Registry Data Suggest Net Clinical Benefit From Pretreating STEMI Patients With Clopidogrel
Clopidogrel pretreatment in patients undergoing coronary angiography appears to improve in-hospital outcomes for those with STEMI but not for those with NSTE-ACS, according to a study published online January 30, 2015, ahead of print in the American Journal of Cardiology. The strategy is accompanied by more minor bleeding in the STEMI cohort but achieves a net clinical benefit.
Manuel Almendro-Delia, MD, PhD, of the Hospital Universitario Virgen Macarena (Seville, Spain), and colleagues looked at data from the ARIAM registry on 9,621 ACS patients (mean age 62 years; 76% male) who underwent coronary angiography and received clopidogrel in the coronary care units of 49 hospitals from 2002 through 2012. Most patients had STEMI (63%), and most of the overall cohort received clopidogrel pretreatment (70%), defined as any dose given at the time of first medical contact prior to angiography or PCI. Patients who received clopidogrel less than 6 hours before catheterization were placed in the no-pretreatment group.
In the overall cohort, pretreatment was associated with lower unadjusted rates of in-hospital MACCE (cardiovascular death, reinfarction, or stroke/TIA), reinfarction, and stent thrombosis and a higher rate of stroke/TIA, driven by an increase in hemorrhagic stroke. There were no differences between the groups in rates of cardiovascular death or ischemic stroke.
Total TIMI-defined bleeding was lower in the pretreatment group, although minor bleeding occurred more frequently.
The findings differed between the STEMI and NSTE-ACS cohorts in both unadjusted and adjusted analyses. On multivariate analysis, pretreatment was associated with better clinical outcomes at the cost of more minor bleeding (but not overall or major bleeding) in STEMI patients, with no such differences observed in those with NSTE-ACS (table 1).
Combining ischemic and bleeding endpoints together, there was a significant reduction in net adverse clinical events for those with STEMI (OR 0.56; 95% CI 0.44-0.70) but not for those with NSTE-ACS (OR 0.91; 95% CI 0.64-1.29).
The results were largely confirmed in propensity-matched and inverse probability-weighted analyses, although some of the relationships observed in STEMI patients failed to reach statistical significance.
In subgroup analyses, there was an interaction (P = .048) suggesting that a shorter duration of clopidogrel pretreatment was associated with a lower likelihood of any bleeding.
Findings Question Current Recommendations
Although administration of dual antiplatelet therapy is advised as soon as possible for patients with ACS, the “recommendations do not reflect current clinical practice, in which time delays and [PCI] techniques have been significantly improved, minimizing the potential benefit of pretreatment when PCI is performed early,” according to the authors.
The current results showing no benefit of pretreatment in patients with NSTE-ACS are consistent with prior research looking at use of clopidogrel and newer P2Y12 inhibitors, they say.
“Recent results from the ACCOAST study, in which upstream therapy with prasugrel in NSTE-ACS was not associated with a reduction in the primary endpoint of efficacy but increased bleedings, [have] revived controversy about the benefit of pretreatment prior to PCI,” Dr. Almendro-Delia and colleagues write, noting that a more recent meta-analysis also failed to show a benefit from pretreatment in this setting.
“The potential benefit of routine upstream pretreatment in patients with NSTE-ACS should be reappraised at the present,” they conclude.
As for STEMI, the authors observe, data supporting pretreatment are somewhat weak and based on post hoc analyses. “However,” they add, “based on the pathophysiology of STEMI that entails a higher thrombus burden and given the delay in the onset of action of [P2Y12 inhibitors] observed in the real world, pretreatment with [P2Y12 inhibitors] before [primary PCI is widely used.]”
The fact that clopidogrel pretreatment was associated with net clinical benefit in STEMI patients in this study “supports the guidelines recommendation to use it from the first medical contact,” they write.
Almendro-Delia M, Torres LG, Alcántara ÁG, et al. Prognostic impact of clopidogrel pretreatment in patients with acute coronary syndrome managed invasively. Am J Cardiol. 2015;Epub ahead of print.
- The ARIAM registry is funded by the Government of Andalusia within the Comprehensive Plan for Heart Diseases in Andalusia (PICA).
- Dr. Almendro-Delia reports no relevant conflicts of interest.