Time to Rethink about routine oral Anti-platelet therapy before PCI for Non-ST-Elevated ACS?

Three most common oral P2Y12 inhibitors available are clopidogrel, prasugrel, and ticagrelor. Clopidogrel, the first P2Y12 inhibitor, was the standard for DAPT until newer options became available. All three agents are recommended equally in the STEMI guidelines. However, recently in 2020, European guidelines changed to recommend against pretreatment in patients with NSTEACS based on several trials and observational studies. But, the debate still remains regarding the optimal approach. Therefore, Dr Luke P. Dawson and his team conducted a study to assess the association between oral P2Y12 inhibitor pretreatment and cardiovascular and bleeding outcomes in patients with NSTEACS.

In this systemic review and meta-analysis, the researchers searched PubMed, MEDLINE, Embase, Scopus, Web of Science, Science Direct, clinicaltrials.gov, and the Cochrane Central Register for randomized clinical trials of patients with NSTEACS. They included a total of 7 trials with 13 226 patients randomized to P2Y12 inhibitor pretreatment (defined as prior to angiography n=6603) or no pretreatment (defined as the following angiography, once coronary anatomy was known n=6623). They used a random-effect model including stratification by (1) P2Y12 inhibitor type, (2) revascularization strategy, and (3) access site. The major outcome assessed was 30-day major adverse cardiac events (MACEs). The researchers also assessed the 30-day myocardial infarction (MI) and cardiovascular death. The safety outcome of the study was 30-day major bleeding.

Key Findings of the study:

• Indication for P2Y12 inhibitors was non-ST elevation myocardial infarction in 7430 patients (61.7%), radial access was used in 4295 (32.6%), and 10 945 (82.8%) underwent percutaneous coronary intervention.
• Upon analysis, the researchers found that pretreatment was not associated with a reduction in

♦30-day MACE (odds ratio [OR], 0.95),

♦30-day MI (OR, 0.90), or

♦30-day cardiovascular death (OR, 0.79).

• They noted that the risk of 30-day major bleeding was increased among patients who underwent pretreatment (OR, 1.51).
• They also noted that the number needed to harm to bring about 1 major bleeding event with oral P2Y12 inhibitor pretreatment was 63 patients.

The authors concluded, " In this study, pretreatment with oral P2Y12 inhibitors among patients with NSTEACS prior to angiography, compared with treatment once coronary anatomy is known, was associated with increased bleeding risk and no difference in cardiovascular outcomes. Routine pretreatment with oral P2Y12 inhibitors in patients with NSTEACS receiving an early invasive strategy is not supported by this study."

In an accompanying editorial, Dr Michel Zeitouni and Dr Jean-Philippe Collet wrote, "The 20-year-long tale of whether pretreatment should be used in NSTE-ACS is important because it reflects on the too-long process of implementation of evidence-based medicine in scientific guidelines and whether interventional cardiologists are able to update their practices."

They further added, "It is now time to change practice as elegantly demonstrated by the systematic review and meta-analysis of Dawson et al who reviewed 7 trials, published during the last 20 years, that evaluated pretreatment with oral P2Y12 inhibitors in patients with NSTE-ACS."

For further information:

DOI:10.1001/jamanetworkopen.2021.34322