Posts

September 16th, 2010

FDA: Dabigatran Gains, Lorcaserin Loses

An alternative to warfarin is one step closer to reality. On Thursday, The FDA released briefing documents for next Monday’s meeting of the Cardiovascular and Renal Drugs Advisory Committee to discuss the new drug application for dabigatran (Pradaxa, Boehringer Ingelheim) for the prevention of stroke in patients with AF. The FDA reviewers agreed that dabigatran was at least as safe and effective as warfarin in the RE-LY trial. Cardiologists on the panel include the acting chair, A. Michael Lincoff, along with Steve Nissen, Sanjay Kaul, and Darren McGuire.

Also on Thursday, the FDA’s Endocrinologic and Metabolic Drugs Advisory Committee recommended against approval of the diet drug lorcaserin (Lorqess, Arena). The vote was 9-5. Panel members felt the drug’s slim margin of efficacy in producing weight loss did not outweigh safety concerns that might arise in the real world.

September 15th, 2010

FDA: Ticagrelor Deadline Extended; No Clear Signal on Sibutramine

FDA watchers require patience.

AstraZeneca announced that the FDA had extended its review of ticagrelor (Brilinta) until December 16. The previous deadline had been September 16. In July, the FDA Cardiovascular and Renal Advisory Committee voted 7-1 in favor of approving ticagrelor for the indication of STEMI and NSTEMI patients, but the committee and the FDA were uncertain about how best to interpret the results of the pivotal PLATO trial because the overall positive effects of the drug were not observed in the subset of patients enrolled in the U.S. (AstraZeneca press release.)

The FDA Endocrinologic and Metabolic Drugs Advisory Committee split down the middle in its review of sibutramine (Meridia). Eight panel members voted in favor of withdrawing sibutramine from the U.S. market, while 8 members voted to keep it on the market, though all 8 agreed it needed a boxed warning and 6 thought it also should have its distribution limited to specially trained physicians. No panel members thought it should be allowed to remain on the market without any changes to the current label.

September 15th, 2010

TREAT Analysis: Target Dosing Is Tricky

A new analysis of TREAT (Trial to Reduce Cardiovascular Events with Aranesp Therapy) is raising questions about the use of target-based strategies for the treatment of anemia in people with chronic kidney disease. (Last year, the main TREAT results showed that treatment with darbepoetin alfa was not beneficial – and was associated with an increase in the risk for stroke – in people with diabetes, chronic kidney disease, and moderate anemia.)

The new report, appearing in the New England Journal of Medicine, analyzes the responsiveness to treatment and achieved hemoglobin levels and finds that patients with a poor response to initial doses of darbepoetin alfa had higher rates of cardiovascular events and death when compared with good responders. The TREAT investigators write that “it is likely that a poor initial response to ESA treatment in this population represents a marker for severity of illness.”

In their conclusion, the TREAT investigators acknowledge that “we cannot determine whether a poor initial response to an ESA places patients at increased risk for these adverse outcomes or whether the risk was augmented by the higher doses of darbepoetin alfa they received. However, these findings raise the question of whether the degree of hematopoietic responsiveness to ESA treatment, and not just the target hemoglobin level, should be taken into account in ESA therapy.”

September 15th, 2010

A Fistful of Stents

CardioExchange welcomes this guest post from Pharyngula, a blog by PZ Myers, an associate professor of biology at the University of Minnesota, Morris. Dr. Myers recounts his PCI experience from the patient’s point of view.

Here’s my status right now, for those who have been wondering.

First of all, I’m not dead yet. Let’s get that out of the way.

Yesterday morning was the big event here in hospital-land: I was to get an angiogram, this procedure where they thread wires up your femoral artery to your heart and start poking around with dyes and things to figure out what’s going on. You’re conscious, mostly, through the procedure, so I thought I’d live-blog it, if I could, but it turns out they don’t want you monkeying around with anything while the doctors are examining you from the inside out, and there were going to be occasional sprays of x-rays, and I was going to be on some mind-altering drugs. So I resolved to use my keen scientific mind to observe and report back later on what it was like.

They wheeled me in and a nice nurse named Phil leaned over me and told me he was going to put some drugs in my IV that would make me drowsy, which was silly — it was 8:00 am, I was wide awake — but he gave them to me anyway. Then someone else appeared on my right side and shaved my pubic hair. Not everything — he left me a short, wide rectangular patch for a landing strip that looked like Hitler’s mustache — and then I noticed that Hitler had a very large nose and two big pink hairy eyeballs, and that kept me amused for about 10 minutes. I think that was my last lucid thought. (Well, it seemed lucid at the time.)

The Jawas came in. They might have been doctors, but they were all covered in robes and hoods and speaking animatedly in some language that wasn’t English — it was very buzzy and abrupt. They didn’t talk to me anyway, but sometimes told Phil things that he would translate for me. They descended on my right thigh and proceeded to build an airlock so they could crawl inside and party on my left ventricle. I tried to tell them that the Left Ventricle was not some trendy nightclub — it’s just a storage unit where I keep my Jesus-shaped hole — but I think what came out of my mouth was a kind of mumbly moan in Ewok, and everyone knows Jawas don’t understand Ewok.

And giant cameras just glided by majestically on motorized trackways above my head.

It hurt quite a bit, in a very remote, distracted, distant way, especially when the anaconda in my leg writhed awkwardly, but I was mostly unperturbed. I actually fell asleep a few times.

Then Phil’s giant head floated into view — I think it was mounted on one of the camera tracks — and he announced, “Good news! No cabbage for you!”, which was very cheering, since I don’t particularly care for cabbage. And then the Jawas stomped on my heart for another hour or so. While I napped.

Later, after the cotton swabbing drained out of my cranium, I realized it was very good news. The threat hanging over me was an angiogram followed by chest-cracking and open heart surgery and prolonged pain, but the clever doctors had looked me over and decided they could patch me up with set of stents instead of that elaborate bypass surgery. Yay, doctors! It’s the difference between 8 weeks of ouchy, hurty, messy convalescence and less than two weeks of taking it easy.

The last fun bit was when they had to strip the hoses from my thigh, which involved a quick yank and then a doctor with very large strong hands holding my naked thigh in a death grip for half an hour. I tell you, that’s a very awkward situation for small talk.

So, I might be getting out today. They’re doing more tests, checking out my kidneys (which had a lot of extra work to do clearing out the contrast dye). Right now, my life consists of lying in bed while a pretty nurse comes by every hour and says, “I need to see your groin!”, whips off my skimpy robe, and coos about how good it looks. I think she’s probably talking about my bloody wound, not anything else (and I hope it’s not because she’s a fan of Adolf Hitler caricatures!)

But soon enough I’ll be off to resting at home, beginning the cardio therapy the doctor will no doubt be putting me on, and back to classes and writing. Expect blogging to be on the light side, though, while I catch up on rest and other pressing projects that were interrupted by this surprise event.

September 14th, 2010

AHA Rejects Smokeless Tobacco Products

Smokeless tobacco products aren’t safe and won’t help people quit smoking, according to a policy statement from the American Heart Association published in Circulation. Although the statement acknowledges that the cardiovascular risks of smokeless tobacco products appear to be reduced compared with cigarette smoking, evidence cited in the statement links smokeless tobacco products to an increased risk for fatal MI and stroke; reduced survival after MI or stroke; and a greater likelihood of cancer and oral disease. The authors also warn against the dual use of cigarettes and smokeless tobacco products and raise concern over “the disturbing trend in the increase in [smokeless tobacco] product initiation and use among adolescent males.”

September 13th, 2010

Three-year SYNTAX Results: Sensible, Not Sensational

In SYNTAX, 1800 patients with multivessel and/or left main disease were randomized to CABG or PCI with DES after a surgeon and an interventional cardiologist reviewed the coronary angiogram and agreed that either procedure was appropriate. (See the CardioExchange News blog for more study information.)

The SYNTAX 3-year results show that patients with a low SYNTAX score have similar outcomes with PCI or CABG, whereas those with an intermediate or high score have a better outcome with CABG.

1) In the cohort as a whole, MACCE rates were higher for PCI than for CABG (28% vs 20%), mainly because of a higher rate of repeat revascularization in the PCI group.

a) Composite safety (death/stroke/MI) was similar in the PCI and CABG groups (14.1% and 12.0%, respectively)

b) MI incidence was nearly twice as high in PCI patients than in CABG patients (7.1% vs. 3.6%)

2) In patients with a low (0-22) SYNTAX score, MACCE rates were similar for PCI and CABG (22.7% and 22.5%, respectively)

3) In patients with an intermediate (23-32) or a high SYNTAX score, MACCE rates were higher with PCI than CABG (27.4% vs 18.9% for an intermediate score; 34.1% vs 19.5% for a high score)

Now be honest….do you calculate a SYNTAX score for your patients?

If you don’t, how do you determine which patients will do as well with PCI as with CABG?

September 13th, 2010

SYNTAX at 3 years: CABG Still Winning, but PCI Acceptable in Low-Risk Patients

Three-year outcomes from the SYNTAX trial continue to show the overall superiority of CABG over PCI in patients with complex disease, but they leave room for the use of PCI in patients with low-risk disease. The results of the trial were presented by A. Pieter Kappetein at the European Association of Cardio-Thoracic Surgery annual meeting in Geneva, Switzerland.

SYNTAX randomized 1800 patients with 3-vessel or left main disease to either surgery or PCI. In the initial 1-year results, published in the New England Journal of Medicine, the rate of major adverse cardiac or cardiovascular events (MACCE) was lower in the CABG group, largely driven by more repeat revascularizations with PCI. However, a higher rate of stroke in the CABG group, and better outcomes for PCI among patients with less complex disease, led many observers to conclude that the message was far from simple. A similar pattern was observed at 2 years.

Now, at 3 years, the rate of MACCE remains significantly higher in the PCI group than in the CABG group, again driven mostly by the higher repeat revascularization rate with PCI. In addition, in the second and third years of the trial, the investigators observed significantly higher MI rates in the PCI group, although the composite safety endpoint (death, CVA, MI) did not differ.

Here are some of the key 3-year data (CABG vs. PCI):

  • MACCE: 20.2% vs. 28.0%
  • Mortality: 6.7% vs. 8.6%
  • CVA: 3.4% vs. 2.0% (nearly all the difference occured in the first year)
  • MI: 3.6% vs. 7.1%
  • Repeat revascularization: 10.7% vs. 19.7%

Here is the yearly breakdown for MI:

  • At 1 year: 3.3% vs. 4.8%
  • At 1-2 years: 0.1% vs. 1.2%
  • At 2-3 years: 0.4% vs. 1.2%

There were no significant differences between the two groups in the MACCE rate among patients with low-risk SYNTAX scores at baseline. CABG was superior to PCI in patients with intermediate and high SYNTAX scores.

Kappetein concluded:

The 3-year SYNTAX results suggest that CABG remains the standard of care for patients with complex disease (intermediate or high SYNTAX Scores); however, PCI may be an acceptable alternative revascularization method to CABG when treating patients with less complex (lower SYNTAX Score) disease.

Note to readers: Rick Lange has started a discussion on this topic in the Interventional Cardiology section of CardioExchange. Click here to join the discussion.

September 13th, 2010

Fellowship Training Around the World

In the last of a series of posts from the ESC meetings, Susan Cheng offered some interesting insights into differences between the ESC and the large U.S. meetings such as AHA and ACC, including major differences in how research is funded and performed in countries outside the U.S. Comoderator Andy Kates and I started thinking about how the training of cardiologists also varies across countries. In the U.S., the “format” of clinical training for cardiovascular specialists is highly regulated (even over-regulated!) by the ACGME and ABIM and so is fairly similar across institutions. However, it differs vastly from the training formats in many other countries. For example, in my interactions with a number of cardiovascular fellows from Brazil, I’ve observed the following differences:

  • Students complete medical school at a younger age than in the U.S.
  • Internal medicine training is brief.
  • “General cardiology” training does not include developing expertise in basic procedures such as diagnostic catheterization and echo interpretation.
  • Fellows may elect or apply for additional training in catheterization, echo, EP, etc., but do not have broad-based training in all of these core skills.

We’d love to hear from you about your insights into differences in training across countries, and in particular, whether there are features that we should consider adopting in the U.S.

September 10th, 2010

Meta-Analysis Finds High Risk for Carotid Stenting in Older Patients

Carotid stenting should not be performed in patients age 70 years or older, according to the results of a new meta-analysis appearing in the Lancet. Researchers in the Carotid Stenting Trialists’ Collaboration combined data from 3433 patients with symptomatic carotid stenosis who were randomized to either endarterectomy or stenting in the EVA-3S, SPACE, and ICSS trials.

At 120 days after randomization, the rate of stroke or death was higher in the stenting group than in the endarterectomy group (8.9% versus 5.8%, RR 1.53, p=0.0006). However, there was no difference between the groups among patients younger than age 70, while in patients age 70 or older, stenting was associated with double the risk associated with endarterectomy:

  • Younger than age 70, stenting versus endarterectomy: 5.8% versus 5.7%
  • Age 70 or older, stenting versus endarterectomy: 12% versus 5.9%, RR 2.04, p=0.0014

A similar pattern was observed in a per-protocol analysis after 30 days restricted to patients who received the allocated treatment:

  • Younger than age 70, stenting versus endarterectomy: 5.1% versus 4.5%
  • Age 70 or older, stenting versus endarterectomy: 10.5% versus 4.4%

The authors write that their “findings suggest that stenting might… be a viable alternative to endarterectomy in younger patients, in whom surgery could otherwise be undertaken without increased risk,” although they express concern about the long-term stroke risk in young patients treated with stents due to “the potentially higher rate of recurrent stenosis after stenting than with endarterectomy.”

September 9th, 2010

Getting to the Heart of the Problem

You told us how you’d handle our latest case: A 53-year-old smoker with a history of diverticulitis and prior gastrointestinal bleeding presents with lightheadedness and bright red blood per rectum. Ultimately, a partial colectomy is recommended. Now, heart-failure specialist Jim Fang weighs in with his recommendations. Do you agree? Tell us why or why not.