August 29th, 2010
ESC First Impressions: Size Matters
Susan Cheng, MD
I’ll admit I was a bit guarded about my first ESC conference, largely due to what seemed to be looming logistical issues. Despite all of Stockholm’s reported charm, it was hard to imagine how a city of this size was going to manage the invasion of over 20,000 — and possibly up to 30,000 — attendees. Several months in advance of the conference, it was already nearly impossible to find a hotel room. This was the case even for presenters and speakers, some of whom threatened to cancel their participation if the ESC couldn’t help to secure them lodging. Arrangements were made for a cruise ship to dock nearby and make its cabins available, attendees were encouraged to consider hotels in neighboring cities up to 40 miles away, and the ESC posted several online announcements to reassure attendees that everything was going to be all right. So, along with others, I braced myself.
But now that I’m here, I’m beginning to think that the event planners were smart to pick Stockholm after all. The large swarm of cardiologists from all over the world into this relatively small city is making what is already a big meeting feel bigger. And Stockholm’s good food and coffee, as well as its charming sights, appear to be keeping the crowds quite contented. Although the convention center main hallway is jam packed with people during the rush between sessions, and you’re lucky to even get into a session due to limited seating capacity, people seem happy so far. Even while guarding precious personal space on the commuter train that shuttles attendees from the convention center back to the city, both the locals and the visitors are upbeat. And you know you’re among the visitors when you’re standing on a crowded subway platform, trying to exit through a narrow passageway, and the person next to you mumbles, “It’s a tight stenosis.”
August 29th, 2010
Genetic Substudies of Large Trials Question Value of Clopidogrel Genotyping
Larry Husten, PHD
Genetic substudies across a broad range of large clinical trials that used clopidogrel raise questions about the clinical utility of clopidogrel genotyping. The substudies come from large and important trials like PLATO, TRITON-TIMI 38, CURE, and ACTIVE A.
A genetic substudy of PLATO finds that ticagrelor is superior to clopidogrel irrespective of genetic subtype. Therefore, according to Lars Wallentin and colleagues in their presentation at the ESC in Stockholm and in a simultaneous publication in the Lancet, “use of ticagrelor instead of clopidogrel eliminates the need for presently recommended genetic testing before dual antiplatelet treatment.” Wallentin et al. analyzed the role of CYP2C19 and ABCB1 polymorphisms in more than 10,000 patients enrolled in PLATO. Among patients with any CYP2C19 variation, the primary endpoint occurred less often in those treated with ticagrelor than in those treated with clopidogrel (8.6% vs. 11.2%). A similar pattern occurred with ABCB1.
In a Lancet press release, Wallentin said that the “findings emphasise that ticagrelor will be a simple and reliable treatment to further improve survival and reduce the risk of recurrences in almost all patients with acute coronary syndrome without the need for any specific tests of its activity before or during routine treatment.”
In a second study appearing in the Lancet, Jessica Mega and colleagues genotyped ABCB1 in nearly 3000 patients enrolled in the TRITON-TIMI 38 trial comparing prasugrel with clopidogrel. They also examined the combined effect of ABCB1 variants and CYP2C19 variants and found that a majority of people have a genetic variation that may reduce the efficacy of clopidogrel. In sharp contrast to the PLATO investigators, they conclude that “as clinicians, professional societies, and patients integrate information about genetic factors affecting the response to thienopyridines, the roles of both ABCB1 and CYP2C19 should be considered.”
In an accompanying comment in the Lancet, Betti Giusti and Rosanna Abbate observe that both studies “confirmed the independent role of the CYP2C19 loss-of-function alleles as a determinant of major adverse cardiovascular events in these patients on clopidogrel… whereas they did not show any effects of CYP2C19 genetic variants in patients on prasugrel or ticagrelor.”
In a third paper, published online in the New England Journal of Medicine, Guillaume Paré and colleagues genotyped patients who had been enrolled in the CURE and ACTIVE A trials and found no reduction in the effect of clopidogrel among patients with a loss-of-function CYP2C19 genotype, although patients with a gain-of-function genotype received greater benefit from clopidogrel.
August 29th, 2010
Superiority of Dabigatran More Evident in Places Where INR Is Not Well Controlled
Larry Husten, PHD
At last year’s ESC meeting, the RE-LY trial heightened interest in the prospect of dabigatran as a potential replacement for warfarin. Now the RE-LY investigators have analyzed the trial data in an attempt to see whether the local standard of care has an impact on the beneficial effects of switching to dabigatran. In a presentation at the ESC in Stockholm and a simultaneous publication in the Lancet, Lars Wallentin and the RE-LY investigators estimated the time in the therapeutic range at each trial center (cTTR). They found that — irrespective of cTTR — when compared with warfarin, high-dose dabigatran was effective at reducing stroke, low-dose dabigatran was effective at reducing bleeding, and both doses reduced intracranial bleeding. The investigators write that the “advantages of dabigatran were greater at sites with poor INR control than at those with good INR control,” and concluded that “overall, these results show that local standards of care affect the benefits of use of new treatment alternatives.”
In an accompanying comment, Deirdre Lane and Gregory YH Lip write that “when oral anticoagulants are clearly appropriate (ie, CHA2DS2-VASc score ≥1), dabigatran should be considered as an alternative to adjusted dose warfarin therapy.” High-dose dabigatran might be appropriate in patients at low risk for bleeding while low-dose dabigatran could be considered in patients with a higher bleeding risk, they write.
August 29th, 2010
Downshifting Heart Rate in HF Found Beneficial
Larry Husten, PHD
In the SHIFT trial, Karl Swedberg and colleagues tested the effects of ivabradine, a selective sinus-node inhibitor, in 6558 patients with heart failure who had a heart rate ≥70 bpm. After a median 23 months of follow-up, the rate of cardiovascular death or hospital admission for worsening heart failure was 24% in the ivabradine group and 29% in the placebo group (hazard ratio, 0.82; 95% CI 0.75–0.90, P<0.0001). The results were presented at the ESC in Stockholm and published simultaneously in the Lancet.
In an accompanying comment in the Lancet, John Teerlink noted that many patients in SHIFT did not receive optimal medical therapy, especially high-dose beta-blockers. Therefore, he writes: “Whether ivabradine can improve outcomes in addition to optimally managed heart failure therapies or its benefits relative to other therapies, especially beta blockers, remains unknown.”
In a second paper published in the Lancet, Michael Böhm and colleagues analyzed data from SHIFT and found that in the placebo group, patients with heart rates in the highest quintile at baseline had double the risk of patients in the lowest quintile. In the placebo group, the investigators observed a direct correlation between heart rate at 28 days and subsequent outcome, and concluded that “the effect of ivabradine is accounted for by heart-rate reduction.”
August 29th, 2010
Alpha Omega Trial Tests Omega-3 Fatty Acids in CV Disease
Larry Husten, PHD
To test the effect of omega-3 fatty acids in cardiovascular disease, Kromhaut and colleagues with the Alpha Omega Trial Group randomized 4837 patients with a history of MI to treatment with one of four margarine preparations: one containing EPA and DHA; one with ALA; one with EPA, DHA, and ALA; or placebo. After 40 months, the rate of major cardiovascular events did not differ significantly across any of the groups. Among women, there was a trend toward a reduction in events in those who received ALA compared with those who received placebo or EPA/DHA. The results were presented at the ESC in Stockholm and published simultaneously in the New England Journal of Medicine.
“The patients in this trial were very well treated,” said Dr. Kromhout, in an ESC press release, “with 98% on antithrombotic agents, 90% on antihypertensive drugs, and 86% on lipid lowering drugs. We found that cardiovascular mortality rate in the study population was only half that expected, probably because of their excellent treatment. This may also be why the rate of major cardiovascular events during follow-up was no lower in the fatty acid groups than in the placebo group. “
August 27th, 2010
High-Risk PCI: Is an IABP Necessary?
Larry Husten, PHD
Simon Redwood and Divaka Perera answer our questions about their randomized trial of IABP insertion during high-risk PCI in patients with severe LV dysfunction and extensive coronary disease. Check out our conversation and then ask them your own questions here.
August 27th, 2010
Compression-Only CPR: It May Help Bystanders Breathe Easier
Mark Steven Link, MD
A recent randomized, controlled study in the NEJM showed that patients with out-of-hospital cardiac arrest who received compression-only CPR or traditional CPR had similar 30-day survival rates. CardioExchange asks Dr. Mark Link, a cardiac electrophysiologist and member of the American Heart Association Advanced Cardiac Life Support Committee, to answer our questions about compression-only vs. traditional CPR.
Are we at a point where we can tell people that ventilation is not necessary during CPR?
The current AHA guidelines state that it is okay for bystanders to give compression-only CPR. In fact, compression-only CPR is recommended to improve the rates of bystander CPR. What is really at issue is whether all individuals, including health care providers, should give compression-only CPR to cardiac-arrest victims. The latest randomized data on compression-only CPR demonstrate equivalent survival of cardiac-arrest victims given standard CPR or compression-only CPR. In some animal studies, compression-only CPR is associated with an improved survival. Even if compression-only CPR and compression-with-ventilation CPR are equivalent in resuscitating victims, there would be a strong argument to recommend what is palatable to bystanders; I don’t think there is any doubt that compression-only CPR would be the most palatable.
However, it is likely that at some stage of CPR — say at 5 to 7 minutes — the oxygen reserves of the blood will be exhausted and ventilation is important. It is at about this time that emergency crews would arrive, so they will still need to be trained to ventilate a cardiac-arrest patient.
What do you think we should tell the public?
I think that we should stress that any CPR is better than no CPR, and that compression-only CPR and compression-with-ventilation CPR are quite similar in efficacy. Thus, CPR should be initiated with compression, and if someone is willing to perform ventilation, then by all means proceed with ventilation in addition to compression.
What should we do on the wards as initial treatment until the defibrillator arrives?
In an in-house cardiac arrest, simple compressions should be initiated while the defibrillator is being readied. Ventilation — and especially intubation — should be delayed until defibrillation is performed.
Outside the hospital, are there any situations or circumstances where ventilation should still be considered a priority?
Ventilation is of primary importance in respiratory arrests. These include asthma, aspiration, and drowning. In most witness cases of arrest, it is not difficult clinically to tell the difference between a cardiac and a respiratory arrest. However, in nonwitnessed arrest it is much more difficult to ascertain the cause.
August 27th, 2010
Door-to-Balloon vs. Total Health System Delay: Which Clock Matters Most?
Larry Husten, PHD
Rick Lange brings the latest research on door-to-balloon times and moderates a free-flowing discussion with David Hillis, Harlan Krumholz, and Richard R. Schneider. Given regional variations, how do you think these patients should be treated? Tell us what you know here.
August 26th, 2010
Getting Ready for the ESC
Larry Husten, PHD
The annual meeting of the European Society of Cardiology starts this weekend in Stockholm, and CardioExchange will be there. Associate Editor Anju Nohria will be blogging from the meeting, and I’ll be covering the most important news stories. Here are a few of the most-anticipated, late-breaking clinical trials.
August 25th, 2010
Studies Probe Cardiovascular Risks of Migraines
Larry Husten, PHD
Two new studies in BMJ provide important new details about the elusive relationship between migraines and cardiovascular disease. In the first study, researchers in Iceland analyzed data from 18,725 middle-aged men and women who were followed for a median of 25.9 years. Larus Gudmundsson and colleagues found that people with migraine with aura were at increased risk for all-cause mortality and mortality from cardiovascular disease. People who had migraines without aura or non-migraine headaches had no increase in risk. In the second study, Tobias Kurth and colleagues in France and Boston analyzed data from the Women’s Health Study and found that women with migraines with aura were at elevated risk for hemorrhagic stroke.
In an accompanying editorial, Klaus Berger discusses the clinical implications of the studies. After “the diagnosis of migraine with aura is made the next important question is whether the clinician should inform the patient about the increased risk of future vascular disorders and death.” He notes that “it is not clear whether patients without other risk factors or morbidities would benefit from being told about their potentially increased risk… For many people the information will cause an unwarranted amount of anxiety, although others may use the opportunity to modify their lifestyle and risk factors accordingly.”
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