A record-setting number of attendees along with hundreds of groundbreaking research presentations again confirmed that TCT is the premier global forum of evidence-based medicine and scientific studies in the field of interventional cardiology. TCT 2009, held for the first time in San Francisco, September 21-25, attracted a record number of nearly 12,000 participants from 116 countries.
The meeting was the result of tens of thousands of hours of planning by Course Directors Martin B. Leon, MD, and Gregg W. Stone, MD, as well as by other CRF faculty and staff. This global gathering featured a wide range of new data from more than 30 late breaking clinical trials and first report investigations whose significant findings will enable physicians to incorporate the most advanced techniques for treating patients with heart disease into their everyday practices.
"TCT once again demonstrated strong leadership in presenting the scientific advances that will directly lead to improvements in patient care," said William A. Himmelsbach, MPH, FACHE, President and Chief Executive Officer of CRF. "In a follow-up survey, nearly all attendees agreed that attending increased their knowledge to improve their practice."
Many of the new findings released at TCT will lead to new directions in treating heart disease.
Current and Next-Generation Stents
SPIRIT IV and COMPARE
The results of the SPIRIT IV and COMPARE clinical trials demonstrated improved safety and effectiveness with the everolimus-eluting Xience V stent vs. the paclitaxel-eluting Taxus stent in patients with heart disease.
Dr. Stone, of Columbia University Medical Center in New York, NY, presented one-year results from SPIRIT IV showing that Xience V significantly lowered the incidence of heart attacks, heart-related deaths, and repeat procedures aimed at the site of the original coronary artery blockage compared with Taxus. Dr. Stone said there also were significant reductions in major heart-related complications for patients who received a Xience V stent. SPIRIT IV also included a large number of patients with diabetes, but results in these patients were equivalent between the two stents.
COMPARE, SPIRIT IV Similar
Results of the COMPARE trial, presented after SPIRIT IV, also demonstrated that the Xience V stent significantly reduced major heart-related complications compared with the Taxus stent, according to presenter Peter C. Smits, MD, PhD, of Maasstad Ziekenhuis in Rotterdam, The Netherlands. Superiority of Xience V was reached mainly due to fewer repeat artery-clearing procedures and fewer cases of dangerous blood clots forming inside the stent within 30 days of the procedure.
Data presented from the COMPARE trial showed that Xience V bested Taxus in preventing more deaths, nonfatal heart attacks and repeat procedures at one year. Xience V also lowered major heart-related complications.
"It was remarkable to me how similar these two trials were," Dr. Stone said of SPIRIT IV and COMPARE. "The significant take-home message is that there's a difference between clinical trials we do for regulatory purposes and clinical trials we do to find the truth . . . . You have to do much larger trials in real world populations to really see the differences between the devices and that’s a trend that needs to continue."
ISAR-DESIRE 2
The ISAR-DESIRE 2 trial randomly assigned 450 patients with coronary artery renarrowing after initial sirolimus-eluting stent implantation to additional sirolimus eluting stents or paclitaxel-eluting stents. The performance of the two drug-eluting stents was equivalent across the board in terms of loss of open vessel area, artery renarrowing, repeat procedures to clear the artery, death, heart attack, major heart-related complications and dangerous blood clots that form inside the stent.
LEADERS
For the LEADERS trial, investigators compared angioplasty using a standard stent that releases the drug sirolimus from a conventional durable coating versus a ‘third-generation’ stent that releases a sirolimus analogue called biolimus from a coating that is absorbed into the body over six to nine months. In a broad-based population over two years, the new stent proved just as effective at preventing major complications as the older stent (13.0% vs. 15.4%).
The potential benefit of an absorbable coating is that it may be less likely to provoke formation of a dangerous clot in the stent, and in a hopeful sign, no such clots occurred even after patients stopped taking blood thinning medication designed to prevent them. If there is a safety advantage of the new stent, however, it may require more time to emerge, experts said.
SIRTAX-LATE
The SIRTAX-LATE trial underlined the importance of long-term follow-up in assessing the relative benefits of different types of drug-eluting stents. In 2005, researchers reported that after one year patients treated with sirolimus-eluting stents had lower rates of major complications compared with those who received paclitaxel-eluting stents and, in particular, less need for vessel reopening. But when the investigators looked again five years after treatment, patients treated with sirolimus stents had caught up with patients treated with paclitaxel stents in terms of complications. Similarly, there was no longer any difference between the two groups in renarrowing of treated vessels.
Old Drugs and New
CURRENT-PCI OASIS 7
Doubling the dose of the blood-thinning drug clopidogrel during angioplasty in patients with severe heart attacks appears beneficial, according to results from the CURRENT-PCI OASIS 7 trial. Compared with a standard clopidogrel dose of 300 milligrams (mg) followed by 75 mg per day, the higher dose (600 mg initially then 150 mg daily) reduced the rates of both dangerous blood clots that can form inside the stents and repeat heart attacks within the first month after treatment with either drug-eluting or bare-metal stents. There was no significant difference between the two doses in terms of major or severe bleeding.
COGENT
Despite earlier evidence to the contrary, the COGENT trial has found no adverse effects from combining clopidogrel and the proton pump inhibitor (PPI) omeprazole. The study, which included over 3,600 patients with heart attack or unstable angina who underwent angioplasty and received drug treatment with aspirin and clopidogrel, showed that using a PPI might also prevent stomach problems.
The results of COGENT are preliminary, because researchers are still evaluating some patients. The trial was halted early because the sponsor, Cogentus Pharmaceuticals, declared bankruptcy.
HORIZONS AMI
Earlier one-year results from the CRF-sponsored HORIZONS AMI trial showed that patients with severe heart attacks who undergo angioplasty fare better with the anticoagulant drug bivalirudin instead of heparin plus a glycoprotein IIb/IIIa inhibitor. In addition, they have better outcomes with Taxus drug-eluting stents vs. Express bare-metal stents.
The new two-year data presented at TCT 2009 indicate that this pattern is maintained: patients continue to do better with bivalirudin and Taxus stents.
At 2 years, bivalirudin significantly reduced major bleeding unrelated to bypass surgery by 36%, repeat heart attacks by 25%, heart-related deaths by 41%, and overall deaths by 25%. The patients given bivalirudin vs. heparin plus glycoprotein IIb/IIIa inhibitors had comparable rates of blood clots that can form inside the stents, repeat procedures to open the artery, and stroke. In the stent analysis, Taxus reduced the need for repeat angioplasty.
Looking at the four possible treatment combinations, rates of death at two years were lowest in patients assigned to bivalirudin plus Taxus (3.8%) and highest in those randomized to heparin plus a glycoprotein IIb/IIIa inhibitor and an Express stent (6.1%).
TRITON-TIMI 38 Economic Substudy
The newly approved antiplatelet drug prasugrel is slightly more cost effective than clopidogrel in patients receiving angioplasty for heart attack or unstable angina, according to the results of an economic analysis of the TRITON-TIMI 38 trial. The substudy compared the total medical costs among 6,705 patients receiving one of the two drugs.
Costs of the initial hospital stay were similar between patients given either of the two drugs ($19,752 with clopidogrel vs. $19,740 with prasugrel), and rehospitalization costs were slightly higher with clopidogrel ($4,982 vs. $4,465). However, the cost of buying the drug prasugrel was higher at $1,862 vs. $1,554 for clopidogrel.
Added together, the overall cost savings favored prasugrel. Those savings were greater over the first 30 days of the trial compared with later on in the study.
PLATO Invasive
Christopher P. Cannon, MD, of Brigham and Women’s Hospital in Boston, MA, presented results from a substudy of the PLATO trial. The substudy, known as PLATO Invasive, followed over 13,000 patients with heart attack or unstable angina for 12 months after receiving an artery-clearing procedure and being randomly assigned to one of two blood-thinning drugs: clopidogrel or the new agent ticagrelor.
By the end of the study period, 11% of the clopidogrel patients versus 9% of the ticagrelor patients had died of cardiovascular causes, had a heart attack or had a stroke. This translated to a 16% risk reduction in favor of ticagrelor. Patients on ticagrelor also had a decrease in overall death rates. No differences were reported between the two medications in terms of bleeding.
Patients with coronary artery stents who were assigned to ticagrelor also had lower rates of definite blood clots that can form inside the stents. However, Dr. Cannon noted that patients on ticagrelor were more likely to report shortness of breath as a side effect compared with patients on clopidogrel.
It’s in the Genes
CHARISMA
Deepak L. Bhatt, MD, MPH, of the VA Boston Healthcare System in Boston, MA, presented data from the CHARISMA trial, which sought to determine the effect of variations in a gene called CYP2C19 on cardiovascular death, heart attack or stroke in patients randomly assigned to the bloodthinning drug clopidogrel or a dummy medicine. A total of 4,862 patients with stable cardiovascular disease consented to genetic testing.
The study found no relationship between a previously identified genetic variant known as CYP2C19*2, which affects clopidogrel response, and cardiovascular outcomes. But patients who carried two copies of that genetic variant, expressed as *2/*2, did have an increased risk of cardiovascular death, heart attack, or stroke. However, the increased risk was present whether the patients took clopidogrel or not.
"Though it is not a significant elevation, the findings suggest that this genotype might be conferring excess risk even in placebo patients," Dr. Bhatt said.
Carrying the genetic variant did not appear to increase the risk of bleeding, however. "Further prospective study is needed to determine the clinical relevance of CYP2C19 polymorphisms on [heart-related events] and bleeding—and the appropriate clinical action to take—before routine testing can be recommended," Dr. Bhatt concluded.
New Twists on Catheter-Based Procedures
FAME
William F. Fearon, MD, of Stanford University Medical Center in Stanford, CA, presented two-year results from the FAME trial, which included 1,000 patients with multivessel heart disease who underwent angioplasty with stenting guided by angiography, a type of X-ray of the heart. Half of the patients were also randomly assigned to an add-on technique to help guide angioplasty that measures fractional flow reserve, or the extent to which oxygen-rich blood is prevented from reaching the heart by the artery blockage.
The total number of heart-related complications was lower in the group of patients who had the add-on technique compared with angiography alone. This translated into lower rates of heart attack, death and other complications.
Dr. Fearon said the improvements seen with the add-on technique were particularly important. "There continues to be a significant decrease in death and [heart attack] favoring the fractional flow reserve-guided approach," he said. "There is also a strong trend towards a lower rate of death, [heart attack] or the need for repeat [artery opening procedures] in the fractional flow reserve-guided arm."
SYMPLICITY I
In the SYMPLICITY I trial, researchers reported that a novel catheter-based treatment reduced hypertension in people whose high blood pressure was uncontrolled despite taking multiple antihypertensive medications. Australian investigators used the heat generated by radio waves emitted from the tip of a catheter to destroy the so-called sympathetic nerves in both kidneys. These nerves help regulate blood pressure and may be dysfunctional in people with treatment-resistant hypertension. After the nerve 'zapping,' 89% of treated patients saw their blood pressure drop dramatically.
At 12 months, the average decline in systolic blood pressure (the higher number, measured when the heart contracts) was 27 points and the average decrease in diastolic pressure (the lower number, measured when the heart is at rest) was 13 points. There was no evidence that the procedure harmed blood vessels or kidney function. How long the benefit will last is unknown. The researchers are now performing a controlled trial to be sure the effect is real.
Zeroing in on Vulnerable Plaque
PROSPECT
Dr. Stone also presented results from PROSPECT, the first prospective, natural history study of hardened arteries using several different types of imaging tests.
The study looked at 700 patients with heart attack or unstable angina in order to examine whether nonculprit artery blockages, or those that did not specifically cause the heart attack or angina, affect a patient’s chance of having future complications even if they look mild on a standard angiogram. For PROSPECT, Dr. Stone and colleagues used intravascular ultrasound and virtual histology to take a closer look at these blockages. What they found suggests that non-culprit and culprit lesions contribute equally to future problems and that non-culprit lesions, on close inspection, have more hardened plaque in them than angiograms suggest they do.
The non-culprit lesions were not linked to any cases of heart-related death or arrest but were most commonly associated with increasing chest pain (8.5%), unstable chest pain (3.3%), and heart attack (1.0%).
"I’m struck by the fact that although we’ve been taught that non-culprit lesions are usually angiographically not severe, Gregg did a great job at showing that many of these lesions are severe. We’re just not very good at assessing them angiographically," commented Cindy L. Grines, MD, of William Beaumont Hospital in Royal Oak, MI.
