November 1st, 2010
ROCKET AF: Is Rivaroxaban Ready for Blast Off?
Harlan M. Krumholz, MD, SM
With the approval of dabigatran and now the preliminary and partial results of ROCKET AF, we’ll need to be familiar with much more than just warfarin to address the anticoagulation needs of our patients. The early word on ROCKET AF, which will be presented at AHA, is that rivaroxaban is at least as effective as warfarin in preventing stroke and non-CNS embolic events in patients with nonvalvular atrial fibrillation.
What is rivaroxaban? It is a direct factor Xa inhibitor that inhibits the conversion of prothrombin to thrombin — and thrombin is what converts fibrinogen to fibrin. You may remember that factor X is the final common pathway of the intrinsic and extrinsic pathways, placing it at a critical position in the cascade.
Rivaroxaban was approved in 2008 in Canada and Europe for the purpose of preventing venous thrombosis after hip and knee replacement surgery. An FDA panel in 2009 recommended the same for the U.S.
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?
November 1st, 2010
Mind the Gap: Real-World ACE Inhibitor Cough Much More Common Than Listed on Labels
Larry Husten, PHD
The real-world incidence of ACE inhibitor-associated cough is much higher than the reported rate on drug labels and printed in the Physicians’ Desk Reference, according to a study published in the American Journal of Medicine. Sripal Bangalore and colleagues analyzed data from 125 published studies with ACE inhibitors including almost 200,000 patients. They found that the pooled weighted incidence of cough for enalapril was 11.48%, compared with the 1.3% rate reported on the drug’s label. The pooled weighted withdrawal rate due to cough was 2.57% in the trials compared with 0.1% on the label. They also found that although the reported cough rates of different ACE inhibitors vary widely on the labels, in trials the incidence of cough is similar across all the ACE inhibitors.
The authors conclude: “Action must be taken to ensure that the drug labeling is regularly updated both for safety and for medication-specific adverse effects.”
November 1st, 2010
AHA Preview: What Is Clyde Yancy Looking Forward to Seeing?
Clyde Yancy, MD
In the first installment of our AHA Preview series, we ask Clyde Yancy, medical director of the Baylor Heart and Vascular Institute and chief of Cardiothoracic Transplantation at Baylor University Medical Center, to list the trials in his field that he is most looking forward to at the AHA Scientific Sessions 2010 meeting. See what Clyde is hoping to check out and share your own suggestions and comments.
Regarding the studies to be vetted at the AHA meeting that focus on heart failure (HF), I expect several to be of great interest:
- ASCEND-HF should provide data regarding the safety and efficacy of nesiritide. These data could be definitive, pro or con, and it will be fascinating to recover past thoughts and arguments and revisit those positions based on the new findings.
- TELE-HF is a randomized trial of community care of HF patients after hospital discharge vs. use of an automated telephone algorithm to support care. Again, this may come closest to definitive evidence, pro or con, regarding the influence of telehealth.
- EMPHASIS-HF — a randomized trial of an aldosterone antagonist added to standard HF therapy vs. placebo plus standard therapy in patients with NYHA Class II HF. The results of this study should allow us to understand whether or not there is a benefit when aldosterone antagonists are used for patients that are less ill from HF. Careful attention to any observed risks of therapy in this less-ill population will be important, as the concern regarding risk has limited the uptake for this approach even in those with more advanced HF.
- ADVANCE: This study should provide the first data regarding a new LVAD platform (HeartWare), one that is presumed to be easier to implant and to have less morbidity. It could be a significant addition to the treatment of advanced HF if the data are positive.
- EMPHASIS-HF — a randomized trial of an aldosterone antagonist added to standard HF therapy vs. placebo plus standard therapy in patients with NYHA Class II HF. The results of this study should allow us to understand whether or not there is benefit when aldosterone antagonists are used for patients that are less ill from heart failure. Careful attention to any observed risks of therapy in this less ill population will be important as the concern regarding risk has limited the uptake for this approach even in those with more advanced heart failure.
November 1st, 2010
Rivaroxaban Equals Warfarin in ROCKET AF
Larry Husten, PHD
Rivaroxaban (Xarelto) was as effective as warfarin in patients with AF in the ROCKET AF study, according to an announcement released by Bayer on Sunday ahead of the trial’s scheduled presentation at the AHA on November 15.
ROCKET AF randomized more than 14,000 patients with nonvalvular AF to either rivaroxaban or warfarin. The goal of the study was to establish the noninferiority of rivaroxaban to warfarin. The primary efficacy endpoint was a composite of all-cause stroke and non-CNS systemic embolism. The primary safety endpoint was the composite of major and non-major clinically relevant bleeding events.
The Bayer announcement states: “Rivaroxaban has met its primary efficacy endpoint versus dose-adjusted warfarin. The rates of the composite of major and non-major clinically relevant bleeding were comparable.”
October 29th, 2010
Is the Time Right for a Preprint Archive for Clinical Trials?
Larry Husten, PHD
Here’s a great idea: a preprint archive for clinical trials.
Taking inspiration from the well-established use of preprint archives in physics, math, and other scholarly areas, Martin Fenner, a cancer researcher, proposes the establishment of a preprint archive for clinical trial research papers.
Fenner points out that “the results of clinical trials are rarely first reported in a peer-reviewed journal, but rather are usually first presented at a conference — in the case of important practice-changing clinical trials, often before an audience of thousands of people.” He writes that “the peer-reviewed paper is usually published months or even years after the conference presentation” and that this publication “is not the first time the medical community learns about the results of a clinical trial, or draws conclusions for their own research or clinical practice.”
It’s probably worth mentioning here that Fenner doesn’t discuss the recently growing trend in which important (and not so important) clinical trials are presented at a meeting and published in a journal simultaneously. In such cases, a preprint archive would not be helpful, but of course, it’s unlikely that simultaneous presentation/publication will ever become a universal practice or eliminate the need for the preprint archive.
Here’s how Fenner envisions the system might work:
The preprints should be uploaded at the time of journal submission, or shortly after the conference presentation. The preprint server should add some structure to the preprints, e.g. linking to both the clinical trials registry (Clinicaltrials.gov, EudraCT, and others) and the published paper. The preprint should fulfill the requirement for reporting results set by the FDA. Articles in the preprint archive should be freely available and should ideally provide the main results as downloadable datasets. The preprint server will only work if medical journals — and ideally the ICMJE — have a clear policy allowing prior publication as preprint.
I hope this idea attracts further attention and discussion. In the meantime, I recommend you read Fenner’s entire post on PLOS Blogs.
October 28th, 2010
Drs. Clueless and Apathetic: The State of Imaging Referrals
Shanti Bansal, MD
Editors’ Note: This text has been modified from its original form. Key elements of the case represent a composite of people and events.
On a bright Saturday morning, I was the fellow on duty in the chest pain center. That meant I was responsible for evaluating and stress-testing patients who had been admitted from the ER with an intermediate probability of coronary artery disease. My first patient that morning was Jack — a burly man with course facial hair and a barrel chest.
As I approached Jack’s bedside armed with his chart and personal information, his sleepy eyes opened and he was startled to see me. After he settled, I began my usual routine. I asked him what had brought him to the ER. He said he was a forklift operator and that he’d had an accident. His chest had apparently rammed into the vehicle’s steering wheel. For a week his chest had been causing him pain, which he now wanted to have evaluated. It took but one gentle push on his chest to reveal that this was a case of muscular injury, not cardiac pain. I asked Jack to excuse me while I consulted the referring ER doctor.
I went to the adjoining room and found a doctor swinging from one emergency room bay to the next. With me nearby, she paused to hear about Jack. I gave her his chart, told her that an exercise test was not appropriate, and advised that the patient be discharged. Glancing quickly through the pages, she said, “Well, first of all, this patient was admitted by the previous ER doc and I am not getting involved. Even so, he is 55 and male, and you can’t prove this isn’t CAD. I want a stress test!”
Stunned by the response from this Dr. Clueless, I left to gain higher ground by turning to my attending physician. Initially he seemed annoyed that I had interrupted him, but I relayed the patient’s clinical history anyway. This Dr. Apathetic just shrugged his shoulders and said, “Well, it doesn’t matter. Just do it.”
Out of options, I returned to the patient and began the stress test. Just before Jack got on the treadmill, he asked me whether I thought the test was necessary. I would have liked to respond with an emphatic “No,” but instead I simply relayed the wishes of the emergency room doctor. While watching the wheels on the treadmill and the nuclear imaging camera spin monotonously, I began to think about the process of patient referrals.
I ask you: How often have you taken an inappropriate referral for an echocardiogram, stress test, or invasive imaging and simply completed the test? Have you ever considered these referrals an educational opportunity to discuss issues at hand with referring doctors — clueless, apathetic, or otherwise? When assessing the quality of imaging services, shouldn’t we go beyond images and consider patients like Jack before we place them on the hamster wheel of cardiology?
October 26th, 2010
Dabigatran to Cost $237 per Month at the Drugstore
Larry Husten, PHD
It looks like Pradaxa (dabigatran) will cost about $237 a month at the drugstore counter. A Boehringer Ingelheim representative says the wholesale acquisition cost (WAC) of the drug is set at $6.75 per day for 2 pills. The price will apply to both the 150-mg and the 75-mg capsules. According to knowledgeable experts, the retail cost of drugs at pharmacies is typically 17% over the WAC. The retail price of Pradaxa is therefore likely to be $7.90 per day, or $237 per month.
Comments are closed on this post, but please join the conversation at our Dabigatran Resource Round-Up.
October 26th, 2010
Updated Appropriate Use Criteria for Cardiac CT Published
Larry Husten, PHD
An alphabet soup of medical organizations (ACCF, SCCT, ACR, AHA, ASE, etc.) have updated their appropriate use criteria for cardiac CT. The lengthy document includes an evaluation of 93 clinical scenarios and finds that cardiac CT is appropriate in 38% of them. Use of cardiac CT in the rest of the scenarios is deemed inappropriate or uncertain.
In general, cardiac CT angiography is deemed appropriate for use in patients with low or intermediate risk for CAD, while its use in high-risk patients, routine repeat testing, and general screening is deemed inappropriate. Calcium scanning is considered appropriate in people at intermediate risk or some low-risk people with a family history of heart disease.
“If we know a patient has existing heart problems or is at high risk for heart disease, doing the test isn’t generally going to add any valuable clinical information,” said Allen Taylor, the chair of the writing committee, in a press release issued by the ACC. “Ordering a test when a patient doesn’t need it — or won’t benefit — is not quality cardiac care.”
The full document is available online and will be co-published in JACC, Circulation, and the Journal of Cardiovascular Computed Tomography.
October 25th, 2010
CardioExchange Breakfast at AHA, Chicago
CardioExchange Editors, Staff
Monday, November 15, 7:00 – 9:00 am
Going to AHA next month? We invite you to join us for breakfast before sessions on Monday, November 15 at McCormick Place.
We’re hosting an informal breakfast where you can meet Editor Harlan Krumholz and other CardioExchange contributors and members. A photographer will be on hand to take professional photographs for use on your profile.
If you’d like to join us, please RSVP below by Wednesday, November 10. This event is limited to the first 50 CardioExchange members who respond, so don’t delay!
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