We read the recently published meta-analysis by Ma et al on randomized controlled trials (RCTs) comparing high and standard clopidogrel maintenance dose (MD) in patients who underwent percutaneous coronary intervention (PCI) with and without high on-treatment platelet reactivity (HTPR). This meta-analysis is an important report in the field of antiplatelet therapy in coronary artery disease (CAD) and a valuable contribution to the current knowledge. Among others, this meta-analysis included a study conducted by our research group. However, as some issues regarding our study were incorrectly described in this meta-analysis, we would like to emphasize and amend several points.

In this meta-analysis, the investigators stated that the intervention duration in our study was only 1 month long. This is not true as our interventions with clopidogrel dose adjustments based on Multiplate Function Analyzer (Roche Diagnostics, Mannheim, Germany) were performed in the study group continuously throughout 12 months after PCI as follows: days 1, 2, 3, 7, and 30 and months 2, 3, 6, 9, and 12. This is one of the major characteristics of our research because it is the first RCT that has investigated serial clopidogrel dose adjustment during 12-month follow-up in patients with acute coronary syndrome (ACS) who underwent PCI with determined HTPR on clopidogrel. The lack of such studies so far in the literature is confirmed by this meta-analysis. The only other RCT that performed serial platelet function testing (PFT) and anti-P2Y12 receptor therapy modification during 12 months was performed by Wang et al. The authors used vasodilator-stimulated phosphoprotein phosphorylation method to guide clopidogrel therapy. They, however, mainly enrolled patients with stable CAD (80%) and excluded patients with ST-segment elevation myocardial infarction (STEMI). PFT and clopidogrel dose tailoring in their study was initiated 30 days after PCI. It is known that patients with ACS, especially STEMI, are at an increased risk of new events that might be caused by HTPR, such as stent thrombosis, compared with patients with stable angina. We believe that improvement of PR inhibition and clinical outcomes should be particularly targeted at patients with STEMI, especially early after PCI as ST usually occurs within the first 30 days after PCI.

Furthermore, some of the patients in our interventional group were not assigned to high clopidogrel MD throughout the whole study period as it might be suggested in the meta-analysis. Clopidogrel MD was tailored on more occasions, both early and late after PCI, as already stated. At each point, clopidogrel MD was tailored to maintain optimal PR set by consensus statement of experts. Therefore, to certain number of patients in our study group, clopidogrel MD was reduced at some point.

We agree with the authors that well-designed large RCTs with long-term follow-up are warranted to fully assess the potential clinical benefit of individualized P2Y12 treatment based on PFT in patients after coronary stenting. Recently published results from the large Dual Antiplatelet Therapy trial indicate that continuation of P2Y12 blockers in addition to aspirin up to 30 months significantly reduces the risk of stent thrombosis and other major cardiocerebrovascular events but at the expense of increased bleeding risk. Individualized P2Y12 inhibition might reduce both ischemic and bleeding events after PCI. We believe that further trials assessing PFT-guided P2Y12 inhibition should be focused on patients with ACS using the strategy of achieving and maintaining optimal PR throughout the period of using a P2Y12 inhibitor. This approach seems reasonable because it was shown that PR is a dynamic variable with high inter- and intraindividual variations on clopidogrel. Assessing PR might not only be important because clopidogrel is still widely in use in treating ACS but also to predict bleeding risk and low PR on new P2Y12 inhibitors as well.