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Cardiac Interventions Today News
 REGULATORY UPDATE

CMS Issues Guide for Technology Approval
August 25, 2008—The Centers for Medicare & Medicaid Services (CMS) announced that it has released the Innovator's Guide to Navigating CMS, which is available at www.cms.hhs.gov/councilontechinnov.

According to CMS, the guide was developed by the CMS Council for Technology and Innovation, a CMS-wide working group charged with streamlining and creating a more transparent process to get new technologies to patients more quickly. The council is composed of senior CMS staff and clinicians and was established by the Medicare Prescription Drug, Improvement, and Modernization Act of 2003.

For the first time in a single resource, the Innovator's Guide provides a road map to Medicare coverage, coding, and payment. According to CMS, the guide offers innovators a new, easily available resource so that Medicare beneficiaries and their healthcare providers may be able to take advantage of new advances in healthcare more quickly. CMS noted that in some cases in which a technological advance is groundbreaking, Medicare may need to make explicit coverage, coding, or payment changes to ensure the coverage of reasonable and necessary new treatment options and the availability of medically appropriate technologies to its beneficiaries.

"Our aim is to provide the highest quality healthcare to people with Medicare and the tools to help them get that care," commented acting CMS administrator Kerry Weems. "We now have the coverage, coding, and payment requirements that developers and technology innovators need in one place. This will help them to better navigate Medicare requirements by explaining how to make their products available to Medicare beneficiaries."

Cordis's Cypher Select Plus Approved in EU to Treat AMI
August 27, 2008—Cordis Corporation (Warren, NJ) announced that it has received CE Mark approval to market the Cypher Select Plus sirolimus-eluting coronary stent for the treatment of acute myocardial infarction (AMI).

According to the company, the Cypher Select Plus features an enhanced stent delivery system, a flexible stent design, a short tip, and the company's Cyph2onic hydrophilic-coating technology. Cordis stated that Cyph2onic is an innovative coating technology that is significantly more lubricious than previous Cypher stent products, thereby greatly increasing the ability to successfully navigate challenging coronary arteries. The Cypher Select Plus stent is not approved or available for sale in the US, the company advised.

Cordis stated that the expanded indication for the Cypher Select Plus in the EU is based on several scientific publications providing clinical evidence for this indication, especially data from TYPHOON (Trial to Assess the Use of the Cypher Stent in AMI Treated with Balloon Angioplasty), the first randomized, multicenter clinical trial to study the safety and efficacy of the Cypher stent in patients who experienced AMI. The TYPHOON trial was conducted at 48 sites in Europe, Israel, and Australia. Clinical trial data were initially presented at the American College of Cardiology annual scientific session in March 2006. Christian Spaulding, MD, et al published the data in the New England Journal of Medicine (2006;355:1093-1104). In TYPHOON, the Cypher stent reduced the risk of target vessel failure by almost half in AMI patients compared to patients who were treated with a bare-metal stent (7.3% vs 14.3%; P<.004). In addition, the overall mortality rate in both the Cypher stent arm of the trial and the bare-metal stent arm was equally low (2.2%), the company noted.

"More than 3,000 patients have been included in nine randomized trials to assess the safety and efficacy of the Cypher Select Plus stent in AMI," commented Dr. Spaulding. "All of these studies have demonstrated significant reductions in repeat revascularization at 1 year with no increase in stent thrombosis, death, or repeat myocardial infarction. Long-term follow-up has also demonstrated that these results are sustained."

OrbusNeich's Sapphire NC Receives CE Mark Approval
July 28, 2008—OrbusNeich (Fort Lauderdale, FL) announced the European approval and market launch of the Sapphire NC coronary dilatation catheter. According to the company, the Sapphire NC is a noncompliant balloon with controlled growth of only 0.6% per atmosphere of pressure over the working pressure range for controlled dilatations. It has a 22-atm-rated burst pressure for confident treatment of tough, calcified lesions and for poststent dilatation. The Sapphire NC's HIST (High Speed Tracking) catheter tip enables flexible tracking along the guidewire, and the company's TIFO (Tight Fold) processing provides a slender profile for enhanced crossability through tight lesions. Sapphire NC is available in a wide range of sizes for precise dilatation to match popular stent lengths, the company stated.
 LITERATURE HIGHLIGHTS

ACUITY 1-Year Subanalysis Published for Angiomax
August 26, 2008—The Medicines Company (Parsippany, NJ) announced that a subanalysis of the ACUITY (Acute Catheterization and Urgent Intervention Triage Strategy) study shows that the company's Angiomax (bivalirudin) monotherapy provides moderate- and high-risk (unstable angina/non-ST elevation myocardial infarction) acute coronary syndrome (ACS) patients, who are undergoing percutaneous coronary intervention (PCI), with similar results from ischemic events and death versus standard therapy (unfractionated heparin [UFH] or enoxaparin plus a glycoprotein [GP] IIb/IIIa inhibitor) as measured at 1 year after PCI. The data were published by Harvey D. White, DSc, et al in the Journal of American College of Cardiology (2008;52:807-814). Additionally, as previously reported by Gregg W. Stone, MD, et al in The Lancet, patients in the PCI subset of ACUITY who were treated with Angiomax experienced a 41% reduction in bleeding at 30 days compared to standard treatment (2007;369:907-919). The company noted that the latest data represent one of seven major randomized trials composed of approximately 25,000 patients that have consistently demonstrated that Angiomax offers improved outcomes for angioplasty patients compared to standard therapy.

According to the company, the analysis of the ACUITY-PCI subset assessed the effect of treatment with Angiomax within 30 days and on 1-year outcomes in 7,789 moderate- and high-risk ACS patients undergoing PCI compared to standard therapy. In the study, patients were randomized to UFH or enoxaparin plus a GP IIb/IIIa inhibitor, Angiomax plus a GP IIb/IIIa inhibitor, or Angiomax alone. Endpoints included assessment of composite ischemia, defined as death, myocardial infarction, or unplanned revascularization, and mortality at 1 year. The endpoints highlighted the impact of bleeding, the company said.

Specifically, the results of the ACUITY trial in patients undergoing PCI showed that:
  • Patients treated with Angiomax experienced comparable composite ischemia (death, myocardial infarction, or unplanned revascularization) and mortality at 1 year compared to patients treated with standard therapy.
  • Composite ischemia results were 19.2% for bivalirudin alone and 19.4% for bivalirudin plus a GP llb/llla inhibitor versus 17.8% UFH/enoxaparin plus a GP llb/llla inhibitor.
  • Mortality rate results were 3.1% bivalirudin alone and 3.3% bivalirudin plus a GP llb/llla inhibitor versus 3.2% UFH/enoxaparin plus a GP llb/llla inhibitor.
  • A 30-day analysis showed major bleeding occurred in 7% of the UFH/enoxaparin plus GP IIb/IIIa inhibitor group compared to 4% in the Angiomax-alone group (P<.0001).
  • Patients who experienced major bleeding had significantly longer hospital stays than those who did not experience a major bleed (5 days vs 3 days; P<.0001).


"These findings are important, as the data suggest treatment with Angiomax provides similar protection against ischemia and death over standard therapy at 1 year," commented Dr. White. "Furthermore, at 30 days, we saw Angiomax reduced major bleeding. Multiple studies have shown a significant association between bleeding complications in ACS and PCI with mortality. The data from the ACUITY subanalysis suggest treatment with Angiomax is an attractive antithrombotic therapeutic option for patients undergoing PCI."

TRITON-TIMI 38 Compares Prasugrel to Clopidogrel
August 21, 2008—Daiichi Sankyo Company, Ltd. (Tokyo, Japan) and Eli Lilly and Company (Indianapolis, IN) announced that a new, prespecified analysis of the phase 3 head-to-head TRITON-TIMI 38 (Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel–Thrombolysis In Myocardial Infarction) study showed that patients who took prasugrel for acute coronary syndromes (ACS) managed with percutaneous coronary intervention (PCI) and had survived their first cardiovascular event and then experienced a subsequent event, were 35% less likely to have a recurrent event (composite endpoint of heart attack, stroke, or cardiovascular death) than those who took clopidogrel (10.8% vs 15.4%; P=.016). Sabina A. Murphy, MPH, et al published these data online ahead of print in the European Heart Journal.

TRITON-TIMI 38 was a phase 3, randomized, double-blind, head-to-head clinical trial comparing the effects of prasugrel versus clopidogrel in patients with ACS who were managed with PCI, including the use of coronary stenting. The study enrolled 13,608 patients at 707 trial sites in 30 countries. The primary endpoint of the study was to compare the effects of prasugrel to clopidogrel on the combined incidence of cardiovascular death, nonfatal heart attack, or nonfatal stroke during a median period of at least 12 months after PCI. Patients were randomly assigned to one of two treatment groups and given a loading dose of either prasugrel (60 mg) or the approved loading dose of clopidogrel (300 mg) followed by a daily maintenance dose of either prasugrel (10 mg) or clopidogrel (75 mg). All patients also received a daily low dose of aspirin. To measure the risk of recurrent events, a Poisson regression analysis was performed to compare the number of occurrences of cardiovascular events over a period of time in patients who had experienced at least one primary endpoint, the companies noted.

According to the companies, the recurrence of subsequent events assessment was part of the larger TRITON-TIMI 38 trial, the primary measure of which showed that prasugrel taken with aspirin reduced the relative risk of the combined endpoint of cardiovascular death, nonfatal heart attacks, or nonfatal stroke by 19% more than clopidogrel taken with aspirin. These benefits were accompanied by an increased risk of serious bleeding with prasugrel overall, some of which may be life threatening. Overall, for every 1,000 people treated, there were six more TIMI major bleeding events but 23 fewer heart attacks in patients taking prasugrel compared with patients taking clopidogrel (referencing data published by the TRITON-TIMI 38 investigators in the New England Journal of Medicine, 2007;357:2001-2015). The risk of cardiovascular death overall in the study was not statistically different between treatment groups (prasugrel, 2% vs clopidogrel, 2.2%).

Additional data from this analysis of recurrent events showed:
  • The reduction in recurrent events among prasugrel patients persisted over the duration of the trial (15 months).
  • Among patients taking prasugrel, there were 58 recurrent events compared with 115 recurrent events in the clopidogrel group.
  • The risk of cardiovascular death after a heart attack while on therapy was significantly reduced with prasugrel (3.7%) compared with clopidogrel (7.1%).
  • Diabetics treated with prasugrel showed a risk reduction of 60% in subsequent events (P=.003).
  • Even after adjusting for variables such as age, gender, tobacco use, and other health conditions, those taking prasugrel still showed a statistically significant reduction of 34% in recurrent events (P=.024).
  • Although recurrent bleeding events occurred infrequently among patients with at least one TIMI non-coronary artery bypass graft surgery major or minor bleeding (17 in the prasugrel group and 13 in the clopidogrel group), the analysis noted the high percentage of discontinuation after an initial major bleeding event, which was similar among those patients taking prasugrel (42%) and those taking clopidogrel (43%).


On August 31, Daiichi Sankyo and Eli Lilly announced that a diabetic subgroup analysis of TRITON-TIMI 38 presented by Stephen Wiviott, MD, at the Congress of the European Society of Cardiology in Munich, Germany demonstrated that patients who were diabetic and diagnosed with ACS were 40% less likely to experience a heart attack if they were treated with prasugrel versus clopidogrel (8.2% vs 13.2%; P<.001). In addition, the combined rate of cardiovascular death, nonfatal heart attack, and nonfatal stroke was reduced by 30% in diabetes patients treated with prasugrel compared to those treated with clopidogrel (12.2% vs 17%; P<.001). In patients without diabetes, there was also improvement in outcomes with prasugrel, with the primary endpoint occurring in 9.2% of patients treated with prasugrel and 10.6% of patients treated with clopidogrel (P=.02). The study by Dr. Wiviott et al was simultaneously published online ahead of print in Circulation.

According to companies, the reduction of cardiovascular events was consistent across the subgroup of diabetes patients regardless of diabetic therapies (insulin vs no insulin). The study showed a significant relative risk reduction in the primary endpoint of cardiovascular death, nonfatal heart attack, and nonfatal stroke with prasugrel: 37% for insulin-treated and 26% (P=.001) for noninsulin-treated diabetics. There was also a significantly lower rate of stent thrombosis among diabetes patients treated with prasugrel, resulting in a 48% relative risk reduction in stent thrombosis compared with clopidogrel (3.6% vs 2%; P=.007). In this subanalysis, the rates of major bleeding events were similar for prasugrel (2.5%) and clopidogrel (2.6%) among patients with diabetes, regardless of diabetes therapies (insulin vs no insulin), the companies noted.

TVR Rates Compared at 2 Years for DES and BMS
August 15, 2008—In the Archives of Internal Medicine, Kevin J. Anstrom, PhD, et al have published findings from a study of long-term clinical outcomes after coronary stenting (2008;168:1647-1655). The investigators concluded that patients receiving drug-eluting stents (DES) in a clinical practice setting have lower target vessel revascularization (TVR) rates than patients receiving bare-metal stents (BMS) but with less absolute benefit than those observed in clinical trials. Patients with multivessel disease experience a greater reduction in TVR than patients with single-vessel disease.

The investigators outlined the background of their study. Clinical trials of DES versus BMS report a reduced need for target lesion revascularization with no difference in death or myocardial infarction. However, these trials selectively enrolled patients with lower-risk, single-vessel coronary artery disease (CAD) and limited the follow-up period to 1 year or less. Thus, it is not known how these short-term results apply to patients with higher-risk, multivessel CAD seen in community practice settings. The objective of this study was to compare the long-term clinical outcomes of patients receiving DES versus BMS in a clinical practice setting.

As detailed in the Archives of Internal Medicine, the study population included patients from the Duke Databank for Cardiovascular Disease undergoing their initial revascularization with DES or BMS from January 1, 2000, through July 31, 2005. Propensity scores and inverse probability-weighted estimators were used to adjust for treatment group imbalances. The study was composed of 1,501 patients who received DES and 3,165 who received BMS. After adjustment, DES reduced TVR rates at 6, 12, and 24 months compared with BMS (24-month rates: DES, 6.6%; BMS, 16.3%; difference, -9.7%; 95% confidence interval [CI], -11.7% to -7.7%; P<.001). The TVR benefit for DES increased among patients with multivessel CAD (one-vessel CAD: -8.3%; 95% CI, -10.9% to -5.8%; P<.001; two-vessel CAD: -9.7%; 95% CI, -3.6% to -5.8%; P<.001; three-vessel CAD: -16.2%; 95% CI, -25.2% to -7.2%; P<.001). However, in the overall cohort, there were no statistically significant differences in the composite of death or myocardial infarction, the investigators reported.

Two-Year Outcomes Reported for DES Side Branch T-Stenting
August 26, 2008—In the Journal of the American College of Cardiology: Cardiovascular Interventions, Helen C. Routledge, MD, et al published findings from a study to determine whether the deployment of drug-eluting stents (DES) in bifurcation lesions, according to a uniform provisional side branch T-stenting strategy (PTS), is a safe and effective treatment in the immediate and long term (2008;1:358-365). The investigators observed that in comparison with simple stenoses, successful percutaneous intervention for coronary bifurcation lesions is limited by a higher incidence of procedural complications and need for repeat revascularization. The investigators conducted this study because the ideal strategy to overcome these limitations remains to be demonstrated, although recent controversy surrounds the long-term safety of DES in bifurcations.

In the study, consecutive patients treated for bifurcation lesions using DES were studied in a prospective single-center registry. From 2003 to 2005, 477 procedures were performed. The PTS strategy was used in 92% of cases, with a side branch stent in 28%, and final kissing-balloon inflation in 95%.

As detailed by the investigators, angiographic success was achieved in 99% with 2.5% in-hospital major adverse cardiac events. The cumulative rate of major adverse cardiac events was 10.7% at 1 year and 13.6% at 2 years, including 6.9% and 8.9% target vessel revascularization, respectively. Deviation from the PTS strategy independently predicted 2-year mortality (odds ratio, 5.5; 95% confidence interval, 1.63–18.3; P<.01). The rate of definite or probable stent thrombosis at 2 years was 2.5%, with half of all events occurring before hospital discharge.

From these findings, the investigators concluded that the PTS strategy for the treatment of bifurcation lesions is applicable to more than 90% of patients in the real world. With DES, both safety and efficacy have been demonstrated in the long term with <10% need for repeat revascularization in the first 2 years and a low incidence of late-stent thrombosis.

Mayo Risk Score Validated for In-Hospital PCI Mortality
August 27, 2008—In Circulation: Cardiovascular Interventions, Mandeep Singh, MD, et al have published findings that validate the recently developed Mayo Clinic Risk Score model for in-hospital mortality after percutaneous coronary intervention (PCI) using an independent data set (2008;1:36-44).

According to the investigators, the Mayo Clinic Risk Score has seven simple clinical and noninvasive variables that are available before PCI for prediction of in-hospital mortality after PCI. The investigators concluded that this model may be useful for providing patients with individualized, evidence-based estimates of procedural risk as part of the informed consent process before PCI. External validation using an independent data set will support broader applicability of the model, the investigators stated.

For their analysis, the investigators studied the in-hospital mortality after PCI of 309,351 patients from the National Cardiovascular Data (NCD) Registry admitted from January 1, 2004, to March 30, 2006. Using the Mayo Clinic Risk Score equation, they assigned predicted probabilities of death to each patient. The area under the receiver-operating characteristics curve was 0.884, indicating excellent discrimination overall as well as among subgroups, including gender, diabetes mellitus, renal failure, low ejection fraction, different age groups, and multivessel disease. The investigators found that 97% of patients undergoing PCI had a Mayo Clinic Risk Score <10, indicating low to intermediate risk. Initially, the Mayo Clinic Risk Score model slightly underpredicted event rates when applied in NCD Registry data (observed, 1.23% vs predicted, 1.1%), but this underprediction was corrected after recalibration. The recalibrated risk score discriminated (c index=0.885) and calibrated well in an NCD Registry validation data set consisting of procedures performed between April 1, 2006, and March 30, 2007, the investigators reported.

COURAGE Quality of Life Analysis Published
August 14, 2008—In The New England Journal of Medicine, William S. Weintraub, MD, et al for the COURAGE (Clinical Outcomes Utilizing Revascularization and Aggressive Drug Evaluation) Trial Research Group have published the findings of their analysis of the benefit of percutaneous coronary intervention (PCI) to quality of life over that provided by optimal medical therapy among patients with chronic coronary artery disease (2008;359:677-687). The investigators concluded that among patients with stable angina, both those treated with PCI and those treated with optimal medical therapy alone had marked improvements in health status during follow-up. The PCI group had small but significant incremental benefits that disappeared by 36 months, the investigators found.

As detailed in The New England Journal of Medicine, the investigators randomly assigned 2,287 patients with stable coronary disease to PCI plus optimal medical therapy or to optimal medical therapy alone. They assessed angina-specific health status (with the use of the Seattle Angina Questionnaire) and overall physical and mental function (with the use of the RAND 36-item health survey [RAND-36]). At baseline, 22% of the patients were free of angina. At 3 months, 53% of the patients in the PCI group and 42% in the medical-therapy group were angina-free (P<.001). Baseline mean (±standard deviation) Seattle Angina Questionnaire scores, which range from 0 to 100, with higher scores indicating better health status, were 66±25 for physical limitations, 54±32 for angina stability, 69±26 for angina frequency, 87±16 for treatment satisfaction, and 51±25 for quality of life. At 3 months, these scores had increased in the PCI group, as compared with the medical-therapy group, to 76±24 versus 72±23 for physical limitation (P=.004), 77±28 versus 73±27 for angina stability (P=.002), 85±22 versus 80±23 for angina frequency (P<.001), 92±12 versus 90±14 for treatment satisfaction (P<.001), and 73±22 versus 68±23 for quality of life (P<.001). The investigators stated that, in general, patients had an incremental benefit from PCI for 6 to 24 months; patients with more severe angina had a greater benefit from PCI. Similar incremental benefits from PCI were seen in some but not all RAND-36 domains. By 36 months, there was no significant difference in health status between the treatment groups, the investigators reported. Eric D. Peterson, MD, and John S. Rumsfeld, MD, have published an accompanying commentary on the substudy's implications in The New England Journal of Medicine (2008;359:751-753).

Responding to the study on August 13, the Society for Cardiovascular Angiography and Interventions stated that the substudy confirms that angioplasty and stents are invaluable for the patients who need them to improve health and quality of life, stop heart attacks, and save lives. The society noted that the findings show a marked benefit from PCI for stable angina patients for up to 2 years or more, especially for those with the most frequent and severe chest pain, and that this is a significant period of time for people to enjoy an immediately improved quality of life after previously suffering debilitating chest pain. The study's results are consistent with the most recent treatment guidelines and state-of-the-art care practiced worldwide by interventional cardiologists, and patients and their primary care physicians can be confident that PCI has proven benefits, the society stated.

Off-Label DES Use Studied
August 27, 2008—In Circulation: Cardiovascular Interventions, David Austin, MD, et al have published a propensity score-matched outcome study of drug-eluting stents (DES) versus bare-metal stents (BMS) for off-label indications (2008;1:45-52). In the study, the investigators sought to determine whether clinical outcomes differ after DES and BMS implantation in a patient cohort defined by DES off-label indications. As background for the study, the investigators noted that the FDA recently concluded that data on off-label DES safety are limited; however, in actual clinical practice, DES are often used for off-label indications, and observational studies demonstrate that complications are higher when compared with on-label use.

The investigators reported that they used the national revascularization registry in Scotland to identify patients who underwent coronary stenting for an off-label indication between January 2003 and September 2005. Individual-level linkage to comprehensive national admission and death databases was used to ascertain the endpoints of death, myocardial infarction (MI), and target-vessel revascularization (TVR). Propensity scores were calculated on the basis of clinical, demographic, and angiographic variables and matched DES to BMS on a 1:1 basis. The final study population consisted of 1,642 patients, well matched for important covariables at baseline. Event-free survival was calculated over 24 months with the Kaplan-Meier method.

The investigators found that all-cause death was more common after BMS implantation during follow-up (7.7% vs 6.6%; hazard ratio (HR), 0.63; 95% confidence interval (CI), 0.4–0.99; P=.04). No difference in the rates of MI was noted (7.3% vs 7.5%; HR, 1.02; 95% CI, 0.69–1.54; P=.92). TVR was reduced in patients treated with DES (13.9% vs 10.7%; HR, 0.67; 95% CI, 0.49–0.93; P=.02). At 24 months, patients treated with DES for off-label indications had lower rates of death and TVR and similar rates of MI, as compared with patients treated with BMS, the investigators concluded.

On August 26, Bruce R. Brodie, MD, et al published results from the STENT (Strategic Transcatheter Evaluation of New Therapies) Group study on outcomes and complication with off-label use of DES in the Journal of the American College of Cardiology: Cardiovascular Interventions (2008;1:405-414). As the investigators noted, DES have been effective in randomized trials, but their safety and efficacy for off-label indications has not been well studied.

According to the investigators, the STENT Registry is the largest multicenter US registry evaluating outcomes of DES. Off-label indications included ostial, left main, long, bifurcation, and in-stent restenotic lesions, saphenous vein grafts, chronic total occlusions, small or large vessels, multilesion or multivessel percutaneous coronary interventions, and ST-segment elevation MI. Outcomes were adjusted using Cox proportional hazards regression and propensity analyses.

The investigators reported that DES were used in an off-label manner in 59% of patients. The patients who received off-label treatment were more often male, had a higher incidence of previous infarction and bypass surgery, and lower ejection fractions. Off-label versus on-label DES use was associated with higher rates of death, MI, target vessel revascularization, major adverse cardiac events, and stent thrombosis at 9 months and 2 years. Off-label use of DES compared with off-label use of BMS had lower rates of death, MI, target vessel revascularization, and major adverse cardiac events at 9 months and 2 years and lower rates of stent thrombosis at 9 months.

The STENT investigators found that off-label DES use is associated with higher event rates compared with on-label DES use, which is consistent with a higher risk clinical and lesion profile. However, event rates with off-label DES use are lower compared with off-label BMS use. Pending results from randomized trials, these data support DES use for off-label indications in selected patients, the investigators concluded.

SES and PES Compared in Diabetes Mellitus Patients
August 26, 2008—In the Journal of the American College of Cardiology, Seung-Whan Lee, MD, PhD, et al published a study that compared the effectiveness of sirolimus-eluting stents (SES) and paclitaxel-eluting stents (PES) in patients with diabetes mellitus (DM) (2008;52:727-733). The investigators conducted the study because comparison of SES with PES in diabetic patients has not been sufficiently evaluated, although it is known that drug-eluting stent implantation significantly improved the angiographic and clinical outcomes compared with bare-metal stent implantation in diabetic patients.

As detailed by the investigators, this prospective, multicenter, randomized study compared SES (n=200) and PES implantation (n=200) for diabetic patients (n=400). The primary endpoint was in-segment restenosis at 6 months according to intention-to-treat principle. The two groups had similar baseline clinical and angiographic characteristics. The investigators found that 6-month in-stent (3.4% vs 18.2%; P<.001) and in-segment restenosis (4% vs 20.8%; P<.001) and 9-month target lesion revascularization (2% vs 7.5%; P=.017) were significantly lower in the SES versus the PES group. The incidence of death (0% in SES vs 0.5% in PES; P=.999) or myocardial infarction (0.5% in SES vs 0.5% in PES; P=.999) at 9-month follow-up was not statistically different between the two groups. Major adverse cardiac events including death, myocardial infarction, and target lesion revascularization at 9 months (2% vs 8%; P=.01) were lower in the SES versus the PES group. The investigators concluded that SES implantation is superior in reducing angiographic restenosis and improving 9-month clinical outcomes in patients with diabetes mellitus and coronary artery disease compared with PES implantation.
 INDUSTRY NEWS

Medtronic Commences US Postmarket PROTECT Study
July 30, 2008—Medtronic Vascular (Santa Rosa, CA) announced the US initiation of PROTECT (Patient Related Outcomes with Endeavor versus Cypher Stenting Trial), a global study comparing Medtronic's Endeavor zotarolimus-eluting coronary stent and the Cypher sirolimus-eluting coronary stent (Cordis Corporation, Warren, NJ) on key safety metrics. PROTECT's primary endpoint is overall stent thrombosis at 3 years; secondary endpoints include death and nonfatal myocardial infarction (MI), as well as customary clinical efficacy endpoints, such as target lesion revascularization and target vessel revascularization.

According to the company, PROTECT was initiated in May 2007 with the first implants in Europe. The study will enroll 8,800 patients, equally randomized to either the Endeavor or the Cypher, at more than 200 medical centers globally. Enrollment through July stands at approximately 5,500 patients. Enrollment is expected to be complete by December 2008, with 3-year data on all study patients available in 2012.

Collectively, data from PROTECT augments the comprehensive ENDEAVOR clinical program, which involves more than 21,000 patients; more than 15,000 of these patients will have received an Endeavor stent. PROTECT sites in the US will provide the FDA with US-specific data on the postmarket experience with the Endeavor stent, which received FDA approval February 1. The US sites will enroll a minimum of 1,000 patients who receive Endeavor stents through PROTECT or, if necessary, through a nonrandomized continued-access arm, the company stated.

The company noted that very late stent thrombosis arose as a safety concern with the first generation of drug-eluting stents in the fall of 2006 when the clinical trials that supported their regulatory approvals revealed a numerical increase in the rate of very late stent thrombosis compared to their bare-metal stent controls. These first-generation drug-eluting stents have been associated with an annual rate of very last stent thrombosis of approximately 0.3% through 4 years of follow-up.

Medtronic stated that the clinical trials that supported the regulatory approvals of the Endeavor stent have shown no increase in the rate of very late stent thrombosis compared with its bare-metal stent control. The annual rate of very late stent thrombosis with the Endeavor stent in the ENDEAVOR clinical program through 4 years of follow-up is .02%, with no events after 2 years. This observation served as the rationale for PROTECT, the company stated.

Philips Launches CX50 and HD15 Ultrasound Systems
August 5, 2008—Philips Medical Systems (Bothell, WA) announced the launch of the Philips CX50 CompactXtreme handheld ultrasound system. The company stated that the portable system is designed for cardiologists to provide clear diagnostic data at the bedside with the image quality expected of a traditional, premium, full-size system. The CX50 delivers consistently high-quality images, even in technically challenging patients. The system supports adult transthoracic and transesophageal cardiology applications, the company stated.

According to the company, the CX50 CompactXtreme features Philips' PureWave transducer, which is clinically proven to improve penetration in difficult-to-image patients and to reduce clutter so clinicians can view fine structures in excellent detail. It also features Philips' XRES adaptive image processing for reduced speckle and haze inherent with ultrasound imaging. As a result, images are virtually free from noise and have extraordinary clarity and edge definition. The device's portability allows it to address multiple scanning environments. The system features Philips intuitive user interface, iSCAN automatic optimization, and on-cart quantification software (QLAB) to maximize ease of use for clinicians, advised the company.

On July 24, the company announced the launch of the Philips HD15 ultrasound system to provide high-quality imaging and workflow performance in a cost-effective system. The HD15 is a new platform designed to deliver an advanced level of image clarity and broad application support for everyday use in small hospitals, clinics, and private practices. The HD15 contains multiple usability features to improve workflow, as well as versatile capabilities for a wide range of exam types, including general imaging, cardiac, vascular, and ob/gyn applications.

According to the company, the device incorporates advanced features such as contrast-enhanced ultrasound and PureWave transducer technology that allow real-time guidance and evaluation of minimally invasive treatment procedures and provide more diagnostic confidence on technically challenging patients and pathologies. The HD15 also features QLAB quantification software, XRES image processing, and PureWave transducer crystal technology. Microfine EX focusing provides sharper images and improved tissue uniformity throughout the depth of field through application of new dynamic receive lens tuning with five times more focal points than previous-generation systems. Tissue Specific Imaging presets and iSCAN one-button image optimization can quickly provide clear images with little to no adjustment. A broad suite of configurable patient reports and exam storage options, such as DVD-CD-R/RW, USB drive, and full DICOM capabilities, provide efficient patient data management and colleague or specialist consulting, the company stated.

The HD15 offers active native data and live compare. The company noted that active native data allow clinicians to manipulate exam parameters and image settings even after the patient has left. Images and cineloops can receive further investigation by manipulating the original image to see new detail. Live compare allows the clinician to compare a previous exam side-by-side with an active exam in order to immediately see changes in structure or blood flow. This can be particularly helpful in comparing changes in cardiac and vascular anomalies, further documenting changes after interventional procedures, or evaluating fetal development, Philips noted.

Radi Medical Launches PressureWire Certus
July 8, 2008—Radi Medical Systems AB (Wilmington, DE) announced the launch of an improved PressureWire Certus, the company's next-generation pressure-sensing guidewire. The device is used in the assessment of fractional flow reserve (FFR), which is 100% specific in identifying which lesions are actually causing the flow restriction and may be treated, the company stated. The updated device features a new ergonomically designed proximal connector. The connector's large entry funnel allows for fast and easy wire reconnection into the proximal connector while exhibiting less insertion friction. In addition, the new locking cap provides positive reinforcement when the wire and the connector are locked in place via a user-intuitive on-and-off twist function.

"I am pleased that improvements to PressureWire Certus occur frequently to assist in measuring FFR in more challenging anatomy, such as we faced in the recently completed FAME (FFR Versus Angiography for Multivessel Evaluation) study," commented Nico Pijls, MD. "In this multicenter randomized trial involving 1,000 patients, FFR was measured in three arteries per patient using PressureWire. Successful, unequivocally interpretable measurement could be achieved in 99.3% of all coronary arteries thanks to recent improvements to the PressureWire."

Boston Scientific Announces 1-Year SYNTAX Data
September 1, 2008—At the annual European Society of Cardiology (ESC) congress in Munich, Germany, Boston Scientific Corporation (Natick, MA) announced the presentation of 1-year data from its trial comparing percutaneous coronary intervention (PCI) using the company's Taxus Express2 paclitaxel-eluting coronary stent system to contemporary coronary artery bypass graft (CABG) surgery. The SYNTAX (Synergy Between PCI With Taxus and Cardiac Surgery) trial's overall results demonstrated no statistically significant differences between PCI and CABG in rates of death or myocardial infarction (MI), the company stated.

According to the company, the results showed comparable safety for the two treatment groups, with a combined rate of all-cause death, stroke, and MI of 7.6% for PCI and 7.7% for CABG (P=.98). The stroke rate was 0.6% for PCI as compared to 2.2% for CABG (P=.003). Overall 12-month MACCE (major adverse cardiovascular or cerebrovascular event rate, including all-cause death, stroke, MI, and repeat revascularization) was significantly higher for PCI (17.8% compared to 12.1% for CABG; P=.0015).

Boston Scientific stated that the SYNTAX trial is the first randomized, controlled clinical trial to compare PCI using drug-eluting stents (DES) to CABG in patients with left main disease and three-vessel disease. These patient groups are typically treated with CABG and represent a population with far more complex anatomy and advanced disease than those studied in prior DES clinical trials. The trial's goal is to expand the body of knowledge of PCI use and to inform physicians on appropriate treatment options for the sickest patients. The SYNTAX trial also demonstrated a significant decrease in the rate of stroke for patients treated with PCI as compared to CABG.

The company noted that the SYNTAX trial enrolled 1,800 patients in its randomized arm, using an innovative consecutive enrollment methodology. All patients were assessed by a multidisciplinary team including an interventional cardiologist and a cardiac surgeon. If both the cardiologist and surgeon felt they could offer equivalent complete revascularization, patients were randomized 1:1 into one of the two treatment methods (PCI or CABG). If either the cardiologist or surgeon felt that PCI or CABG was the preferred option, then patients were placed in one of two parallel registries for PCI or CABG. The patients recruited in SYNTAX are a unique study group in the PCI field, given their complex anatomy and advanced disease. The average SYNTAX patient received 4.6 stents, with one patient receiving 14 stents. By contrast, the average number of stents implanted in a PCI patient in everyday practice is 1.5. In addition, the patient profile includes 33% of patients with >100-mm stented length, 84% with bi/trifurcations, 22% with chronic total occlusions, and 39% with left main disease. Some of the sickest patients in the trial were not eligible for surgery and were treated with DES.

SYNTAX is notable for scientifically defining a new measure for anatomical complexity, the SYNTAX Score, which seeks to provide guidance to physicians on optimal treatment options for this high-risk group of patients. The SYNTAX Score characterizes vasculature based on lesion frequency, complexity, and location, relying on data from the SYNTAX trial as well as information collected through other sources, Boston Scientific said.

"The study failed to meet its primary endpoint for noninferiority," stated investigator Patrick Serruys, MD, adding that the outcome was, nevertheless, hypothesis generating. He said, "The results for the first time open the way for DES in patients with more complex anatomy and advanced disease who have traditionally been treated with CABG."

Commenting on the SYNTAX findings, the Society for Cardiovascular Angiography and Interventions (SCAI) stated that the landmark SYNTAX trial data indicate that patients with very complex coronary artery disease can safely choose to be treated with angioplasty and DES rather than CABG and that that most patients with left main and multivessel disease who undergo angioplasty and stenting will not need a second revascularization procedure in the first year.

"Starting today, I can tell my patients with left main and multivessel disease that angioplasty and drug-eluting stents are just as safe for them as surgery in terms of death or heart attack," commented SCAI Past-President, Ted Feldman, MD, who is a SYNTAX Steering Committee member. "The SYNTAX results are good news for patients and physicians because we now have another treatment option for the most complex patients. PCI is less invasive than surgery, and it takes days, not weeks, to recover from."

Noting that less than 8% more PCI than bypass patients underwent either a second angioplasty procedure or bypass surgery by the end of the year following their procedure, Dr. Feldman said, "Historically speaking, this is remarkable. It means that more than 85% of patients can choose the less-invasive angioplasty/stenting option and won't need another procedure a year later. On the revascularization question, we have never seen such a small difference between PCI and bypass surgery, even in less complex patients. The take-away message is that SYNTAX has extended the spectrum of care for a large number of patients with very complex coronary artery disease. For some, bypass surgery will still be the most appropriate option, but many more patients now have another choice."

Additional presentations from the European Society of Cardiology congress will be included in Conference Coverage in the News section of the October/November issue of Cardiac Interventions Today.