Meta-analysis: No Need for Thienopyridine Loading Dose in NSTE-ACS Patients

Thienopyridine pretreatment in patients with non–ST-elevation acute coronary syndrome (NSTE-ACS) fails to reduce mortality and leads to an excess of major bleeding, reports a meta-analysis published online October 24, 2014, ahead of print in BMJ.

Results are consistent regardless of whether patients ultimately undergo PCI, researchers say, suggesting that routine pretreatment in NSTE-ACS patients is unjustified.

Pretreatment was not associated with lower risks of all-cause or CV death, either in the overall cohort or those undergoing PCI. Yet both groups showed increases in major bleeding (table 1).

Analysis restricted only to randomized trials showed similar findings but no bleeding increase for PCI patients.

In the overall cohort, pretreatment reduced the secondary endpoint of MACE (OR 0.84; 95% CI 0.72-0.98), but the hint of effect on MI did not reach significance (OR 0.81; 95% CI 0.64-1.03). Stoke and urgent revascularization risks were similar irrespective of pretreatment. In PCI patients, only urgent revascularization was reduced, a benefit driven by the PCI subgroup of the CURE study, in which pretreatment occurred at an average of 10 days before PCI.

An Outdated Strategy

Based on the current findings, “the concept of systematic and immediate pretreatment with P2Y12 antagonists in [NSTE-ACS patients] needs to be reconsidered,” the researchers say, noting that the strategy emerged after the CURE trial, published in 2001.

CURE and its PCI substudy “did not really evaluate pretreatment, a treatment given before catheterization or PCI, but evaluated dual antiplatelet therapy in patients managed medically with a minority undergoing delayed catheterization, often several days after admission,” they write. Looking at more recent data, they add, allows for a better understanding of contemporary practice but increases heterogeneity.

The reduction in MACE seen in the meta-analysis stemmed from the observational studies and the 2 oldest randomized trials, Dr. Montalescot and colleagues point out.

“Routine pretreatment is even more questionable nowadays, when patients reach the catheterization lab within 3-4 hours of admission, a delay that does not allow adequate inhibition with clopidogrel in case of PCI but still exposes all patients, sometimes unnecessarily, to the risk of bleeding for several days after loading,” they comment, adding that the need for pretreatment is lessened by the availability of new P2Y12 antagonists with rapid onset of action.

Source: 
Bellemain-Appaix A, Kerneis M, O’Connor SA, et al. Reappraisal of thienopyridine pretreatment in patients with non-ST elevation acute coronary syndrome: a systematic review and meta-analysis. BMJ. 2014;Epub ahead of print.

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