November 13th, 2011
TRACER: Novel Antiplatelet Vorapaxar Runs Into Trouble in ACS
Larry Husten, PHD
The novel antiplatelet vorapaxar, which blocks the thrombin receptor to inhibit platelet activation, ran into trouble in the TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) trial, which was stopped prematurely earlier this year due to safety concerns.
TRACER was presented at the AHA by Ken Mahaffey and published simultaneously in the New England Journal of Medicine.
The trial randomized 12,944 patients with ACS, most of whom were receiving antiplatelet therapy. After enrollment in the trial was complete, the follow-up was terminated early due to an increase in major bleeding, including intracerebral hemorrhage. (A companion trial, the TRA-2P TIMI 50 trial testing vorapaxar for secondary prevention, was not halted, butt vorapaxar was discontinued in patients with a history of stroke.)
After a median follow-up of 502 days, the primary endpoint, a composite of cardiovascular death, MI, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization, occurred in 18.5% of patients in the vorapaxar group versus 19.9% in the placebo group (HR, 0.92; 95% CI, 0.85-1.01; P=0.07). The investigators reported a significant reduction in the composite endpoint of cardiovascular death, MI, or stroke, from 16.4% in the placebo group to 14.7% in the vorapaxar group (HR, 0.89; 95% CI, 0.81-0.98; P=0.02).
However, moderate and severe bleeding occurred in 7.2% of the vorapaxar group and 5.2% of the placebo group (HR, 1.35; 95% CI, 1.16-1.58; P<0.001). Intracranial hemorrhage occurred in 1.1% of the vorapaxar group versus 0.2% of the placebo group (HR, 3.39; 95% CI, 1.78-6.45; P<0.001).
The investigators remained hopeful that future research might “lead to a better understanding of whether different strategies” of thrombin receptor blockade might be beneficial.
November 12th, 2011
Controversy Over Cholesterol Testing for Children
Larry Husten, PHD
New guidelines from the NHLBI and the American Academy of Pediatrics recommend that all children age 9 to 11 should undergo cholesterol screening. Screening should then be repeated at 17 and 21 years of age. The new guidelines are scheduled to be officially introduced by panel member Patrick McBride at the AHA in Orlando on Sunday.
“Previous targeted screening missed more than 50 percent of children with high cholesterol,” McBride told ABC News. “Atherosclerosis begins very early in life, even in infancy for children with genetic cholesterol problems. So increased screening is a necessary step.”
But the guidelines are likely to meet with considerable skepticism.
“I don’t know of any data that screening children ages 9 to 11 is of any benefit to them,” Rita Redberg told the Wall Street Journal. “We don’t need to do cholesterol tests to advise children to eat fruits and vegetables, watch their weight and get regular physical activity.” Redberg also said that screening could provoke anxiety and cause additional unnecessary tests.
November 12th, 2011
AHA.11: How Does One Choose What to Do?
Eiman Jahangir, MD
Several Cardiology Fellows who are attending AHA.11 this week are blogging together on CardioExchange. The Fellows include Revathi Balakrishnan, Eiman Jahangir, John Ryan (moderator), and Amit Shah. Read the first post here. Check back often to learn about the biggest buzz in Orlando.
Sitting in the plane, waiting for it to take off, I think of the number of programs, sessions, exhibits, etc., at the AHA.11 conference. Every day, the agenda shows multiple, concurrent sessions to attend. For instance, on Saturday there are both the Early Career Day general session and workshops for peripheral vascular disease fellows in training. For someone going into interventional cardiology, as I am, it would be nice to attend both (and I actually registered for both), but this will not be possible due to the scheduling.
Sunday appears more manageable with only one time, 3:45, where I have a conflict between two programs, Oral Abstracts and Late-Breaking Clinical Trials. Now while you might think that the obvious choice is to attend the Late-Breaking Clinical Trials session, if your co-fellows were presenting at the Oral Abstracts session, I would imagine that you would want to support them. Then each day of the rest of the sessions, Monday thru Wednesday, is scheduled entirely with concurrent events — plenary sessions and oral abstracts.
For now, at the airport, I am still unsure about what I will see. While I will attend some sessions because of my specific interests, I might select others solely based on what my other colleagues are going to attend. Aside from the opportunity to learn the latest medical news and science, national conferences like the AHA are also the one time in the year that I can see friends with whom I attended medical school, residency, or fellowship. What I look most forward to is not necessarily the sessions but seeing these friends and colleagues. National conferences allow for time to socialize with friends and time to meet new colleagues that may lead to future collaboration on research, job prospects, and other opportunities.
How do you balance your different objectives at AHA?
November 12th, 2011
AHA.11: An Orlando Eating Tour
John Ryan, MD
As at previous major cardiology meetings, CardioExchange has fellows from around the country blogging about their experiences at the Scientific Sessions at the AHA. Revathi Balakrishnan, first-year fellow at NYU; Eiman Jahangir, third-year fellow from Vanderbilt; Amit Shah, second-year fellow at Emory; and John Ryan, third-year fellow at University of Chicago will be sharing us with their first-hand experiences at “the grandfather of all the major meetings.” To kick things off, John Ryan provides us with his now traditional restaurant guide on the eve of the AHA. Check back often to learn about the biggest buzz in Orlando.
They said it could not be done. Orlando is known for a lot of things, most famously theme parks and shuttle launches. However, when it comes to cuisine, O-town is not as renowned as other convention cities such as Chicago or New Orleans. Fortunately for CardioExchange readers who are going to Florida this week, I have been to enough conferences in Orlando to provide a restaurant guide. I’ve come up with a mixture of high-end steakhouses and local spots, as well as a coffee house serving gator and “choffee” 20 miles east that is well worth the trip. So, here is our culinary guide to Orlando. Reservations recommended, and don’t forget to tell them that CardioExchange sent you!
Victoria and Albert’s
Disney’s Grand Floridian Resort and Spa, Walt Disney World, 4401 Grand Floridian, Orlando, 407-939-3862
This high-end romantic restaurant serves fine cuisine ( typically American and British) with wine pairings. The menu is prepared fresh every day, and the price reflects the attention to detail. The Victoria Room is as romantic as it gets — but also very expensive.
Chatham’s Place Restaurant
7575 Dr. Phillips Blvd. , Orlando, 407-345-2992
Chef Tony and Maitre d’ Maurice, and the entire staff are a cut above, as is the shrimp and pasta puttanesca. The manicotti is also worth trying. For a main course, the Corvina is very tasty and well prepared- but you cannot go wrong with whatever you order here.
Padrino’s Cuban Bistro
13586 Village Park Dr. (GPS use: S. John Young Pkwy), Suite 304, Orlando, 407-251-5107
This Cuban restaurant in the Hunter’s Creek neighborhood has a famous bread pudding, as well as stellar open-faced gyros.
Seasons 52
Plaza Venezia, 7700 W. Sand Lake Rd, Orlando, 407-354-5212
This restaurant hosts a fresh grill and wine bar. Request a table on the patio overlooking the lake. Highlights include the mahimahi, fresh cobia, and the excellent flat bread appetizers.
CRAVE
Mall of Millenia, Orlando, 407-345-8788
Outstanding American cuisine in a casual atmosphere. Notable items include shrimp & fruit salad, cioppino, and buttermilk chicken sliders.
Dragonfly Robata Grill and Sushi Lounge
7972 Via Dellagio Way, Orlando, 407-370-3359
For your sushi needs, enjoy outstanding sushi, sashimi, and robatayaki served tapas style. There is also a full saké bar in a relaxed lounge atmosphere. Try their signature dragonfly foll.
Old School Coffee Stop
26205 E Colonial Dr (next door to Jungle Adventures, Highway 50), Christmas, 407- 568-4005
Located 20 miles east of Orlando, this bistro requires a special trip, but is well worth it. They sell gator (bites and sauteed), East-Coast, Wild Shrimp, choice chicken and great bread pudding ever. They even serve “choffee.” They are open only from Thursday to Sunday from noon to 10 pm. Oh, and everything is served and prepared in an old school bus!
KRES Chophouse
17 W. Church St. (Orange Ave.), Orlando, 407-447-7950
Classic steakhouse with steak tartare prepared tableside, but the oysters and mushroom risotto are just as good for those avoiding steak.
Jiko –The Cooking Place
Disney’s Animal Kingdom Lodge, Walt Disney World Resort, 2901 Osceola Pkwy. Lake Buena Vista, 407-939-3463
Jiko is pretty neat- African cuisine is the highlight of this unusual Disney restaurant. Highlights include grilled shrimp curry with citrus-coconut basmati rice, or herb-crusted potato with pepper-dusted chicken
Brunch suggestions
Peach Valley Café
5072 Dr. Phillips Blvd., Orlando, 407-522-6201
The walnut salad with salmon is well worth trying, as is the California omelet, which comes with potatoes, artichokes, and a homemade biscuit.
Ethos Vegan Kitchen
(407) 228-3898 Ivanhoe Village 1235 N Orange Ave, Orlando, FL 32804
This vegan restaurant successfully creates a unique brunch experience with a tasty breakfast burrito
La Coquina
Hyatt Regency Grand Cypress Resort 1 Grand Cypress Blvd., Orlando, 407-239-3853
A great spread for Sunday brunch. The restaurant also has an intimate chef’s table where on Saturday evenings you can watch the chefs create honey-glazed lamb, Chilean sea bass, and Hawaiian tuna tartare.
November 11th, 2011
Transapical TAVR on the Ropes: Is It Down for the Count?
Richard A. Lange, MD, MBA and L. David Hillis, MD
STACCATO showed more adverse events with transapical transcatheter aortic valve replacement (TAVR) than with aortic valve replacement (AVR) in low risk, elderly patients.
In patients with severe, symptomatic aortic stenosis who are believed to have high surgical risk, PARTNER substudy results presented at the AHA show
- Transapical TAVR provided no increase (and even a possible decrease) in quality of life compared to AVR; and
- Transapical TAVR increased procedural, index admission, and 12 month costs (by ~$10,000/patient) when compared to AVR.
In short, the results of these studies are consistent.
What is the problem? Is it the procedure, the equipment, or the training? Should we stop the fight and throw transapical TAVR out of the ring?
November 11th, 2011
Shaky Start Ends STACCATO
L. David Hillis, MD and Richard A. Lange, MD, MBA
The STACCATO trial planned to randomize 200 low-risk patients to transcatheter aortic heart valve implantation (TAVI) via the transapical approach (with the Sapien valve from Edwards Lifesciences) or surgical aortic valve replacement (AVR). The primary endpoint was a composite of death, stroke, and renal failure at one month. After enrolling only 70 patients (34 TAVI and 36 surgical AVR), the study was stopped prematurely by the data safety and monitoring board because of an excess of events in the TAVI arm. The primary endpoint was met in five patients in the TAVI group (2 deaths, 2 strokes, and 1 case of renal failure) and one patient (stroke) in the AVR group.
It is distinctly unusual to stop a study prematurely after only one third of the enrollment has occurred.
What went wrong?
1) Is TAVI via the transapical approach inherently dangerous?
2) Were the physicians inadequately trained or inept?
3) Were the patients selected for TAVI unsuitable for it?
4) Is application of TAVI to low-risk patients inappropriate?
As a condition of FDA approval of the Sapien valve, Edwards Lifesciences committed to monitoring the outcomes with the valve through a national registry on transcatheter valve therapy. The American College of Cardiology and the Society of Thoracic Surgeons have been working with the FDA and the Centers for Medicare and Medicaid Services to create this national registry, which will serve as a platform for post-market evaluation of the Sapien valve and future transcatheter devices.
However, STACCATO sends a clear message. To quote our NASA friends, “Houston, we have a problem.”
It’s critical that we find out what went wrong in STACCATO before Edwards embarks on its ambitious efforts to roll out TAVI to 150-250 sites in the first year of commercialization.
November 11th, 2011
TAVI at TCT: Enthusiasm Tempered by Poor Transapical Outcomes
Larry Husten, PHD
Continued enthusiasm for transcatheter aortic valve implantation (TAVI) with the Edwards’ Sapien device was tempered somewhat by poor outcomes observed in the group of patients for whom the procedure was performed using the transapical instead of the transfemoral approach. Results of 3 new studies from the PARTNER trials and a controversial new trial, STACCATO, were presented on Thursday at the TCT conference in San Francisco.
The overall good news for TAVI came from the 2-year results of the PARTNER B trial. In this trial of patients who were not eligible for open heart surgery, the advantages for TAVI over medical therapy previously observed at 1 year have now been extended out to 2 years. The rate of all-cause mortality at 2 years was 18.2% in the TAVI group versus 35.1% in the control group. Repeat hospitalization was cut in half from 72.5% in the control group to 35% in the TAVI group. However, the stroke rate at 2 years remained higher in the TAVI group: 13.8% versus 5.5%. Three strokes and 2 TIAs occurred in TAVI patients in the second year.
“The ultimate value of TAVR in ‘inoperable’ patients will depend on careful selection of patients who are not surgical candidates, and yet do not have extreme co-morbidities that overwhelm the benefits of TAVR and render the intervention futile,” concluded Raj Makkar, who presented the results at TCT.
Transapical Approach Under Scrutiny
Two other PARTNER studies presented at TCT cast a shadow on the value of TAVI in patients who require the transapical approach. The quality-of-life study of the PARTNER A trial, presented by David Cohen, found an improvement in quality of life in patients whose TAVI was performed via the transferal approach but not via the transapical approach, when compared with surgery. In fact, said Cohen, the results raised the possibility of a worse quality of life in the transapical TAVI group.
A cost-effectiveness study of PARTNER A presented by Matthew Reynolds found a small but significant gain in 12-month quality-adjusted life-years (QALY) for TAVI performed via the transfemoral approach. For the transapical approach, by contrast, there was no increase — and a possible decrease — in QALY. Total expenses in the transapical group were also significantly higher than in the surgical group.
“Current results for transcatheter aortic valve replacement via the transapical approach, compared with surgical aortic valve replacement, are unattractive from a health economic perspective,” said Reynolds in a TCT press release. “Whether the transapical approach can be refined to provide faster recovery and better results from a cost perspective should be the subject of further study.”
On their CardioExchange interventional cardiology blog, Rick Lange and David Hillis ask whether these findings cast a shadow on the future of the transapical approach.
Finally, a study performed in Denmark, called STACCATO, attempted to compare transapical TAVI with surgery in elderly patients but was discontinued early after only 70 out of a planned 200 patients had been enrolled. The discontinuation was due to an excess of events in the transapical TAVI group.
“In its present phase of development, transapical transcatheter aortic valve implantation may be inferior to surgical aortic valve replacement in operable elderly patients,” said Leif Thuesen, the lead investigator of the trial, in a TCT press release.
Lange and Hillis also scrutinize STACCATO and write:
It’s critical that we find out what went wrong in STACCATO before Edwards embarks on its ambitious efforts to roll out TAVI to 150-250 sites in the first year of commercialization.
November 10th, 2011
What’s This Fellow Looking Forward to at AHA?
John Ryan, MD
Fellowship Training co-moderator John Ryan discusses the studies he’s most looking forward to checking out at the AHA Scientific Sessions 2011 meeting. See what he has to say and share your own suggestions and comments.
- ADOPT: The past twelve months have seen the now famous introduction of novel anticoagulants for AFib. The potential for these agents to change the face of treatment options for other conditions that require anticoagulation is enormous. In the ADOPT (Apixaban Dosing to Optimize Protection from Thrombosis) study, Goldhaber et al compare the effect of enoxaparin with that of apixaban for preventing deep vein thrombosis and pulmonary embolus in patients admitted with acute medical illness. This study, which enrolled over 6500 patients, has the potential to change our traditional management of DVT/PE prevention, unless it suffers from the bleeding complications that plagued APPRAISE-2.
- Post-MI FREEE: I am also excited to learn about the results of the Post-MI FREEE (Post-MI Free Rx Event and Economic Evaluation Trial) study, in which patients were randomized to have their pharmacy benefits changed so that they have no out-of-pocket costs for any ACEi, ARB, β-blocker, or statin. In the interventional arm, all co-pays are waived, as is any amount that the cost of the drugs contributes to a patient’s deductible. This study interests me for two reasons: (1) it addresses the long-held question of whether patients would be more compliant if they get their medicine for free, and (2) more importantly, it represents a deviation from the usual pharmaceutical-sponsored research. This study was performed in collaboration with the insurance company Aetna, a practice that may become increasingly common.
- POWER: The obesity epidemic continues to cripple U.S. healthcare, and there are few recognized long-term successful treatments available aside from bariatic surgery. I think the POWER (Evaluating Weight Loss Programs for Obese People at Risk for Heart Disease) study will be useful, as it compares the effects of self-directed weight loss, cell-center directed programs, and in-person weight loss counseling. As well as weight loss at 2 years follow up, the investigators have also studied BP control, lipid levels, insulin sensitivity, and Framingham Risk factors. There does not appear to be cost-analysis in this part of the study, but demonstration of efficacy will at least be the first step to address this epidemic.
November 10th, 2011
The AHA in Orlando: A Preview
Larry Husten, PHD
The AHA 2011 Scientific Sessions start this weekend in Orlando. CardioExchange received a preview of some of the many expected highlights of the meeting from Program Chair Elliott Antman. (Click here to view AHA videos of Antman’s meeting previews.)
Antman stressed the sheer size and magnitude of the meeting: 742 individual sessions, 4238 abstracts selected out of more than 9000 submitted, 295 invited sessions, and 5 late-breaking clinical trial sessions.
Here are a few of the late-breaking clinical trials highlighted by Antman:
ADOPT (Apixaban Dosing to Optimize Protection from Thrombosis) will be the first of several trials evaluating the newer anticoagulants. The ADOPT Trial randomized 6,528 hospitalized, medically ill patients to evaluate apixaban 2.5 mg twice daily for 30 days compared to enoxaparin for at least 6 days to reduce the incidence of venous thromboembolism.
TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) is a large new trial investigating the novel agent vorapaxar, which is a thrombin receptor antagonist, in the setting of ACS. Merck, the trial’s sponsor, announced earlier this year that the trial had been stopped prematurely by the data and safety monitoring board, but few details have been available until now.
ATLAS ACS 2-TIMI 51 (Anti-Xa Therapy to Lower Cardiovascular Events in Addition to Standard Therapy in Subjects with Acute Coronary Syndrome-Thrombolysis in Myocardial Infarction 51) is a large trial testing whether the addition of rivaroxaban to standard care in patients with ACS can reduce major cardiovascular events. The sponsor of the trial announced that the trial was positive for the primary endpoint but that there were also more bleeding complications in the rivaroxaban arm. Antman noted that “many important questions remain open,” including whether the trial shows an impact on mortality.
PALLAS, which tested the role of dronedarone in patients with permanent atrial fibrillation, was stopped early because of harm. Many observers are keen to learn the details of this trial, and whether it will have implications for the use of dronedarone in other indications.
AIM-HIGH tested the effect of extended-release niacin in patients with CV disease and low HDL cholesterol and high triglycerides. The trial was stopped for futility. “We don’t know if that means if the trial was underpowered, if niacin doesn’t work, or if HDL therapies don’t work,” said Antman. “There will be lots of implications for the future of HDL.”
Antman also pointed to a plenary session on Monday morning that will feature a status report from the NHLBI on 3 major new guidelines for blood pressure (JNC 8), lipids (ATP 4), and obesity that are expected to be published in 2012. In addition, a separate symposium will focus on the PARTNER trial and the integration of percutaneous aortic valve implantation into clinical practice.
Click here for a complete list of the AHA late-breaking clinical trials.
November 9th, 2011
Obstructive Lesions Found in Patients with Calcium Scores of Zero
Larry Husten, PHD
A small but significant number of symptomatic patients with calcium scores of zero have obstructive coronary artery disease (CAD), according to a new study published in the Journal of the American College of Cardiology.
Todd Villines and colleagues studied 10,037 symptomatic patients without known CAD enrolled in the CONFIRM (Coronary CT Angiography Evaluation for Clinical Outcomes: An International Multicenter) registry who underwent coronary CT angiography (CCTA). Half of the patients (51%) had a coronary artery calcium (CAC) score of 0 and although most (84%) had no CAD, 13% had a nonobstructive stenosis, 3.5% had a stenosis of 50% or greater, and 1.4% had a stenosis of 70% or greater. Some 3.9% of patients with a CAC score of 0 and obstructive CAD had an adverse event during follow-up as compared to 0.8% in the group with a CAC score of 0 and no obstructive CAD.
The authors write that their results reaffirm “the importance of properly assessing patient pretest probability for obstructive CAD” when calcium scores are used in symptomatic patients. They conclude that “the absence of CAC reduces but does not fully eliminate the occurrence of obstructive CAD” and that calcium scoring “does not appear to offer significant incremental prognostic information when combined with clinical risk factors and CAD severity on CCTA.”
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