February 11th, 2013
Selections from Richard Lehman’s Literature Review: February 11th
Richard Lehman, BM, BCh, MRCGP
CardioExchange is pleased to reprint selections 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 6 Feb 2013 Vol 309
Effect of Ramipril on Walking Times and Quality of Life Among Patients With PAD and Intermittent Claudication (pg. 453): Stone the crows, a great little study from Oz that will change your practice at a stroke. They recruited 212 patients with intermittent claudication who had never had invasive treatment—which immediately made me realise the study couldn’t have been done in America, where at the first twinge of calf pain you get a stent or balloon stuck down your femoral artery. No, these were mostly fine specimens of Australian manhood, mean age 65, getting pains below the level of their shorts if they walked too far, despite the fact that one third of them had never smoked and all of them had normal blood pressure. One half of them were randomized to a well-known drug and after six months they found they could walk four minutes longer before they had to stop. The wonder drug? Ramipril 10mg. This is the kind of trial that makes nobody millions of dollars, but which we should all be doing in our fields of interest. It took just three interested hospitals in Southern Australia.
NEJM 7 Feb 2013 Vol 368
Genetic Associations with Valvular Calcification and Aortic Stenosis (pg. 503): And now back to the Northern Hemisphere where the big boys live. This study was done in over 30 centres across North America and Europe, and in Iceland, which is somewhere between. Compared with the little fishing boats the Australians used to bring in their useful catch, this looks like an imperial Navy, with battle cruisers and aircraft carriers in full steam. What do they sail forth to capture for the benefit of mankind? “One SNP in the lipoprotein(a) (LPA) locus (rs10455872) reached genomewide significance for the presence of aortic-valve calcification (odds ratio per allele, 2.05; P=9.0×10−10), a finding that was replicated in additional white European, African-American, and Hispanic-American cohorts (P<0.05 for all comparisons). Genetically determined Lp(a) levels, as predicted by LPA genotype, were also associated with aortic-valve calcification, supporting a causal role for Lp(a).” Genomic true believers will argue that this is a real step forward, because it is another piece of evidence that this lipoprotein fraction is implicated in valvular calcification. I leave this for you to decide.
Rivaroxaban for Thromboprophylaxis in Acutely Ill Medical Patients (pg. 513): If you are a major medical journal with a business model that involves large payments for reprints from pharmaceutical companies, then you are bound to love the two wars that ensure your income stream—the Stent Wars (see this week’s Lancet) and the Clotbusting Wars. Given the number of competing products and possible study designs, these two wars alone could go on forever, boring and confusing clinicians and filling the coffers of the NEJM and the Lancet throughout eternity. Rule One for selling reprints is that you make the conclusion of the Abstract as favourable as possible, because this is all that most clinicians read:
“In acutely ill medical patients, rivaroxaban was noninferior to enoxaparin for standard-duration thromboprophylaxis. Extended-duration rivaroxaban reduced the risk of venous thromboembolism. Rivaroxaban was associated with an increased risk of bleeding.” And for your further information: “The study was designed and supervised by the steering committee and was sponsored by Bayer HealthCare Pharmaceuticals and Janssen Research and Development. The members of the steering committee signed confidentiality agreements with the study sponsors. The data were collected and analyzed by the sponsors. All the authors had full access to the data and analyses and contributed to the writing of the manuscript. Editorial assistance was provided by Chameleon Communications.” But even the best chameleon cannot disguise the fact that that rivaroxaban is more than twice as likely as enoxaparin to cause a bleed requiring two or more units of blood by day 10, and similarly by day 35. So an honest Abstract conclusion might read: “In acutely ill medical patients, compared with rivaroxaban, enoxaparin provides equal protection from thromboembolism and is considerably safer.” And the editor of this journal was telling us a few weeks ago that we should not mistrust the reporting of industry trials.
Lancet 9 Feb 2013 Vol 381
Paclitaxel-Eluting Balloons, Paclitaxel-Eluting Stents, and Balloon Angioplasty in Patients with Restenosis After Implantation of a Drug-Eluting Stent (pg. 461): Not that all non-pharma trials are much better. I utterly fail to understand why this one is published in a leading journal, because it has no endpoints of clinical significance but simply measured the angiographic effect of a paclitaxel eluting balloon as opposed to a non-eluting balloon or a paclitaxel eluting stent in patients who had restenosis after drug-eluting stent implantation. Having some paclitaxel around – whether from the balloon or the stent – seemed to improve the coronary diameters measured 6 months later. “Frequency of death, myocardial infarction, or target lesion thrombosis did not differ between groups.” So?
Acute Pneumonia and the CV System (pg. 496): “Pneumonia tends to affect individuals who are also at high cardiovascular risk. Results of recent studies show that about a quarter of adults admitted to hospital with pneumonia develop a major acute cardiac complication during their hospital stay, which is associated with a 60% increase in short-term mortality.” Golly, somebody has finally twigged that the heart and the lungs are joined up to each other and live in this space called the chest, or thorax. This could have major implications. We could start thinking of providing services for elderly breathless patients rather than making them wander from chest physicians to cardiologists and back again: we could tackle the problem of the post-hospital syndrome by attending to the cardiovascular risks of chest infections and the right ventricular contribution to heart failure; we could even ask patients what their main problems are and whether they are sufficiently addressed to make them feel safe at home. But all this requires a level of genius far beyond the reach of any known health service.
BMJ 9 Feb 2013 Vol 346
Dietary Linoleic Acid for Secondary Prevention of CHD and Death: Evaluation of Recovered Data from the Sydney Diet Heart Study and Updated Meta-Analysis: The BMJ was lucky to scoop this paper based on retrieved follow-up data from the Sydney Diet Heart Study (1966-73) which recruited men who had had coronary events and successfully lowered their cholesterol by substituting safflower oil for animal fat. This raised mortality by a third over five years. Beware omega 6 linoleic acid which abounds in safflower oil and constitutes more than 50% of sunflower, cottonseed, corn and soy oils. Stick to healthy butter, lard, goose fat and olive oil, as civilised people have done through the centuries.
February 11th, 2013
FDA Wants Cardiovascular Safety Data Before Approving Insulin Degludec
Larry Husten, PHD
The FDA informed Novo Nordisk on Friday that it would not approve the company’s highly anticipated long-acting insulin degludec products (Tresiba and Ryzodeg) until it receives data from a cardiovascular outcomes trial. Approval of the drugs had been widely anticipated for this year, following a positive recommendation from an FDA advisory committee last fall. But the committee also unanimously recommended that the company be required to perform a cardiovascular outcomes trial.
In a Complete Response Letter, the FDA told Novo Nordisk that it will require “additional cardiovascular data from a dedicated cardiovascular outcomes trial before the review of the New Drug Applications can be completed.” In a press release, Novo Nordisk said it did not expect it would be able to supply the requested data this year. Sanford Bernstein analyst Timothy Anderson speculated that the earliest possible date for approval is now 2015. Anderson also noted that the delay for insulin degludec would help to bolster Sanofi’s insulin glargine (Lantus) franchise.
Novo Nordisk CEO, Lars Rebien Sørensen, said: “We are surprised and disappointed to receive this letter, but we acknowledge this decision by the FDA and will work with the agency to determine the best path forward to completing the review.”
February 9th, 2013
A Cardiologist Tests an Activity Tracker
Shengshou Hu, M.D.
CardioExchange welcomes this guest post from Dr. Westby Fisher, an electrophysiologist practicing at NorthShore University HealthSystem in Evanston, Illinois, and a Clinical Associate Professor of Medicine at the University of Chicago’s Pritzker School of Medicine. This piece originally appeared on his blog, Dr. Wes.
The Fitbit One Activity Tracker
I have been testing the Fitbit One activity tracker (Fitbit.com) over the past several weeks to see how it might help me lose a few pounds. I’d heard a lot about these things and have friends who use this or other competing devices, so I felt it was time to test one myself.
Simple in design, the Fitbit One looks similar to a small USB memory stick and has a single button on one side of the device and two small gold-colored electrodes on the back of the device that connect to a small USB-based charger that plugs into your computer. It uses an accelerometer and altimeter to monitor movement counting “steps” and “stairs” climbed or descended. Using your weight and age provided to the Fitbit website as your starting point, it calculates calories burned, estimated miles walked, and provides a motivational flower icon with a growing “stalk” for the level of activity achieved at different times of the day based on pre-set goals you select for yourself:
Toggling the button on the device shows the various information available.
The device is either placed in a small rubber clip that holds it on a wasteband or bra or it can be placed in a wriststrap that can be worn at night (more on this later). It should be noted the device is NOT waterproof so it cannot be worn swimming.
The device comes with a number of tiny attachments that are critical to its function, so keeping these in a safe place is a good idea. They include the charging cable (one charge worked for 4-5 days for me and it quickly charges in about 60-90 minutes), a USB Bluetooth communicator, the rubber clip-on cover and the wrist strap.
The device communicates effortlessly via Bluetooth to an iPhone 4s or iPhone 5 automatically once a 4-digit unique handshake code is shared by the device and your cellphone. Information stored on the phone also syncs with a (non-HIPAA compliant) website online where your daily, weekly, and lifetime activity levels, food consumption, and weights are stored. Viewing data over time is a simple process.
The Fitbit iPhone app is downloaded on to your iPhone and permits you to enter your weight as you progress, food consumed, or to log your activities. You can also connect with others via the app (something HIPAA rules discourage, but most people using these don’t care). Still, if you want to see how you compare to other like-minded souls throughout the day, you can do so using their iPhone app. Real gluttons for punishment can even share their achievements using the device on Facebook. (Sorry, not me.) While the website can send you “badges” for activity milestones via email or text message on your phone, I preferred to turn off this functionality because I really didn’t need to look at my cell phone any more than I already do. Also, I don’t need any more spam.
Interestingly, the Fitbit One can also track your time sleeping. This is accomplished by pressing and holding down its single button for over 2 seconds until a timer starts. Pressing the timer for two seconds upon awakening will then record the time slept. As you sleep, the device reportedly records periods of being “awakened” because it senses motion as you sleep. (I’ll let you use your imagination for other purposes at night as well because, yes, there are interesting stories about this elsewhere). It also has the ability to set (via your iPhone) a silent alarm that vibrates the device to wake you without waking others near you.
Impressions
I found there was value in using this device for me. Fitbit’s charm was its way of making even simple exercise like walking and climbing stairs matter. While I enjoy racquet sports and they provide plenty of steps to achieve my self-imposed daily goal, I found walking the halls of our large hospitals worked pretty well, too. Also, I found that I didn’t have to obsessively track my food intake for too long since it became very obvious that every little thing I consumed quickly added to my daily allotment of calories. Just understanding what you are eating, paired with your calories burned, was eye opening. I learned first-hand how much activity it takes to burn off those calories consumed. Most important, a pacemaker battery change burned about 105 calories.
I tried showing this device to a few of my more stubborn overweight patients in clinic, and they appeared interested, but whether I can convince them to make the plunge will have to come after I test my own ability to stick with the use of the device for a bit longer. (If I lose weight, will it help me keep it off?) Also, I found patients hesitated when I disclosed the price for the Fitbit One ($99 U.S.), though a cheaper version called the “Zip” is available for $60 U.S. that tracks fewer items. Still, given what we pay for monthly cell phone service, this price seemed fairly reasonable over the lifetime that the device is likely to be used.
I worried that I might lose the tiny device and quickly turned to clipping it to a belt loop rather than my belt since it held better there. And although I haven’t had my device go through a wash cycle yet, I’m sure that scenario commonly occurs and would likely destroy it.
Overall, it seems to be helping make weight loss fairly fun so far, though weight loss still requires discipline. Still, geeks like me have found it’s helped so far, having lost 7 lbs in two weeks using the device. But I have also come to appreciate what others have noticed using these devices: there is a thin line between healthy and unhealthy obsession with gadgets when using them for weight loss.
February 8th, 2013
Xarelto Effective in Medically Ill Patients, But at High Bleeding Cost
Larry Husten, PHD
The recent arrival of novel oral anticoagulants has provided important new options for treating and preventing venous thromboembolism (VTE). New indications for these drugs have been granted for patients with atrial fibrillation and for patients who have undergone orthopedic surgery. But an additional indication, for acutely ill medical patients at risk for VTE, does not appear likely in the near future, as a new trial published in the New England Journal of Medicine shows that one of these novel drugs, though effective at preventing VTE, also significantly increased bleeding risk.
In the Multicenter, Randomized, Parallel Group Efficacy and Safety Study for the Prevention of Venous Thromboembolism in Hospitalized Acutely Ill Medical Patients Comparing Rivaroxaban with Enoxaparin (MAGELLAN), first presented at the American College of Cardiology meeting in 2011, more than 8000 medically ill patients were randomized to subcutaneous enoxaparin for 10 days, followed by placebo for 25 days, or oral rivaroxaban (Xarelto, Johnson & Johnson) for 35 days.
In terms of efficacy, at 10 days rivaroxaban was found to be noninferior to enoxaparin; at 35 days it was found to be superior to enoxparin (for the first 10 days) and placebo:
- By 10 days, the primary efficacy measure (a composite of asymptomatic proximal DVT, symptomatic DVT, symptomatic nonfatal PE, and VTE-related death) had occurred in 2.7% of patients in each group.
- By 35 days, a primary outcome event had occurred in 4.4% of patients in the rivaroxaban group compared with 5.7% in the enoxaparin and placebo group (relative risk, 0.77; 95% CI, 0.62-0.96; P=0.02).
However, there were significantly more major or clinically relevant minor bleeding episodes in the rivaroxaban group at both day 10 and day 35:
- At 10 days, clinically relevant bleeding occurred in 2.8% of rivaroxaban recipients versus 1.2% of enoxaparin recipients (RR, 2.3; P< 0.001).
- At 35 days, clinically relevant bleeding occurred in 4.1% of patients in the rivaroxaban group versus 1.7% of patients in the enoxaparin group (RR, 2.5; P<0.001).
Rivaroxaban is currently indicated in the U.S. for stroke reduction in patients with atrial fibrillation, for the treatment and prevention of recurrence of deep venous thrombosis and pulmonary embolism, and for DVT prophylaxis after orthopedic surgery. The FDA recently rejected an indication for the use of rivaroxaban in patients with acute coronary syndrome.
February 7th, 2013
Arms and the Interventionalist
Megan Coylewright, MD MPH, Michael Tempelhof, MD MSc, Micah Eimer, MD, L. David Hillis, MD, Richard A. Lange, MD, MBA and John Ryan, MD
According to an ESC consensus document published last week, radial artery access should be the “default” choice for PCI. CardioExchange’s John Ryan interviewed cardiologists and interventional cardiologists at different stages of their careers to find out how they view radial artery catheterization, and if the views differ among interventional fellows, faculty, and those in leadership roles.
Dr. Ryan: Do you agree with the ESC statement that radial artery access should be the first choice for PCI? Why or why not?
Megan Coylewright, MD, MPH (interventional fellow, Mayo Clinic): I do agree that radial PCI should be a part of every interventionalist’s toolkit, and I agree with the need to maintain proficiency with appropriate annual volume. I believe the statement stops short of declaring that it “should be” the first choice, but rather that it is “feasible.” This reflects the ongoing controversy surrounding the issue at many institutions, particularly as smaller sheaths and less use of GP IIb/IIIa inhibitors are becoming the norm for PCI; some feel this diminishes the difference in bleeding between the two approaches.
Michael Tempelhof, MD (interventional fellow, Northwestern University): Transradial access has been shown to be beneficial on many levels. For patients, the transradial approach is well tolerated and associated with earlier ambulation times and reduced length of hospital stay. Physicians and patients alike benefit from significant reductions in bleeding risk and cardiac death. Healthcare systems benefit from reductions in cost associated with complications and prolonged hospitalization. Finally, as recently reported in the RIFLE-STEACS trial, the patients with the highest complication rates associated with PCI have been demonstrated to derive the greatest benefit from the transradial approach.
For these reasons, I do concur with the ESC statement advocating for the transradial approach for coronary angiography and intervention. A caveat is that the transradial approach is a learned skill requiring strict adherence to a regimented, progressive training plan, as outlined in the ESC document.
Micah Eimer, MD (cardiologist, Glenview, IL): The data are pretty convincing on the lower rate of complications, and my clinicial experience confirms that. Patients who have undergone both radial and femoral approaches consistently and strongly prefer the radial approach for several reasons, including less discomfort at the site, not having to lie flat on their backs for hours, lack of bruising, and quicker recovery. As a clinician, I am happy to see fewer complications (hematomas, psuedoaneurysms, emboli) and appreciate the ability to send patients to cath without stopping warfarin.
Therefore, I do agree with the concept, but I am always cautious about substituting guidelines for clinical judgement.
L. David Hillis, MD, (Chair, Department of Internal Medicine) and Richard Lange, MD (Professor, University of Texas Southwestern Medical School): Although we think interventionalists should be proficient in both femoral and radial techniques, we’re not persuaded that “one access fits all.” Although radial access is associated with fewer vascular complications (primarily hematoma and pseudoaneurysm), its use does not convincingly reduce the occurrence of MACE. Compared with the femoral approach, the radial approach requires a higher level of training and proficiency (which may not be universally attainable). Furthermore, even in centers with extensive experience in its use, radial access is associated with a 7–10% rate of crossover to femoral access, increased operator radiation exposure, and radial artery occlusion.
Dr. Ryan: Do you feel comfortable using the radial approach?
Dr. Coylewright: Yes, we use it frequently at Mayo Clinic. Speaking with interventional fellows across the country, I anticipate that the use of the radial approach will rise steeply in the next 10 years as a result of the excellent training we are receiving from our institutions’ experienced radial operators.
Dr. Tempelhof: Proficiency in the transradial approach for PCI and catheterization of complex coronary anatomy is limited by the nascence and underutilization of the approach in the U.S. Compared with the femoral approach, there is a paucity of advanced equipment and live mentorship programs, which are required to quickly develop an interventionalist into a facile transradial operator. I am comfortable with the transradial approach for diagnostic angiography and type A PCI. However, I recognize that additional experience is required to become competent for complex PCI or cannulation of complex coronary anatomy.
Drs. Hillis and Lange: Not really. As old dogs (admittedly late in learning new tricks), we’re a part of “Gen-S” (“S” for Sones). Since we’re very comfortable with femoral and brachial approaches, using a non-femoral approach is not a problem. However, with these approaches, we don’t have to confront radial loops, spasm, and occlusion, and we are not restricted from using large guiding catheters that can be helpful in approaching complex lesions (i.e., chronic total occlusions and bifurcation or calcified lesions). In Texas, where everything is bigger and better, we don’t feel a need to abandon the femoral approach.
Dr. Ryan: What percent of your current cases are radial, and what percent do you expect to be radial in 3 years?
Dr. Coylewright: For an interventional fellow, the percent of radial cases depends a bit on the attending with whom we are working; there is a lot of variability among the staff. It is not yet a default approach in our lab. My cases are currently approximately one-third to one-half radial. My future practice will depend in part on my patient population; I see the need for complex left main PCI, rotablation for heavily calcified vessels, and CTO procedures potentially rising as our population ages. Sheath size limits the performance of these interventions via the radial artery, particularly in smaller patients.
Dr. Tempelhof: I currently complete 24% of all my coronary cases via the transradial approach. Patients’ expectations and demonstrated outcomes benefit will require that I complete 50–70% of cases via the transradial approach in 3 years.
Dr. Eimer: Our interventionalist is probably at 90% radial, and I expect that to stay the same, as its use is limited primarily by unsuitable anatomy.
Drs. Hillis and Lange: At our hospital, approximately 10–15% are performed via the radial approach. In 3 years, that will likely double.
February 6th, 2013
Genetic Study Identifies Strong Links to Aortic Valve Disease
Larry Husten, PHD
A genetic component is believed to play an important role in valvular heart disease, but the specific genes involved have not been identified. Now an interntional group of researchers has identified genetic variations that increase the risk for valvular calcification.
In an article published in the New England Journal of Medicine, members of the Cohorts for Heart and Aging Research in Genome Epidemiology (CHARGE) consortium report on their search for genes associated with aortic valve calcification and mitral annular calcification in several study cohorts. They found one SNP, in a gene previously shown to be associated with lipoprotein(a) levels and the risk for coronary artery disease, to be significantly associated with a doubling of the risk for aortic-valve calcification. This finding was replicated in additional cohorts.
Previous studies that linked Lp(a) with aortic valve disease could not sort out whether Lp(a) “was a cause or simply a marker of disease,” the authors write. The new findings, they claim, “provide evidence for a causal relationship between Lp(a) and calcific aortic-valve disease and strongly implicate genetic variation at the LPA locus in the pathogenesis of the disease.”
Although the researchers focused on aortic calcification as a marker for clinical aortic disease, they found that variations in the LPA genotype were associated with aortic stenosis and aortic-valve replacement. “Our results suggest that lifelong elevations in Lp(a) levels lead to a markedly increased prevalence of aortic-valve calcification in adulthood and implicate Lp(a) in the development of aortic-valve disease.”
The group also identified two SNPs associated with mitral annular calcification, but this finding could not be consistently replicated.
The researchers noted that additional studies will be required “to evaluate whether lowering Lp(a) levels will reduce the incidence or progression of aortic-valve disease.”
An NHLBI press release included this statement from coauthor Christopher O’Donnell, the NHLBI’s senior director for genome research: “No medications tested to date have shown an ability to prevent or even slow progression of aortic stenosis, and treatments are limited beyond the major step of replacing the aortic valve. By identifying for the first time a common genetic link to aortic stenosis, we might be able to open up new therapeutic options.”
February 6th, 2013
FFR vs. iFR: All That Glitters Is Not Gold
Richard A. Lange, MD, MBA and L. David Hillis, MD
The “Gold Standard”: Fractional flow reserve (FFR) is a pressure-derived index of coronary stenosis severity that has been validated for assessing the hemodynamic significance of stenoses that are of “intermediate” angiographic severity. In fact, FFR use during PCI carries a Class 1A recommendation from the European Society of Cardiology and a Class IIA recommendation from the American College of Cardiology, despite the fact that it requires additional instrumentation of the coronary arteries and pharmacologic vasodilation to induce maximal hyperemia.
Easier Money? The instantaneous wave-free ratio (iFR) is an alleged index of coronary stenosis severity that is independent of hyperemia. It is based on the hypothesis that coronary microvascular resistance is minimal during mid and late diastole (when coronary flow is maximal), so the administration of a vasodilator is unnecessary. It is thought that by avoiding the need to administer adenosine, iFR is more likely than FFR to expand the practice of pressure wire-guided decision making.
Convertible Currency? Unfortunately, the results of two new studies suggest that iFR is unlikely to replace FFR.
Using a simulation model to study the relationship between iFR and FFR, then validating their predictions with data from a large, multicenter cohort of humans, Johnson and colleagues found that:
- iFR systematically overestimates FFR, with wide limits of agreement that would often alter management decisions.
- In individual patients, iFR is not interchangeable with FFR.
In VERIFY, a prospective study of 206 consecutive PCI patients compared with a retrospective analysis of 500 archived pressure recordings, Berry and colleagues showed that:
- The diagnostic accuracy of iFR was only 60% compared with the FFR cut-off value of <0.80 (a value that has been validated in randomized trials for clinical management).
Pyrite (Fool’s Gold): The VERIFY authors conclude “…that iFR cannot be recommended for clinical decision making in patients with coronary artery disease.” Too bad, since iFR would be a convenient and quick use of a pressure-wire alone — without a vasodilator — to assess coronary stenosis severity.
With all the concerns of inappropriate PCI, do you feel compelled to use FFR to justify PCI?
In what percentage of patients with “intermediate” coronary stenoses do you use FFR?
Does the hassle associated with administering a vasodilator prevent you from measuring FFR in patients with intermediate stenoses?
February 5th, 2013
Back To The Future: Resurrected Data From 1960s Trial Might Impact Contemporary Dietary Fat Debate
Larry Husten, PHD
In an exceedingly strange turn of events, data from a clinical trial dating from the 1960s, long thought to be lost, has now been resurrected and may contribute important new information to the very contemporary controversy over recommendations about dietary fat composition.
The American Heart Association has long urged people to increase their consumption of polyunsaturated fatty acids (PUFAs), including omega 6 PUFAs, and reduce their consumption of saturated fatty acids (SFAs). The recommendations are based on the simple observation that PUFAs lower total and LDL cholesterol while SFAs have the opposite effect. However, the cardiovascular effects of substituting PUFAs for SFAs have never been tested in randomized, well-controlled clinical trials, and a growing proportion of experts now suspect that simple changes in total cholesterol and LDL cholesterol may not tell the whole story.
One trial that actually tested the hypothesis was the Sydney Diet Heart Study, which ran from 1966 through 1973. In the trial, 458 men with coronary heart disease (CHD) were randomized to a diet rich in linoleic acid (the predominant omega 6 PUFA in most diets) or their usual diet. Although total cholesterol was reduced by 13% in the treatment group during the study, all-cause mortality was higher in the linoleic acid group than in the control group. However, in the original publications, and consistent with the practice at the time, deaths from cardiovascular disease (CVD) and CHD were not published.
Now, in a new paper published in BMJ, Christopher Ramsden and colleagues report that they were able to recover and analyze data from the original magnetic tape of the Sydney Diet Heart Study. The new mortality findings are consistent:
- All cause: 17.6% in the linoleic group versus 11.8% in the control group (HR 1.62, CI 1.00-2.64)
- CVD: 17.2% versus 11% (HR 1.70, CI 1.03-2.80)
- CHD: 16.3% versus 10.1% (HR 1.74, CI 1.04-2.92)
The investigators then used these data to perform an updated meta-analysis and found similar but nonsignificant trends for overall mortality and for CVD and CHD mortality. They concluded that their findings “could have important implications for worldwide dietary advice to substitute” PUFAs for SFAs.
In an accompanying editorial, Philip Calder agrees:
These findings argue against the ‘saturated fat bad, omega 6 PUFA good’ dogma and suggest that the American Heart Association advisory that includes the statement ‘higher [than 10% of energy] intakes [of omega-6 PUFAs] appear to be safe and may be even more beneficial’ may be misguided.
February 5th, 2013
The Sun Is About to Shine
Joseph S. Ross, MD, MHS
When the Patient Protection and Affordable Care Act was passed in 2010, the rules required to implement Section 6002, better known as the Physician Payment Sunshine Act (PPSA), were expected to be in place by 2011. But the sun was slow to shine and we waited until the first day of February 2013 for the Centers for Medicare and Medicaid Services (CMS) to release their final rules.
The Sunshine Act has great relevance to all CardioExchange members, as it requires all pharmaceutical, medical device, and biologic companies to report gifts and payments made to physicians and hospitals in the U.S., otherwise known as transfers of value, to the U.S. Secretary of Health and Human Services.
“Transparency” reporting is expected to begin in August 2013, with all payments being made publicly available in a searchable, sortable, downloadable website by 2014. The following information will be publicly reported:
- Name, address, and other identifiers (e.g., NPI number or state license number) of who received the payment (or other transfer of value)
- Amount and form of the payment (e.g., honorarium, reimbursement for travel)
- Explanation of the payment’s purpose (CMS provides 16 potential categories, including consulting, education, and meals)
- Product(s) associated with the payment (e.g., honorarium to attend an educational event discussing drug X)
There are some notable exceptions to transparency reporting. For instance, payments made for research are reported using special rules. In addition, unless a physician receives $100 or more annually from a company, individual payments less than $10 are exempted. And most controversially, payments related to ACCME-accredited educational event speaking where a medical product company supports the event but does not choose the speaker or pay them directly are not required to be reported.
To be clear, the responsibility to report these payments falls on the companies, not individual physicians. However, physicians and hospitals have the opportunity to dispute reported payments (although dispute does not prevent reporting). In addition, any penalties for not reporting are exacted on the companies (although penalties are currently limited to $1.15M per company per year, raising questions about compliance). But given the increased public scrutiny of industry payments to physicians, we should all be ready for more sun to shine on us.
Importantly, the legislation requires public disclosure, but does not limit these financial relationships. The logic behind the legislation is that by shining the light on the extensive and complicated financial relationships that exist between physicians, hospitals, and the medical products industries (pharmaceutical, medical device, and biologic companies), those relationships that may not be considered ethical or appropriate, such as receiving payments to listen to marketing presentations or for enrolling patients in clinical research studies when no rigorous research is taking place, will become less common with greater public scrutiny.
However, physicians, hospitals, and industry worry that those completely ethical and appropriate relationships, such as collaborating to conduct clinical research, will be similarly scrutinized and inhibited.
I think we gain the public’s trust by being open and transparent about the work we do in collaboration with industry. And individuals should be paid appropriately for their time.
But what do others think? Do you think this legislation will curb inappropriate payments or just add to the scandals our profession has weathered in the last few years? Will the Sunshine Act help to prevent those relationships that nearly all of us would frown upon or will it limit good science?
February 5th, 2013
ACE Inhibitor Improves Walking in People with Peripheral Artery Disease
Larry Husten, PHD
Giving an ACE inhibitor to people with peripheral artery disease (PAD) and intermittent claudication reduces pain and increases walking time, according to a new study published in JAMA. Currently the pharmacologic options for this patient population are few and have limited efficacy.
Researchers at three Australian hospitals randomized 212 patients with PAD to receive the ACE inhibitor ramipril or placebo for 24 weeks. Compared to the patients on placebo, patients on the ACE inhibitor had a mean 75-second increase in their pain-free walking time (156 seconds in the placebo group versus 229 seconds in the ramipril group, p<0.001) and a 255-second increase in their maximum walking time (259 seconds in the placebo group versus 512 seconds in the ramipril group, p<0.001). The ACE inhibitor was also associated with improvements in other secondary measures of walking and physical quality of life.
The authors note that although the HOPE trial demonstrated that ramipril reduces cardiovascular events in PAD patients, ACE inhibitors are not “specifically recommended for the relief of intermittent claudication. To our knowledge, this is the first adequately powered randomized trial demonstrating that treatment with ramipril is associated with improved treadmill walking performance in patients with PAD.”
In an accompanying editorial, Mary McGrae McDermott writes that “given the paucity of effective therapies for treating functional limitation in PAD and recent randomized controlled clinical trials that have failed to demonstrate improved walking performance in response to novel medical therapies in PAD, the magnitude of improvement associated with ramipril… is particularly notable.” But, she observes, the results may not apply to other ACE inhibitors, and ramipril may not have the same efficacy in other PAD patient populations.
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