Daily aspirin for prevention of death from MI unwarranted in most people

Interviewed by Steven Greer, MD

For decades, doctors have recommended daily aspiring to prevent death from myocardial infarction to patients with certain risk factors other than previous MI (i.e. primary prevention). However, numerous randomized trials have been adding to the mounting evidence that the serious bleeding risks from aspirin outweigh the benefits. Dr. Kausik Ray from St. George’s University of London was an author of the latest meta-analysis of these trials, and discusses the findings.

(In full screen 1080i HD)

Current guidelines and methods for treating knee and head injuries in NCAA athletes

September 14, 2010

Lee Kaplan, MD, Chief of Sports Medicine at The University of Miami Health System and team doctor for the Miami Hurricanes football team discusses the state-of-the-art methods for surgically repairing torn knee meniscus injuries and for repairing torn ACL’s.

Clifton Page, MD, internists for the Miami Hurricanes football team, discusses the new guidelines for handling the return to play for athletes who have suffered a concussion, testing for sickle cell, and for monitoring heat exhaustion. (See Op-Ed How to Eliminate Head Injury in Football)

Mauricio Cohen, MD: The REG 1 anticoagulation system

August 9, 2010

Dr. Mauricio Cohen, Director of the cardiac cath lab at the University Miami Medical Center discusses his recently published paper on a Phase 2 trial testing the novel reversible anticoagulation system by Regado Biosciences called REG 1. If the product makes it to the market, it will be a major advance for interventional procedures.

Laced cocaine causing skin necrosis and marrow suppression

Update, June 22, 2011

Since our first report one year ago about the toxic effects of cocaine laced with levamisole, the NEJM published a case study of their own. A 54 year old woman was doing cocaine and lost her face and ears.

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June 20, 2010

An interesting letter in Annals of Internal Medicine by Mark Bradford et al describes two case reports of skin necrosis due to use of recreational cocaine laced with levamisole. An estimated 70% of the U.S. supply of cocaine is now laced with this drug. It is not clear why this additive is being used. Some speculate that it adds to the dopaminergic euphoric “high”.

Levamisole is banned for human use in the U.S. but is still used as a veterinary anti-worming medication. It was also formerly used as a chemotherapy agent to treat colon cancer, melanoma, and other cancers.

Several deaths of celebrities caused by cocaine overdoses, among other drugs, have been linked to levamisole. ABC News’ Ted Koppel recently lost a son to an overdose of cocaine laced with levamisole. CM.TV interviewed Dr. Bradford on this matter.

A primer on JNJ’s Xarelto for A-fib

Update: November 15, 2010

The following is from a Barclays Capital research note (Mark Purcell et al)

BAYER/JNJ: Why Xarelto doesn’t seem superior

ROCKET-AF, the pivotal trial for Xarelto in stroke prevention, has demonstrated that the drug was non-inferior to Warfarin with regard to all-cause stroke and non-central nervous system embolism. Disappointingly, however, the intention-to-treat superiority analysis failed to show the drug had an advantage, statistically, over Warfarin. This would suggest that the drug failed its pre-specified test for superiority. The ROCKET-AF design paper published in the American Heart Journal states: ‘If the noninferiority criterion is satisfied, then superiority for the primary efficacy end point will be tested in the safety population…’. The safety population is NOT the per protocol population used to show the 21% risk reduction mentioned in the press release and hence the trial seems to have failed the test. This means that the commercial perspectives are unclear relative to the competitor Pradaxa, as differentiation will have to rely on dosing and other aspects that may be considered secondary to the primary efficacy and bleeding risk.

(The following is our original note)

November 9, 2010

One of the bigger drug trials to be discussed next week at the AHA meeting will be the Bayer/JNJ trial called ROCKET-AF, which studied Xarelto (rivaroxaban) (a direct factor Xa inhibitor) to prevent stroke in patients with non-valvular atrial fibrillation. Recall, Xarelto already went before an FDA advisory committee to review the indication to prevent deep vein thrombosis (DVT) after orthopedic surgery and the FDA surprisingly issued CR letter, effectively rejecting that indication. The FDA wanted more data on possible liver damage caused by the drug.

Bayer/JNJ did not bother to reply to the CR letter for DVT and they now plan to pursue the bigger indication of A-Fib. Therefore, ROCKET-AF is crucial to the future of this drug.

The unmet clinical need that Xarelto would satisfy is an oral anticoagulant that is easier to take and safer than warfarin. Boehringer Ingelheim recently received FDA approval for their own warfarin alternative called Pradaxa (dabigatran) (a direct thrombin inhibitor downstream in the cascade from factor Xa, see our previous video stories). Although Pradaxa’s RE-LY trial was a non-inferiority trial, the drug was actually superior to warfarin. The big question to be answered at the AHA is whether Xarelto too was superior. The press release did not address this.

In addition to the superiority claim, which is not in the Pradaxa label, by the way, the marketing battle between Xarelto and Pradaxa will also revolve around the QD dosing for Xarelto versus the BID for Pradaxa. Also, the dual renal/liver excretion of Xarelto makes it safer for renal failure patients, whereas Pradaxa is excreted only by the kidneys and the dosage must be reduced.

Harlan M. Krumholz, MD, of Yale wrote, “Now we await the ROCKET AF presentation. The key questions will be:

• Were the event rates comparable to what might be expected in practice — or is there evidence that the study population was highly selected?
• Was the warfarin treatment optimized? How well was the INR maintained?
• Are there any safety concerns with rivaroxaban? How do bleeding rates compare?
• Is there any suggestion that the drug is particularly good or bad for a particular subgroup? This would be an exploratory analysis and would not likely be considered definitive.
• Is there any evidence that rivaroxaban is more effective than warfarin?

And then, if at the end of the day, rivaroxaban really looks to be no better than warfarin — will it find a niche in clinical care?”

Sanjay Kaul, MD, of Cedars Sinai Medical Center, and member of the first Xarelto FDA AdCom, wrote, “Rivaroxaban represents the first of an interesting class of drugs (oral Xa inhibitors) that have the potential to alter the landscape of anticoagulant therapy. Whether rivaroxaban finds a niche in clinical care will depend on the balance of ancillary advantages in convenience, safety, and tolerability versus ‘noninferior’ or ‘superior’ efficacy. if superiority is demonstrated, then it will likely be eminently competitive with the recently approved dabigatran.”

Pradaxa (dabigatran) approval,

October 29, 2010

In Part 1 of The Weekly Summary show, Robert Myerburg, MD, Professor and Cardiologist, leads the discussion about the recent FDA approval of dabigatran, branded by Boehringer Ingelheim as Pradaxa, as stroke prophylaxis in non-valvular atrial fibrillation patients. Pradaxa promises to be a safer oral anticoagulant than warfarin.

Topics discussed include:

• Review of the RE-LY trial
• Is the greater cost of the drug, compared to pennies-a-day warfarin, justified by less need for expensive INR testing?
• Will off-label use in patients with prosthetic mitral valves, etc. be dangerous?