment of in-stent restenosis with a paclitaxel-coated balloon showed no late catch-up in TLR compared with an identical uncoated balloon. Clinical outcomes including, death, MI, stroke, and stent thrombosis remained similar for the 2 technologies.
A meta-analysis of patient-level data on 4,052 subjects from the randomized ISAR-TEST 3, ISAR-TEST 4, and LEADERS trials showed that at 3 years biodegradable polymer DES compared with durable-polymer SES reduced TLR and halved the rate of definite stent thrombosis, although there was no difference in combined cardiac death or MI.
Disappointments for Antiplatelet Adjustment, New Contrast Agent
In the ongoing effort to overcome poor response to standard antiplatelet therapy, new data threw cold water on a straightforward strategy. In the RECLOSE 2-ACS trial, ACS patients determined to have high residual platelet reactivity after a 600-mg loading dose of clopidogrel experienced more long-term cardiac mortality and other thrombotic events than responders despite receiving an increased maintenance dose (150-300 mg daily) or being shifted to ticlopidine (500-1,000 mg daily).
And in a common invasive complication, despite hints of reduced contrast-induced nephropathy in previous research, the iso-osmolar, high-viscous agent iodixanol (Visipaque, GE Healthcare, Waukesha, WI) appeared to be no less nephrotoxic than low-osmolar, low-viscous iopromide (Ultravist, Bayer Schering Pharma AG, Berlin, Germany). In the DIRECT trial, 562 high-risk patients with chronic renal insufficiency (eGFR 30-59 mL/min) who underwent angiography or PCI experienced the same low rates of contrast-induced nephropathy regardless of which agent they received.
Dissolving CTOs, Improving Vascular Closure
First-in-man results were reported on a novel means of facilitating guidewire crossing of difficult-to-treat chronic total occlusions (CTO). In the CTO-1 trial, Canadian researchers pretreated 20 patients with increasing intracoronary doses of bacterial collagenase to soften up the fibrous cap in CTOs that had previously resisted guidewire crossing. The next day, CTOs were successfully crossed and stented, primarily with soft guidewires, in 16 of 20 patients. There were few complications. All stented arteries remained patent at 3 months.
After angiography, use of a vascular closure device shortens the time to hemostasis compared with manual compression, according to results from the randomized CLOSE-UP trial. Patients who received the FemoSeal (St. Jude Medical, St. Paul, MN), a semi-automatic device that is fully resorbable, also experienced fewer in-hospital hematomas greater than 5 cm (2.2% vs. 6.7% for manual compression; P = 0.002).
Late Healing of First-Generation DES Evaluated
Late imaging of first-generation stents showed that neointimal thickness and volume are low and similar between PES and SES. But the persistence of uncovered struts and differences in protruding/malapposed struts indicate that although healing remains incomplete, it tends to cluster in a few lesions. In the SIRTAX LATE study, investigators used optical coherence tomography to assess markers of arterial healing in 88 stented patients, showing a higher rate of protruding/malapposed struts in SES compared with PES but similar levels of overall strut coverage.
Presentations at: EuroPCR; May 17-20, 2011; Paris, France.
EuroPCR 2011: Novel Technologies with Transformative Potential Stand Out
- Dr. Wijns reports serving as the chairman of the international advisory board for Cordis J&J and holding an ownership interest in Cardio3 Biosciences through the Cardiovascular Research Center Aalst, which also receives research grants from multiple device and pharmaceutical companies.