ACC 2006 ANNUAL SESSION HIGHLIGHTS
i2 Innovation in Intervention Summit
William D. Knopf, MD, FACC*
Cardiac Services of St. Joseph’s Hospital of Atlanta, Atlanta Cardiology Group of Georgia, Atlanta, Georgia.
* Reprint requests and correspondence: Dr. William D. Knopf, Cardiac Services of St. Joseph’s Hospital of Atlanta, Atlanta Cardiology Group of Georgia, 5665 Peachtree Dunwoody Road, Atlanta, Georgia 30342-1701. (Email: wknopf{at}acgmd.com).
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Abbreviations and Acronyms
| | ACUITY = Acute Catheterization and Urgent Intervention Triage Strategy Timing trial | | BMS = bare-metal stent | | GP = glycoprotein | | ICE = intracardiac echocardiography | | MACE = major adverse cardiac events | | MI = myocardial infarction | | MIST = Migraine Intervention with StarFlex Technology | | PASSION = Paclitaxel-Eluting Stent Versus Conventional Stent in ST-Segment Elevation Myocardial Infarction trial | | PCI = percutaneous coronary intervention | | PES = paclitaxel-eluting stent | | PFO = patent foramen ovale | | PROGRESS-AMS = Clinical Performance and Angiographic Results in Absorbable Metal Stents study | | SES = sirolimus-eluting stent | | STENT = Strategic Transcatheter Evaluation of New Therapies study | | TLR = target lesion revascularization | | TYPHOON = Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated With Angioplasty |
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On behalf of the co-chairs of the first Innovation in Intervention or i2 Summit—William O’Neill, MD, FACC, Ted Feldman, MD, FACC, FSCAI, and myself—I will be discussing the highlights of our inaugural meeting, attended by more than 4,000 individuals, which was far more than envisioned. This first i2 Summit attracted 743 submitted abstracts, of which 230 were selected for presentation.
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Stenting
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Pivotal randomized trials have shown the safety and efficacy of drug-eluting stents to reduce restenosis in patients undergoing percutaneous coronary intervention (PCI). However, these drug-eluting stent trials systematically excluded patients with acute myocardial infarction (MI) based on their high-risk profile. Now we have the results of the Paclitaxel-Eluting Stent Versus Conventional Stent in ST-segment Elevation Myocardial Infarction (PASSION) trial (1). This was a randomized comparison of the Taxus paclitaxel-eluting stent (PES) compared with a bare-metal stent (BMS), which has already been shown to be safe and effective in patients with a recent MI. At one year, there was no statistical difference in major adverse cardiac events (MACE) between the two PASSION groups (PES 8.7% vs. BMS 12.6%; p = 0.12), although it should be noted that the MACE rate was lower than expected in the BMS arm. Although the primary end point was similar, the hazard ratio of 0.68 was clinically meaningful and stent thrombosis at one year, although low, was similar in the two treatment groups. Overall, the PES system in patients with ST-segment elevated MI was safe and at least as effective as BMS placement in this late-breaking clinical trial.
A similar group of patients were enrolled in the Trial to Assess the Use of the Cypher Stent in Acute Myocardial Infarction Treated With Angioplasty (TYPHOON) trial, which evaluated sirolimus-eluting stents (SES) for primary PCI in acute MI patients (2). Patients were randomized to SES (n = 355) or BMS (n = 357). At one year, there was a 49% reduction in the primary end point of target vessel failure with SES (7.3% vs. 14.3%; p = 0.0036), largely attributable to a reduction in target vessel revascularization (3.7% vs. 12.6%; p < 0.001). Although comparable between the groups, the incidence of stent thrombosis was higher than expected by the investigators, suggesting perhaps the hypercoagulable state of ST-segment elevated MI patients. The combination of rapid reperfusion via primary PCI and stenting, combined with glycoprotein (GP) IIb/IIIa inhibitors (used in 
70% of the patient population), plus clopidogrel resulted in a favorably lower rate of death and repeat MI. Use of SES further increased the long-term clinical benefit of primary PCI, which has been shown to be the most efficient therapy for acute MI when performed rapidly by an experienced team. Both the PASSION and TYPHOON trials show that drug-eluting stents were safe and effective in this very high-risk population.
Late clinical outcomes of stenting in diabetic patients were the focus of the Strategic Transcatheter Evaluation of New Therapies (STENT) trial (3). These are high-risk patients prone to restenosis after PCI. For non–insulin-treated patients with diabetes mellitus, there was no significant difference at nine months between the two stents in terms of mortality, MI, target vessel revascularization, MACE, or subacute thrombosis. The results were very similar for insulin-treated patients, although there was a slight trend in MACE rate favoring PES (Fig. 1). This important trial suggests to interventionalists that both the PES and the SES procedure produce similar favorable results in terms of late clinical outcomes in diabetic patients overall, with restenosis rates comparable to those reported in prior studies for nondiabetic patients.
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Figure 1 Nine-month clinical outcome for insulin-treated diabetic patients enrolled in the Strategic Transcatheter Evaluation of New Therapies (STENT) trial. Completed nine-month follow-up: 5,566, 93.7%. p = NS for all. Blue bars = sirolimus-eluting stent; yellow bars = paclitaxel-eluting stent. MACE = major adverse cardiac events; MI = myocardial infarction; TVR = target vessel revascularization.
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Another trial of interest was the Taxus V In-Stent Restenosis (Taxus V ISR) study, a prospective multicenter randomized trial of 396 patients comparing Taxus PES (n = 195) with vascular brachytherapy (n = 201) in patients treated previously with BMS who experienced in-stent restenosis (4). At nine months, PES proved superior in reducing ischemic target lesion revascularization (TLR) (6.3% vs. 13.9%; p = 0.01), ischemic target vessel revascularization (10.5% vs. 17.5%; p = 0.46), and overall MACE (11.5% vs. 20.1%; p = 0.02). Angiographic restenosis was 14.5% with stenting versus 31.2% with vascular brachytherapy (p < 0.001). Thus, for BMS patients in whom in-stent restenosis develops, a drug-eluting stent represents a simple, safe therapy with a high rate of success over nine months. This is a reassuring option for an otherwise difficult-to-treat group of patients.
A novel stent composed of an absorbable magnesium alloy was the focus of the Clinical Performance and Angiographic Results in Absorbable Metal Stents (PROGRESS-AMS) study, which assessed the feasibility, clinical performance, and angiographic results of this absorbable metal stent (5). Although the study involved only 63 patients, there were no late incomplete apposition or adverse edge effects seen on angiography. There was evidence of a significant reduction in vessel, stent, and lumen volumes as the stent began to be resorbed (Fig. 2). Still, the PROGRESS-AMS Investigators met their primary end point, which was a four-month MACE event rate <30%. In this trial, MACE was defined as cardiac death, nonfatal MI, and ischemic-driven TLR. No patient experienced late stent thrombosis.
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Figure 2 Clinical Performance and Angiographic Results in Absorbable Metal Stents (PROGRESS-AMS) study: volumetric intravascular ultrasound parameters. No late incomplete opposition; no adverse edge effect. *p < 0.01. Blue bars = post-implantation; yellow bars = four-month follow-up. EEM = external elastic membrane.
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The PROGRESS-AMS researchers further suggested that the absorbable stent was compatible with magnetic resonance tomography as well as computed tomography follow-up. Intravascular ultrasound was able to detect the absorbable stent degradation at four months, and the TLR rate shown in this trial was comparable with that documented for BMS. Therefore, this is a very exciting early trial looking at a novel stent platform that can be absorbed by the body; long-term results will be forthcoming at future i2 meetings.
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Additional trials and cases
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A relatively complex trial that involved 13,800 patients at a number of centers worldwide, compared routine up-front initiation of GP IIb/IIIa inhibitors (99% of patients randomized to early initiation) with the selective use of these agents (in 56% of patients randomized to delayed administration). The Acute Catheterization and Urgent Intervention Triage Strategy (ACUITY) Timing Trial was a prospective, randomized study of patients with acute coronary syndrome (6). There was no difference in net clinical benefit (composite end point occurred in 11.7% of patients in both groups; p < 0.001 for noninferiority), and there were similar rates of adverse ischemic events at 30 days (7.1% for upstream use vs. 7.9% for GP IIb/IIIa administration as needed, which did not meet the criteria for noninferiority). The rates of major and minor bleeding were reduced significantly in the delayed cohort. The implications of these results will be studied further. In the context of the entire ACUITY trial, however, both strategies of upstream and selective or delayed use of GP IIb/IIIa inhibitors showed inferior clinical outcomes compared with the use of bivalirudin alone (11.7% for both GP IIb/IIIa inhibitor arms vs. 10.1% for bivalirudin alone, p = 0.009).
Another exciting study presented at i2 was the Migraine Intervention with StarFlex Technology (MIST) trial, a prospective, multicenter, randomized, double-blind, placebo-controlled trial to evaluate the efficacy of patent foramen ovale (PFO) closure with the StarFlex septal repair implant to prevent refractory migraine headaches. There has been a correlation seen between the presence of a PFO and migraine headaches. In the double-blind MIST trial, 73 patients underwent a sham operation and 74 patients had their PFO closed (7). Although there was no difference in complete cessation of migraines between the groups, more patients who had their PFO closed versus those undergoing sham surgery had a 50% or greater reduction in headaches (42% vs. 23%; p = 0.038) (Fig. 3). This is the first trial to show at least some benefit of PFO closure in terms of reducing the incidence of migraines. The MIST Investigators concluded that with longer follow-up, larger numbers of patients, and perhaps even better closure devices, a second MIST trial may help to validate the treatment trends seen in this study. Further analysis of the current data also may help physicians to determine which patients with migraines may have a significant treatment response.
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Figure 3 Reduction in headache burden (frequency x duration) in the Migraine Intervention with StarFlex Technology (MIST) trial. p = 0.033. Blue bars = baseline; yellow bars = analysis.
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The i2 meeting also included a number of state-of-the-art presentations on subjects such as endothelial progenitor cells; the future of interventional cardiology; coronary stenting, where we are and where we are going; coronary artery bypass graft versus PCI; the status of various large trials; vulnerable plaque in the future; devices or drugs; cell therapy; ST-elevated MI management; and the current status of percutaneous valve therapy. There were also exciting sessions about emerging technologies, including a review of complications.
Finally, it is very helpful when interventional meetings include live cases, and we had the best live cases from around the world: six centers presenting two and one-half days of live cases, or approximately 40 live cases, presented throughout our meeting. Among these cases, we saw a severe high-risk lesion involving a tight carotid stenosis in a patient with a tracheostomy. Stenting produced an excellent result with no sequelae, and the patient went home the following day. Another case presented a complex bifurcating left main stenosis, presented by colleagues in Toulouse, France. In this case, excellent results were achieved with a bifurcating stent in the circumflex and left anterior descending artery, a very high-risk procedure.
From Belgium, participants observed a complex, very large PFO in which the bubble formation on the intracardiac echocardiography (ICE) could be seen clearly. The case used a combination of angiography and ICE, and angiography permitted visualization of the catheter placed across the PFO from the right atrium to the left atrium. At this point, the physicians were able to place the novel StarFlex device, which uses nitinol technology, through the PFO; capture the tissue; and deploy the device to occlude the PFO. The final result showed what a truly remarkable procedure this is.
In another case, a combination of ICE and angiography was used to perform a left atrial appendage occlusion in which the catheter was placed using a trans-septal approach into the left atrial appendage. A device similar to the StarFlex device, also made of nitinol, was deployed in the left atrial appendage, which was occluded in a patient with atrial fibrillation.
A complex left anterior descending artery aneurysm rupture brought together eight high-volume operators to decide how to deal with the challenges of the particular case. Intravascular ultrasound was used to image the very large aneurysm, which was then excluded with a coronary stent graft. However, the panel members had different ideas regarding how to manage this patient, underscoring the difficulty in treating these fortunately rare cases.
Finally, only through the i2 mechanism were we able to show all of these very difficult cases from around the world, all successfully done throughout our meeting. All in all, i2 proved to be an outstanding inaugural meeting.
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References
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- Dirksen MT, Suttorp MJ, vanHearebeel L, et al. PASSION investigators Randomized comparison of paclitaxel eluting stent versus conventional stent in ST-segment elevation myocardial infarction. results of the PASSION trial. 2006Presented at: ACC 55th Annual Scientific Session; Atlanta, GA: March 11–14.
- Spaulding C, Henry P, Teiger E, et al. Final results of the TYPHOON studya multicenter, randomized trial comparing the use of sirolimus-eluting stents to bare metal stents in primary angioplasty for acute myocardial infarction. (abstr) J Am Coll Cardiol 2006;47(Suppl B):50B.
- Simonton C, Brodie B, Cheek B, et al. STENT Investigators Comparative late clinical outcomes of paclitaxel and sirolimus-eluting coronary stents in diabetic patients from a large prospective multicenter registry. results from the Strategic Transcatheter Evaluation of New Therapies (STENT) Group. 2006Presented at: ACC 55th Annual Scientific Session; Atlanta, GA: March 11–14.
- Stone GW, Ellis SG, O’Shaughnessy CD, et al. Taxus V ISR Investigators Paclitaxel-eluting stents vs vascular brachytherapy for in-stent restenosis within bare-metal stentsthe Taxus V ISR randomized trial. JAMA 2006;295:1253-1263.[Abstract/Free Full Text]
- Erbel R, Bonnier JJRM, Koolen J, et al. PROGRESS-I Investigators The PROGRESS-AMS study. clinical performance and angiographic results of the coronary stenting with absorbable metal stents. 2006Presented at: ACC 55th Annual Scientific Session; Atlanta, GA: March 11–14.
- Stone GW, ACUITY Investigators Prospective, randomized comparison of routine upfront initiation versus selective use of glycoprotein IIb/IIIa inhibitors in patients with acute coronary syndromes. the ACUITY Timing Trial. 2006Presented at: ACC 55th Annual Scientific Session; Atlanta, GA: March 11–14.
- Dowson A, Wilmshurst P, Mullen M, et al. MIST Investigators A prospective, multicenter, randomized, double blind, placebo-controlled trial to evaluate the efficacy of patent foramen ovale closure with the StarFlex septal repair implant to prevent refractory migraine headaches. the MIST Trial. 2006Presented at: ACC 55th Annual Scientific Session; Atlanta, GA: March 11–14.
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K. E. Kip, K. Hollabaugh, O. C. Marroquin, and D. O. Williams
The Problem With Composite End Points in Cardiovascular Studies The Story of Major Adverse Cardiac Events and Percutaneous Coronary Intervention.
J. Am. Coll. Cardiol.,
February 19, 2008;
51(7):
701 - 707.
[Abstract]
[Full Text]
[PDF]
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Stenting
Additional trials and cases