Originally published by 2 Minute Medicine® (view original article). Reused on AccessMedicine with permission.

1. Pretreatment with oral P2Y12 inhibitors in patients with non-ST elevation acute coronary syndromes demonstrated no reduction in major cardiovascular events, yet an increase in bleeding risk, at 30 days compared to patients who did not receive pretreatment.

Evidence Rating Level: 1 (Excellent)

Study Rundown:

Oral P2Y12 inhibitors are commonly used in patients with non-ST elevation acute coronary syndromes (NSTEACS) while awaiting percutaneous coronary intervention (PCI). However, it is unclear whether pretreatment (administration of medication prior to angiography) with PGY12 inhibitors improves cardiovascular outcomes. This systematic review and meta-analysis investigated the association of oral P2Y12 inhibitor pretreatment with cardiovascular and bleeding outcomes in patients with NSTEACS. Studies published before March 20, 2021, were included if: they were a randomized clinical trial (RCT), enrolled patients with NSTEACS, and compared pretreatment versus no pretreatment with oral P2Y12 inhibitors. The primary outcomes were major adverse cardiovascular events (MACEs) and major bleeding events at 30 days where possible. There were seven RCTs included with 13 226 patients. At the primary endpoint, there were no differences in MACEs between patients who received oral P2Y12 inhibitor pretreatment and those that did not (odds ratio [OR]: 0.95 [95% CI: 0.78-1.15]; I2= 28%). The lack of significant difference was also observed for 30-day myocardial infarction risk and 30-day cardiovascular death risk. Furthermore, major bleeding risk at 30 days was higher among those who received P2Y12 inhibitor pretreatment compared to patients who did not (OR: 1.51 [95% CI: 1.16-1.97]; I2= 41%). On average, one major bleeding event with pretreatment occurred in every 63 patients. Notably, there was an exception in patients who received clopidogrel (a type of oral P2Y12 inhibitor). Pretreatment with clopidogrel decreased the risk of MACEs compared to no pretreatment (OR: 0.77 [95% CI: 0.62-0.97]). Overall, despite the widespread use of P2Y12 inhibitors as pretreatment for patients with NSTEACS, their application is not supported by this systematic review and may instead be harmful as bleeding risk increases with its use. One limitation of this study, however, is that there were different time intervals from pretreatment to angiography in these studies, which may have played a factor in the outcomes of these studies.

Relevant Reading: Effects of pretreatment with clopidogrel and aspirin followed by long-term therapy in patients undergoing percutaneous coronary intervention: the PCI-CURE study

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