Registry: Newer P2Y12 Inhibitors Reduce Stent Thrombosis, Mortality Over Clopidogrel
CHICAGO, IL—Compared with clopidogrel treatment, prasugrel and—even more so—ticagrelor reduce the risk of stent thrombosis and mortality over 2 years in patients with acute coronary syndromes (ACS), according to results of a prospective registry study presented on November 17, 2014, at the American Heart Association Scientific Sessions.
Researchers led by Javaid Iqbal, MBBS, MRCP, PhD, of the University of Sheffield (Sheffield, England), looked at all ACS patients (n = 6,742) at a single center receiving coronary angiography between January 2009 and February 2013. Most patients (64%) presented with NSTE-ACS, while the remainder presented with STEMI. P2Y12 inhibitor distribution was:
- Clopidogrel (n = 4,525)
- Prasugrel (Effient, Eli Lilly/Daichii Sankyo; n = 1,007)
- Ticagrelor (Brilinta, AstraZeneca; n = 1,210)
Only 1.2% of NSTE-ACS patients received prasugrel, compared with 39.4% of STEMI patients. Mean age was 64 years, 70% were men, and 14% had diabetes.
Both definite and definite or probable stent thrombosis were lowest among ticagrelor-treated patients at 2 years (table 1).
This result for definite or probable stent thrombosis was confirmed after adjustment for confounders (log-rank P = .037).
Multivariable analysis demonstrated several independent predictors of stent thrombosis including age (per year increase; HR 1.02), TIA/stroke (HR 1.87), STEMI (HR 1.94), creatinine > 200 µmol/L (HR 2.49), and cardiogenic shock (HR 5.44). Compared with clopidogrel, ticagrelor reduced the risk of stent thrombosis by about half (P = .01) and prasugrel by 13% (P = .45).
Both prasugrel and ticagrelor combined reduced the risk of death over 2 years compared with clopidogrel (log-rank P = .012). A similar pattern was seen when each drug was analyzed separately (log-rank P = .042), but this relationship disappeared after adjustment (log-rank P = .356).
Among the limitations of the study, Dr. Iqbal said, were its observational nature and lack of both bleeding and DAPT data.
Prasugrel, Ticagrelor Both Give ‘Efficient’ Loading Doses
He explained that the choice of drug largely reflected European guidelines at the time, and the changes in guidelines over the study period are part of a “natural evolution.”
In response to a question about changing stent technology in line with advancing pharmacology, Dr. Iqbal observed that all patients in this study received second-generation DES and none received bivalirudin—rather they were treated with heparins plus bailout GPIs. But the study collected limited data on postdilatation, he added.
Contributing to the discussion, a study co-author who was in the audience reported that as policy, all ticagrelor-treated NSTE-ACS patients were pretreated before angiography. “So all patients coming to cath lab… would have had a very good level of P2Y12 inhibition at the time they proceeded to PCI,” he said. “Whereas with prasugrel—reflecting the guidelines—most patients would have been pretreated with clopidogrel, and then if they were diabetic and proceeded to PCI, they would switch to prasugrel at the physician’s discretion.
“This likely was the reason for higher stent thrombosis in the prasugrel-treated cohort rather than the efficiency of the dose,” he continued. “Because we know that prasugrel gives a very effective level of P2Y12 inhibition although you do get a bit more variability in the maintenance period.”
Source:Iqbal J. Lower mortality and stent thrombosis rates associated with introduction of potent P2Y12 inhibitors in patients with acute coronary syndromes. Presented at: American Heart Association Scientific Sessions; November 17, 2014; Chicago, IL.
- PLATO Substudy: Ticagrelor Reduces Mortality in NSTE-ACS Patients Regardless of Revascularization
- PLATO Subanalysis: Ticagrelor Safe, Effective in Primary PCI
- Prasugrel, Ticagrelor Reduced Incidence of Stent Thrombosis
- Dr. Iqbal reports no relevant conflicts of interest.