CD&D Washington Editor and Staff Reports

WASHINGTON – The question of the appropriate duration of dual anti-platelet therapy (DAPT) for patients getting coronary artery stents has generated almost as much controversy as the late stent thrombosis issue, with the stent makers hewing more or less to their own ideas as to the ideal length of time on DAPT. At TCT 2008, participants in a "town hall meeting" hosted by the Department of Health and Human Services unveiled a massive trial that will look at the effect of DATP on as many as 20,000 patients and will likely cost about $100 million, a sum that will be funded by industry. The study – aptly named the Dual Antiplatelet Therapy (DAPT) trial – will review two primary endpoints, stent thrombosis and major adverse cardiac and cerebrovascular events, and the study's sponsors hope to enroll patients by the end of this year with the aim of completing the study by the end of 2012.

The idea of such a trial has been making the rounds since the December 2006 advisory committee meeting during which FDA examined the DES question, and Mitch Krucoff, MD, of the Duke Clinical Research Institute (Durham, North Carolina), filed an investigational device exemption for the CODA (Clopidogrel: Optimal Duration of Antiplatelet Therapy) trial earlier this year.

CODA won no support from industry because the design did not help establish the safety profile of a DES or the effect of DAPT on late stent thrombosis.

Andrew Farb, MD, a medical officer at FDA, told Cardiovascular Devices & Drugs that the patients will be on aspirin and either clopidogrel (Plavix) or prasugrel (Effient) for 12 months and then will be randomized either to a placebo or ongoing DAPT for up to 30 months. He acknowledged that given the fears that have surrounded stents and stent thrombosis, "getting patients to consent to randomize may be difficult." Still, there is little choice, he said, because a registry will not answer the questions that have to be answered for DES use.

Farb also said that the Harvard Clinical Research Institute (HCRI; Boston) will conduct the study at a number of centers across the U.S. Laura Mauri, MD, of HCRI is the co-principal investigator along with Dean Kereiakes, MD, of the Linder Research Center at Ohio State University (Columbus). No sites outside the U.S. will participate in the study.

Endeavor data reveal some safety issues

Medtronic (Minneapolis) reported the target lesion revascularization (TLR) rate for the company's Endeavor drug-eluting stent in the real-world Danish trial, SORT OUT III, was 4% at the Transcatheter Cardiovascular Therapeutics (TCT) Scientific Symposium in Washington in mid-October.

This result at nine months is consistent with the ENDEAVOR-Five real-world study, which reported an overall TLR of 4.5% at 12 months. The rates of myocardial infarction in the SORT OUT III study were very low for both the Endeavor (1.4%) and Cypher (0.5%) stents. The rate of stent thrombosis in SORT OUT III for Endeavor was 1.2% (ARC definite), consistent with typical rates of stent thrombosis for both drug-eluting and bare-metal stents after nine months of patient follow up.

Surprisingly, however, the SORT-OUT III study at nine months reported a 1% TLR rate for Cypher, considerably less than the 4.5% TLR reported in the similar SORT OUT II study (Galloem et al, JAMA 2008) previously conducted in the same five centers by the same group. In addition, the stent thrombosis rate for the Cypher stent was 0.2%, compared to 1.7% reported in the SORT OUT II study.

Jens Flensted Lassen, the study investigator said, "We were very surprised by these results — specifically those for Cypher and especially compared to the SORT OUT II data." It was also noted during the presentation that late stent thrombosis becomes meaningful as a safety signal only after one year.

"We expect a negative but manageable impact from these studies," said Larry Biegelsen, senior analyst, medical supplies & devices, Wachovia Capital Markets (Charlotte, North Carolina). "We forecast worldwide Endeavor sales of $674 million in FY09 or about 4% of total MDT sales. We think this data will probably shave a few share points off Endeavor's share in the U.S. and Europe."

Lassen commented on the safety outcomes in the study, which reported stent thrombosis for Endeavor of 1.2% at nine months, "This is only half the story, as we saw with ENDEAVOR IV, we expect late catch-up with Cypher."

Lassen's comments acknowledge that while early events were also seen with Endeavor in the ENDEAVOR IV study at 12 months, there were no instances of late stent thrombosis with Endeavor after 369 days, in follow up to two years.

Medtronic soon will complete enrollment in the PROTECT clinical study. The PROTECT study is the largest randomized trial focusing on the safety of drug-eluting stents. This 8,800-patient trial is being conducted at 200 centers worldwide and will compare Medtronic's Endeavor stent and Cypher, made by Cordis (Miami Lakes, Florida), using key safety endpoints and other clinically relevant outcomes. The primary endpoint for the PROTECT study will be overall stent thrombosis at three years.

Fewer MIs with Endeavor than Taxus

Two-year results from the ENDEAVOR-IV clinical trial show that the Endeavor drug-eluting stent (DES) from Medtronic is associated with statistically fewer heart attacks than Boston Scientific's (Natick, Massachusetts) Taxus DES.

Martin Leon, founder and chairman emeritus of the TCT-sponsoring Cardiovascular Research Foundation (New York) and principal investigator of ENDEAVOR-IV, presented the results at the TCT meeting as part of a late-breaking clinical trials session.

"Through two years of follow up in the ENDEAVOR-IV clinical trial, the Endeavor drug-eluting stent has proven to be statistically safer than Taxus on the important measure of myocardial infarction, and no different in terms of efficacy as measured by the need for repeat procedures," said Leon. "The latest data clarify the comparative safety and efficacy of these two drug-eluting stents beyond one year. As importantly, the data also show that Endeavor is associated with numerically fewer instances of very late stent thrombosis."

The latest update to an independently conducted pooled data analysis shows the Endeavor DES is distinguished by persistently strong safety benefits for patients with coronary artery disease. Called ENDEAVOR-Safety, the analysis now includes more than 1,100 patients followed to four years.

Compared to a bare-metal stent, the Endeavor DES has been shown at four years to be associated with numerically lower rates of death, cardiac death, major adverse cardiac events (MACE), myocardial infarction (MI) and stent thrombosis, with the differences in rates of cardiac death and MI between the two devices reaching statistical significance in this retrospective analysis.

Laura Mauri, chief scientific officer of the Harvard Clinical Research Institute, an interventional cardiologist at Brigham and Women's Hospital (Boston) and principal author of the ENDEAVOR-Safety analysis, said: "These data are truly remarkable when you remember that we're not comparing Endeavor to another DES but to a bare-metal stent. The stent thrombosis figures alone present a compelling case. Despite more than 70 percent of Endeavor patients being off dual-antiplatelet therapy at 12 months, the cumulative incidence of ARC-defined (Academic Research Consortium) stent thrombosis at four years is only 0.7%, almost half the rate observed for the bare-metal stent."

Medtronic also reported that of those treated with its Endeavor Resolute DES in the RESOLUTE IDE trial only two patients required repeat procedures – a 1.5% rate of target lesion revascularization (TLR) – at two years following implant.

There were no instances of stent thrombosis among the 130 study subjects, all receiving an Endeavor Resolute DES, through 24 months of follow-up.

"The goal of the RESOLUTE clinical program is to extend the proven long-term safety and durable efficacy benefits that our flagship Endeavor DES offers to patients who are underserved by currently available treatment alternatives," said Sean Salmon, VP and general manager of Medtronic's Coronary and Peripheral Vascular business. "The Resolute DES will complement our coronary stent portfolio as we seek to address the unmet clinical needs of patients at high risk of restenosis."

Medtronic also released new data from the ENDEAVOR clinical program that reinforces the strong performance of the company's Endeavor drug-eluting stent (DES) across diverse patient populations affected by coronary artery disease.

One-year results from the ENDEAVOR-Five registry – including those for subsets of diabetics and patients with acute myocardial infarction – demonstrate that the Endeavor DES performs comparably in a real-world population of patients with complex disease and in specific patient subsets, the company said.

Positive results from Taxus registry

Boston Scientific reported positive one-year results from the Intercontinental and European launch phases of its global Taxus OLYMPIA registry, which it said is the world's largest prospective, post-approval registry for a single drug-eluting stent (DES).

OLYMPIA is designed to analyze real-world clinical outcomes data for Boston Scientific's second-generation Taxus Liberte paclitaxel-eluting coronary stent system in the treatment of patients with coronary artery disease.

Outcomes from the 22,000-patient study are focused on high-risk lesion subgroups and patients with serious co-morbid conditions. Results were presented by Waqar Ahmed, MD.

Boston Sci said the Taxus OLYMPIA registry employs a consecutive enrollment process and consists of diverse and high-risk patient populations, reflecting real-world patients found in everyday clinical practice.

One-year data were collected for a total of 22,345 patients to date in 57 countries, with cardiac events validated by independent medical review. A large majority of patients (75%) were considered "expanded use" cases consisting of challenging lesions or complex clinical characteristics.

The overall OLYMPIA population included patients with multi-vessel disease (56.5%), prior percutaneous coronary intervention (27.9%), multiple stents (32.3%) and medically treated diabetes (27%).

The company said one-year data demonstrated "excellent outcomes" for the Taxus Liberte stent in patients with high-risk lesions (small vessels, long lesions, B2/C lesions) and patients with co-morbid conditions (prior stroke, acute MI, chronic renal disease).

Results demonstrated a low overall 4.4% rate of Taxus Liberte stent-related composite cardiac events, including cardiac death (1.4%), myocardial infarction (0.9%), and re-intervention (3.1%). The definite stent thrombosis rate was 0.8% after one year. The Taxus Liberte stent also exhibited a high degree of procedural success at 99.7%.

Boston Scientific also reported results from an analysis of nearly 7,500 patients from its TAXUS ARRIVE 1 and 2 registries, designed to confirm the performance of the TAXUS Express2 in real-world practice. The two-year pooled ARRIVE data showed that the TAXUS Stent reduced restenosis in patients with diabetes as effectively as in patients without diabetes, with no incremental risk of myocardial infarction or stent thrombosis.

"The ARRIVE diabetic subset data demonstrated that the TAXUS Stent mitigated the adverse effect of diabetes as a risk factor for restenosis and repeat procedures in the patients studied," said John Lasala, MD, professor of medicine at Washington University School of Medicine (St. Louis). "While the diabetic patients had more cardiac risk factors, comorbidity and higher mortality than non-diabetics, the rates of reintervention, MI and stent thrombosis in the ARRIVE 1 and 2 registries were similar in both groups, regardless of risk profile."

Boston Scientific also reported data from the TAXUS ATLAS clinical program, a series of global, prospective, multi-center, single-arm controlled trials, which evaluate the TAXUS Liberte in a variety of lesions and patient groups.

"The TAXUS ATLAS studies reinforce the long-term safety and efficacy of the TAXUS Liberte Stent while demonstrating the ability to access complex lesions. The data showed significantly reduced restenosis in small vessels and positive results in direct stenting procedures," said Mark Turco, MD, director of the Center for Cardiac and Vascular Research at Washington Adventist Hospital (Takoma Park, Maryland), and co-principal investigator of the trial. "The positive ATLAS data suggest that improvements in stent design and a reduction in strut thickness may contribute to improved clinical outcomes for patients treated with the TAXUS Liberte stent."

The company also reported 12-month left main and three-vessel disease subset data from its SYNTAX trial comparing percutaneous coronary intervention (PCI) using the TAXUS Express2 Paclitaxel-Eluting Coronary Stent System to contemporary coronary artery bypass graft (CABG) surgery.

The results reinforced previously reported data demonstrating no overall statistically significant differences between PCI and CABG in rates of death or myocardial infarction. The Company also presented an analysis of the data based on the SYNTAX Score, a new tool that seeks to provide guidance to physicians on optimal treatment options for this high-risk group of patients, showing similar safety and efficacy outcomes for two thirds of SYNTAX randomized patients.

The SYNTAX trial is the first large-scale, randomized, controlled clinical trial comparing PCI using DES to CABG in patients with left main disease and three-vessel disease.

"The data announced today will provide important additional information for doctors as they evaluate treatment options for complex coronary patients," said Keith Dawkins, MD, associate chief medical officer of Boston Sci.

"The comparable safety and efficacy outcomes with PCI and CABG in patients with left main disease in this trial indicate PCI is a good treatment alternative for this patient population," he said. "Physicians will also be able to consider the SYNTAX Score analysis, demonstrating no difference in safety and efficacy outcomes between PCI and CABG in approximately two-thirds of the SYNTAX patient population, when assessing the appropriate treatment for their patients."

Xience V tops Taxus in meta-analysus

Data from an independent meta-analysis of Abbott Laboratories' (Abbott Park, Illinois) SPIRIT II and SPIRIT III randomized clinical trials demonstrated that the Xience V everolimus-eluting coronary stent system continues to deliver clinically significant benefits for patients compared to the Taxus paclitaxel-eluting coronary stent system out to two years.

In this meta-analysis, which included patients from the U.S., Europe and Asia-Pacific, Xience V demonstrated clinical superiority to Taxus in the endpoints of target vessel failure (TVF) and major adverse cardiac events (MACE) at two years. Xience V also demonstrated significantly lower clinical events rates than Taxus in the key efficacy (target lesion revascularization) and safety (cardiac death or heart attack) components of MACE at two years. The results were presented by Gregg Stone, MD, principal investigator of the SPIRIT III trial. The meta-analysis of 1,302 patients from the SPIRIT II and SPIRIT III trials demonstrated several notable results for Xience V at two years:

A clinically significant 31% reduction in the risk of ischemia-driven Target Vessel Failure (TVF, cardiac events related to the treated vessel) compared to Taxus (10.4% for Xience V vs. 14.7% for Taxus). TVF is a composite clinical measure of safety and efficacy outcomes defined as cardiac death, heart attack (myocardial infarction or MI) or target vessel revascularization (TVR).

"With the subgroup analysis, we saw encouraging trends of lower event rates between one and two years for patients treated with Xience V compared to patients treated with Taxus, regardless of patient or lesion complexity," said John Capek, PhD, executive VP, medical devices at Abbott. "Even though the SPIRIT III trial was not designed for statistical comparisons in subgroups, these positive trends demonstrate that Xience V performs in a consistent manner and gives physicians confidence in Xience V as they consider what is the most effective treatment for their patients."

Abbott also reported two-year data from 30 patients in its ABSORB clinical trial, demonstrating that its bioabsorbable drug eluting stent successfully treated coronary artery disease and was absorbed into the walls of treated arteries within two years, leaving behind blood vessels that appeared to move and function similar to unstented arteries.

Patients who received Abbott's bioabsorbable DES and followed out to two years experienced no stent thrombosis and no new MACE between six months and two years. These results confirmed earlier positive one-year clinical results, Abbott said.

Positive results for Catania stent trial

Clinical investigators at an "Innovative Devices and Futuristic Therapies" session reported 12-month follow-up data from the ATLANTA Trial. The trial was sponsored by CeloNova BioSciences (Newnan, Georgia) maker of the Catania stent. The results include zero percent thrombosis in patients discontinuing dual anti-platelet therapy after only 30 days.

The ATLANTA Trial is a first-in-man (FIM), prospective, single center, non-randomized, single-arm study involving 55 patients (76 lesions) treated with the Catania coronary stent system with NanoThin Polyzene surface modification for symptomatic ischemic heart disease due to de novo, obstructive lesions of native coronary arteries.

At 12 months, in an unusually complex FIM patient population, the results showed 0% stent thrombosis (Academic Research Consortium, or ARC-defined), death, myocardial infarction, stroke, or coronary artery bypass graft. Target lesion revascularization was 10.9% (only 3.6% clinically driven, 7.3% non-clinically driven), with a binary restenosis rate of 6.8% (five of 74 lesions analyzed at twelve months). Of note, all patients stopped dual anti-platelet therapy after 30 days, but continued aspirin (100 mg/d) throughout the 12-month period.

The acute angiographic and procedural success rate in the ATLANTA trial was 100%. Independent core laboratories analyzed quantitative coronary angiography and intravascular ultrasound data for all patients immediately after stent implantation and at 6-month follow-up. Further analysis of 1,904 cross sections (19,028 struts) by investigators using Optimal Coherence Tomography at baseline and again at 6-month follow-up in a subset of 15 randomly selected patients revealed complete endothelialization and 99.5% stent strut coverage.

GE, Boston Sci in U/S deal

GE Healthcare (Waukesha, Wisconsin) and Boston Scientific reported a collaboration focused on improving intravascular ultrasound (IVUS) workflow between the GE Healthcare Innova Cardiovascular X-ray System and the Boston Scientific's iLab Ultrasound Imaging System. The iLab and Innova Systems are both being featured at the TCT gathering.

GE Healthcare says that the Innova help physicians to visualize fine vessels, precisely place stents and perform critical procedures. Cardiologists use it when performing procedures in the cath lab to view and treat potential coronary artery blockages that could cause heart attacks or other cardiovascular damage.

Jayant Saha, general manager, Interventional Global Marketing for GE Healthcare, said, "IVUS has proved to be an important and indispensable diagnostic tool in interventional cardiology. Boston Scientific, a leading IVUS solutions provider, and GE look forward to offering the technological advances in the field of IVUS to our joint customers …"

Boston Scientific's iLab Ultrasound Imaging System can be directly installed into the cardiac catheterization lab or radiology suite alongside the GE Innova X-ray System, enabling physicians to readily incorporate IVUS technology into their procedures. With IVUS, a tiny catheter is inserted into the heart or into a vessel where high-frequency sound waves reflect off tissue or vessel walls. The reflected sound waves create a cross-sectional image from within the vessel or heart to aid in visualizing vessel and heart structure.

Additionally, visitors to GE Healthcare's exhibit at TCT got a glimpse into the future of interventional cardiology, including the Innova cardiovascular X-ray system, aided by the new Innova Dose, Innova 3D and Innova with Stent Technologies features. Designed to further improve on the industry's leading dose efficiency technologies, GE's Innova Dose package delivers superb image quality and custom dose management, according to the company.

Intended to enhance, but not replace, 2D fluoroscopic imaging, the Innova 3D imaging technique aids in acquiring and reconstructing 3D cardiac anatomy images right in the cath lab. Innova with Stent Technologies simplifies lesion assessment and provides exceptional stent visualization, with one-button activation and can be fully integrated with Innova IVUS systems.

Other TCT news …

• Elixir Medical (Sunnyvale, California) reported results from three multi-center, first-in-human studies of novolimus- and myolimus-eluting coronary stent systems.

At the 12-month clinical follow-up, the novolimus-eluting coronary stent system demonstrated sustained efficacy and clinical safety with no MACE events or incidents of stent thrombosis.

Six-month clinical, angiographic and IVUS results from the myolimus-eluting coronary stent system with Elixir's bioabsorbable polymer revealed that one patient experienced a non Q-wave myocardial infarction and one patient experienced a target lesion revascularization.

Six-month angiographic and IVUS results from the first cohort of 15 patients demonstrated an in-stent late lumen loss of 0.37 ± 0.44 mm and a volume obstruction of 14.2 ± 7.7%. There were no incidents of stent thrombosis.

• Research presented by Stephen Silberstein, MD, director of the Jefferson Headache Center at Thomas Jefferson University Hospital (Philadelphia) suggests that two-thirds of all chronic migraine sufferers have a hole in their heart or a right-to-left shunt. This leads to abnormal blood flow that bypasses the filtration process within the lungs and may be a significant contributor to chronic headache pain.

Silberstein's presentation was titled "First Report of Clinical Trial Results: The Prevalence of PFO in Patients with Chronic Migraine." In the study, 66% (86 of 131) of adult chronic migraine sufferers in the statistically valid research effort were found to have an abnormal right-to-left shunt of blood that travels to the left side of the heart without being properly filtered by the lungs. According to Silberstein, the most common form of RLS heart defects are patent foramen ovales (PFOs), a condition that previous research shows is typically found in 25% of all people.

According to Silberstein, not all PFOs cause clinical problems in patients; however, this new data may indicate that patients who suffer from chronic migraine have a higher prevalence on PFO vs. the general population.

"Instead, we found a correlation more than 2.6 times the expected results (86 patients). This is a very significant difference. In other words, it's highly likely there's a strong connection between PFO/RLS heart defects and chronic migraines. If our results are borne out in future research, such studies will suggest a fairly simple way to eliminate or reduce chronic migraine pain – close PFO defects."

• Lumen Biomedical (Plymouth, Minnesota) reported that principal investigator Subbarao Myla, MD, presented the results from the EPIC Clinical Trial: Evaluating the Use of the FiberNet Embolic Protection System in Carotid Artery Stenting.

From March 2007 to May 2008, the multi-center, single-arm EPIC clinical trial evaluated the FiberNet Embolic Protection System (EPS) during carotid artery stenting of 237 high surgical risk patients with a critical carotid artery stenosis.

The FiberNet EPS captures particles released during the carotid artery stenting procedure with a filter made of a 3-D matrix of fibers, designed to prevent microscopic debris from traveling to the brain. After the particles have been captured, the FiberNet filter is then retrieved into the retrieval catheter, Lumen Biomedical's FDA-cleared Xtract Aspiration Catheter, and removed from the patient.

The mean age of the patients participating in the clinical trial was 74 years (21% were octogenarians), 64% male and 20% were symptomatic.

Overall, the combined major adverse event rate at 30 days for all death, stroke and myocardial infarction was 3%. There were five strokes for a 30-day stroke rate of 2.1%. There were no unanticipated adverse device effects. The results demonstrate that FiberNet EPS' unique features may contribute to a lower stroke rate during carotid artery stenting in high surgical risk patients, according to the company.

"Results from the EPIC trial confirm Lumen Biomedical has set the bar for the next generation of embolic protection devices," said Matthew Ogle, CEO of Lumen. "As the market continues to yield positive data and engineer superior product advancements, it will provide the fuel to further propel the growth of carotid stenting worldwide."

• St. Jude Medical (St. Paul, Minnesota) reported FDA and European CE mark approval of the Angio-Seal Evolution Vascular Closure Device during the conference.

The Angio-Seal Evolution device is designed to enable physicians to seal femoral artery punctures made during minimally invasive catheter-based procedures. Effectively sealing the puncture helps achieve hemostasis (cessation of bleeding) quickly, enabling the patient to walk and resume activities sooner.

The Angio-Seal Evolution platform features a delivery system that reduces the variability that can occur as physicians deploy and secure the Angio-Seal closure system. Consistent with its Angio-Seal predecessors, Angio-Seal Evolution achieves hemostasis through the deployment of an anchor, suture and collagen seal (each of which is bioabsorbable). The company said that with Evolution, however, single-handed deployment has been made possible for the first time, which enables physicians to more easily support the puncture site.

The device's automated collagen compaction system is said to ensure consistent compaction of the collagen against the exterior wall of the vessel reducing procedural variables. With fewer variables in device deployment, physicians gain greater control and consistency in achieving rapid, safe and reliable hemostasis for their patients.

"The Angio-Seal Evolution takes a major step forward by automatically compacting the collagen," said Robert Applegate, MD, Wake Forest University Baptist Medical Center, (Winston-Salem, North Carolina) "The confidence it provides physicians in closing the puncture in such a short period of time with such effectiveness is outstanding."

• L. Nelson Hopkins, MD, of the University of Buffalo and national co-principal investigator, presented positive results of the Gore EMPiRE Clinical Study, designed to demonstrate the safety and efficacy of the GORE Flow Reversal System for neuroprotection during carotid artery stenting (CAS) in patients at high risk for carotid endarterectomy.

The GORE Flow Reversal System, made by W. L. Gore & Associates (Flagstaff Arizona) provides neuroprotection by reversing the flow of blood at the carotid stenosis, thereby directing embolic particles away from the brain.

The study met the primary endpoint of major adverse events of death, stroke, transient ischemic attack and myocardial infarction (MI). The 30-day stroke, death, and MI rate was 3.7% (4.5% including TIA) and the death / any stroke rate was 2.9%.

Importantly, the study also showed encouraging results in some of the most challenging patient popu

lations with a low death, stroke, and MI rate of 2.6% for octogenarians and 3.8% for symptomatic patients. The results of the pivotal Gore EMPiRE Clinical Study were based on the enrollment of 245 patients at 28 clinical sites.

Daniel Clair, MD, of the Cleveland Clinic Foundation and national co-principal investigator for the Gore study, said, "The GORE Flow Reversal System is not only a significant advancement in neuroprotection, it is an important step forward for carotid stenting that may help establish CAS as the therapy of choice for a greater number of patients."

• Volcano (San Diego) reported the launch of its PrimeWire pressure guide wire, and the s5-FFR option for its existing installed base of s5 and s5i imaging consoles in the U.S. The PrimeWire is Volcano's newest pressure guide wire, capable of measuring pressure gradients across a lesion to determine the ischemic nature of the stenosis, and also can help determine the extent to which the blockage is flow-limiting.

The initial target market for ECOM is for the 600,000 major cardiac surgeries performed annually in the U.S. At a later stage, it will targeted at the 7 million surgeries that use an arterial line. Conmed expects to place about 100 ECOM units by year-end 2008, and 300 to 500 units in 2009.