April 19th, 2012
A Fellow at ISHLT: First-Day Impressions
Kathryn Jesseca Lindley, MD
I’ve arrived in beautiful Prague, Czech Republic, for the annual meeting of the International Society for Heart & Lung Transplantation. It’s been a fantastic adventure thus far. The city is amazing, and there’s been an exciting variety of presentations and posters at the meeting.
ISHLT is unique in many ways. It’s much smaller, more “intimate” than AHA or ACC, and this has been kind of neat. The meeting also brings together a real potpourri of cardiologists, surgeons, and pulmonologists who all have such insight and unique perspectives on the many clinical issues we all face in this patient population.
The focus on the global burden of end-stage heart and lung diseases is particularly interesting to me. How differently international communities have dealt with the issues of organizing organ allocation and training physicians to care for these patients across political borders. I have heard much discussion of the ways in which politics play into the advancement and/or stagnation of transplant medicine. This includes the need to overcome the effects of years of oppressive government rule in the Eastern Bloc countries and the education of the American public on today’s common scientific issues.
I’m looking forward to another exciting day of both scientific and personal meetings with some of the great minds at work on the challenges in advanced heart failure management around the world!
April 19th, 2012
Should We Pull the Trigger on Platelet Reactivity Testing (and Put It out of Its Misery)?
Richard A. Lange, MD, MBA and L. David Hillis, MD
In a previous blog about the GRAVITAS trial — which showed that high-dose clopidogrel didn’t improve outcomes following PCI in patients with high on-treatment platelet reactivity (HTPR) when compared to clopidogrel given at conventional doses — we noted that an assessment of platelet reactivity by this method doesn’t effectively identify individuals at high risk for a cardiovascular event following PCI. Although more than 40% of patients have HTPR (according to the VerifyNow P2Y12 Test), very few have a cardiovascular event in the 6 months following PCI.
In the most recent issue of JACC, the TRIGGER-PCI (Testing Platelet Reactivity in Patients Undergoing Elective DES Placement on Clopidogrel to Guide Alternative Therapy with Prasugrel) trial investigated the effectiveness of prasugrel versus clopidogrel in 456 patients with HTPR undergoing elective PCI with DES.
The results shown in the table below demonstrate (a) a low rate of ischemic events in patients with HTPR and (b) no demonstrable benefit to switching from clopidogrel to prasugrel when HPTR is detected.
|
Prasugrel |
Clopidogrel |
P value |
|
| PRU * | |||
| Baseline |
245 |
249 |
NS |
| 3 mos |
80 |
241 |
<0.001 |
| Endpoints | |||
| CV death or MI |
0 (0%) |
1 (0.5%) |
NS |
| CV death |
0 (0%) |
0 (0%) |
NS |
| MI |
0 (0%) |
1 (0.5%) |
NS |
| Urgent TVR |
2 (1.0%) |
1 (0.5%) |
NS |
| Major bleeding |
3 (1.4%) |
1 (0.5%) |
NS |
*PRU=P2Y12 reaction units, according to the VerfiyNow P2Y12 Test
We said it before, and we’ll say it again: an assessment of platelet reactivity by this method doesn’t effectively identify individuals at high risk for a cardiovascular event following PCI.
We agree with the authors when they state, “The low observed ischemic event rate in the control group even without correction of HTPR demonstrates that testing platelet function in such patients for consideration of more intensive antiplatelet therapy is not warranted, especially given the potentially increased risk of bleeding.”
Critics of the GRAVITAS trial argued that the study may have been negative because the cut point for defining HTPR (P2Y12 reaction units [PRU] > 235) may have been too high. However, in Trigger-PCI, the cut point was much lower (PRU >208), yet switching to prasugrel yielded no improvement in clinical outcomes in patients with HTPR who were put on clopidogrel after elective PCI with DES.
It appears that the utility of VerifyNow platelet testing is………unverified.
Should we be routinely testing platelet reactivity in our PCI patients? If so, what should we do with that information?
April 18th, 2012
Selections from Richard Lehman’s Literature Review: Week of April 16th
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.
Week of April 16th
JAMA 11 April 2012 Vol 307
Should This Patient Get Statin Therapy? (pp. 1489 and 1491): The new editor of JAMA feels that his worthy journal needs a bit of livening up, and who can disagree? He has borrowed an old idea from the BMJ, in the form of head-on For and Against articles. “Should a 55-year-old man who is otherwise well, with systolic blood pressure of 110 mm Hg, total cholesterol of 250 mg/dL, and no family history of premature CHD be treated with a statin?” This is an awful question for several reasons. It implies that the doctor is the one who should decide, and the “patient” is the object who should, or should not, “be treated.” But in what way is this man a patient? Why is he “otherwise” well? Is his illness being 55, having low blood pressure, or having a total cholesterol of 250 mg/dL? In this exchange of views, three doctors think he should “be treated”, and two doctors (one the editor of Arch Intern Med) think he shouldn’t. I would argue that it is none of their business: give him the evidence and let him decide.
Should This Patient Get an ECG? (p. 1497): Gah, this is so boring! Are major and minor ECG abnormalities associated with coronary heart disease events? Yes. Does this mean that everybody should have a regular ECG? No. And why? Oh for goodness sake don’t bother me – just go back to medical school or read Overdiagnosed.
ARBs and HF (p. 1506): Next, a Danish nationwide database study looking at everyone over 45 admitted with heart failure for the first time and treated with an angiotensin receptor blocker. Does it make any mortality difference whether they are given candesartan or losartan? No, provided they are given a decent dose (100 mg losartan).
NEJM 12 Apr 2012 Vol 366
CCTA in the ED (p. 1393): Coronary computed tomographic angiography (CCTA) is a high-radiation procedure which is very good at ruling out significant coronary artery disease. This important study from the Commonwealth of Pennsylvania shows that it can be used in emergency departments to rule out coronary ischaemia as the cause of chest pain in patients with low-moderate probability. That way more patients can go home more quickly. But I can see drawbacks. For a start, CCTA picks up coronary artery disease in 9% of these patients, as opposed to a 3.5% pick-up rate if CCTA is not used. A lot of this will represent overdiagnosis of asymptomatic disease, and may lead to further (radiation- and cost-intensive) investigation. Secondly, the routine use of CCTA to save an average of 6 hours waiting for biochemical tests will drive up costs and increase the “defensive” use of radiation, meaning that in some instances patients going to different hospitals with recurrent non-cardiac chest pain and getting pretty massive cumulative X ray doses. I think this is a development to be welcomed with caution.
Vorapraxar for Secondary Prevention (p. 1404): Vorapaxar is a novel antithrombotic agent which works by preventing thrombin binding to platelets, by blocking the protein-activated receptor (PAR-1). To test such agents these days requires enormous trial sizes – this one recruited 26,449 subjects with a history of myocardial infarction, ischaemic stroke or peripheral artery disease to see how well it prevented further events. The prize for Merck would have been a new blockbuster drug for the whole secondary prevention market. But Fate, bleeding Fate, intervened and the trial was halted. There were fewer ischemic events in the group who got vorapaxar rather than a thienopyridine, but more cerebral hemorrhage. Vorapaxar is an interesting drug which may have some kind of future, but blockbuster it is unlikely ever to be.
Lancet 14 April 2012 Vol 379
Stent Wars (p. 1393): In 1998, when I first started writing these brief notes on the journals for a few friends and colleagues, I decided that coronary artery stents were an interesting new development that I should tell people about whenever they cropped up in the literature. How dearly I (and you who have followed me) have paid for that decision! Paclitaxel, sirolimus, everolimus, zotarolimus… I have tried to make them interesting by pretending they were creatures from Star Wars, or minor characters from Antony and Cleopatra, or members of a zany family called Olimus, whose next son will no doubt be called boralotimus. And now it turns out we may have been looking at the wrong thing all along: what matters in the Stent Wars is not the drug these things elute, but the metal they are made of. According to this “comprehensive network meta-analysis” of 49 trials with 50,844 randomly assigned patients, the clear winner is a cobalt-chromium stent which elutes everolimus. For the first time in 14 years, my remarks on stents will actually be read by some interventional cardiologists, thanks to their appearance on the CardioExchange website run by the NEJM. OK you guys, start quarreling about this study: the rest of us are off for a nice snooze.
April 18th, 2012
AHA: No Convincing Evidence That Periodontal Disease Causes CV Disease
Larry Husten, PHD
Demonstrating once again that association and causation should not be confused, the American Heart Association today published a scientific statement in Circulation asserting that there is no convincing evidence showing that periodontal disease causes cardiovascular (CV) disease or that treating periodontal disease will reduce CV disease risk. The statement does not rule out the possibility that periodontal disease can cause CV disease, and even notes that a cause and effect relationship is “biologically plausible,” but it concludes that statements that claim “a causative association… or claim that therapeutic interventions may be useful on the basis of that assumption are unwarranted.”
“There’s a lot of confusion out there,” said Peter Lockhart, co-chair of the statement writing group and professor and chair of oral medicine at the Carolinas Medical Center in Charlotte, NC, in an AHA press release. “The message sent out by some in healthcare professions that heart attack and stroke are directly linked to gum disease, can distort the facts, alarm patients and perhaps shift the focus on prevention away from well known risk factors for these diseases.”
In recent years there has been an explosion of studies exploring the relationship of PD disease and CV disease, many looking at inflammation as a common factor underlying both diseases. However, sorting out the precise nature of the relationship is difficult because both diseases share common risk factors, including cigarette smoking, age, and diabetes.
April 18th, 2012
Preoperative Statins Found to Reduce AF and Length of Stay but Not Mortality
Larry Husten, PHD
In a systematic review published in the Cochrane Library, investigators at the University of Cologne in Germany analyzed data from 11 trials that tested the effects of preoperative statins in 984 patients undergoing heart surgery. Preoperative administration of statins reduced the risk for developing atrial fibrillation (AF) and shortened the length of stay in the ICU and in the hospital, but did not have a statistically significant effect on mortality or MI:
- Postoperative AF: OR: 0.40, CI: 0.29 to 0.55, p<0.01
- ICU length of stay: WMD (weighted mean difference): -3.39 hours, CI -5.77 to -1.01
- Hospital length of stay: WMD: -0.48 days, CI: -0.85 to -0.11
- Short-term mortality: OR: 0.98, CI: 0.14 to 7.10, p=0.98
- MI: OR: 0.52, CI: 0.2. to 1.30
The authors noted that the studies mostly contained patients undergoing myocardial revascularization, so the findings might not apply to other cardiac procedures.
“To get a clearer picture of the potential benefits of taking statins before a heart operation, we need to have more clinical trials and find out whether clinical outcomes can be further improved if patients use special statin dosing regimens shortly before a heart procedure,” said lead researcher Oliver Liakopoulos, in a Cochrane Library press release.
April 17th, 2012
Why Make A Stent Out of Cornstarch?
Richard A. Lange, MD, MBA and L. David Hillis, MD
Why the interest in “disappearing” stents?
Drug-eluting stents (DES) release drugs from durable polymer coatings on the stent that suppress neointimal proliferation, thereby reducing the risk of restenosis compared with bare metal stents (BMS). However, the use of DES is associated with an increased risk of very late (>1 year) stent thrombosis compared with BMS. Several mechanisms have been proposed for this phenomenon, including delayed endothelialization, chronic arterial inflammation, hypersensitivity reactions (eosinophilic infiltration), and incomplete stent apposition with vessel remodeling. These problems can potentially be solved by using polymers and/or stents that resorb.
What happens if you make the polymer disappear?
A biodegradable polymer-based DES allows controlled drug release followed by subsequent degradation of the polymer coating, ultimately rendering the stent surface similar to that of a BMS and devoid of a chronic inflammatory stimulus. A recent published pooled analysis of individual patient data from the ISAR-TEST 3, ISAR-TEST 4, and LEADERS randomized trials showed that biodegradable polymer DES reduce the risk of stent thrombosis at 4 years in patients undergoing PCI when compared to conventional DES.
What happens if you make the entire stent disappear?
A recently released study evaluated the long-term (i.e., 10 year) safety of the first-in-man fully biodegradable coronary stent made of poly-l-lactic acid (i.e., a cornstarch-based material). Between September, 1998, and April, 2000, 50 patients with 63 lesions were treated electively with 84 biodegradable non-DES. The investigators noted acceptable major adverse cardiac event rates — similar to those of BMS — without stent recoil or vessel remodeling (see table).
|
Event Rate at 10 yrs |
Rate |
| Freedom from death |
87% |
| Freedom from cardiac death |
98% |
| Freedom from target lesion revascularization |
72% |
| Freedom from death, nonfatal MI, and target lesion or vessel revascularization |
50% |
Although the investigators expected the stent to degrade within 6 months, complete degradation actually took up to 3 years in some subjects. Two definite scaffold thromboses (1 subacute, 1 very late) were noted: the former occurred in a patient who discontinued antiplatelet therapy because of a bleeding gastric ulcer, the latter a decade after implantation of the biodegradable stent (i.e., it was totally resorbed) that appeared to be related to a sirolimus-eluting stent implanted proximally.
Do you think biodegradable stents are here to stay…..or will they disappear?
April 17th, 2012
Million Dollar Bonuses for Five Ohio State University Electrophysiologists
Larry Husten, PHD
Five Ohio State University electrophysiologists received 2011 bonus payments greater than $1 million, resulting in total pay for the year for each cardiologist of about $2 million. The news was first reported by the Dayton Daily News and subsequently covered by Heartwire.
Five out of seven bonuses that topped $1 million at OSU went to the electrophysiologists. The football coach and the basketball coach were the recipients of the additional million dollar bonuses. Here are the compensation figures for the seven OSU employees who received bonuses greater than $1 million, as reported by the Daily News:
|
Name |
Title |
Base earnings |
Bonus |
Other |
Total 2011 pay |
|
Steven Jack Kalbfleisch |
Professor, clinical |
$658,150 |
$1,383,141 |
NA |
$2,041,291 |
|
John David Hummel |
Professor, clinical |
$650,856 |
$1,383,137 |
NA |
$2,033,993 |
|
Emile Georges Daoud |
Professor, clinical |
$650,856 |
$1,330,548 |
NA |
$1,981,404 |
|
Ralph Sayre Augostini |
Assistant professor, clinical |
$650,856 |
$1,329,604 |
NA |
$1,980,460 |
|
Raul Weiss |
Associate professor, clinical |
$652,902 |
$1,311,966 |
NA |
$1,964,868 |
|
Thad Matta |
Men’s basketball coach |
$563,508 |
$1,095,000 |
$545,004 |
$2,203,512 |
|
Jim Tressel |
Football coach |
$330,037 |
$1,047,920 |
$435,000 |
$1,812,957 |
The Daily News quoted Richard Vedder, professor of economics at Ohio University and director of the Center for College Affordability and Productivity: “I have never seen anything like this — never.”
OSU spokesman Jim Lynch told Heartwire that the compensation system at OSU is modeled on other public and private universities and colleges. The Daily News reported that OSU officials said that medical school and athletic department bonuses were “self-funded and don’t draw from tax or tuition dollars.” Lynch told the Daily News that the five electrophysiologists “were hired five years ago to build a nationally respected program in cardiac electrophysiology. Today, that program is the largest in the state and treats patients from throughout a multistate region.”
April 17th, 2012
What’s in a Name? Go for the Generic
Nicholas Downing, MD
A recent report published in the Archives of Internal Medicine highlights some “low-hanging fruit” for anyone trying to deliver more cost-effective healthcare. The authors (I am the first author and Harlan Krumholz, CardioExchange editor-in-chief, is the senior author) describe how branded formulations of fenofibrate — marketed by Abbott as Tricor and Trilipix — account for the vast majority of fenofibrate prescriptions, even though generic fenofibrate has been available for almost a decade.
Abbott was able to stay one step ahead of the generic competition by repeatedly changing the dose of its branded formulations: clinicians continued to prescribe branded versions of the drug and pharmacists were powerless to switch these prescriptions for generics due to the differences in dose. We have helped reward Abbott with an astonishingly high market share, even though the company never demonstrated the incremental benefit of its reformulations.
As physicians, we should ask how this happened. Why did we not switch patients over to generic fenofibrate? Were we unaware that generics were available? Did we take for granted that generic substitution would happen at the pharmacy? Did we fail to notice the repeated changes made to the doses of branded fenofibrate?
Unlike most cost-effectiveness calculations, this one should be easy. This is not a complicated decision in which we need to weigh relative efficacy against relative cost: clinicians have a choice between branded fenofibrate and generic versions of the exact same drug — but the generics are half the price.
We should also remember that there is an ongoing debate about the appropriate role of fibrate therapy in lipid management in light of the findings from the FIELD and ACCORD trials, which showed that fenofibrate did not significantly improve cardiovascular outcomes. Regardless of your views on the efficacy of fenofibrate, do your patients and the healthcare system a favor – write the generic.
April 16th, 2012
The Audible
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 University of Chicago’s Pritzker School of Medicine. This piece originally appeared on his blog, Dr. Wes.
The EKG hung outside the door with a new name attached. On a cursory glace, it looked pretty normal. He entered the room. There before him was a relatively young patient, medium build, nothing unusual. The computer schedule suggested it was just another case of atrial fibrillation (AF). You’ve got an hour, he thought. Plenty of time. But he knew there was never just another case of AF. There are just too many plays in the playbook for this disorder.
But he was a seasoned veteran at the game. He had seen most things and had strategies for most of them. If X, then Y. If Y, then Z. Not that hard, really. Most of the time. But this was not to be “most of the time.”
He reviewed the story, examined the patient, and reviewed the tracings. Delightful patient: productive, married, young kids, otherwise healthy, no risk factors for stroke. Amongst the screens and screens of collected data on this nice person, there it was: classic paroxysmal AF with relatively fast ventricular response, starting and stopping, starting and stopping, again and again on the Holter recording.
At first, it seemed like a chip shot: “I can fix this.”
Until he inquired further. “Seriously, you don’t feel this?”
Didn’t feel a thing. Felt fine, in fact. If it weren’t for the spouse, the patient wouldn’t be here.
He paused.
“But I can fix this!”
Then he thought: “But what if the cure is worse than the disease? What if there was a complication? What if he made things worse instead of better? Imagine a stroke in this person, this parent, this worker. How much better can you make someone who’s asymptomatic?”
“But I can fix this!”
There are a million things we can do to patients with AF: ablations, cardioversions, atrial occlusion devices, lariats, endocardial and epicardial mazes, all in the interest of curing the disorder. Our training, skills, equipment, reimbursement, marketing teams, egos, productivity clauses, and culture of care constantly drives this process. In turn, we splash the happy patient who was cured from their disorder across our billboards, ever eager to do more.
But what most people will never see is the patient who is turned away; the one for whom doing nothing invasive was the safest and best treatment, even though the procedure, more likely than not, would have been successful.
Such a play is not sexy. It’s not innovative. It occasionally results in an adverse patient online rating. And for the system, it’s not lucrative.
But good medicine often calls an audible to the playbook.
April 13th, 2012
CT Angiography for Safe Discharge of Patients
(Reprinted with permission from NOW@NEJM, a blog for physicians about the New England Journal of Medicine)
Chest pain is the second most common reason for Emergency Room visits in this country, and although only 10-15% of patients admitted with chest pain are ultimately diagnosed with an acute coronary syndrome, the majority of patients get admitted. So common, in fact, is this admission diagnosis, that during cardiology rounds the other week, when I asked a resident how the patient was doing, she responded, “Oh fine, we’re just rome-eee-ing him,” (a new twist on the acronym “ROMI” for “Rule out MI”). Sure, on a busy floor, it’s easy enough to deem the “soft” rule-outs as unnecessary. But put yourself in the shoes of the ED docs. GI distress from a bad tuna sandwich can look a lot like the pain of unstable plaque. So how to decide who is safe to go home?
One method that has shown initial promise is Coronary CT Angiography, (CCTA), which in previous trials has demonstrated a robust negative predictive value among patients with low to intermediate risk of CAD. However, previous trials were not statistically powered to really answer the question as to whether CCTA was a safe strategy to effectively triage patients who required some further form of testing*. Thus, in this week’s NEJM, Litt et al present the results of “CT Angiography for Safe Discharge of Patients with Possible Acute Coronary Syndromes,” a “real-world” trial which aims to get at this lingering question.
The study, which included five sites, enrolled low to intermediate risk patients who presented to the ED with chest pain and possible ACS. Patients were 30 years or older, with symptoms possibly representing ACS, TIMI, (Thrombolysis in Myocardial Infarction), scores between 0 to 2, and ECGs that were without evidence of acute ischemia. The study was powered to address the hypothesis that patients without CCTA evidence of coronary-artery stenoses ≥50% would have a 30-day rate of cardiac death or myocardial infarction of less than 1%. Secondary outcomes included rates of discharge from the ED, length of stay if admitted, and 30-day rates of death, myocardial infarction, revascularization, and resource utilization.
Nearly 1400 patients were randomized in a 2:1 fashion to either CCTA, or usual care, (the treating team decided which tests, if any, were warranted). Of the 908 patients assigned to the CCTA strategy, 84% ultimately underwent CCTA, with tachycardia, an impediment to image acquisition, being the most common reason for failure to undergo testing. Notably, 64% of patients in the usual care arm underwent some form of diagnostic testing. Among the 640 patients found to have a negative CCTA, there were no deaths or MIs within 30 days of presentation, thus confirming the study’s primary hypothesis. Regarding secondary outcomes, it was notable that patients in the CCTA group were more likely to be discharged from the ED, had shorter length of stay when admitted, and were more likely to be identified as having coronary disease on invasive angiography.
But does this answer our question: is CCTA a safe strategy to effectively triage low risk chest pain patients in the ED? I think the jury’s still out. What this study suggests is, if your patient in the ED has a negative CCTA, he’s safe to go home. However, the study was not adequately powered to address whether CCTA should be the standard ED strategy to make triage decisions in these low risk chest pain patients. Unfortunately, studies of diagnostic testing among low risk patients are extremely challenging, as event rates are so low that more patients, more time, and more money, are required to really answer whether this strategy, per se, is safe. As we await further trials, I suspect we will continue to do a lot of ro-mee-ing on the floor.
* Goldstein JA, Chinnaiyan KM, Abidov A, et al. The CT-STAT (Coronary Computed Tomographic Angiography for Systematic Triage of Acute Chest Pain Patients to Treatment) trial J Am Coll Cardiol 2011;58:1414-1422
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