March 30th, 2011
Choosing a PARTNER for Life: A or B?
Richard A. Lange, MD, MBA and L. David Hillis, MD
What is TAVI?
During Transcatheter Aortic Valve Implantation (TAVI), a bioprosthetic valve is inserted through a catheter and implanted within the native stenotic aortic valve. The self-expanding CoreValve (Medtronic) and balloon-mounted Edwards SAPIEN (Edwards Lifesciences) valve are approved in Europe and under investigation in the U.S. for TAVI and can be implanted via the transfemoral, subclavian, or transapical route.
Is one valve better than the other?
Don’t know, as no comparison has been performed.
Are there randomized trials of TAVI, or is all experience to date anecdotal?
In PARTNER A, patients with severe, symptomatic AS who were considered candidates for aortic valve replacement (AVR) but had an increased surgical risk (i.e., a predicted perioperative mortality >15%) were randomized to TAVI or surgical AVR. The results will be presented at the 2011 ACC meeting.
In PARTNER B, “high risk” elderly patients with severe, symptomatic AS who were thought not to be candidates for AVR (i.e., a predicted perioperative mortality > 50%) were randomized to TAVI or “standard therapy” (which included balloon valvuloplasty in 84%). When compared with standard therapy at 1 year, TAVI significantly reduced the rate of death as well as the composite of death and repeat hospitalization, despite higher incidences of major stroke and other major vascular events.
PARTNER B: Outcomes at 1 yr
|
TAVI |
“Standard Therapy” |
P value |
|
| Death |
31% |
50% |
<0.001 |
| Death or repeat hospitalization |
43% |
70% |
<0.001 |
| Stroke |
11% |
5% |
0.04 |
| Major vascular complications |
17% |
2% |
<0.001 |
Who was not a candidate for TAVI in PARTNER?
Patients with any of the following:
– bicuspid aortic valve
– CAD requiring revascularization
– left ventricular EF <20%
– severe (> 3+) MR or AR
– TIA or stroke in the previous 6 months
– severe renal insufficiency
– severe iliofemoral arterial or aortic (abdominal or thoracic) disease
What are the concerns with TAVI?
- The incidence of permanent pacemaker placement within 30 days of TAVI is ≈14% (range, 0%-34%). The incidence is higher with the CoreValve (mean, 21%; range 9–30%) than with the Edwards SAPIEN valve (mean, 5%; range 0%–10%).
- Although the incidence of periprocedural major strokes is only 1.5%-3.0%, the incidence of cerebral silent embolic lesions is very high (70%-90%) with TAVI. The impact of these lesions on neurocognitive dysfunction needs to be assessed.
- Durability of the valves is unknown. Since TAVI has been used only in older patients, valve durability has not been an issue. However, it will be an important consideration if they’re implanted in younger patients (who expect to live a long time with the valve).
- Is TAVI as good as AVR in patients who are suitable for conventional surgery but considered to be high risk? We’ll know soon, when the PARTNER A results are presented at the ACC.
Are the cardiac surgeons worried about TAVI?
Not really — at least not yet — because it’s only performed in patients who are considered unsuitable or high risk for conventional AVR (i.e., patients whom they try to avoid). In addition, the surgeons are actually doing the procedure, especially the subclavian and transapical approaches.
For more of our ACC.11 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Roundup.
March 30th, 2011
FDA Warns Against Repackaging Dabigatran
Larry Husten, PHD
The FDA has issued a safety communication regarding dabigatran (Pradaxa). Because the drug is subject to product breakdown and loss of potency due to moisture, the FDA recommends that it should be dispensed and stored in its original packaging and that consumers avoid using pill boxes or pill organizers with it.
Pradaxa is supplied as either a bottle with a 30-day supply of the drug and a desiccant in the cap or in a blister package. The current label states that the drug should be discarded 30 days after the bottle has been opened, but the FDA now says that the drug maintains its potency for up to 60 days as long as it is stored in the original bottle and the cap is closed tightly. The bottle should be kept away from excessive moisture, heat, and cold, according to the FDA. The agency advises that only one bottle of Pradaxa should be open at a time.
Here is the FDA’ advice for healthcare professionals:
- Tell patients it is important to follow the special storage and handling requirements for Pradaxa.
- Tell patients that Pradaxa must be kept in the original bottle or blister package to protect from moisture. The bottle contains a dessicant in the cap, and the blister package protects unopened pills from moisture.
- Tell patients that Pradaxa capsules must not be stored in pill boxes or pill organizers.
- Pharmacists should only dispense Pradaxa in the original manufacturer bottle with the original dessicant cap. Do not repackage Pradaxa capsules in standard amber pharmacy vials.
- Pharmacists should not open the Pradaxa bottle when dispensing. When more than one bottle is dispensed, tell the patient to only open one bottle at a time.
- Pharmacists should place an auxiliary expiration label on the bottle and instruct the patients to date the bottle to expire 60 days after opening.
- Pharmacists can also number the bottles (e.g., bottle #1 and bottle #2) when dispensing multiple bottles so the patient can keep track of which bottle they opened.
- Report adverse events involving Pradaxa to the FDA MedWatch program.
For more of our coverage on dabigatran, check out the Dabigatran Resource Round-Up.
March 30th, 2011
ACC Preview: A STICH in Time
Eric Jose Velazquez, MD
Eric Velazquez is the principal investigator of the STICH (Surgical Treatment for Ischemic Heart Failure) trial. He will present the main results of the trial at the Late’Breaking Clinical Trials II session on Monday morning. Velazquez relates the origins of STICH more than a decade ago and discusses some of the fascinating challenges of completing such a unique trial.
________________________________________________
Next week, I will present results of the Surgical Revascularization Hypothesis of the Surgical Treatment for Ischemic Heart Failure, or STICH, trial at the ACC. The trial’s origins go back more than a decade and emanated from three related clinical observations:
1. Heart failure patients were commonly referred for noninvasive testing to determine whether they should be considered candidates for CABG. For many physicians, those test results drove decision making
2. Although, overall, CABG rates were flat, or at some centers even decreasing, the proportion of patients with heart failure and left ventricular dysfunction who were referred for CABG was rising.
3. The Coronary Artery Surgery Study (CASS) and other randomized clinical trials that informed the formulation of CABG guidelines excluded heart failure patients. These studies were performed in the 1970s, before the initiation of contemporary evidence-based medical therapy, leaving substantial clinical uncertainty regarding the incremental value of CABG for such patients.
Medical therapy and CABG have improved dramatically since then for heart failure patients. For instance, aspirin was used in less than a quarter of CASS patients, beta blockers were contraindicated for heart failure, and ACE inhibitors didn’t even exist. In surgery, the internal mammary artery was used in only 11% of cases.
We’ve also changed our interpretation of earlier results. We now believe that CABG benefits those with the highest risk, and we don’t remember that in the CASS trial and in the CASS registry reports, the presence of HF symptoms with no angina suggested no benefit from CABG. Clinical practice has changed: PCI is used preferentially in lower-risk coronary cohorts while CABG is increasingly used in people with low EFs. In the New York database, for instance, upwards of 40% of the population who received CABG had an EF that would have excluded them from previous randomized trials of CABG versus medical therapy.
Beginning in 2000, in response to these developments, we submitted an investigator-initiated request to the NIH to evaluate the role of surgical revascularization in patients with heart failure. We were also interested in, and have previously reported on, the effect of adding SVR to CABG. We enrolled patients whose physicians held in genuine equipoise the question of whether continuing medical therapy or CABG was in that patient’s best long-term interest. This enrollment strategy was challenging, because many patients, cardiologists, and surgeons had preformed ideas on the issue and were hesitant to leave a decision regarding surgery to randomized assignment, but that’s what was needed to clearly answer the question.
With the help of 1212 patients enrolled by 99 clinical investigative teams in 22 countries, the STICH trial went forward. I remember presenting cases at some of the best surgical investigative sites in the world, and watching the debate unfold regarding the best strategy for a particular patient. It was not unusual for several physicians to present completely different perspectives on how the patients should be evaluated and treated. These debates brought home to me that the answers were critically needed, despite any difficulties. There is tremendous heterogeneity in how heart failure patients with similar baseline features are evaluated and treated by excellent, well-intentioned physicians who are hampered by the lack of adequate data and evidence.
We achieved excellent follow-up and are excited to present these results early next week at ACC. Following my presentation of the main results of the trial, Bob Bonow will present the results of an important substudy of patients who had SPECT or dobutamine.
For more of our ACC.11 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Roundup.
March 30th, 2011
Many Elderly Patients Excluded from Heart Failure Trials
Larry Husten, PHD
Despite the large and growing burden of heart failure in the elderly population, older people are often excluded from heart failure clinical trials. In a paper in the Archives of Internal Medicine, Antonio Cherubini and colleagues examined 251 heart failure trials and found that a quarter of the trials excluded patients by an arbitrary upper age limit, while 43% included poorly justified exclusion criteria that might have reduced the number of older subjects.
The authors write that “the discrepancy between the patients evaluated in most” clinical trials and the real world patient population “is particularly marked in the field of HF, a condition common in older age.” They observe that only a relatively small number of elderly hospitalized HF patients would have been eligible for the landmark clinical trials that established the current standard of care for these patients.
In an accompanying commentary, Jerry Gurwitz and Robert Goldberg propose several initial steps to improve the evidence base of care for older heart patients:
- “Eliminate arbitrary age-based exclusions in cardiovascular clinical trials;
- “Require strong justification for exclusion criteria that could adversely affect the inclusion of older individuals, including those criteria relating to comorbidity, medication use, and functional and cognitive impairment;
- “Encourage the design and conduct of RCTs specific to older individuals through targeted funding; and
- “Report and publicize trends in the inclusion of elderly patients in cardiovascular clinical trials to assess progress in improving the generalizability of research findings to this high-risk population.”
March 29th, 2011
Conflicts of Interest in Cardiovascular Guidelines
Larry Husten, PHD
More than half of authors and reviewers of cardiovascular clinical practice guidelines (CPGs) have at least one conflict of interest (COI), according to a study in the Archives of Internal Medicine. Todd Mendelson and colleagues analyzed the 17 most recent ACC/AHA CPGs through 2008 and found that 56% of the participants reported a COI. The most common COI was being a consultant or a member of an advisory board.
The authors conclude that “although restricting participation may prevent some qualified individuals from serving in the guidelines production process, we found that a large percentage of individuals with guidelines experience reported no disclosures, suggesting there is a substantial pool of potential guideline writers and reviewers without COIs.”
In an accompanying commentary, Steve Nissen writes that the authors “raise disturbing questions about the independence and reliability of CPGs in cardiovascular medicine” and that “the depth and breath of industry relationships… are extraordinary.” Nissen also notes that “professional societies and their leadership are often plagued by the same commercial relationships as the CPG-writing committees.”
In response to the Archives article and an IOM report on CPGs, the AHA and the ACC issued a statement pointing out that the two groups had “refined their policies in 2010 to require even more stringent management of relationships with industry, to align with the Council of Medical Specialty Societies (CMSS). Thus the data within and the conclusions drawn by the article do not reflect the reality of the guidelines development process today.”
March 28th, 2011
Updated Unstable Angina/Non-STEMI Guidelines Released by ACC & AHA
Larry Husten, PHD
The AHA and ACC have released a focused update of the 2007 guidelines for the management of unstable angina and non-STEMI. The guidelines incorporate new information from recent clinical trials, and deal with controversial topics such as the choice of antiplatelet agents, the use of platelet-function and genetic tests with antiplatelet agents, and the timing and indication for invasive therapy.
The document endorses the FDA label for prasugrel that states “it is reasonable to consider selective use of prasugrel before catheterization in subgroups of patients for whom a decision to proceed to angiography and PCI has already been established for any reason” but also cautions clinicians about the “potential bleeding risks from prasugrel compared with clopidogrel.” The update also notes that another oral antiplatelet agent, ticagrelor, has not yet been approved by the FDA and is therefore not recommended for use but acknowledges that “it may have a future role in patients with [unstable angina and non-STEMI].”
The update includes a full discussion of platelet function and genetic testing for CYP2C19 allelles but does not include a recommendation for their use. Noting the absence of clinical trials to support platelet function tests, the update states that “the lack of evidence does not mean lack of efficacy or potential benefit, but the prudent physician should maintain an open yet critical mind-set about the concept until data are available from ≥1 of the ongoing randomized clinical trials examining this strategy.”
Regarding the use of PPIs with clopidogrel, the update agrees with a recent ACC statement that “does not prohibit the use of PPI agents in appropriate clinical settings, yet highlights the potential risks and benefits from use of PPI agents in combination with clopidogrel.”
An early invasive strategy within 12 to 24 hours of admission is recommended only for initially stabilized high-risk patients. For patients at lower risk, a delayed invasive approach is “reasonable.”
The document also clarifies the use of dual antiplatelet therapy versus triple antiplatelet therapy and the role of invasive therapies in patients with advanced renal dysfunction.
March 25th, 2011
A Meeting That Could Change How You Practice
John Ryan, MD
There is a lot on offer this year at ACC in New Orleans. Whether you are going to live the high life and dine at the Commanders Palace, or crank out the karaoke tunes at Cat’s Meow on Bourbon Street, most fellows lucky enough to attend ACC this year will come away with a vision of the future of cardiology or, possibly, even the decline of cardiac surgery.
The PARTNER group is planning to present the results of its comparison of transcatheter vs. surgical aortic valve implantation in high-risk patients. Attendees will learn about the PRECOMBAT data on left main stenting compared to bypass surgery. Also, researchers will present the STICH literature on surgical management of ischemic heart failure.
So, a few short days in New Orleans have the potential to produce a paradigm shift in referral patterns and standards of care. I can recommend one thing: well in advance of arriving in NOLA, plan what sessions you are definitely going to attend.
How will all of these results affect us, the cardiology fellows going to the conference?
With the growing trend in transcatheter valvular procedures, will more of us be considering interventional cardiology fellowships and spending time at the concurrent i2 Summit, with its interventional emphasis?
Or what about the larger picture — for example, the trials looking at the effect that specialized A-fib clinics have on outcomes? Are these results going to influence the type of jobs that are available to us?
Sadly, a fellow’s life is such that he has to choose one conference each year. I am not traveling to ACC, but rather am keeping the home fires burning here in Chicago. That is why I hope you can provide some updates and on-the-ground insights into the events in New Orleans. If you are interested, please contact us.
For more of our ACC.11 coverage of late-breaking clinical trials, interviews with the authors of the most important research, and blogs from our fellows on the most interesting presentations at the meeting, check out our Coverage Roundup.
March 25th, 2011
FDA Approves 2 New Cardiac Resynchronization Therapy-Pacemaker Systems From Medtronic
Larry Husten, PHD
The FDA has approved two new cardiac resynchronization therapy-pacemaker (CRT-P) systems manufactured by Medtronic, the company announced. Both the Consulta® and Syncra™ CRT-P systems include an ECG reporting system, which works with the company’s network data monitoring system to offer remote follow-up of heart-failure patients. In addition, the Consulta includes Medtronic’s fluid monitoring system and a capture management feature that provides automatic pacing adjustment in response to physiologic changes.
March 25th, 2011
The Best Tool for Treating Atrial Fibrillation
John Mandrola, MD, FACC
John Mandrola is a cardiac electrophysiologist and blogger on matters medical and general. Here is a recent post from his blog, Dr John M.
Today, I would like to tell you about the most effective way to treat the most common heart ailment — atrial fibrillation (AF).
It’s not the novel new blood-thinner, dabigatran (Pradaxa). Though it’s obvious that preventing stroke without using a rat poison represents a huge advance.
It’s not burning the left atrium with an ablation catheter. Though it’s clearly true that we can ablate AF much more safely and efficiently than we did in past years.
It’s not freezing the atria with cryo-balloons. Though I look forward to learning this new technique.
You know it’s definitely not Multaq.
By far, the most effective way to treat AF patients is to provide them with information. Knowledge is king. AF patients need to know stuff about their crazy new disease.
AF is nuts. It can cause heart failure and stroke, or it can cause nothing. It can disable some, and others don’t know they have it. Its incidence increases with age, degree of inflammation, and general wear-and-tear, but it can also afflict the athletic and nimble. (Though there is little doubt that doctors, lawyers, and engineers have more AF than yoga instructors.)
Here’s a sampling of twelve things that I often tell AF patients:
1. I am sorry that you have AF. Welcome to the club, there are many members.
3. Your fatigue, shortness of breath, and uneasiness in the chest are most likely related to your AF.
4. AF may pass without treatment.
5. AF isn’t immediately life-threatening, though it feels so.
6. Worrying about AF is like worrying about getting gray hair and wrinkles. Plus, excessive worry makes AF more likely to occur.
7. Emergency rooms treat all AF in the same way.
8. There is no “cure” for AF.
9. The treatment of AF can be worse than the disease.
10. The worst (and most non-reversible) thing that can happen with AF is a stroke. For AF patients with more than one of these conditions: Age >75, high blood pressure, diabetes, heart failure, or previous stroke, the only means of lowering stroke risk is to take a blood thinner. Sorry about the skin bruises; a stroke is worse.
11. The treasure of AF ablation includes eliminating AF episodes without taking medicines. But AF ablation is not like squishing a blockage or doing a stress test. It will be hard on you. It works 60-80% of the time, has to be repeated one-third of the time, and has a list of very serious complications.
12. If your AF heart rate is not excessive, it’s unlikely that you will develop heart failure. Likewise, if you have none of the 5 risks for stroke, or you take blood-thinning drugs, AF is unlikely to cause a stroke. In these cases, you don’t have to take an AF-rhythm drug(s) or have an ablation. You can live with AF. You might not be as good as you were, but you will continue to be.
There’s obviously more than twelve things to say about AF. It’s a complicated disease with many different ways to the same end. We need adequate time with our patients to give them this kind of powerful knowledge. They need time to digest all the possible treatments, or perhaps no treatment. Patients need to weigh the disease against the treatments.
That’s why AF treatment shouldn’t be rushed.
March 24th, 2011
Study Finds Pioglitazone Prevents Progression To Diabetes
Larry Husten, PHD
Pioglitazone significantly reduces the development of type 2 diabetes in people with impaired glucose tolerance, according to the results of the ACT NOW study published in the New England Journal of Medicine.
Ralph DeFronzo and colleagues randomized 602 patients with impaired glucose tolerance to pioglitazone or placebo. During a median followup of 2.4 years, diabetes developed in 16.7% of the placebo group versus 5% in the pioglitazone group (HR for pioglitazone 0.28, CI 0.16-0.49, p<0.001). The investigators calculated that 18 people needed to be treated for one year to prevent one case of diabetes. In addition to its beneficial effects on glucose metabolism, pioglitazone was associated with a decrease in diastolic blood pressure, reduced CIMT thickening, and increased HDL cholesterol. On a less positive note, pioglitazone caused a significantly larger weight gain (3.9 kg vs 0.77 kg) and more edema than did placebo.
The investigators acknowledged that the effect of pioglitazone on long-term diabetic complications has not been determined.
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