November 9th, 2011
18 Months After ACCORD, FDA Says Fenofibrate May Not Lower Risk for MI or Stroke
Larry Husten, PHD
Eighteen months after the ACCORD (Action to Control Cardiovascular Risk in Diabetes ) trial found no benefit for the addition of fenofibrate to simvastatin in patients with type 2 diabetes, the FDA has issued a safety communication. The agency changed the label for Trilipix (fenofibric acid, Abbott) and is notifying healthcare professionals that the drug “may not lower a patient’s risk of having a heart attack or stroke.” The information about ACCORD has been added to the Important Limitations of Use and Warnings and Precautions sections of the label, as well as the patient Medication Guide.
The FDA has also required Abbott to conduct a randomized, double-blind, placebo-controlled clinical trial to test the hypothesis that fenofibrate in combination with a statin versus statin alone significantly reduces cardiovascular events in high-risk men and women who are at their LDL cholesterol goal on statin therapy, but have residually high triglycerides and low HDL cholesterol.
November 9th, 2011
How to Prep for AHA: An Expert’s Advice for Fellows
John Ryan, MD and Thomas Ryan, MD
Dr. Thomas Ryan explains how fellows can get the most from the American Heart Association Scientific Sessions, both as attendees and as presenters. Dr. Ryan is Professor of Medicine (Emeritus) at Boston University, a former AHA president (1984–1986), a former Chief of Cardiology at Boston University (1971–1994), and a recipient of the AHA Chairman’s Award (2001). He was interviewed by cardiology fellow and comoderator of the Fellowship Training blog on CardioExchange, Dr. John Ryan (no relation).
The interview touched on other topics relating to the changing world of cardiology. You can hear the entire interview, including Dr Thomas Ryan’s description of his first AHA in 1957, when F. Mason Sones presented his first selective coronary angiogram, and the famous 1977 standing ovation for Dr Andreqs Gruentzig.
Q: Do you think it’s important for fellows to go to AHA?
A: It’s critical. AHA isn’t just the grandfather of all the major meetings — the presenters have the strongest scientific background: future Nobel laureates, leaders in the field, rising stars presenting their first work. In the cardiology division at BU, half of the fellows attend AHA in any one year and they go with the obligation to report back on several of the presentations, for the benefit of those who did not attend. I think it is important for a fellow to go to at least one AHA during training. I have been to 45 of the last 48 meetings, having missed three in my first couple of years in practice.
Q: How should fellows spend their time at the meeting?
A: I wish someone had advised me before my first AHA, which was back in 1957. The information overload can be truly overwhelming. The core content is so diverse and voluminous that you can’t digest more than 10% of it. By your third year as a fellow, you will have gotten the hang of it a bit more, so it will be easier to narrow your focus.
My advice is to spend 60% of your time going to small sessions in your area of interest. It’s the question-and-answer sections that are so relevant and instructive, especially for fellows. Make sure you go to one small session in a field of cardiology that you know little or nothing about. I do that to this day. It stretches your mind and is a good way of discovering what is truly new in cardiology.
Dedicate no more than 20% of your time to the main presentations and the big late-breakers. These can be very exciting, and they give you new data to go home with, but they have been less exciting of late, and they don’t allow for the personal interaction.
Spend maybe 10% to 15% of your time with the posters. You can get utterly lost in the poster hall, so you should read the program and identify the posters in your key area or areas of interest. Find the fellow who is working in your area, look at the work, and strike up a conversation — it can be very instructive and can lead to lifelong professional relationships.
Then you’ve got 5% to 10% of your time left to wander around the exhibit hall, but that’s a bit of a tourist trap, in my opinion. The role of industry support is important to the ability to hold these conferences, but it’s a bit of a spectacle and the commercialization is problematic.
Q: I presented for the first time last year and found it very stressful. I offered my neophyte’s advice to other fellows. What is your seasoned advice?
A: Practice, practice, practice. First, formulate what you are going to say — only then turn to your slides. Include no more than 7 to 10 slides, and present slowly. If you know it cold, you can present it in your sleep, but you need to let your audience keep up.
I tell people to practice in an auditorium setting with a microphone and with the screen at such an extreme angle that you can barely read the slides, because that’s how it might be. And when you are presenting for the first time, you are so nervous that you will try to just read the slides, and you can’t depend on that. Also, things will go wrong — you’ll forget to turn the pointer on or you’ll have trouble going back and forth between the slides, so you need to keep practicing until you can keep your cool and focus simply on instructing your audience. The heart of the meeting is when lowly fellows and rising stars of tomorrow present their first work – achieving a career pinnacle by having their research judged worthy by the abstract viewing committee and getting the chance to present at the AHA meeting.
Q: How do you feel the AHA meeting has changed over time?
A: I have seen the annual meetings grow in size and subject matter — so much so that you cannot absorb more than 10%. . . . But I do wonder how we can sustain the expense of these national meetings. Like the rest of the world, we are facing globalization. I do think we are going to see globalization of the meeting more and more. You current fellows will see it in your lifetime.
Readers, are you planning to go to AHA? Will it be your first time? What are you doing to prepare for the event, either as an attendee or as a presenter?
November 8th, 2011
Financial Incentives Increase Use of Stress Tests
Larry Husten, PHD
Following coronary revascularization, patients are more likely to undergo cardiac stress testing if their physician has a financial interest in the test, according to a new study published in JAMA.
Bimal Shah and colleagues examined insurance data from 17,847 patients who underwent revascularization, dividing their physicians into three groups: those who billed for technical and professional fees, those who billed for professional fees only, and those who billed for neither.
The overall rate of nuclear or echo stress testing within 30 days was 12.2%, but there was a large difference in the testing rate across the three groups:
Nuclear stress testing:
- 12.6% for physicians who billed for both technical and professional fees
- 8.8% for those who billed for professional fees only
- 5.0% for those who billed for neither
Stress echocardiography:
- 2.8% for physicians who billed for both technical and professional fees
- 1.4% for those who billed for professional fees only
- 0.4% for those who billed for neither
The authors found that “up to 1 in 10 patients who were not coded as having symptoms at their outpatient visit still underwent stress testing.” They note that current guidelines “do not recommend routine use of early stress testing following coronary revascularization,” and they conclude that their results “suggest the need for broader application of AUC [appropriate use criteria] to minimize the possible influence of financial incentives on the decision to perform cardiac stress testing after revascularization.”
In an accompanying editorial, Brent Hollenbeck and Brahmajee Nallamothu place the study in the context of new trends in reimbursement from CMS and the large structural shift in cardiology toward hospital-based practices. They point out that “controversies surrounding physician self-referral and associated incentives wax and wane, and are seemingly repeated each decade.” As an alternative, they suggest that “the focus should be less about eliminating incentives altogether, and more about getting the price right in the first place.”
November 8th, 2011
Wrestling with Uncertainty in Clinical Practice
John E Brush, MD
About a week ago I was asked to consult on a patient I’ll call Betty. This delightful 92-year-old woman, who lived alone, was admitted during the night with pain in the upper chest and shoulders. She had been feeling this discomfort off and on for 2 days, and when it woke her from sleep, she came to the ER. She also reported a history of hypertension, hyperlipidemia, and mild diabetes treated with oral medication. She was pain-free when I met her, and her exam was unremarkable. Both her troponin and her CPK levels were borderline elevated, and her EKG showed extensive T-wave inversion in the precordial leads.
So what was I to do with these worrisome clinical findings? Evidence-based medicine provides me with very little, well, “evidence” to apply to this patient. At 92, she was much older than the mean age of patients in trials such as CURE (64 years), FRISC (69 years), and the original trial of heparin in unstable angina (58 years). We know that treatments for acute coronary syndrome are all double-edged swords, with both benefits and risks. What about the dictum “first do no harm?”
I must admit that I didn’t pay much attention to the kind of medical uncertainty that Betty’s case illustrates until I made a transition from academic medicine to private practice years ago. In academia, we focused a lot on what was known. Betty’s case would have presented a bundle of teaching opportunities. If Betty had been discussed on our rounds, we would have made a group decision and moved on to the next patient. But my busy new practice had no teaching rounds, no team. In practice, such decisions made me feel utterly alone, and the uncertainty of medicine hit me like a ton of bricks.
I am pretty sure that no clinical trials apply to Betty. But am I even certain of that? This is the uncertainty that drives us to specialize in narrow fields, hoping to develop some sense of security in our decisions.
I discussed the options with Betty. She was firm that she wanted to pursue medications and avoid any cardiac procedures. Given the extensive EKG changes, I was a little uneasy about her decision, but I was pleased that she resolved my own decisional conflict. Her pain resolved, too, and she was discharged back to her home on a variety of medications, including a beta-blocker, nitrates, a statin, and dual antiplatelet therapy.
Betty returned to the ER yesterday, this time complaining of mild shortness of breath that occurred in the middle of previous night. The ER physician noted that she seemed quite comfortable without any particular treatment. Her exam was normal, labs were unremarkable, chest X-ray was clear, and EKG was unchanged. An echocardiogram showed an ejection fraction of 70% with LV hypertrophy, aortic sclerosis (no stenosis), and moderate mitral annular calcification — all expected findings for a 92-year-old woman.
On her first visit Betty had presented a therapeutic dilemma; on her second the uncertainty I experienced was of a different sort. What was troubling her? Was she simply anxious about being at home alone with a new cardiac diagnosis? What was the true origin of her symptoms?
Often a patient’s true condition is obscure. The human body is infinitely complex, and patients are infinitely variable. We use tests that are imprecise because of resolution constraints and artifacts. Many of those tests are indirect, creating problems with reproducibility, sensitivity, and specificity. Their predictive value is affected by how they are used. All of these factors contribute to diagnostic uncertainty.
Predicting an outcome for an individual patient is even more imprecise. A second order of uncertainty called ambiguity arises. It’s like an error bar around a point estimate. A patient may ask you, “Doc, how long do I have?” We can give a number, but the range of uncertainty around that number can make your answer almost meaningless.
Uncertainty is why we use clinical reasoning, intuition, induction, and inference. Probability is uncertainty quantified, and most probability calculations in clinical medicine are subjective and intuitive. It’s imperative that we apply basic scientific principles, evidence from clinical trials, and hard clinical data as we make decisions, but doing that for an individual patient requires judgment.
Sometimes we wear a mask of certainty, often an arrogant one: “Pay no attention to the man behind the curtain. I am the all powerful Wizard of Oz!” We all know a colleague who is “sometimes wrong but always certain.”
A better approach is to recognize uncertainty and to become familiar with the ways that human decision makers adapt to it, as I’ve discussed in previous posts. In doing so, we replace arrogance with confidence and develop a greater sense of comfort as we struggle to provide the best care for our patients.
Is the optimal treatment for Betty uncertain?
When you are uncertain about something in your care of a patient, do you discuss it with the patient?
November 7th, 2011
ACC and AHA Release New PCI and CABG Guidelines
Larry Husten, PHD
The AHA and the ACC have released updated 2011 guidelines for PCI and CABG. The guidelines are available online on the JACC website (here and here) and on the Circulation website.
The new guidelines include for the first time a strong recommendation that hospitals adopt a “heart team” approach in choosing a treatment strategy for patients with coronary artery disease. For patients with unprotected left main or complex CAD, the team approach is a Class I recommendation.
“The 2011 guideline includes an unprecedented degree of collaboration in generating revascularization recommendations for patients with CAD,” said Glenn Levine, chair of the PCI guideline writing committee, in a press release from the ACC and AHA. The PCI and CABG committees coordinated their efforts and joined forces to write the section comparing the two revascularization procedures.
The PCI guidelines recommend using the SYNTAX score in patients with multivessel disease, and include specific recommendations for every anatomic subgroup of patients with stable CAD.
Drug-eluting stents (DES) gain a Class 1 recommendation to decrease the incidence of restenosis. However, this recommendation is “counterbalanced,” according to Levine, by the recommendation that before DES implantation, patients should be evaluated to assess whether they are suitable for dual antiplatelet therapy.
Low-dose aspirin gains a Class IIA recommendation while clopidogrel, prasugrel, and ticagrelor all receive Class I recommendations following PCI.
L. David Hillis, chair of the CABG guideline writing committee, said that physicians will pay close attention to the section on “whom to revascularize and how to do it,” in particular “because the debate over PCI versus CABG has seen the most action since the 2004 guideline was written.”
Because PCI has improved so much since the previous guidelines were issued in 2004, the new guidelines support the use of PCI as “a reasonable alternative to CABG in stable patients with left main CAD who have a low risk of PCI complications and an increased risk of adverse surgical outcomes.” CABG, however, still retains the advantage over PCI for most patients with three-vessel disease.
November 7th, 2011
TAVI Approval: An Alternate Perspective
Norman Silverman, md
The FDA’s decision to release for general use the Sapien transcatheter aortic heart valve implantation (TAVI) technology ends the conflicting reports of either imminent approval or six months delay for further evaluation. This had created quite a stir.
Self-proclaimed patient advocates aver that enough vetting has occurred and decry that excessive regulatory obstruction is denying the American public the benefits of noninvasive valve replacement. They cite the safety and hemodynamic benefits reported by many European centers. And these results have accrued in very high-risk, elderly patients who MAY (my emphasis added) not have been considered as candidates for conventional open heart surgery. Moreover, they warn that the harmful effects of inordinate delay will be amplified as next generation improvements to this technology become available while USA medical practice languishes in the backwater. This point is reinforced by the recent successful implantation of a newer device that might be replaceable percutaneously. They omit to say that these three procedures were performed by American surgeons, but in Paraguay where patient consent, institutional review, and government supervision of medical standards are in essence nonexistent.
On the other side, defenders of a more measured approach defend further evaluation as necessary for patient safety. They correctly point out that TAVI is not suitable for patients with aortic insufficiency or dilated annuli or for patients needing concomitant CABG and/or other valvular repair. Accurate assessment of not just perioperative, but mid-term results, requires setting standards for patient selection, operator and institutional certification, and outcome documentation. TAVI may be noninvasive, but that does not mean it is inherently easier to perform and safer than standard valve replacement. Therefore, there is no rush to judgement.
As the antagonists hurl charge and countercharge at each other, I want to posit another lens through which to view this controversy — the present medicoeconomic state of cardiac surgery. Over the past decade, cardiac surgical volumes have diminished by at least half, primarily due to decreased surgical coronary revascularization. Concomitantly, reimbursement by insurers and government agencies has also decreased by almost the same amount (even more if adjusted for inflation). Yet, there are still over 1,000 institutions performing open heart surgery in the U.S., which has a population of more than 300,000,000. By contrast, there are 55 centers serving the cardiac surgical needs of 85,000,000 Germans. As a consequence, only 10% of U.S. centers are “high-volume,” performing more than 450 cases per year. The 25% of “low-volume” German centers are defined as those doing fewer than 1,500 cases per year, none of which do as few as 450.
With every hospital scrambling to remain financially viable with less case load for less reimbursement, does not the potential exist for hype and marketing to supplant scientific evidence as the basis for introducing new technology? Isn’t the surgical decision-making process vulnerable to the patient desire for a procedure that is less invasive, causes no scarring and less pain, and permits faster discharge and rehabilitation? Premature release by the FDA could easily push TAVI down the slippery slope, encouraging inadequately qualified interventionists to perform procedures on patients falsely deemed at high risk due to economic concerns and the superficial attractions of the procedure.
Personally, I support a more thorough FDA review of TAVI because I am a patient advocate. Sometimes to protect the public the public must be protected from their own whims and ways.
November 4th, 2011
FDA Approves Rivaroxaban for Stroke Prevention in AF
Larry Husten, PHD
The FDA has approved rivaroxaban (Xarelto, Johnson & Johnson) for stroke reduction in people with non-valvular atrial fibrillation. The label will include a boxed warning that people should not discontinue taking the drug without talking with a healthcare professional. The FDA will also require that patients getting the drug receive a Medication Guide describing the risks and adverse reactions associated with the drug.
The label does not provide firm guidance on the relative merits of rivaroxaban and warfarin in AF patients:
There are limited data on the relative effectiveness of XARELTO and warfarin in reducing the risk of stroke and systemic embolism when warfarin therapy is well-controlled.
Some panelists at the FDA advisory panel in September had suggested that rivaroxaban should only be used in patients unable to take warfarin.
Click here to download a PDF of the Xarelto label.
Click here to read the FDA announcement.
Click here to read the press release from Johnson & Johnson.
November 4th, 2011
AHA and ACC Update Secondary Prevention Guidelines
Larry Husten, PHD
The AHA and ACC have released an update of their guidelines for secondary prevention in patients with heart disease. The guidelines are available in Circulation and the Journal of the American College of Cardiology.
The updated guidelines place a new emphasis on cardiac rehabilitation for patients who have had an MI or CABG. They also stress the importance of diagnosing and treating depression in patients with heart disease. In addition, the guidelines now recommend ticagrelor and prasugrel as well as clopidogrel in addition to aspirin for stent patients.
In anticipation of new guidelines next year from the NHLBI, the guidelines do not include new recommendations regarding blood pressure or cholesterol.
November 3rd, 2011
FDA Approves TAVR But Remains in the Crosshairs
Richard A. Lange, MD, MBA
I participated in the panel that recommended approval of the Sapien Transcatheter Heart Valve (THV) for patients with inoperable severe aortic stenosis: so-called transaortic valve replacement (TAVR).
The recommendation for approval was based on (a) the perceived strength of the results of the PARTNER study; (b) collaboration and support of the Society of Thoracic Surgeons and the American College of Cardiology; and (c) a commitment to create a national registry for post-marketing studies.
I was surprised — perhaps naively — by the wide range of opinions regarding the FDA process.
In the past several weeks, the FDA was blasted by a former Food and Drug Administration deputy commissioner for taking too long to approve the THV, and a group of senators introduced the Medical Device Regulatory Improvement Act, seeking to streamline FDA’s pre-market device oversight by directing the agency not to ask companies for more data than it needs.
Simultaneously, in a JAMA piece, Harlan Krumholz recommended a new industry model that encourages more — not less — scrutiny of study results. Specifically, Harlan called for:
- An external coordinating organization (an academic center) to contract with the medical device manufacturer, which agrees to provide access to all of its source material (i.e., patient-level clinical research data), post-marketing studies, and safety programs
- The coordinating organization to contract with two qualified groups to conduct independent reviews of the data
- A steering committee, consisting of subject-matter experts as well as patients, investigators, and policy makers, that is selected by the coordinating organization to provide oversight and guidance.
- All data to be made available by the coordinating organization to other investigators
A recent NEJM opinion piece acknowledges that the FDA has been “simultaneously faulted for inadequate assurance of safety and efficacy and for suppressing innovation.”
You can’t have it both ways. So which is it?
Does the FDA need fewer rules and a more streamlined process, or does it need additional oversight? Which best serves our patients?
November 3rd, 2011
Success in Heart Failure? Hospitalizations Decline
Jersey Chen, MD MPH
We welcome Jersey Chen to answer questions about his recent study in JAMA documenting that heart failure hospitalization rates declined nearly 30% between 1998 and 2008. Risk-adjusted 1-year mortality in patients hospitalized for heart failure also fell, but by a more modest 6.6%. CardioExchange editor Harlan Krumholz was senior author on the paper.
CardioExchange: How can you be sure that these are real changes and don’t result from, say, changes in coding practices?
Dr. Chen: There has not been substantive changes in hospital reimbursement for HF, so coding practice is unlikely to be major factor. That the rate of myocardial infarction has declined substantially in the US (an important precursor of HF) during this time period suggests that these HF hospitalizations changes were real.
CardioExchange: Can you place these declines in heart failure hospitalizations in context? How dramatic are they compared with overall declines in ischemic heart disease?
Dr. Chen: MI hospitalization rates have dropped by 23% in the Medicare population from 2002-2007, so HF hospitalization declines are comparable.
CardioExchange: With the caveat that this was an epidemiologic study, do the data give us any indication of what may or may not be driving these changes?
Dr. Chen: Major drivers very likely are:
- improved primary prevention of HF risk precursors such as CAD and hypertension,
- improved secondary prevention such as increased use of ACE inhibitors, ARBs, and beta-blockers in patients with existing HF, and
- improved transition of HF care from inpatient to outpatient settings.
CardioExchange: HF hospitalization rates did decline for black men in your study, but at a slower rate than for the population as a whole. Any hints as to the underlying cause for this disparity? What of other disparities?
Dr. Chen: A similar pattern of racial disparity has also been documented with acute myocardial infarction. Studies show that black men have less primary prevention screening, so this may be a reason. Genetics may explain why black patients have higher prevalence of HF but not the change over time. We also noted some substantial geographic variations across states, both in HF hospitalizations and mortality. These data may reflect differences in primary prevention, public health efforts regarding risk factors, or patterns in care for inpatient versus outpatient treatment for patients at the threshold of admission.
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