Voiceover: The central attraction in Orlando, Florida, was cardiology, and the major theme was prevention at the 2009 annual scientific session of the American College of Cardiology and i2 Summit. An estimated 15 thousand professionals from around the world learned about the latest developments in clinical cardiology, interventional procedures, drugs, and devices.
SEGMENT 1: JUPITER: Rosuvastatin for VTE, Primary Prevention
Voiceover: All eyes once again turned toward JUPITER, a clinical trial looking at the potential benefits of statins for primary prevention.
In the first of 2 studies, both funded by rosuvastatin maker AstraZeneca, JUPITER investigators reported that rosuvastatin was associated with a significant reduction in venous thromboembolic events in healthy people. Dr. Robert Glynn presented the findings.
Glynn: "Rosuvastatin was associated with a significant 43% reduction in risk with no increase in bleeding. The benefit was comparable in magnitude and independent of the effect seen on arterial events, and the bottom line is that widening the treatment target to include prevention of VTE and death, in addition to arterial thrombosis, increases the estimated benefits of statin use.
Voiceover: ACC 2009 program chair Dr. Aaron Kugelmass calls the JUPITER VTE findings "provocative."
Kugelmass: "I think there's a lot of promise and I think it begs a lot of questions — I think it begs further studies. These aren't patients who had venous thromboembolism, these are patients who were enrolled for completely different reasons, yet they seemed to identify something which had been looked at previously and somewhat identified previously in registries, which is that people who are on statins seem to have lower levels of venous events, and so in this very large clinical trial, they were able to test that."
Voiceover: A separate analysis of JUPITER data showed that lowering both low-density lipoprotein and high-sensitivity C-reactive protein, or CRP, results in higher event-free survival than either intervention alone. Dr. Paul Ridker presented the findings.
Ridker: "For patients with raised LDL cholesterol or raised hs-CRP, our initial intervention should remain dietary restriction, exercise and smoking cessation. However, as demonstrated in these prospective randomized controlled clinical trial data, for those initiating drug therapy at primary prevention, reductions in both LDL cholesterol and hs-CRP are indicators of the success of treatment with statin therapy, and these data are highly consistent with prior studies in multiple other acute coronary syndrome and chronic coronary artery disease settings where statins were given for treatment."
Kugelmass: "I think this is promising. I think this may be a little bit more in the beneficial range than the venous thromboembolism study, but I still think it begs the issue of whether we really are ready to start treating to target high-sensitivity CRPs."
SEGMENT 2: Polypill
Voiceover: A so-called "polypill" combining aspirin, a statin and 3 antihypertensive agents lowered the risk for future cardiac events in average, healthy adults. But the degree of cholesterol reduction was lower than with a statin alone, and reductions in blood pressure were lower than predicted with the antihypertensives included in the pill. Dr. Salim Yusuf explained why study on the polypill would likely continue.
Yusuf: "It's well tolerated, and in theory it could reduce cardiovascular disease in healthy, average people over the age of 50 by half. This needs to be proven in future studies."
Voiceover: The polypill has the potential to address the growing problem of cardiovascular disease in both industrialized nations and in the developing world, according to Dr. William T. Abraham.
Abraham: "The results of this study demonstrate significant improvement in all of the surrogates or biomarkers that have in the past translated into improved clinical outcomes. So for example, cholesterol levels went down, blood pressure fell, other markers of cardiovascular risk were improved, and if one translates that into clinical outcomes we would expect about a 50% reduction in cardiovascular endpoints."
Voiceover: But ACC 2009 scientific program co-chair Dr. Hani Sabbah cautioned that larger studies of the polypill will be needed to prove its safety and efficacy.
Sabbah: "I just want to remind everyone that while I do share the enthusiasm of Dr. Yusuf, that this trial was only 2000 patients divided into 9 groups, small numbers, it's very encouraging, but the trials that will really eventually be pivotal in order to determine what patient population and for that matter whether anybody that's normal or otherwise would be treated with this pill will be 20 to 30 thousand patients, will be multinational and will cost as much as 100 million dollars to do.
Yusuf: [off camera] "None of that — it's only if you do it in the United States."
Sabbah: "In the United States."
SEGMENT 3: ARMYDA RECAPTURE and NAPLES II
Voiceover: In other promising news for statins, 2 Italian studies pointed to the benefits of pretreating with statins for patients scheduled to undergo percutaneous corornary intervention, or PCI. Dr. Germano DiSciascio explained the investigators' thinking.
DiSciascio: "We wanted to test the hypothesis that a reload, an acute reload of a bolus of statin in those patients on chronic therapy would have the same cardioprotective effect during PCI."
Voiceover: ARMYDA-RECAPTURE investigators showed that atorvastatin 80 milligrams given to statin-treated patients 12 hours before PCI, followed by 40 milligrams just before the procedure, reduced the risk for major adverse coronary events, specifically, the risk for myocardial infarction at 30 days.
Voiceover: In the NAPLES II study, investigators showed that atorvastatin 80 mg loaded 24 hours before PCI in statin-naive patients significantly reduced the incidence of periprocedural MI. Dr. Carlo Briguori described their findings.
Briguori: "What we found is that the increase of CK-MB more than 3 times upper limit of normal was 9.5% in atorvastatin group as compared to the 15.8% in the control group, and it was statistically significant. We got a 44% relative risk reduction with a high loading dose of atorvastatin."
SEGMENT 4: AURORA Trial
Voiceover: One trial that failed to show a benefit for statin therapy was the 4-year AURORA study. Investigators reported that although statins protect patients with either normal kidney function or mild renal disease from cardiovascular events, the same protection does not extend to patients in end-stage renal disease who are on hemodialysis. Dr. Bengt Fellstrom discussed the findings.
Fellstrom: "So the question is, how do we interpret the results? Well, I believe very strongly that the vascular disease that these patients are suffering from is so different, with a lot of calcification that may not be treatable with statins. "
SEGMENT 5: PROTECT AF
Voiceover: In patients with nonvalvular atrial fibrillation, device closure of the left atrial appendage may provide an alternative to warfarin for prevention of stroke, according to Dr. David Holmes and investigators from the Mayo Clinic in Rochester, Minnesota.
Holmes: "How often does that happen? How often can we in fact tell our patients that they can stop their warfarin? As you can see, at 45 days, 87% of the patients can get off warfarin. At 12 months, 93% of the patients in the device limb can get off of the warfarin, permanently."
Voiceover: Dr. Kugelmass says that if it's proven to be safe, device closure of the left atrial appendange may help solve the problem of achieving appropriate INR targets with warfarin.
Kugelmass: "It is obviously a landmark trial: there was a significant reduction in hemorrhagic strokes in the patient population that got the Watchman device. Clearly what we've learned from this trial is that there's obviously a learning curve; procedurally associated complications, particularly pericardial effusion, dropped over time. Where exactly this device will fall out in our armamentarium in the treatment of atrial fibrillation I don't know. I wouldn't be surprised if it first isn't used in a population that wasn't studied, which is a group in whom they are at very high risk for thromboembolic stroke, but they can't tolerate Coumadin."
SEGMENT 6: RECALL Trial
Voiceover: In a five-year analysis of the RECALL study, coronary artery calcium scoring can help predict who may have a myocardial infarction or cardiac death among those patients at intermediate risk for coronary events according to traditional risk-factor assessments. Dr. Raimund Erbel presented the findings.
Erbel: "Coronary calcium scoring is a strong predictor of acute coronary events, improves risk prediction beyond traditional risk factors, may be valid more in men than women, can be used for reclassification of individuals at ATP III risk, is not recommended in ATP III low-risk subjects, but may improve risk predictions in ATP III high-risk individuals when low calcium values are found."
Voiceover: Dr. Michael Davidson from the University of Chicago Pritzker School of Medicine agrees that coronary artery calcification can be a strong predictor of risk, but he cautions that testing could lead to overtreatment.
Davidson: "I think one of the things all of us always worry about with these coronary calcium testing is that it doesn't lead to further inappropriate testing, like stress testing, nuclear testing, angiography and then putting in stents. And that happens, that's not an uncommon scenario where someone is asymptomatic, gets a coronary calcium scan, has an abnormal stress and then gets a procedure done. So to me that's what I worry about. I think we need to re-emphasize that these tests are really for predictive purposes, and the greatest benefit that we can give to them is risk-factor changes, especially statins, lowering their LDL, lowering their other risk factors to stop the progression of atherosclerosis."
SEGMENT 7: FIX HF-5, Cardiac Contractility Modulation
Voiceover: Dr. William Abraham presented data on a device aimed at improving ventricular contractile function and increasing heart-pumping efficiency in patients with late-stage heart failure. The OPTIMIZER 3 implantable device delivers pulses to the right side of the heart during the cardiac cycle refractory phase, resulting in increased contractile force at a reduced work level and myocardial reverse remodeling.
Abraham: "This is an electrical form of therapy for the heart, but unlike a pacemaker it is not intended to induce a heartbeat or capture the heart, but rather the electricity is delivered or applied during the absolute refractory period of the cardiac cycle, and as shown, it increases the force of muscle contraction."
Voiceover: The clinical trial of the cardiac contractility modulation, or CCM, device did not meet its primary endpoint of change in anaerobic threshold at 6 months compared with optimal medical therapy alone, an unconventional endpoint used at the recommendation of the FDA. In addition, Dr. Clyde W. Yancey said there is some concern about the safety of the technique.
Yancey: "I would agree with Dr. Abraham that this does set the stage for future investigation but does not yet reach the bar for something we can move forward with in the clinical space. It is quite provocative, but by the same token, there is something about CCM that bespeaks of an inotropic effect. So we have to continue to be very thoughtful and circumspect and follow up on larger populations for a longer period of time to understand if there is a unique safety signal that might emerge."
Voiceover: However, the investigators did see significant benefits for the device in patients with severely weakened hearts.
Abraham: "We did prespecify a hypothesis-generating subgroup analysis and identified a group of patients with ejection fractions of at least 25% and a New York Heart Association class III that benefited remarkably from cardiac contractility modulation, and that subgroup of patients will comprise the focus of future studies."
SEGMENT 8: STICH Trial
Voiceover: Another trial that failed to meet its primary endpoint was the STICH trial, examining the strategy of surgical reshaping of the left ventricle to improve cardiac performance in patients with heart failure secondary to coronary artery disease. Surgical remodeling added to coronary artery bypass graft, or CABG surgery, plus evidence-based medical therapy, was not better than surgery alone at reducing symptoms, deaths, or cardiac hospitalizations, and did not improve patients' exercise tolerance. Dr. Robert Jones described the study's clinical implications.
Jones: "We believe that the STICH trial definitively shows that adding SVR to CABG provides no clinical benefit beyond that of CABG alone in this study population. Both operative strategies provided similar short- and long-term relief of angina in heart failure and improvement in 6-minute walk test performance. SVR added to CABG decreased LV size significantly more than CABG alone, and confirms the anatomic change recorded in prior ASV studies."
Voiceover: The STICH trial results are important and will influence the management of patients with heart failure in clinical practice, says Dr. Abraham.
Abraham: "Now we've only seen part of the results of the STICH trial, because there really are 2 important questions being answered with the STICH trial. One: Is surgical revascularization with or without surgical ventricular reconstruction better than medical therapy alone. We don't yet have the answer to that question. That'll come in a couple of years. But the question that was answered today was: in patients who do get surgery, does surgical ventricular restoration or reconstruction add any incremental on top of coronary artery bypass grafting? To make a long story short, the answer is no."
SEGMENT 9: SYNTAX Trial
Voiceover: Finally, a new analysis of costs and quality-of-life outcomes in the SYNTAX trial suggests that CABG-treated patients have more angina relief at 1 year, but percutaneous coronary interventions are more cost-effective, at least in low-risk and moderate-risk patients. The study was funded by stent maker Boston Scientific. Dr. David Cohen discussed the findings.
Cohen: "Among patients undergoing revascularization for left vein or three-vessel coronary disease, angina relief was slightly better with bypass surgery than drug-eluting stents at 6 and 12 months. The magnitude of benefit was smaller than in previous comparisons, however, and below the threshold that most patients would find clinically meaningful. All of the other quality-of-life endpoints favored PCI at 1 month although these differences were transient and largely resolved by 6 months. On the cost-effective side, despite substantially higher procedural costs for PCI, initial treatment costs were about $6000 per patient higher with bypass surgery, mainly due to differences in length of stay, complications, and physician costs."
Voiceover: Dr. Aaron Kugelmass says that SYNTAX analysis may help physicians weigh the pros and cons of drug-eluting stents and CABG in patients with complex coronary artery disease.
Kugelmass: "From the economic perspective — and some of this was in fact driven by the quality of life — but from the economic perspective, those patients with low SYNTAX scores used fewer stents, were more amenable to angioplasty from a clinical perspective, were the most cost-effective when it came to the use of angioplasty or PCI. The patients who in the main trial were better served by bypass surgery clinically were also better served societally with less of a cost burden with bypass surgery, so it was more cost-effective to go back to bypass surgery in those high SYNTAX-score patients. So it was very nice that the clinical answer and the economic answer run in parallel."
Voiceover: For full reports on these and other studies from the ACC's 2009 Scientific Sessions, visit Medscape Cardiology at cardiology.medscape.com.
Medscape Medical News © 2009 Medscape, LLC
Cite this: Video Highlights From the American College of Cardiology (ACC) 58th Annual Scientific Session - Medscape - Apr 14, 2009.