SciQuest.org

I think Americans that are in a Union have pretty good health insurance overall because the unions use health coverage as one of their bargaining chits for employer based coverage. If you have AFL-CIO coverage, you are probably not one of the 47 MILLION uninsured! You also don’t have Medicaid.

So I was surprised to find a survey of more than 26,400 Americans, conducted by the AFL-CIO found that people are fed up with U.S. health care. Half of the respondents said they were union members, others were family members or self insured. I see this as the famous middle class. Because it was an online survey, they at least had computer access, and were working Americans. Listen up, Washington…the people have had it!

Among the findings:

• 95% said the health care system in the U.S. needs fundamental change or overhaul
• 46% reported spending $1000-$5000 in out-of-pocket costs over the past year
• 48% said they or a family member stayed in a job just for the health insurance
• Nearly 1/3 said their insurance company refused to cover a medical treatment that should have been covered.
• 97% said they plan to vote in the upcoming election

To read the full story go here.

Results of ENHANCE (Ezetimibe aNd simvastatin in Hypercholesterolemia enhANces atherosClerosis rEgression), an imaging trial in 720 patients with heterozygous familial hypercholesterolemia (HeFH), a rare genetic condition that causes very high levels of LDL “bad” cholesterol and greatly increases the risk for premature coronary artery disease, were presented at the 57th annual scientific sessions of the American College of Cardiology and also were published on-line in The New England Journal of Medicine.i

As previously reported on Jan. 14, 2008, despite the fact that ezetimibe/simvastatin 10/80 mg (VYTORIN® *) significantly lowered LDL “bad” cholesterol more than simvastatin 80 mg alone, there was no significant difference between treatment with ezetimibe/simvastatin and simvastatin alone on the pre-specified primary endpoint, a change in the thickness of carotid artery walls over two years as measured by ultrasound. There also were no significant differences between treatment with ezetimibe/simvastatin and simvastatin on the four pre-specified key secondary endpoints: percent of patients manifesting regression in the average carotid artery intima-media thickness (CA IMT); proportion of patients developing new carotid artery plaques >1.3 mm; changes in the average maximum CA IMT; and changes in the average CA IMT plus in the average common femoral artery IMT.

In ENHANCE, when compared to simvastatin alone, ezetimibe/simvastatin significantly lowered LDL “bad” cholesterol, as well as triglycerides and C-reactive protein (CRP). Ezetimibe/simvastatin is not indicated for the reduction of CRP. In the ENHANCE study, as previously reported, the overall safety profile of ezetimibe/simvastatin in the study was generally consistent with the product label.

“LDL cholesterol remains the primary target of lipid-modifying therapy and physicians should continue to lower patients’ elevated LDL cholesterol and get their patients to their goals based on guidelines,” said Michael Davidson, M.D., professor, director of preventive cardiology, The University of Chicago, Pritzker School of Medicine.

In the ENHANCE publication, the authors provided three theoretical explanations why, despite ezetimibe/simvastatin significantly lowering LDL “bad” cholesterol more than simvastatin (56 percent vs. 39 percent, p<0.01), there was no significant difference between treatment groups on the primary endpoint and four key secondary endpoints: (1) lowering of LDL cholesterol with non-statin therapy, such as ezetimibe, might affect IMT differently than statin therapy, (2) the imaging technology selected was not sensitive enough to detect a difference, or (3) that these HeFH patients were extensively pretreated with lipid-lowering therapy, thereby limiting the amount that CA IMT could change with further LDL cholesterol-lowering therapy, consequently limiting the ability to detect a differential response to the two treatments. The authors concluded that the reason for the failure to observe an incremental effect on CA IMT thickness in spite of a reduction of level of LDL cholesterol remains unknown.

In the publication, the authors addressed the premise that the lack of a difference in change of mean CA IMT between ezetimibe/simvastatin and simvastatin despite greater LDL cholesterol-lowering could be attributed to lipid-independent effects of statins on arteries. The authors presented several facts that argued against this concept, including a discussion of clinical studies involving statin and non-statin therapeutic approaches that demonstrated that cardiovascular risk reductions were associated with the degree of LDL-cholesterol lowering. The authors suggested that clinical outcomes data are needed to answer this question.

As for the hypothesis that the results may reflect the imaging technology, the authors noted this seems unlikely given the precision of the imaging measurement results seen in the ENHANCE trial.

With respect to the hypothesis that the ENHANCE results were due to the characteristics of the patients studied, the authors pointed out that in an earlier imaging study (extension of ASAP or Atorvastatin vs. Simvastatin on Atherosclerosis Progression study) use of potent lipid-lowering therapy in HeFH patients produced “regression” or “thinning” of CA IMT during the first one to two years of therapy, but further decreases during the following two years on the same therapy were not seen. In ENHANCE, approximately 80 percent of the enrolled patients reported taking statin treatment at the time of screening for the study, and had a mean baseline CA IMT of 0.69 to 0.70 mm. In another recent IMT study in HeFH patients (RADIANCE 1 or Rating Atherosclerotic Disease Change by Imaging with A New CETP Inhibitor study), the baseline CA IMT was also lower than in the earlier IMT study and similar to ENHANCE and, importantly, the pattern of change in CA IMT in this IMT study was very similar to that observed in both treatment groups in the ENHANCE study.

The authors noted that “these data raise the possibility that there may be limits to the extent to which the lowering of LDL cholesterol levels can result in a further decrease in the progression of intima-media thickness in the context of previous statin therapy and a modest baseline intima-media thicknessii.”

“Although a definitive explanation is never possible with a finding like this, we believe that the most likely explanation for the failure to see a significant difference between treatment groups in ENHANCE relates to the behavior of IMT in this population of HeFH patients,” noted Thomas Musliner, M.D., executive director, Cardiovascular Disease, Clinical Research, Merck Research Laboratories. “The large majority of these patients were previously treated with LDL cholesterol-lowering therapy and presumably experienced an effect on CA IMT from that treatment, as reflected in the patients’ relatively low CA IMT values when they began the study. The findings of the ASAP extension, RADIANCE 1 and ENHANCE suggest there are limits to how much IMT can be decreased in HeFH study cohorts in the context of the widespread and prolonged use of effective LDL cholesterol-lowering treatment starting at an earlier age, which is now the standard of care for these patients.”

Endpoint data and cardiovascular events

ENHANCE investigators found no statistically significant difference between the two treatment groups on the primary endpoint, the change in the average CA IMT at three carotid artery locations. The change from baseline in the mean (average) CA IMT in the ezetimibe/simvastatin group was 0.0111 mm, which did not significantly differ from the simvastatin group’s change of 0.0058 mm (P=0.29). The median data for the primary endpoint, which also showed no statistical difference between treatments, was 0.0058 mm in the ezetimibe/simvastatin group and 0.0095 mm for the simvastatin group. The treatment groups also did not have statistically significant differences for each of the three carotid artery locations that comprised the primary endpoint: the common carotid, the internal carotid and the carotid bulb. The data for these analyses, key secondary endpoints and cardiovascular events are included in the attachment.

The ENHANCE study was not designed nor powered to evaluate cardiovascular clinical events. IMPROVE-IT is underway and is designed to provide cardiovascular outcomes data for ezetimibe/simvastatin in patients with acute coronary syndrome. No incremental benefit of ezetimibe/simvastatin on cardiovascular morbidity and mortality over and above that demonstrated for simvastatin has been established.

Lipid parameters of LDL cholesterol, triglycerides and HDL cholesterol; and C-reactive protein Over the two-year period of the ENHANCE study based upon the “last observation carried forward” endpoint approach, the group treated with ezetimibe/simvastatin had a 56 percent mean reduction of LDL cholesterol (from a baseline of 319 mg/dL) that was significantly greater than the 39 percent mean reduction of LDL cholesterol (from a baseline of 318 mg/dL) in the group treated with simvastatin alone (P<0.01). The LDL cholesterol-lowering observed in patients treated with ezetimibe/simvastatin in the ENHANCE trial was generally consistent with the LDL cholesterol-lowering of ezetimibe/simvastatin seen in separate head-to-head studies vs. simvastatin, vs. Crestor® and vs. Lipitor®.

In addition, by study completion, the ezetimibe/simvastatin group had a 30 percent median reduction in triglycerides (from baseline 157 mg/dL), significantly more than the 23 percent median reduction (from baseline 160 mg/dL) in the simvastatin group (P<0.01). Also, the ezetimibe/simvastatin group had a 49 percent median reduction in CRP (from baseline 1.70 mg/L), significantly more than the 24 percent median reduction in CRP (from baseline 1.70 mg/L) in the simvastatin group (P<0.01). The ezetimibe/simvastatin group had a 10 percent increase (from baseline 46.7 mg/dL) in HDL “good” cholesterol; the simvastatin group had an 8 percent increase from baseline 47.4 mg/dL (P=0.05, no statistical significance).

Safety data

As previously reported, the overall safety profiles of ezetimibe/simvastatin and simvastatin alone were similar and generally consistent with their product labels. Both medicines were generally well tolerated. Also, the overall incidence rates of treatment-related adverse events were 34 percent for ezetimibe/simvastatin (122/357) and 29 percent (107/363) for simvastatin only; the incidence rates for discontinuations due to adverse events were 8.1 percent for ezetimibe/simvastatin (29/357) and 9.4 percent for simvastatin only (34/363). Additional adverse event data are included in the attachment.

About the study design and methodology

The ENHANCE study was an international two-year, randomized, double-blind, controlled trial in 720 HeFH patients between the ages of 30 to 75. All of the ENHANCE patients had HeFH, which affects approximately 0.2 percent of the population. The rationale for studying HeFH patients is that these patients are known to be at increased risk for premature coronary artery disease and, if untreated, exhibit increased IMT progression rates beginning in childhood. Prior LDL cholesterol-lowering therapy of any kind was not an exclusion criterion for ENHANCE, although such therapies were discontinued at the start of the study. Also, there wasn’t a minimum value for CA IMT specified for inclusion in study. Following a six-week, single blind, placebo lead-in/drug “wash-out” period, patients were randomized to receive either daily ezetimibe/simvastatin 10/80 mg (N=357) or daily simvastatin 80 mg (N=363).

ENHANCE investigators took digitized single-frame CA IMT images at the three locations of the patients’ right and left carotid arteries, the main arteries in the neck that provide blood to the brain. These images were taken at several time points: study baseline, 6, 12, 18 and 24 months.

“Examination of the CA IMT collected during ENHANCE proved to be a far more challenging process than originally anticipated when the study design was drawn up. Therefore, preparation of the images for entry into a database took significantly longer than expected, as the blinded investigators and CA IMT evaluators took numerous steps in 2006 and 2007 to address image quality control and finalize the analysis,” said Enrico P. Veltri, M.D., co-author of the ENHANCE study publication and group vice president, Global Clinical Research, Cardiovascular and Metabolic Diseases, Schering-Plough Research Institute. “Our companies acted with integrity and good faith in connection with the trial,” he said.

Important information about VYTORIN

Ezetimibe/simvastatin is indicated as adjunctive therapy to diet for the reduction of elevated total cholesterol, LDL cholesterol, Apo B, triglycerides and non-HDL cholesterol and to increase HDL cholesterol in patients with primary (heterozygous familial and non-familial) hypercholesterolemia or mixed hyperlipidemia.

Ezetimibe/simvastatin is also indicated for the reduction of elevated total cholesterol and LDL cholesterol in patients with homozygous familial hypercholesterolemia, as an adjunct to other lipid-lowering treatments (e.g. LDL apheresis) or if such treatments are unavailable.

Ezetimibe/simvastatin is a prescription medicine and should not be taken by people who are hypersensitive to any of its components. Ezetimibe/simvastatin should not be taken by anyone with active liver disease or unexplained persistent elevations of serum transaminases. Women who are of childbearing age (unless highly unlikely to conceive), are nursing or who are pregnant should not take ezetimibe/simvastatin.

Selected cautionary information for VYTORIN

Muscle pain, tenderness or weakness in people taking ezetimibe/simvastatin should be reported to a doctor promptly because these could be signs of a serious side effect. Ezetimibe/simvastatin should be discontinued if myopathy is diagnosed or suspected. To help avoid serious side effects, patients should talk to their doctor about medicine or food they should avoid while taking ezetimibe/simvastatin.

In three placebo-controlled, 12-week trials, the incidence of consecutive elevations (>3 X ULN) in serum transaminases were 1.7 percent overall for patients treated with ezetimibe/simvastatin and 2.6 percent for patients treated with ezetimibe/simvastatin 10/80 mg. In controlled long-term (48-week) extensions, which included both newly-treated and previously-treated patients, the incidence of consecutive elevations (>3 X ULN) in serum transaminases was 1.8 percent overall and 3.6 percent for patients treated with ezetimibe/simvastatin 10/80 mg. These elevations in transaminases were generally asymptomatic, not associated with cholestasis and returned to baseline after discontinuation of therapy or with continued treatment. Doctors should perform blood tests before, and periodically during treatment with ezetimibe/simvastatin when clinically indicated to check for liver problems. People taking ezetimibe/simvastatin 10/80 mg should receive an additional liver function test prior to and three months after titration and periodically during the first year.

Due to the unknown effects of increased exposure to ezetimibe in patients with moderate or severe hepatic insufficiency, ezetimibe/simvastatin is not recommended in these patients. The safety and effectiveness of ezetimibe/simvastatin with fibrates have not been established; therefore, co-administration with fibrates is not recommended. Caution should be exercised when initiating ezetimibe/simvastatin in patients treated with cyclosporine and in patients with severe renal insufficiency.

Ezetimibe/simvastatin has been evaluated for safety in more than 3,800 patients in clinical trials and was generally well tolerated at all doses (10/10 mg, 10/20 mg, 10/40 mg, 10/80 mg). In clinical trials, the most commonly reported side effects, regardless of cause, included headache (6.8 percent), upper respiratory tract infection (3.9 percent), myalgia (3.5 percent), influenza (2.6 percent) and extremity pain (2.3 percent).

About Merck/Schering-Plough Pharmaceuticals

Merck/Schering-Plough Pharmaceuticals is a joint venture between Merck & Co., Inc. and Schering-Plough Corporation formed to develop and market in the United States new prescription medicines in cholesterol management. The collaboration includes worldwide markets (excluding Japan). VYTORIN is also marketed as INEGY outside the U.S.

Merck Forward-looking Statement

This press release contains “forward-looking statements” as that term is defined in the Private Securities Litigation Reform Act of 1995. These statements are based on management’s current expectations and involve risks and uncertainties, which may cause results to differ materially from those set forth in the statements. The forward-looking statements may include statements regarding product development, product potential or financial performance. No forward-looking statement can be guaranteed and actual results may differ materially from those projected. Merck undertakes no obligation to publicly update any forward-looking statement, whether as a result of new information, future events, or otherwise. Forward-looking statements in this press release should be evaluated together with the many uncertainties that affect Merck’s business, particularly those mentioned in the risk factors and cautionary statements in Item 1A of Merck’s Form 10-K for the year ended Dec. 31, 2007, and in any risk factors or cautionary statements contained in the Company’s periodic reports on Form 10-Q or current reports on Form 8-K, which the Company incorporates by reference.

Ortho-Clinical Diagnostics announced U.S. Food and Drug Administration approval of a new diagnostic assay for the detection of antibodies to Human Immunodeficiency Virus types 1 and/or 2 (anti HIV-1 and anti HIV-2). The new VITROS® Anti-HIV 1+2 assay1 can be run in a fully automated, random access format on the VITROS ECi/ECiQ Immunodiagnostic System, with results readily available in less than 50 minutes.

This FDA approval and availability to laboratories in the U.S., Puerto Rico and U.S. territories marks the first anti-HIV 1+2 test capable of being run in full random access with other tests and providing immediate result reporting capability upon test completion. VITROS Anti-HIV 1+2 tests can be run at any time, in any order and with other types of tests. The features of automation and random access can increase productivity and efficiency in the laboratory.

The VITROS Anti-HIV 1+2 assay can help meet the demand on laboratories created by new U.S. Centers for Disease Control and Prevention (CDC) testing recommendations. The CDC now recommends routine, voluntary HIV testing in all health care settings, including health clinics and emergency rooms, for all individuals ages 13 to 64 without written informed consent. In addition, testing is recommended at least once a year for those at high risk.2

By latest estimates, approximately 1,039,000 to 1,185,000 people in the United States are living with HIV/AIDS, with 24 to 27 percent undiagnosed and unaware of their HIV infection.3 Costs associated with unrecognized or late-recognized HIV infection are growing.

Two multicenter research teams supported in part by the National Institute on Drug Abuse, National Institutes of Health, have independently determined through the development of computer models that routine screening for HIV in health care settings is as cost effective as screening for other conditions such as breast cancer and high blood pressure, and can provide important health and survival benefits. The studies also suggest that screening that leads to a diagnosis of HIV infection may further lower health care costs by preventing high-risk practices and decreasing virus transmission.4

Doctors announce findings in new drug therapy, gender disaparities

Penn experts present research findings that could come to define new standards of cardiovascular diagnostics and care at the conference of the American College of Cardiology, the foremost professional society representing heart specialists throughout the world. These experts gathered in Chicago to present and discuss the latest advances in cardiovascular medicine, science and education.

The Effect of Darapladib on Plasma Lipoprotein-Associated Phospholipase A2 Activity and Cardiovascular Biomarkers in Patients with Coronary Heart Disease or Risk Equivalent

Emile R. Mohler, MD, Director of Vascular Medicine and Associate Professor of Medicine
Sunday, March 30

Dr. Mohler presented results of a trial that may herald a new class of medications to prevent heart attack and stroke. Researchers at Penn and several other sites around the world studied the safety and efficacy of the drug darapladib (manufactured by GlaxoSmithKline) on Lp-PLA, an enzyme associated with inflammatory activity and increased risk for heart attack and stroke.

The drug was tested among patients already taking a cholesterol-lowering statin drug. After 12 weeks on a daily regimen of 160 mg of darapladib, blood tests revealed a decrease in two important circulating biomarkers, suggesting a possible reduction in systemic inflammatory burden.

While the drug doesn’t necessarily act to shrink plaque, Mohler says the research suggests that darapladib may reduce plaque inflammation and therefore lower rates of clot formation and heart attacks among patients with coronary heart disease.

These findings will be published in an upcoming issue of JACC, the Journal of the American College of Cardiology.

Under-Referral of Women for Atrial Fibrillation Ablation: Can This Be Explained by Gender Differences in Outcome?

Andrea M. Russo, MD, Electrophysiology Laboratory Director and Clinical Associate Professor of Medicine
Sunday, March 30

Dr. Russo and her colleagues from the division of cardiovascular medicine at Penn presented research on disparities in treatment of women suffering atrial fibrillation, one of the most common abnormal heart rhythms.

Although women represent more than half of patients with this serious rhythm problem, they are less likely to be referred for atrial fibrillation ablation - a therapy that uses radiofrequency energy to cauterize the heart tissue around each pulmonary vein to keep abnormal electrical signals from reaching the rest of the heart and triggering the faulty rhythm - than men.

Russo studied 1,165 women and men who underwent ablation at Penn and found that both groups had similar arrhythmia control at 24 months after the procedure (84 percent of women and 89 percent of men), suggesting that more women should be referred for ablation therapy.

Women Face Higher Risk for Decline in Left Ventricular Ejection Fraction Following Orthotopic Liver Transplant

James N. Kirkpatrick, MD, Assistant Professor of Medicine
10 a.m., Tuesday, April 1

Chronic liver disease patients often have low systemic vascular resistance that causes low blood pressure before liver transplant, but after receiving a new liver, they may suffer post-operative heart problems that leave the left ventricle unable to pump out an adequate amount of blood. This situation puts patients at a greater risk of organ failure and death.

Dr. Kirkpatrick and his colleagues studied 80 patients who received an orthotopic liver transplant - the procedure in which the patient’s native liver is removed and replaced with a donor organ in the same spot - to determine who would be more likely to suffer post-transplant complications of the left ventricle.

Researchers found that female patients were more likely to exhibit a left ventricular ejection fraction depression following transplant, with 36.7 percent of women suffering the complication, compared to 16 percent of men.

Kirkpatrick believes that careful pre-operative ventricular assessment may help identify patients who could benefit from careful monitoring of blood pressure, heart rate and volume status, and, possibly, serial echocardiograms. Some of these patients may benefit from aggressive treatment with medications like ACE-inhibitors and beta blockers. The Penn researchers plan to test newer echocardiographic techniques before and after transplant to refine ways to identify these patients.

Prasugrel has been shown to block platelet activity in patients with acute coronary syndromes (ACS) more effectively than clopidogrel, and to cut by more than half the risk of thrombosis, or blood clotting, inside the coronary stent. Now a new analysis of data from the Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel (TRITON-TIMI 38) reveals that the investigational drug maintains its edge over clopidogrel regardless of the type of stent, the amount of time since the stenting procedure, or the way stent thrombosis is defined.

The results of the TRITON-TIMI 38 analysis are being reported in a Late-Breaking Clinical Trials session at the SCAI Annual Scientific Sessions in Partnership with ACC i2 Summit (SCAI-ACCi2) in Chicago. SCAI-ACCi2 is a scientific meeting for practicing cardiovascular interventionalists sponsored by the Society for Cardiovascular Angiography and Interventions (SCAI) in partnership with the American College of Cardiology (ACC). The study will be simultaneously published online in The Lancet.

For the main TRITON-TIMI 38 study, researchers recruited 13,608 patients with ACS who needed stenting from 707 medical centers in 30 countries. Patients were randomly assigned to anti-platelet therapy consisting of either a 300-mg loading dose of clopidogrel before the procedure, followed by a maintenance dose of 75 mg daily for one year, or to a loading dose of 60 mg of prasugrel, followed by 10 mg daily for one year. Both medications prevent unwanted blood clotting by inhibiting the ability of platelets to clump together.

Stephen D. Wiviott, MD, Brigham and Women’s Hospital, Boston, led the new stent analysis. Of the 12,844 patients who ultimately were treated with at least one coronary stent, 6,461 patients received only bare-metal stents (BMS), and 5,743 patients received only drug-eluting stents (DES). Overall, prasugrel reduced both early stent thrombosis — within 30 days of stenting — when compared with clopidogrel (0.64 percent vs. 1.56 percent, hazard ratio 0.41, p<0.001) — and late stent thrombosis — more than 30 days after stenting (0.49 percent vs. 0.82 percent, hazard ratio 0.60, p=0.035). For bare-metal stents, the respective rates of stent thrombosis with prasugrel and clopidogrel were 1.3 percent vs. 2.4 percent, hazard ratio 0.52, p=0.009, and for drug-eluting stents, 0.8 percent vs. 2.3 percent, hazard ratio 0.36, p<0.001. Prasugrel’s advantage remained highly statistically significant across a broad array of patient and procedural characteristics.

Dr. Wiviott will present the results of the “Trial to Assess Improvement in Therapeutic Outcomes by Optimizing Platelet Inhibition with Prasugrel” (TRITON-TIMI 38) stent substudy on Saturday, March 29 at 9:00 a.m. CDT in the Grand Ballroom, S100. The study will be simultaneously published online in The Lancet.

Boston Scientific Corporation (NYSE: BSX) announced results from an analysis of 4,772 patients from its TAXUS ARRIVE 1 and 2 registries, designed to assess the performance of the TAXUS(R) Express2(TM) Paclitaxel-Eluting Coronary Stent System in real-world practice. The one-year pooled ARRIVE data confirmed the known higher mortality rate for diabetics versus non-diabetics with cardiovascular disease(1), but showed that the TAXUS Stent had similarly low rates of stent-related cardiac death, myocardial infarction (MI), stent thrombosis, and major cardiac events (MCE) across those two patient subsets. The study also showed similar rates of target vessel re-intervention (TVR) and TAXUS-related TVR in indicated patients(2) per the European Union (EU) label, whether or not they had diabetes. Analysis of the data was presented by D. Lynn Morris, M.D., at the SCAI Annual Scientific Sessions in Partnership with the ACC/i2 Summit in Chicago.

The pooled analysis included one-year data on 1,530 medication-requiring diabetic patients and 3,242 non-diabetic patients from the ARRIVE registry program. Due to significant disparity in baseline characteristics between diabetic and non-diabetic patients, propensity score analysis was used to allow for adjustment of baseline differences (other than the presence of diabetes) between the two groups.

The results showed diabetic patients had the well-known higher overall adjusted one-year mortality rate than patients without diabetes (3.7% vs. 2.3%, respectively, p=0.016), with the difference being driven by the cardiac death rate (2.3% vs. 1.2%, p=0.014), and reflecting the more advanced cardiac disease associated with diabetes. However, this difference was not related to the TAXUS Stent as the TAXUS Stent-related cardiac death rates at one-year were comparable in diabetics and non-diabetics, respectively (1.0% vs. 0.7%, p=0.29) in this patient population(2). Additionally, TAXUS Stent-related MCE rates (cardiac death, MI, and re-intervention) at one year were comparable (5.7% vs. 5.6%, p=0.80), as was the incidence of TAXUS Stent-related MI (1.6% vs. 1.2%, p=0.26), in both groups. Stent thrombosis at one year was low and showed no significant difference between diabetics and non-diabetics under Protocol definition (1.5% vs. 1.3%, p=0.59) or ARC Definite/Probable (1.7% vs. 1.2%, p=0.29). Unadjusted one-year rates of TAXUS Stent-related cardiac death, TAXUS Stent-related MCE, TAXUS Stent-related MI, and protocol-defined stent thrombosis showed no differences between the two populations (p-values of 0.30, 0.74, 0.31, and 0.65, respectively), suggesting that the safety profile is comparable for the two groups despite increased underlying risk in patients with diabetes.

Additionally, the ARRIVE analysis confirmed that the TAXUS Stent maintained comparable re-intervention rates in the diabetic and non-diabetic patient populations in ARRIVE 1 and 2. Rates of one-year TVR, whether adjusted or unadjusted, were similar between the patient groups (6.1% vs. 6.0%, p=0.80, adjusted). TAXUS Stent-related re-intervention of a target vessel (equivalent to target lesion revascularization, or TLR) was also similar between the patient groups (4.3% vs. 4.5%, p=0.70), despite the known higher risk for re-intervention in diabetic patients.

“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 Dr. Morris of the Albert Einstein Medical Center in Philadelphia, PA. “While the diabetic patients had more cardiac risk factors and co-morbidities than non-diabetics, the TAXUS- related cardiac death, MI and stent thrombosis in the ARRIVE 1 and 2 registries were similar in both groups, even without adjustment for risk factors.”

“Our extensive ARRIVE registries provide valuable insights into diabetic patients who are often at higher risk for mortality and repeat stenting procedures,” said Paul LaViolette, Chief Operating Officer at Boston Scientific. “The ARRIVE data demonstrated that the TAXUS Stent neutralized diabetes as a risk factor for clinical restenosis in the patients studied.”

The growing diabetic subset accounts for more than one-quarter of all coronary interventional procedures in the United States. Diabetes is generally associated with an increased risk of cardiovascular events and patients with diabetes are more likely than non-diabetic patients to require repeat procedures due to a higher incidence of restenosis following angioplasty and stenting.

The safety and effectiveness of the TAXUS Express Stent has not been established in patients with diabetes in the United States.

Boston Scientific is a worldwide developer, manufacturer and marketer of medical devices whose products are used in a broad range of interventional medical specialties. For more information, please visit: http://www.bostonscientific.com.

The investigational antiplatelet drug prasugrel plus aspirin produced a marked and highly statistically significant reduction in the risk of coronary stent thrombosis (ST) - a major concern for physicians and patients with potentially fatal consequences - in patients who received a stent as compared to standard therapy with clopidogrel (Plavix(R)) plus aspirin (1.13 percent vs. 2.35 percent, p<0.0001), according to a stent analysis from the head-to-head TRITON-TIMI 38 trial.

The findings were presented today by Dr. Stephen Wiviott, an assistant professor of medicine at Harvard Medical School and investigator with the Thrombolysis in Myocardial Infarction (TIMI) Study Group, at the Society for Cardiovascular Angiography and Interventions Scientific Sessions with the American College of Cardiology’s Innovation in Intervention: i2 Summit, in Chicago. In addition, the manuscript was simultaneously published online by the British medical journal, The Lancet.

In the TRITON-TIMI 38 trial, whose overall results were previously published, 12,844 of the 13,608 enrolled patients received at least one intracoronary stent. Of those patients, 6,461 received a bare metal stent (BMS), 5,743 patients received a drug-eluting stent (DES), and 640 patients received both BMS and DES at the time of enrollment. Stent thrombosis was a pre-defined secondary endpoint in the trial.

Prasugrel reduced the relative risk of coronary stent thrombosis (a new clot at the implanted stent site) over clopidogrel by 52 percent (1.13 percent vs. 2.35 percent, p<0.0001). In patients who received drug-eluting stents (DES), treatment with prasugrel reduced relative risk by 64 percent over clopidogrel (0.84 percent vs. 2.31 percent, p<0.0001), and by 48 percent in patients who received bare metal stents (BMS) (1.27 percent vs. 2.41 percent, p=0.0009).

In the analysis, prasugrel was consistent in reducing stent thrombosis, compared to clopidogrel, whether assessment occurred early or late (<30 days and greater than or equal to 30 days, out to 450 days, the median duration of therapy), regardless of the type of stent used (bare metal or drug-eluting), and regardless of which academic research consortium (ARC) definition of stent thrombosis was used - definite/confirmed stent thrombosis, definite/confirmed plus probable stent thrombosis, and definite/confirmed plus probable plus possible stent thrombosis. Definite/probable stent thrombosis was reduced by 59 percent in prasugrel-treated patients within 30 days of stent placement (0.64 percent vs. 1.56 percent, p<0.0001), and by 40 percent after 30 days (out to 450 days, 0.49 percent vs. 0.82 percent, p=0.03).

“Stent thrombosis is very serious, given the high risk of mortality. In TRITON, among 210 patients with definite or probable stent thrombosis, 186 (89 percent) either died or experienced an MI as a result of the event,” said Francis Plat, M.D., vice president, clinical development, Daiichi Sankyo Company, Limited. “We were excited by the results of this study and the possibility that prasugrel may someday provide an alternative treatment for ACS patients undergoing PCI and receiving coronary stents.”

A 19 percent reduction in risk was observed with prasugrel compared with clopidogrel among all patients receiving a stent (9.7 percent vs. 11.9 percent, p=0.0001) in TRITON’s primary endpoint of cardiovascular death, non- fatal heart attack, or non-fatal stroke. A 20 percent relative reduction favoring prasugrel was observed in the primary endpoint in patients who received only a bare metal stent (10.0 percent vs. 12.2 percent, p=0.003), and in patients who received only a drug-eluting stent, results showed an 18 percent relative reduction in the primary endpoint favoring prasugrel (9.0 percent vs. 11.1 percent, p=0.019). Fatal stent thrombosis occurred in 18 (0.28 percent) patients treated with prasugrel and 29 (0.46 percent) patients treated with clopidogrel (p=0.10). Of note, of the 210 patients with stent thrombosis, 89 percent either died or had a myocardial infarction associated with the event.

The rate of major bleeding was higher in all patients receiving a stent treated with prasugrel vs. clopidogrel (2.4 percent vs. 1.9 percent, p=0.06). Major bleeding in both DES and BMS prasugrel-treated groups when compared to clopidogrel-treated patients was 3 percent vs. 2 percent (p=0.34 DES) and 2 percent vs. 2 percent (p=0.09 BMS).

In addition to a reduction in the primary endpoint (CV death, non-fatal heart attack, or non-fatal stroke), a significantly lower rate of the composite endpoint of cardiovascular death, heart attack or urgent target vessel revascularization (UTVR) was observed with prasugrel vs. clopidogrel for both bare metal stents (10 percent vs. 12 percent, p=0.009) and for drug- eluting stents (9 percent vs. 11 percent, p=0.004). A significant reduction was also seen in heart attack alone (8 percent vs. 10 percent, p=0.003, BMS and 7 percent vs. 9 percent, p=.006, DES). In DES-implanted patients, regardless of those receiving only sirolimus-eluting or paclitaxel-eluting stents, there was a similar magnitude of event reduction with prasugrel compared to clopidogrel.

For the entire cohort, sub-acute stent thrombosis (24 hours to 30 days) was 0.36 percent in prasugrel-treated patients vs. 1.19 percent in clopidogrel-treated patients (p30 days following the DES implantation (0.42 percent vs. 0.91 percent, p=0.04).

“The reduction in risk seen in patients in this analysis treated with prasugrel over patients treated with clopidogrel is encouraging for high-risk patients with acute coronary syndrome being managed with PCI,” said J. Anthony Ware, M.D., Lilly vice president for cardiovascular/acute care.

HIV-Based Lentiviral vector VRX1023 Shows Promising Results

GAITHERSBURG, Md., March 28 /PRNewswire/ — VIRxSYS Corporation will present initial scientific data for VRX1023 today at the Keystone Symposia Conference in Banff, Alberta. VRX1023 is part of a new vaccine approach — using HIV-based lentivector as vector boost. VRX1023, an HIV antigen expressing lentiviral vector, has produced positive results in mice and in preliminary non-human primate studies. A larger, confirmatory study in Rhesus Macaques has been initiated.

“VRX1023 shows exciting promise,” says Dr. Franck Lemiale, Director of Research and Development, Immunobiology for VIRxSYS. “The results from these mouse studies are very encouraging. We have seen significant long term response against HIV proteins both in terms of cellular immunity, which is mediated by T Lymphocytes, and humoral immunity, which is mediated by antibodies.”

VIRxSYS takes a different approach as anti-HIV vaccine than recently publicized failed vaccines. The company is using an engineered HIV-based lentiviral vector to deliver the vaccinating antigens. In small animals, the VRX1023 lentivector has induced long-lasting cellular and humoral response against HIV. Using a DNA prime/vector boost strategy, VIRxSYS has obtained with VRX1023 greater anti-HIV immune responses than with other viral vector boost approaches currently used in the clinic, including adenoviral vectors similar to those that have been extensively tested in patients.

The ultimate goal for an anti-HIV vaccine is to suppress the impact of the initial infection, thereby significantly slowing the process of the disease. Due to the properties of the virus, a traditional total sterilizing goal may not be achievable for an anti-HIV vaccine. The next step would be to a prophylactic vaccine, which would reduce the impact of hyper-viremia in the first weeks of the infection. The aim of this vaccine is to suppress initial viremia, preventing the massive destruction of CD4 T cells, and also to halt the subsequent slow destruction of the immune system by the latently dormant virus. Individuals will be protected but not totally sterilized, minimizing the likelihood of new infections.

“The use of a HIV-based lentiviral vector represents a truly innovative approach to anti-HIV vaccine and to all vaccination strategies in general. With VRX1023 in particular, we are turning HIV against itself. We are exploiting the virus ability to efficiently produce proteins for vaccination purposes,” said Riku Rautsola, PhD, President and CEO of VIRxSYS. “VRX1023 presents us with a renewed hope for the delivery of an anti-HIV vaccine.”

About VIRxSYS

VIRxSYS is a private biotechnology company using proprietary lentiviral vector delivery and RNA payload platforms to develop therapies for serious human diseases. The Company’s initial lentiviral delivery technology was exclusively licensed from The Johns Hopkins University and has been substantially advanced in the Company’s laboratories. The RNA payload technology was acquired and has been integrated with the Company’s lentiviral delivery technology. In addition to preclinical programs for genetic and other serious diseases, the Company is currently developing gene and vaccine therapies for HIV, one of which, VRX496, has advanced to Phase 2 human clinical trials. More information regarding VIRxSYS can be found at www.virxsys.com. Details for the Phase II study can be found at the NIH clinical trials website at clinicaltrials.gov/show/NCT00131560.

Contact: Jeneane Smith / Russell LaMontagne

Phone: 212.255.5340

Source: VIRxSYS

CONTACT: Jeneane Smith or Russell LaMontagne, +1-212-255-5340, both for
VIRxSYS

Web site: http://www.virxsys.com/
http://clinicaltrials.gov/show/NCT00131560

Implantable Device Designed for Type-2 Diabetes Patients Who Are Overweight and Do Not Respond to Current Oral Anti-Diabetic Treatments

Device Applies Electrical Stimulation to Stomach as Person Eats

NEW YORK, March 28 /PRNewswire/ — New York-Presbyterian Hospital/Weill Cornell Medical Center is recruiting patients for a national clinical research study of an investigational implantable device designed to help those with type-2 diabetes who are overweight and do not respond to current oral anti- diabetic treatments.

The Tantalus(R) System is designed to sense naturally occurring electrical activity of the stomach in real time and automatically apply electrical stimulation when a person eats. The device is implanted though a minimally invasive laparoscopic procedure that can be performed in an outpatient setting.

New York-Presbyterian/Weill Cornell is the first New York metro area medical center to recruit and actively enroll patients in this study. Diabetes affects more than one million New Yorkers.

“Even with current medications and lifestyle changes, controlling type-2 diabetes in patients who are overweight can be difficult. This new treatment potentially offers new hope for patients who have been unsuccessful in managing their diabetes and weight,” says Dr. Louis Aronne, clinical site principal investigator, director of the Comprehensive Weight Control Program at New York-Presbyterian/Weill Cornell and clinical professor of medicine at Weill Cornell Medical College.

An earlier, smaller study published in the Journal of Obesity Surgery found that the device reduced hunger and body weight in morbidly obese patients. Improvements in blood pressure were also seen.

“The primary objective of the current study is to evaluate the safety and efficacy of the Tantalus in treating overweight patients with type-2 diabetes. The device’s impact on weight loss, blood pressure and other clinical and metabolic parameters will also be studied,” says Dr. Gregory F. Dakin, the study’s co-principal investigator, bariatric and laparoscopic surgeon at New York-Presbyterian/Weill Cornell and assistant professor of surgery at Weill Cornell Medical College.

To be considered for the trial, patients must meet certain inclusion criteria, including a diagnosis of type-2 diabetes (treated with oral medications, only), a body mass index (BMI) between 28 and 45 kg/m2 and an age between 18 and 70 years. BMI can be determined by using an online calculator and entering weight and height information (one example here: http://www.nhlbisupport.com/bmi/).

New York-Presbyterian/Weill Cornell is one of thirty sites in the U.S. participating in the study, which is funded by MetaCure, the manufacturer of Tantalus. The device is currently CE-marked in Europe.

The national epidemic of type-2 diabetes, most often associated with being overweight, continues to accelerate and affects more than 20 million Americans. About one million new people are diagnosed with the disease annually. The most common form of diabetes, type-2 diabetes, left untreated, may result in damage to the eyes, kidneys, nerves or heart and lead to major health complications later in life, or to death.

For more information on and to be considered for the study, please call the study coordinator at (212) 583-1000 or email smw2004@med.cornell.edu.

Source: MetaCure

CONTACT: Erich A. Sandoval for MetaCure, +1-212-867-1773,
esandoval@lazarpartners.com

Web site: http://www.nhlbisupport.com/bmi