Archive for category News

By: Bruce Sylvester

STOCKHOLM, SWEDEN – Rivaroxaban is effective and safe for treating of patients with acute, symptomatic deep vein thrombosis, researchers said at the European Society of Cardiology Congress 2010.

Results from the phase 3 Oral Direct Factor Xa Inhibitor Rivaroxaban in Patients With Acute Symptomatic Deep-Vein Thrombosis or Pulmonary Embolism (EINSTEIN-deep vein thrombosis) trial were presented.

Harry R. Büller, MD, Department of Vascular Medicine, Academic Medical Center, Amsterdam, the Netherlands said that results from the EINSTEIN-deep vein thrombosis trial showed that it is possible for this single-drug approach to provide clinicians and patients with a new way to treat deep vein thrombosis.

“This remains a significant unmet medical need and oral rivaroxaban could provide clinicians and patients with a simple, single-drug approach for the acute and continued treatment of deep vein thrombosis,” Dr. Büller said.

Current standard to prevent recurrent deep vein thrombosis therapy is enoxaparin plus warfarin.

The study was conducted in the Netherlands and included more than 3,400 adults with symptomatic deep vein thrombosis.

Researchers randomised patients to rivaroxaban 15 mg twice daily for 3 weeks followed by a 20-mg daily maintenance dose (n = 1,731) for 3, 6, or 12 months, according to individual clinical need; or to enoxaparin 1 mg/kg twice daily for 5 or more days, followed by warfarin (n = 1,718).

Dr. Büller, reported that 2.1% (n = 36) of the rivaroxaban-treated patients experienced recurrent deep vein thrombosis versus 3.0% (n = 51) of controls (P < .0001).

The safety endpoint, combined major and minor clinically relevant non-major bleeding, was the same in both study groups, 8.1% (P = .77).

Dr. Büller noted that rivaroxaban showed no evidence of liver toxicity, a concern with Factor Xa inhibitors, and no signal for cardiovascular danger.

Rivaroxaban is currently approved in Europe and Canada but not in the United States.

Funding for this study was provided by Bayer Schering Pharma.

- MFP Wire Services
- 09-06-2010

By: Bruce Sylvester

STOCKHOLM, SWEDEN – A single, high-dose treatment with epoetin alfa after a successful percutaneous intervention for ST segment elevation myocardial infarction (STEMI) did not improve left ventricular ejection fraction after 6 weeks, researchers said at the European Society of Cardiology Congress 2010.

Researchers from a prospective, randomised study to examine the effects of a single bolus epoetin alfa on left ventricular function in patients with an acute myocardial infarction (HEBE III) trial presented their findings at the congress.

Adriaan Voors, MD, University Medical Center, Groningen, Groningen, the Netherlands, said that the “positive effects of erythropoietin on this patient group” seen previously in smaller studies were not confirmed in this larger clinical trial.

The investigators randomised 529 patients, who had undergone a successful percutaneous intervention for a first STEMI, to receive either standard medical care (n = 266), or standard care and a single bolus with epoetin alfa 60,000 IU within 3 hours after percutaneous intervention (n = 263).

The goal was a minimum 3% increase of left ventricular ejection fraction in patients treated with epoetin alfa compared with standard care. Secondary endpoints included enzymatic infarct size and major cardiovascular events.

Both study cohorts had similar patient characteristics.

The investigators reported that, after 6 weeks, left ventricular ejection fraction was 53% in the epoetin alfa group and 52% in the control group (P = .41), a nonsignificant difference.

Infarct size, measured by blood proteins, was also not significantly different between the 2 groups.

Notably, significantly more major adverse cardiac events appeared in the standard-care group than in the epoetin alfa group (19 vs 8; P = .032).

Dr. Voors emphasised that the secondary endpoint reduction in major cardiac effects for epoetin alfa is noteworthy, but since the study was designed to study primarily reduction in cardiac effects, and the patient numbers in HEBE III were small, interpretation of the finding should be conservative.

Funding for this study was provided by Janssen-Cilag Ltd.

– MFP Wire Services
- 09-06-2010

By: Bruce Sylvester

STOCKHOLM, SWEDEN – Atopaxar (E5555) may be a valuable add-on therapy for patients with acute coronary syndrome or high-risk coronary artery disease whose platelets remain activated despite treatment with current standard therapies, according to researchers presenting at the European Society of Cardiology Congress 2010.

The finding from 2 phase 2 studies (both part of J-LANCELOT [Japanese-Lesson From Antagonizing the Cellular Effect of Thrombin]) evaluating the novel protease-activated receptor 1 (PAR-1) inhibitor were presented on August 30 in a “Hotline” session by Shinya Goto, MD, Tokai University School of Medicine, Kanagawa, Japan, on behalf of the J-LANCELOT investigators.

Session comoderator Clyde W. Yancy, MD, American Heart Association and Baylor University Medical Center in Dallas, Texas, called Dr. Goto’s presentation “intriguing” and “one that could really change the way we do things.” He also said, “It is clear that through the current CYP [cytochrome P450] approach, we have any number of patients who still have platelet aggregation and are at risk for thrombotic events. This may yield a new opportunity to improve acute care outcomes.”

Dr. Goto noted that thrombin plays a critical role in the development and propagation of thrombus through both blood coagulation and platelet aggregation. In early-phase trials among healthy volunteers, atopaxar inhibited platelet aggregation induced by thrombin without affecting blood coagulation, fibrinolysis, or bleeding time. For coronary artery disease patients included in the trial, high risk was defined by >=1 of the following: diabetes (under treatment), history of peripheral artery disease, or thromboembolic transient ischaemic attacks or stroke within the past year.

The primary safety endpoint was bleeding events, and the secondary endpoint was major adverse cardiac events (MACE) comprised of cardiovascular death, myocardial infarction, stroke, recurrent ischaemia, and inhibition of platelet aggregation induced by thrombin receptor activation peptide.

The trial comprised 241 acute coronary syndrome patients (mean age ~65 years, 81% men) and 263 high-risk coronary artery disease patients (mean age ~67 years, 89% men).

Acute coronary syndrome and coronary artery disease patients were randomised to receive atopaxar 50, 100, or 200 mg or placebo once daily for 12 (acute coronary syndrome) or 24 (coronary artery disease) weeks. In the 1:1:1:1 randomisation, acute coronary syndrome patients received atopaxar 400 mg or placebo on day 1, and coronary artery disease patients received aspirin 75 to 325 mg daily.

All atopaxar doses achieved significant levels of platelet inhibition (>90% for 100 and 200 mg and 20%-60% for 50 mg). Analysis of bleeding according to Thrombolysis in Myocardial Infarction (TIMI) and Clopidogrel in Unstable Angina to Prevent Recurrent Events (CURE) criteria revealed similar incidence of TIMI major, minor, and minimal bleeds requiring medical attention in the placebo and combined atopaxar groups (acute coronary syndrome 6.6% placebo vs 5.0% atopaxar; coronary artery disease 1.5% placebo vs 1.5% atopaxar). Clinically significant bleeding events were not increased in acute coronary syndrome and coronary artery disease patients. A dose-related trend toward increased “nuisance” bleeding events not requiring medical attention was seen.

The rate of MACE was numerically lower in the combined atopaxar group than in the placebo group (acute coronary syndrome 5.0% vs 6.6%, P =.73; coronary artery disease 1.0% vs 4.5%, P =.066), but differences were not significant. The researchers determined that significant dose-dependent increases in liver function test abnormalities and increases in the QTcF interval would require further study.

Dr. Goto concluded, “E5555 added to standard antiplatelet therapy may reduce MACE in patients with acute coronary syndrome and in high-risk coronary artery disease populations.”

Jean-Pierre Bassand, MD, University Hospital Jean-Minjoz, Besançon, France, commented that all prior advances in platelet inhibition (eg, aspirin, clopidogrel, prasugrel, and ticagrelor) lengthen bleeding time and produce at least some increase in bleeding risk. PAR-1 inhibition, however, prevents platelet function activation without prolonging bleeding time.

“If phase 3 trials confirm these results for atopaxar and those of vorapaxar [SCH 530348], that will be a major splash,” Dr. Bassand said.

Phase 2 results for vorapaxar on top of aspirin and clopidogrel also revealed no bleeding increases, with a trend toward better efficacy than standard treatment. Dr. Bassand stated that no safety signals were evident.

- MFP Wire Services
- 09-06-2010