February 3rd, 2014
Selections from Richard Lehman’s Literature Review: February 3rd
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
NEJM 30 Jan 2014 Vol 370
Proteome-wide Analysis and CXCL4 as a Biomarker in Systemic Sclerosis (pg. 433): The Preacher has an ambivalent relationship to biomarkers. A lot of them are jut vanity and vexation of spirit, but there are one or two—cardiac troponins being a prime example—that are of huge clinical value and redefine an entire condition, albeit at the potential expense of overdiagnosis. Systemic sclerosis is many thousands of times less common than myocardial infarction, but it is a very nasty disease without a diagnostic or prognostic marker. So full marks to the Dutch team who through proteome-wide analysis and validation showed that CXCL4 is the predominant protein secreted by plasmacytoid dendritic cells in systemic sclerosis, both in circulation and in skin. This study shows that careful and arduous science can bring real progress in medicine: “Levels of CXCL4 were elevated in patients with systemic sclerosis and correlated with the presence and progression of complications, such as lung fibrosis and pulmonary arterial hypertension.”
Ann Intern Med 21 Jan 2014 Vol 160
Effectiveness of ICDs for Primary Prevention of Sudden Cardiac Death in Subgroups (pg. 111): I keep mentioning implantable cardioverter defibrillators in these reviews, partly because they keep coming up in the literature, but also because I am worried by them. I will spare you the detail of this systematic review of ICD effectiveness for primary prevention of sudden cardiac death across subgroups by sex, age, New York Heart Association class, left ventricular ejection fraction, heart failure, left bundle branch block, QRS interval, time since myocardial infarction, blood urea nitrogen level, and diabetes: but the bottom line is that for none of these groups taken alone can it be shown that ICDs are of any benefit at all. It is only if you aggregate them that you can show an effect. This tells you two things: that their benefit is very small, and that you cannot predict if implanting an ICD is going to help the patient in front of you. So it seems to me that these devices should be reserved for the tiny minority of patients who have a strong theoretical preference for being kept alive at any cost rather than running a risk of dying suddenly and painlessly.
JAMA Intern Med Jan 2014 Vol 174
Deathbed Shock (pg. 88): At present, more than 100,00 ICDs are fitted to American patients every year. You can read about dying with one in situ in a commentary from JAMA Intern Med.
Interpreting Treatment Effects From Clinical Trials in the Context of Real-World Risk Information: When you start somebody on medication for “hypertension,” do you calculate their overall cardiovascular risk and explain the benefit of treatment in absolute terms such as a number-needed-to treat? Of course not, because even if you wanted to, you wouldn’t be able to find a suitable tool and you might lose QOF points. That’s how good we are at being patient-centred doctors. And if that’s awful, turn to the domain of “chronic kidney disease,” as Ken Covinsky and colleagues do in this analysis. Even if you can extrapolate accurately from the clinical trials to the elderly patient in front of you (which, by the way, you can’t), you would find NNTs in excess of 100 for any treatment you might give them in order to prevent end-stage renal failure, unless they are on the brink of it already. This is where tunnel-vision interpretations of “evidence-based” medicine have got us.
Lancet 1 Feb 2014 Vol 383
DUTCH PEERS (pg. 413): Strictly for Stent War enthusiasts and pharma-watchers only: “Third generation zotarolimus eluting and everolimus eluting stents in all comer patients requiring a percutaneous coronary intervention (DUTCH PEERS): a randomised, single blind, multicentre, non inferiority trial.” “Both stents were similarly efficacious and safe, and provided excellent clinical outcomes, especially in view of the large number of patients who presented with acute myocardial infarctions.” It’s beyond parody. Is this an academic paper or an advertisement? Do I need to tell you that his trial was sponsored by the makers of the two stents?
Association Between Change in Daily Ambulatory Activity and CV Events in People with Impaired Glucose Tolerance: Wanted: a pharma-sponsored trial that doesn’t push a pharmaceutical intervention. Found: an analysis of NAVIGATOR that dwells on the dose related benefits of daily activity in individuals at high cardiovascular risk. Thank you, Novartis. See, I can be nice to a drug company.
Acute MI: A Comparison of Short-Term Survival in National Outcome Registries in Sweden and the U.K.: “We used data from national registries on consecutive patients registered between 2004 and 2010 in all hospitals providing care for acute coronary syndrome in Sweden and the UK. The primary outcome was all cause mortality 30 days after admission.” I really wouldn’t have predicted the result of this comparison: 30-day mortality was 7•6% (95% CI 7•4—7•7) in Sweden and 10•5% (10•4—10•6) in the UK. One factor driving this may be the finding that “in Sweden, compared with the UK, there was earlier and more extensive uptake of primary percutaneous coronary intervention (59% vs 22%) and more frequent use of β blockers at discharge (89% vs 78%).” If a country with such a scattered population as Sweden can achieve such a good rate of primary PCI, what excuse do we have in the UK?
February 3rd, 2014
FDA Evaluating Safety Of Testosterone Products
Larry Husten, PHD
The FDA has announced that it is evaluating the cardiovascular safety of testosterone products. The investigation is prompted by two recent published studies that found a significant increase in cardiovascular events in men who received testosterone therapy.
The FDA said it had not concluded that testosterone is unsafe but recommended that “health care professionals should consider whether the benefits of FDA-approved testosterone treatment is likely to exceed the potential risks of treatment.” Testosterone is approved for use only in men who lack or have low testosterone levels in conjunction with an associated medical condition.
The first study, published in JAMA last November, followed 8,709 male veterans with low testosterone levels undergoing coronary angiography. After adjusting for baseline differences, the group of men who went on to start testosterone therapy after their angiogram had a 29% increase in risk for death, MI, or stroke.
The second study, published earlier this week in PLoS ONE, followed 55,593 men and compared the MI rate in the year before their first prescription for testosterone therapy with the rate in the 90 days after filling that prescription. For men 65 years and older the start of testosterone therapy was associated with a two-fold increase in the risk of MI. For men under 65 years with a history of heart disease there was a two- to three-fold increase in risk. However, there was no increase in risk for men under 65 with no history of heart disease.
January 31st, 2014
A (Not So) New Drug Landscape for Pulmonary Arterial Hypertension
John Ryan, MD
Just in the past several months, the FDA has approved three new medications for pulmonary arterial hypertension (PAH):
- macitentan, an endothelin-receptor antagonist (ERA);
- riociguat, the first-in-class soluble guanylate cyclase (sGC) stimulator; and
- treprostinil, an oral prostacyclin.
As a clinician and researcher who works a lot in this area, I thought it might be time for a quick primer.
What Does the Research Show?
As the saying goes, “The more things change, the more they stay the same.” Yes, the new drugs for PAH are different from what we already have, but not dramatically so.
Macitentan joins bosentan and ambrisentan, two other ERAs on the market, as an oral therapeutic options for PAH. The SERAPHIN placebo-controlled trial of macitentan, the largest PAH trial to date, used a combined endpoint of morbidity and mortality as its primary outcome, unlike prior studies that relied on changes in 6-minute walk distance. In SERAPHIN, the primary endpoint was significantly lower among patients on 10 mg of macitentan than among placebo recipients (31% vs. 46%). However, from an outcomes perspective, the differences between macitentan and the other available ERAs appear to be minor. Macitentan is given once daily, which is an advantage over bosentan, and also has fewer hepatic side effects than have been documented with bosentan. Perhaps the biggest potential win is that, with the introduction of a third ERA to this market, prices might go down.
Riociguat is designed as an oral stimulator of soluble guanylate cyclase; it causes vasodilation of the pulmonary arterial vasculature. In the PATENT trial, the drug improved 6-minute walk distance by 30 meters at 12 weeks of therapy. However, riociguat’s mechanism is similar to that of phosphodiesterase 5 inhibitors (PDE5i), such as sildenafil and tadalafil, which are among the most commonly used agents for PAH. Therefore, riociguat is contraindicated in patients already on a PDE5i. It remains to be seen whether physicians will routinely use riociguat instead of a PDE5i or reserve it only for patients who do not tolerate PDE5i therapy. In addition, riociguat has a complex dosing protocol, designed to be initiated at 1 mg three times daily and then, by week 8, to be increased to a target dose of 2.5 mg three times daily. What may be most exciting about this drug is its indication for inoperable or persistent chronic thromboembolic pulmonary hypertension (CTEPH). Until now, no oral agent has been available for this disease process. But as Stephen Archer notes, the first-line therapy for CTEPH remains pulmonary endarterectomy (PEA), and riociguat should not replace that.
Oral treprostinil has been shown to improve 6-minute walk distance in patients with PAH who are naive to PAH medicines and are not already on background therapy. This differs a bit from common practice, which has been to add prostacyclin therapy in patients who are deteriorating on oral agents or to use intravenous, subcutaneous, or inhaled prostacyclins in patients who are in functional class III or IV. The side-effect profile of oral treprostinil is noteworthy: headaches in >70% of patients and diarrhea in >50%.
How Do the New Drugs Change Practice?
At my institution, our approach will probably remain a PDE5i or an ERA as a first-line agent, with the addition of a second oral agent if the patient deteriorates clinically. We will continue to use parenteral prostacyclin if patients are in functional class III or IV. What is new, though, is that we are likely to introduce riociguat in patients who do not tolerate PDE5i therapy. However, given that the annual mortality rate for patients with PAH is 15% to 30%, management must remain aggressive, with the timely introduction of advanced therapies.
What’s the Future of Therapy for PAH?
We need to develop better therapeutic options for the clinical finding of pulmonary hypertension that is secondary to heart and lung disease. Notably, 90% of clinical pulmonary hypertension is secondary to left-sided heart disease (valvular disease, systolic or diastolic dysfunction), chronic lung disease (COPD, idiopathic pulmonary fibrosis), or both. Pulmonary arterial hypertension remains incredibly rare, affecting 7 to 10 patients per million population. ERAs, PDE5i therapy, and prostacyclins have not been shown to be effective in pulmonary hypertension that is secondary to left-sided heart disease or chronic hypoxia, and they have even been harmful in some cases. Riociguat is currently being studied in clinical trials of group 2 pulmonary hypertension (LEPHT trial), as is tadalafil (
CTEPH is also very rare, even less common than PAH. Again, nearly all patients with CTEPH should first be offered PEA; only after being evaluated—and declining PEA or being deemed inoperable—should riociguat be introduced. An alternative circumstance would be to use riociguat if pulmonary hypertension persists after PEA, as in the CHEST trial. However, this is also an uncommon situation, as PEA often cures the associated pulmonary hypertension.
JOIN THE DISCUSSION
Share your thoughts on the new treatments for PAH.
January 31st, 2014
American College of Cardiology Announces Late-Breaking Clinical Trials
Larry Husten, PHD
The American College of Cardiology announced the lineup of late-breaking clinical trials for its upcoming annual meeting in Washington, DC. The opening session will include the most eagerly anticipated trials — the main results of Symplicity HTN-3 and the comparison of Corevalve and surgery in high-risk patients. Subsequent sessions will include several phase-3 trials of PCSK9 inhibitors. Here is the complete list of trials:
ACC.14 Opening Showcase and the Joint ACC/JACC Late-Breaking Clinical Trials
- March 29, 2014, 8:00 – 10:00 AM
- Chair: John Gordon Harold
- Panelists: Valentin Fuster, David E. Kandzari, Sanjay Kaul, Michael J. Mack
9:10 – 9:25 AM 451-13 – A Randomized Comparison of Self-expanding Transcatheter and Surgical Aortic Valve Replacement in Patients with Severe Aortic Stenosis Deemed High-Risk for Surgery
- David H. Adams, Michael J. Reardon, Steven J. Yakubov, Joseph S. Coselli, G. Michael Deeb, Thomas G. Gleason, Maurice Buchbinder, Blase Carabello, James Hermiller, Jr., Patrick W. Serruys, Neal S. Kleiman, Stanley Chetcuti, John Heiser, William Merhi, George Zorn, Peter Tadros, Newell Robinson, George Petrossian, G. Chad Hughes, J. Kevin Harrison, John Conte, Jae K. Oh, Jeffrey J. Popma, Mount Sinai Medical Center, New York, NY, USA
9:35 – 9:50 AM 451-15 – The Main Results of SYMPLICITY HTN-3
- Deepak L. Bhatt, David Kandzari, William O’Neill, Ralph D’Agostino, Murray Esler, John Flack, Barry Katzen, Martin Leon, Minglei Liu, Laura Mauri, Manuela Negoita, Suzanne Oparil, Krishna Rocha-Singh, Paul Sobotka, Raymond Townsend, George Bakris, for the SYMPLICITY HTN-3 Investigators, Brigham and Women’s Hospital Heart and Vascular Center, Boston, MA, USA, University of Chicago, Chicago, IL, USA
- March 30, 2014, 8:00 – 9:15 AM Hall D (Main Tent)
- Co-Chairs: Howard C. Bauchner, Prediman K. Shah
- Panelists: Joseph S. Alpert, Roger S. Blumenthal, Jeffrey T. Kuvin, Roxana Mehran, Nathan D. Wong
8:00 – 8:10 AM 402-08 – Effect of Inhibition of Lipoprotein-Associated Phospholipase A2 with Darapladib on Ischemic Events in Patients with Chronic Coronary Heart Disease: The STABILITY (STabilisation of Atherosclerotic plaque By Initiation of darapLadIb TherapY) Trial
- Harvey D. White, Claes Held, Ralph Stewart, Philippe Steg, Andrzej Budaj, Robert Harrington, Elizabeth Tarka, Rebekkah S. Brown, Christopher Cannon, Lars Wallentin, the STABILITY Investigators., Green Lane Cardiovascular Service, Auckland City Hospital, Auckland, New Zealand, Uppsala Clinical Research center, Uppsala, Sweden
8:15 – 8:25 AM 402-10 – The Low-density Lipoprotein Cholesterol Assessment With PCSK9 Monoclonal Antibody Inhibition Combined With Statin Therapy – 2 Trial: A Phase 3, Double-blind, Randomized, Placebo and Ezetimibe Controlled, Multicenter Study to Evaluate Safety, Tolerability and Efficacy of Evolocumab (AMG 145) in Combination With Statin Therapy in Subjects With Primary Hypercholesterolemia and Mixed Dyslipidemia
- Jennifer Robinson, Bettina S. Nedergaard, William Rogers, Jonathan Fialkow, Joel Neutel, David Ramstad, Ransi Somaratne, Jason Legg, Patric Nelson, Robert Scott, Scott Wasserman, Robert Weiss, for the LAPLACE-2 Investigators, Amgen Inc., Thousand Oaks, CA, USA
8:30 – 8:40 AM 402-12 – Evaluation of the Dual PPAR-αγ Agonist Aleglitazar to Reduce Cardiovascular Events in Patients with Acute Coronary Syndrome and Type 2 Diabetes Mellitus: the AleCardio Trial
- A. Michael Lincoff, Jean Claude Tardif, Bruce Neal, Stephen Nicholls, Lars Ryden, Gregory Schwartz, Klas Malmberg, John Buse, Robert Henry, Hans Wedel, Arlette Weichert, Anders Svensson, Ruth Cannata, Diederick Grobbee, AleCardio Study Investigators, Cleveland Clinic, Cleveland, OH, USA
8:45 – 8:55 AM 402-14 – Two-year Outcome of a Trial Comparing Second Generation Drug-eluting Stents Using Either Biodegradable Polymer or Durable Polymer: the NOBORITM Biolimus-Eluting versus XIENCETM/PROMUSTM Everolimus-eluting Stent Trial (NEXT)
- Masahiro Natsuaki, Ken Kozuma, Takeshi Morimoto, Kazushige Kadota, Toshiya Muramatsu, Yoshihisa Nakagawa, Takashi Akasaka, Keiichi Igarashi, Kengo Tanabe, Yoshihiro Morino, Tetsuya Ishikawa, Hideo Nishikawa, Masaki Awata, Mitsuru Abe, Hisayuki Okada, Yoshiki Takatsu, Nobuhiko Ogata, Kazuo Kimura, Kazushi Urasawa, Yasuhiro Tarutani, Nobuo Shiode, Takeshi Kimura, Kyoto University, Kyoto, Japan, Saiseikai Fukuoka General Hospital, Fukuoka, Japan
9:00 – 9:10 AM 402-16 – A Phase 3 Double-blind, Randomized Study to Assess the Safety and Efficacy of Evolocumab (AMG 145) in Hypercholesterolemic Subjects Unable to Tolerate an Effective Dose of Statin
- Erik S.G. Stroes, David Colquhoun, David Sullivan, Fernando Civeira, Robert Rosenson, Gerald F. Watts, Eric Bruckert, Ricardo Dent, Allen Xue, Robert Scott, Scott Wasserman, Michael Rocco, GAUSS-2 Investigators, Amgen Inc., Thousand Oaks, CA, USA
Late-Breaking Clinical Trials III
- March 30, 2014, 10:45 – 12:00 PM Hall D (Main Tent)
- Co-Chairs: Rick A. Nishimura, Evan M. Zahn
- Panelists: George L. Bakris, Massimo Imazio, Allan S. Jaffe, Michael Shehata, Ronald G. Victor
10:45 – 10:55 AM 403-08 – Efficacy And Safety Of Colchicine In Patients With Multiple Recurrences Of Pericarditis: Results Of A Multicenter, Double-blind, Placebo-controlled, Randomized Study (corp-2 Trial).
- Massimo Imazio, Riccardo Belli, Antonio Brucato, Roberto Cemin, Stefania Ferrua, Yehuda Adler, David H. Spodick, Rita Trinchero, Cardiology Department, Maria Vittoria Hospital, Torino, Italy
11:00 – 11:10 AM 403-10 – The Global SYMPLICITY Registry: Safety and Effectiveness of Renal Artery Denervation In Real World Patients With Uncontrolled Hypertension
- Michael Bohm, Markus Schlaich, Krzysztof Narkiewicz, Luis Ruilope, Bryan Williams, Roland Schmieder, Felix Mahfoud, Giuseppe Mancia, Universitätskliniken des Saarlandes, Klinik für Innere Medizin III, Homburg/Saar, Germany
11:15 – 11:25 AM 403-12 – One Year Follow-up of the Melody Transcatheter Pulmonary Valve Multicenter Post Approval Study
- Aimee K. Armstrong, David Balzer, Allison Cabalka, Robert Gray, Alexander Javois, Jacqueline Kreutzer, John Moore, Jonathan Rome, Daniel Turner, Thomas Zellers, University of Michigan C.S. Mott Children’s Hospital, Ann Arbor, MI, USA, Children’s Hospital of Pittsburgh, Pittsburgh, PA, USA
11:30 – 11:40 AM 403-14 – Long-term Survival with Cardiac Resynchronization Therapy in Patients with Mild Heart Failure
- Ilan Goldenberg, Valentina Kutyifa, Helmut Klein, Scott McNitt, Scott Solomon, Arthur Moss, MADIT-CRT Executive Committee, University of Rochester Medical Center, Rochester, NY, USA, Sheba Medical Center, Tel Hashomer, Israel
11:45 – 11:55 AM 403-16 – Negative High-Sensitive Troponins in the Emergency Department and Risk of Myocardial Infarction
- Nadia Bandstein, Magnus Johansson, Rickard Ljung, Martin Holzmann, Karolinska Institutet, Stockholm, Sweden
Joint American College of Cardiology/New England Journal of Medicine Late-Breaking Clinical Trials
- March 31, 2014, 8:00 – 9:15 AM Hall D (Main Tent)
- Co-Chairs: John A. Jarcho, Steven E. Nissen
- Panelists: Yochai Birnbaum, Scott Cunneen, Michael H. Davidson, D. Craig Miller, Freek W. A. Verheugt
8:00 – 8:10 AM 404-08 – The Impact of Acetyl-Salicylic Acid on Major Arterial and Venous Complications in Patients Undergoing Noncardiac Surgery
- P.J. Devereaux, POISE-2 Investigators, Population Health Research Institute, Hamilton, Canada
8:15 – 8:25 AM 404-10 – A Large International Trial Assessing the Effects of Clonidine on Major Arterial Events in Patients Having Noncardiac Surgery
- Daniel I. Sessler, P.J. Devereaux, POISE-2 Investigators, Outcomes Research, Cleveland Clinic, Cleveland, OH, USA
8:30 – 8:40 AM 404-12 – Steroids in Cardiac Surgery Trial (SIRS)
- Richard Whitlock, Population Health Research Institute, McMaster University/Hamilton Health Sciences, Hamilton, Canada
8:45 – 8:55 AM 404-14 – Metformin in Acute Myocardial Infarction
- Chris PH Lexis, Iwan CC van der Horst, Erik Lipsic, Jan Tijssen, Pim van der Harst, Dirk van Veldhuisen, GIPS-III Investigators, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
9:00 – 9:10 AM 404-16 – Effect of Bariatric Surgery vs. Intensive Medical Therapy on Long-term Glycemic Control and Complications of Diabetes: 3-Year STAMPEDE Trial Results
- Philip Raymond Schauer, John Kirwan, Kathy Wolski, Stacy Brethauer, Sankar Navaneethan, Ali Aminian, Claire Pothier, Steven Nissen, Deepak Bhatt, Sangeeta Kashyap, Cleveland Clinic, Cleveland, OH, USA
Late-Breaking Clinical Trials V: TCT@ACC-i2
- March 31, 2014, 10:45 – 12:00 PM Hall D (Main Tent)
- Co-Chairs: Cindy L. Grines, Gregg Stone
- Panelists: David L. Brown, David E. Kandzari, Dean J. Kereiakes, Roxana Mehran, William W. O’Neill
10:45 – 10:55 AM 405-08 – One Year Outcomes from the STS/ACC Transcatheter Valve Therapy (TVT) Registry
- David R. Holmes, J. Matthew Brennan, John Rumsfeld, Dadi (David) Dai, Fred Edwards, John Carroll, David Shahian, Frederick Grover, E. Murat Tuzcu, Eric Peterson, Ralph Brindis, Michael Mack, Mayo Clinic, Rochester, MN, USA
11:00 – 11:10 AM 405-10 – A Randomized Comparison of Self-Expandable and Balloon-Expandable Prostheses in Patients Undergoing Transfemoral Transcatheter Aortic Valve Replacement – The CHOICE Trial
- Mohamed Abdel-Wahab, Julinda Mehilli, Ulrich Schäfer, FJ Neumann, Thomas Kurz, Ralph Toelg, Bettina Schwarz, Ken Gordian, Volker Geist, Steffen Massberg, Christian Frerker, Mohamed El-Mawardy, Gert Richardt, Heart Center, Segeberger Kliniken, Bad Segeberg, Germany
11:15 – 11:25 AM 405-12 – Unfractionated Heparin versus Bivalirudin in Primary Percutaneous Coronary Intervention: A Unique Randomized Controlled Trial with Consecutive, Unselected Patient Enrollment (using Delayed Consent), Designed to Reflect Real-World, Contemporary Practice
- Adeel Shahzad, Ian Kemp, Christine Mars, Rob Cooper, Claire Roome, Keith Wilson, Rod Stables, HEAT-PPCI investigators, Institute of Cardiovascular Medicine and Science, Liverpool Heart and Chest Hospital NHS Trust, Liverpool, United Kingdom
11:30 – 11:40 AM 405-14 – Bare Metal vs. Zotarolimus-eluting stent in Uncertain Drug-eluting Stent Candidates: A Randomized Controlled Trial
- Marco Valgimigli, ZEUS investigators, , Thoraxcenter, Erasmus MC, Rotterdam, The Netherlands
11:45 – 11:55 AM 405-16 – Autotransplantation of Bone Marrow Derived Mesenchymal Stromal Cells in Patients with Severe Ischemic Heart Failure: The MSC-HF Trial
- Anders Bruun Mathiasen, Abbas Qayyum, Erik Jørgensen, Steffen Helqvist, Anne Fischer-Nielsen, Klaus Kofoed, Mandana Haack-Sørensen, Annette Ekblond, Jens Kastrup, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark, Denmark
January 30th, 2014
Johnson & Johnson Will Share Clinical Trial Data
Larry Husten, PHD
In a major victory for advocates of open access to data from clinical trials, Johnson & Johnson today announced that it will make all of its clinical trial data available to outside researchers. The company said that the Yale University Open Data Access (YODA) Project will serve as an independent third party “to review requests from investigators and physicians seeking access to anonymized clinical trials data.”
The company said that this program “is the first time any company has collaborated with a completely independent third party to review and make decisions regarding every request for clinical data.” Last year Glaxo SmithKline and Pfizer announced that they would share clinical trial data, but the full extent of their commitment is still unclear and they have not arranged for an independent third party to review requests for data. Through its arrangement with YODA, J&J appears to have made a more substantial commitment to sharing its data. Other pharmaceutical and device companies will now undoubtedly face increased pressure to share their data as well.
“This is a remarkable action by Johnson & Johnson that should accelerate the movement of the clinical research enterprise toward more cooperative learning and sharing,” said Harlan Krumholz, leader of the YODA Project and CardioExchange Editor-in-Chief, in a Yale press release. “By establishing this fair and independent process to release data, Johnson & Johnson has taken a leadership position in this emerging era of open science.”
“Sharing anonymized data from clinical trials is critical to advance public health because it furthers our understanding of diseases, expands the base of knowledge needed to develop new treatments, and generates new insights and more complete evidence to enable better healthcare decisions for patients — all while protecting patient privacy and confidentiality,” said Joanne Waldstreicher, J&J’s Chief Medical Officer. YODA, she said, will “ensure that each and every request for access to our pharmaceutical clinical data is reviewed objectively and independently. This represents a new standard for responsible, independent clinical data sharing.”
In its announcement J&J said it would first make data available from Janssen, its pharmaceutical unit. But the company said it was “also committed to sharing data from clinical trials of its medical device and consumer products.”
In addition to Yale’s YODA, the AllTrials.Net project in the U.K. has been a major force in advocating for open data from clinical trials.
January 30th, 2014
To Merge or Not to Merge: Physician Professional and Personal Identities on Social Media
Vineet Arora, MD, MAPP
Vineet Arora and colleagues recently published a letter in JAMA about how physicians can find a balance between professional and personal online identities. We asked Vineet, an associate professor at the University of Chicago, to share why they wrote the letter and her advice for colleagues about their online presence.
As an avid user of social media, I was recently asked how I manage my online identity as a physician. Specifically, how do I deal with “friend requests” from trainees or patients? Also, how do I decide what to tweet or not tweet about?
As I pondered my answer, I thought of a recent article in JAMA which posited that total separation of personal and professional identities is impossible and that physicians should be aware of their online identity as “one” identity. While true that it is not easy to separate your identities entirely, it does not mean that a singular identity approach works for everyone. The reason to use a certain social media site may vary — and so does your identity with that reason. My colleagues and I thought that this perspective was important to share, so we collaborated on our letter to JAMA.
Here are a few ways I have chosen to maintain a separation of my professional and personal identity using social media:
- Consider the professional value and message of what you tweet. There are many things I consider tweeting about. But I often “pause before posting” and consider if the tweet is in line with the professional identity that I am curating on Twitter.
While I may use Twitter to learn about the latest celebrity gossip, I don’t use my professional account to retweet that information to my followers unless it’s of interest to the medical community, as well (there are certain stories that could be relevant to both!).
Having said that, I am well aware of physicians who do tweet their personal love of sports or music and I do not believe that is “unprofessional.” They choose to share their hobbies with the professional audience. This is likened to a physician posting in his or her office a favorite photo of an athlete or a picture of them engaged in a hobby. Physicians are free to make this choice to share personal information, but it does not mean they are obligated to.
- Reserve Facebook for personal photos and messages to friends and family. I use Facebook for photos or messaging with friends and family. Posting these photos on Twitter would not make as much sense because my audience would not understand the significance. More importantly, as a matter of personal preference, I do not wish to disseminate personal photos to the larger audience of Twitter.
Additionally, numerous ethical guidelines and key opinion leaders guard against “friending” patients on Facebook. For physicians looking to use Facebook, instead of using their “personal profile”, KevinMD highlights the importance of using a separate Facebook page for your professional practice.
- Tolerate a potential overlap provided that it does not “overtake the purpose” of the feed. I may post something on Twitter and Facebook at the same time that is of interest both professionally and to my personal network. Someone in my Facebook network may post something professionally related about me, such as a paper or interview. I am not a purist to the point of scrubbing my profiles to preserve their meaning, but I do make sure that these posts do not “overtake” the nature of my feed.
I have many personal friends and colleagues on Twitter who may post something that is not directly related to my professional feed (e.g., “Great to see you!”), but it does not undermine the professional purpose and image of my Twitter feed.
- Accept that Facebook, while reserved for personal use, does not give carte blanche to behave unprofessionally. Using Facebook for “personal use” does not mean you have an unrestricted license to say whatever you want or that it will stay “personal.” This goes for anyone, not just physicians.
Despite the privacy settings, which get increasingly more difficult to decipher with each update, Facebook posts are not technically “private” — they can be reposted by friends to their networks. Recently, a University of Chicago professor attending a neuroscience meeting posted about the lack of beauty among the women in his field. An annoyed “friend” sent the screenshot to Jezebel, which was quickly followed by public outcries for him to be fired. While freedom of speech is a fundamental right, that does not mean you won’t face the repercussions of what you say!
Another murky area, especially for trainees, is what to do with pictures of escapades out on the town. While setting your profile to private can help, it is not a safeguard against someone finding incriminating photos and reconsidering your future at their institution. The American College of Obstetrics and Gynecology has a great cautionary video depicting this scenario. In addition, if questionable pictures were seen by state medical boards, it would likely result in an investigation. So, it pays to pause before posting to consider the ramifications.
JOIN THE DISCUSSION
How do you balance your private and professional identities on social media?
January 30th, 2014
Selections from Richard Lehman’s Literature Review: January 30th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint this selection from Dr. Richard Lehman’s weekly journal review blog at BMJ.com. Selected summaries are relevant to our audience, but we encourage members to engage with the entire blog.
JAMA 22/29 Jan 2014 Vol 311
FDA Approval of Cardiac Implantable Electronic Devices via Original and Supplement Premarket Approval Pathways, 1979-2012 (pg. 385): I told you the other day that you could go into the market with any medical device you wanted, from a cotton wool bud to an implantable defibrillator, and you would probably get approval if you had the right glossy brochure. This is called the Premarket Approval (PMA) process. If you are already in the business, it is even easier than that. “Many cardiac implantable electronic device models currently used by clinicians were approved via the PMA supplement process, not as original PMAs. Most new device models are deemed safe and effective without requiring new clinical data, reinforcing the importance of rigorous postapproval surveillance of these devices.”
Lancet 25 Jan 2014 Vol 383
Aggressive Medical Treatment With or Without Stenting in High-Risk Patients with Intracranial Artery Stenosis (pg. 333): In 2005, the FDA approved the Stryker Wingspan stent system for use in stenosed intracranial arteries, on the basis of a single-arm study of 45 patients. Eleven thousand of these devices have been sold in the USA since then, but the fact is that they can harm patients and should never have been licensed at all. This is shown by the first adequately powered randomized controlled trial of the device, SAMMPRIS. Patients on “aggressive medical treatment”, i.e. statins and antiplatelet agents, did better than those who were stented, yet the FDA has not pulled Wingspan. Just how far does industry capture of regulation extend? See Rita Redberg’s article below.
BMJ 25 Jan 2014 Vol 347
Presumed Safe No More: Lessons from the Wingspan Saga on Regulation of Devices: Rita Redberg, editor of JAMA Intern Med, appears in a terrific piece this week about the Stryker Wingspan device.
Off-Hour Presentation and Outcomes in Patients with Acute Myocardial Infarction: The BMJ is popular in the USA, and getting more so, but there may be a backlash over here if it continues to feature spellings like “color” on its website and run titles like “Off-hour presentation and outcomes of patients with acute myocardial infarction.” I don’t know if “off-hour” is an expression used in the USA: I have never heard it either there or here. In fact all this American systematic review tells us is what we already knew from excellent single studies like Harlan Krumholz’s comprehensive analyses of Medicare data a few years ago: have your heart attack near a hospital on a weekday morning. If you follow your clinical judgement, you will sometimes miss things, patients will suffer, and you will feel guilty. If you follow diagnostic decision aids, the same will happen, perhaps more frequently, perhaps less.
January 29th, 2014
What’s the Best Blood Transfusion Protocol for Anemic ACS Patients?
Sunil Rao, MD
CardioExchange’s John Ryan interviews Sunil V. Rao about his approach to blood transfusions in patients with acute coronary syndromes. Dr. Rao recently wrote an editorial on TRANSFUSION-2, a study of the platelet and inflammatory effects of blood transfusions in ACS and non-ACS patients with anemia. Rao’s editorial, coauthored with Matthew W. Sherwood, is published in JACC.
Ryan: What is your practice in patients with ACS and a hemoglobin level ≤8 g/dL? Do you give them transfusions? Under what circumstances would you or wouldn’t you? Does the use or nonuse of bleeding-avoidance strategies (e.g., vascular closure devices, bivalirudin, or a radial approach) influence your decision?
Rao: Our protocol calls for withholding transfusion from asymptomatic patients who have a hemoglobin level >8/dL. If they have symptoms attributable to anemia or the hemoglobin level is ≤8 g/dL, then transfusion is usually administered one unit at a time with re-evaluation of the clinical status and hemoglobin level. We are a very high-volume transradial center, so we try to avoid situations where transfusion may be necessary, but in some patients it is still an issue. The challenge is that our protocol and the European Society of Cardiology guidelines are based on observational data, so we have to recognize that these studies may be confounded by indication. Ultimately, as in all clinical decisions, the risks and benefits must be weighed at the bedside before deciding to order a blood transfusion.
Ryan: Given the discrepant practice and guideline recommendations, how can we get to the bottom of this issue? What sort of trials must we do to define best practices for managing anemia in patients with ACS?
Rao: That is an excellent question, and I think only a randomized trial will ultimately address the issue. The challenge with doing a trial in ACS patients with anemia is that those who would qualify do not fit the profile of a patient who would be considered for the “standard” industry-funded ACS trial. In contemporary clinical practice, where bleeding avoidance strategies are used and the hospital length of stay is quite a bit shorter than in years past, patients who are anemic in the setting of ACS are elderly, frail, and have many comorbidities such as chronic kidney disease. Of course, these are also the patients for whom a transfusion may yield the most benefit or harm. A trial that aims to answer the hemoglobin threshold question in ACS will include very high-risk patients who are generally not approached for clinical trials. It will be difficult, but I think that this is an area where we need solid evidence to guide clinical practice.
JOIN THE DISCUSSION
How does your institution handle blood transfusions for anemic ACS patients?
January 28th, 2014
Problems Persist Despite Gains in Oral Anticoagulant Use
Larry Husten, PHD
Although significant progress has been made in recent years, a new survey from the European Society of Cardiology finds that there are still too many atrial fibrillation patients who are not taking the best medications to reduce their elevated risk for stroke. Many elderly patients are not receiving oral anticoagulants — either traditional warfarin or one of the newer agents — and overall, too many patients are still taking aspirin, despite the fact that it is not recommended for this group of patients.
In a paper published in the American Journal of Medicine, Gregory YH Lip and colleagues analyzed data from more than 3100 patients surveyed in the Euro Observational Research Programme on Atrial Fibrillation from February 2012 to March 2013. They found that the use of oral anticoagulants has improved over the past decade. A large majority — 72% — received warfarin, while only 8% received one of the newer oral anticoagulants.
“Novel oral anticoagulant uptake is still a bit low, probably because of differences in regulatory approval, costs and access to drugs in different countries,” said Dr. Lip, in an ESC press release. “But the main point is that overall oral anticoagulant uptake as a whole has improved in the last 10 years.”
The authors expressed concern about the persistent high use of aspirin among patients in the survey. “The perception that aspirin is a safe and effective drug for preventing strokes in AF needs to be dispelled,” said Lip. “If anything, you could say that giving aspirin to patients with AF is harmful because it is minimally or not effective at stroke prevention, yet the risk of major bleeding or intracranial haemorrhage is not significantly different to well-managed oral anticoagulation.” Aspirin is commonly prescribed as an antiplatelet agent in patients with coronary artery disease, especially following an acute coronary syndrome. In the survey, AF patients with coronary disease were eight time more likely to be taking aspirin.
A finding of particular concern was the underuse of oral anticoagulants in elderly patients. Said Lip: “Elderly patients are at the highest risk for stroke and yet they are given aspirin which is not recommended and potentially harmful. There is a perception that elderly patients do not do well on anticoagulation.” But, he said, warfarin is actually “far superior” to aspirin in these patients for the prevention of stroke.
January 28th, 2014
Cholesterol Guidelines: Annals of Internal Medicine Offers a Guide for the Perplexed
The guidelines on assessing cardiovascular risk and cholesterol levels that were released in November have not had a calming effect on clinicians, according to commentators. The Annals of Internal Medicine offers four articles meant to allay fears — or at least provide some perspective. The articles include a synopsis of the guidelines.
Skeptical commentators argue that lowering the treatment threshold to a 7.5% 10-year risk will lead to overtreatment. (Other commentators argue that the ideal threshold may lie between 5% and 15%, given the limitations of the risk calculator, which is scheduled for revision in the coming months.)
From an even more practical standpoint, another group reminds clinicians that finding time for the patient discussions recommended in the guidelines will be difficult. The discussions might best be planned to occur over a series of visits, in their view.
An editorial sagely advises that readers “listen to the evidence, not the noise.”
Originally published in Physician’s First Watch
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