The AVERROES (Apixaban Versus Acetylsalicylic acid (ASA) to Prevent Strokes) trial randomized 5600 AF patients who were unable to take warfarin to receive either aspirin or apixaban, a Factor Xa inhibitor. (Another trial still underway, ARISTOTLE, is a direct comparison of warfarin and apixaban in AF.) AVERROES was stopped early after the Data Monitoring Committee found clear evidence of clinically important benefit and an acceptable safety profile.

Stuart Connolly reported a reduction in the primary endpoint of the study, a composite of stroke or systemic embolism, from 3.6% per year in the aspirin group to 1.7% per year in the apixaban group (HR 0.46, CI 0.33-0.64, p<0.001). The rate of major bleeding was 1.4% per year on apixaban and 1.2% per year on aspirin (HR 1.14, CI0.74–1.75, p=0.56). Hemorrhage stroke occurred at a rate of 0.2% per year in both treatment groups.
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The EINSTEIN-DVT study tested the effect of the new oral anticoagulant rivaroxaban in the setting of DVT. The open-label, non-inferiority study randomized more than 3,400 patients with acute, symptomatic DVT to either oral rivaroxaban or conventional therapy with enoxaparin followed by warfarin or acenocoumarol for three, six or 12 months, based on the attending physician’s assessment at baseline.

Dr Harry Büller reported that recurrent symptomatic venous thromboembolism took place in 2.1% of patients in the rivaroxaban group compared to 3.0% of the subjects on conventional therapy (p<0.0001 for non-inferiority). The rate of major and clinically relevant non-major bleeding was 8.1% in each group. Büller reported there were no signals of liver toxicity and that the drug was well-tolerated during the trial.
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Getting into the guidelines can be a slow and laborious process. Some critics complain that it takes too long for new therapies to receive the guideline seal of approval. But with the new guidelines released at the ESC it’s unlikely that anyone will complain about such dawdling.

With unprecedented speed, dronedarone  and ticagrelor have achieved  class 1 recommendations in the new ESC guidelines released in Stockholm this week. Dronedarone (Multaq, Sanofi) gained a class 1 recommendation for the first line treatment of AF patients who do not have heart failure in the ESC guidelines for the management of atrial fibrillation, while ticagrelor (Brilinta, Astra-Zeneca) which has not yet received regulatory approval anywhere in the world, received a class 1 indication for the treatment of NSTE-ACS and STEMI in the new ESC guideliens for myocardial revascularization. But not everyone is convinced that such haste is warranted.
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The ESC has responded to the controversy surrounding the previous publication of data presented in Sunday’s Hot Line session of the STAR Heart Study of stem cell therapy. (See our earlier story here.) The ESC statement said ”this clearly breaks ESC rules for Hot Line Sessions which state that information must be first presented at ESC Congress in order to qualify for presentation in a Hot Line session.”
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At last year’s ESC the RE-LY trial heightened interest in the prospect of dabigatran as a potential replacement for warfarin. Now the RE-LY investigators have analyzed the trial in an attempt to see whether the local standard of care has an impact on the beneficial effects of switching to dabigatran. In a presentation at the ESC in Stockholm and a simultaneous publication in the Lancet, Lars Wallentin and the RE-LY investigators estimated the time in the therapeutic range at each center (cTTR) in the trial. They found that, irrespective of cTTR, when compared to warfarin  high dose dabigatran was effective at reducing stroke, low dose dabigatran was effective at reducing bleeding, and both doses reduced intracranial bleeding. The investigators wrote that the “advantages of dabigatran were greater at sites with poor INR control than at those with good INR control,” and concluded that “overall, these results show that local standards of care affect the benefits of use of new treatment alternatives.”
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The thing about hot line sessions is that the trials are supposed to be hot, or at the very least lukewarm. Certainly they’re not supposed to be cold. But at the press conference for the first hot line session here in Stockholm today, reporters and other observers were caught off guard when they learned that all of the data in one of the day’s hot line trials, The STAR Heart Study, had been previously published in the July isue of the European Journal of Heart Failure.

Update: The ESC has responded to the STAR controversy.
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Novartis announced that it had received FDA approval to market Tekamlo, a combination of aliskiren and amlodopine. The drug has been approved as initial therapy for patients who are likely to need multiple drugs to achieve their blood pressure goals, and as replacement therapy for patients whose blood pressure is not adequately controlled with either aliskiren or amlodipine alone.
Click here to read the press release from Novartis…

The FDA has announced that dabigatran (Pradaxa, Boehringer Ingelheim) for the prevention of stroke in atrial fibrillation will be the subject of a Cardiovascular and Renal Drugs ADvisory Committee on September 20. (h/t to Larry Biegelsen)

The AHA has published the list of late-breaking clinical trials to be presented at scientific sessions in November. Some highly anticipated trials include:

• ASCEND-HF– the 7000 patient trial with nesiritide designed to resolve the long-standing controvery over the drug)
• ROCKET-AF– the pivotal trial for the factor Xa inhibitor rivaroxaban for stroke prevention in AF
• GRAVITAS– standard versus high-dose clopidogrel according to platelet function testing after PCI
• BASKET PROVE– late stent thrombosis in DES compared to BMS
• ASCOT– CRP as an independent predictor of cardiovascular outcomes
• DEFINE– a first look at anacetrapib, a new CETP inhibitor

Click here for the complete list of late-breakers…

A letter describing the July FDA advisory panel on Avandia that was sent by GlaxoSmithKline to TIDE investigators has sparked criticism from some FDA officials and panel members, according to an article by Gardiner Harris in the New York Times.
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Back in June (Listening to industry: what’s the ROI of medical education?) I commented on some statements made by Bill Cooney, the President & CEO of Medpoint Communications, which is, in its own words, “a global leader in diversified communications services for leading pharmaceutical and biotechnology companies.” Cooney recently commented on my post, and this has provoked a debate which I hope may continue. In any case, I’ve copied and posted here the two rounds of debate. Readers are invited to join the discussion.
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The CRESCENDO (Comprehensive Rimonabant Evaluation Study of Cardiovascular Endpoints and Outcomes) trial testing the effects of the endocannabinoid receptor blocker rimonabant for the prevention of cardiovascular events was terminated early at the request of regulatory agencies in several countries following growing concern at the time that people taking rimonabant were more likely to commit suicide. At the time of termination 18,695 patients had been enrolled for a mean of 13.8 months. In a report in the Lancet Eric Topol and colleagues report no significant difference between the rimonnabant and placebo groups in the combined rate of cardiovascular death, MI, or stroke. There were 4 suicides in the rimonabant group and 1 in the placebo group. Gastrointestinal, neuropsychiatric, and serious psychiatric side-effects occurred more frequently in the rimonabant group. In their conclusion the investigators note that the trial has significant implications for clinical research and regulators: “The new precedent here is the capacity for such regulatory agencies to stop an ongoing clinical research project.”
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Earlier this week we reported that SHAPE was preparing to update its controversial guidelines. It now appears that the guidelines are only the public facade of a larger program designed to encourage the growth of, and take a larger share of, the business of cardiovascular screening. Although conflict-of-interest concerns have previously swirled around SHAPE, new evidence suggests that the non-profit organization has aligned itself with a commercial venture, and presumably stands to benefit from the success of these projects.

A key player is Jeffrey Fine, MS, PhD, the President and CEO of J&J Medical, LLC. The announcement from SHAPE about the new Task Force lists Fine as the “SHAPE Task Force II Executive Coordinator.” On his company website Fine is described in glowing terms:

Dr. Fine is a nationally recognized expert in the fields of coronary artery disease identification, and heart attack prevention including coronary calcium scoring.

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