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Genotype No Game Changer in PLATO
The superiority of ticagrelor (Brilinta) over clopidogrel (Plavix) in the PLATO study was not driven by so-called poor metabolizers of clopidogrel, a sub-analysis of the PLATO genetic sub-study found.
In the 18,000-plus patient PLATO study, ticagrelor given twice a day to patients with acute coronary syndrome was found to reduce the rate of strokes, heart attacks, and cardiovascular deaths compared with clopidogrel.
But some have suggested the improvement had more to do with poor metabolizers of clopidogrel, those with loss of function alleles, than with the efficacy of ticagrelor itself.
So Lars Wallentin, MD, and colleagues from the University of Uppsala in Sweden analyzed DNA samples from 10,000 patients in the study and excluded those with loss of function alleles.
There still was a significant reduction in the primary endpoint per year for those on ticagrelor (8.8% versus 10.4%, HR 0.85, 95% CI 0.74 to 0.96, P=0.01), and major bleeding rates were similar between the two drugs, researchers reported at the recent American College of Cardiology (ACC) meeting.
Vytorin Trial Given the Go-Ahead
The IMPROVE-IT trial, which will compare the efficacy of ezetimibe/simvastatin (Vytorin) with simvastatin alone to reduce cardiovascular events, has been given the green light to continue.
The decision was made based on the Data Safety Monitoring Board's pre-specified interim efficacy analysis, according to a statement from Merck, the drug's maker.
IMPROVE-IT involves more than 18,000 patients and is meant to establish ezetimibe/simvastatin as a combination drug that can be substituted for treatment by statins alone.
Although the drug does well for Merck, it has been hampered by negative results and other controversies.
In 2008, results of the ENHANCE trial showed that the combo drug did not reduce carotid intima-media thickness compared with simvastatin alone in patients with familial hypercholesterolemia, even though the drug significantly reduced low-density lipoprotein (LDL) cholesterol.
At the time, Merck was suspected of trying to delay or even alter the results.
Also in 2008, the SEAS trial suggested an increase in cancer in patients taking the combination drug. This was later proved to be a chance finding via analysis of interim IMPROVE-IT results, but even that announcement was met with controversy as critics complained that early release of IMPROVE-IT trial results was forced upon investigators by Merck.
In January 2012, the FDA approved new labeling for Vytorin to include its beneficial effect in those with kidney disease, but the agency refused to approve a new indication for the drug.
Intra-Aortic Balloon Pump Works in PCI
Long-term mortality data support the elective use of intra-aortic balloon pump in high-risk percutaneous coronary intervention (PCI) patients, according to longer-term data from the randomized BCIS-1 trial.
After five years of follow-up of 301 high-risk patients, elective intra-aortic balloon pump (IABP) use during PCI was associated with a 34% relative risk reduction in all-cause mortality, a significantly lower rate than in patients who had no planned IABP insertion prior to PCI (P=0.039), reported Divaka Perera, MD, of St. Thomas' Hospital in London.
Although initial 6-month results published in 2009 found a negative result for the primary and secondary outcomes, the numerical difference in mortality drove the follow-up study, Perera told attendees at the 2012 ACC meeting.
According to a time-varying analysis, after 1 year, the hazard ratios stayed the same for all events. "As more events occurred, the confidence intervals became narrower and narrower, which suggests a real effect that was present from the beginning," Perera told 鶹ý.
The Balloon Pump-Assisted Coronary Intervention Study (BCIS-1) involved 17 centers in the U.K. Perera said the use of IABP should be considered for certain high-risk patients, such as those with hemodynamic challenges and those with cardiogenic shock.
"We need to do more analysis to determine who these patients are up front. Groups who seem to deteriorate during PCI are those with very poor left ventricular function and lots of coronary artery disease," Perera said.
"Another identifying characteristic is the risk of treating the lesion itself, which has not been addressed in any trial, but when assessed appropriately, could warrant the use of an intra-aortic balloon pump. We should have our staff prepared and use the standby approach," he told 鶹ý.
Stent for Diabetics Holds True at 2 Years
Two-year data from the RESOLUTE US trial bolster the 1-year results, showing sustained safety and efficacy for the zotarolimus-eluting Resolute stent (Medtronic) in coronary arteries.
Overall, the target lesion failure rate was 7.3%, broken down as 1.5% for cardiac death, 4.3% for target lesion revascularization, 1.9% for target vessel myocardial infarction, and 0.2% definite/probable stent thrombosis, Laura Mauri, MD, from Brigham and Women's Hospital reported at the 2012 ACC meeting.
The Resolute Integrity drug-eluting stent (DES) was recently given the distinction of being the first DES to be approved specifically for diabetic patients.
In RESOLUTE US, which used the first-generation Resolute DES rather than the Integrity DES, the findings for diabetics versus non-diabetics were the following:
- Target lesion failure -- 8.9% versus 6.4%
- Cardiac death -- 2.1% versus 1.1%
- Target vessel MI -- 1.6% versus 2.1%
- Target lesion revascularization -- 6.7% versus 3.5%
- Definite/probably stent thrombosis -- 0.0% versus 0.3%
Compared with an FDA matched cohort rate of 14.5% for target vessel failure (TVF), the analysis of pooled diabetes data from all RESOLUTE studies showed a 7.8% TVF rate at 1 year, reported Alan C. Yeung, MD, from Stanford University in Stanford, Calif., and colleagues at the ACC meeting. At 2 years, the rate was 9.5% versus 7.1% for non-diabetics.
CoreValve Improves Function in High-Risk TAVI
At 6 months, the ADVANCE real-world registry showed good safety and efficacy of the CoreValve (Medtronic) prosthesis in high-risk patients who underwent transcatheter aortic valve implantation (TAVI).
Assessment of nearly 1,000 patients showed that the 80% of patients with NYHA class III and IV at baseline had dropped to below 15% at 1 and 6 months, Axel Linke, MD, from University of Leipzig Heart Center in Germany, reported at the 2012 ACC meeting.
In addition, Kaplan-Meier estimates of freedom from all-cause and cardiovascular survival at 1 month were 96% for both, which had dropped to 87% and 91%, respectively, at 6 months. And 96% of patients were free from stroke at 6 months compared with 97% at 30 days.
A higher Euroscore predicted increased all-cause and cardiovascular mortality.
The ADVANCE study was conducted in 44 centers from 12 countries, not including the U.S., from March 2010 to July 2011. Operators had to have performed at least 40 procedures before enrollment into the trial. The average age of patients was 81.
Along with the Canadian Multicenter Experience, which found the Sapien aortic valve to be durable out to 4 years, the ADVANCE study has the potential to be a game-changer, Gordon Tomaselli, MD, of Johns Hopkins in Baltimore, told 鶹ý in an exclusive video interview.
From the American Heart Association: