ABC | Volume 112, Nº2, February 2019

Original Article Somuncu et al Antiplatelet resistance in young MI patients Arq Bras Cardiol. 2019; 112(2):138-146 Figure 2 – Kaplan-Meier analysis showing 3-year cardiac mortality rate according to antiplatelet response. Patients with adequate response to aspirin and/or clopidogrel were considered “responders”. Patients with both aspirin and clopidogrel resistance were considered non-responders. 100 80 60 40 20 0 0 200 400 600 800 1.000 1.200 Time Survival rate (%) Log Rank < 0.001 Cardiac Mortality Responders non-responders When studies on clopidogrel response are reviewed, it can be seen that clopidogrel resistance is clinically expressed in different patient groups. In a meta-analysis investigating the ability of different platelet-function tests to reliably identify patients at risk of developing secondary cardiovascular events, Wisman et al. 7 evaluated high on‑aspirin and high on‑clopidogrel platelet reactivity in 55 studies with 22,441 patients and in 59 studies with 34776 patients respectively. The high on‑aspirin platelet reactivity rate was 22.2%, which was associated with an increased risk for cardiovascular events (relative risk [RR] 2.09; 95% confidence interval [CI] 1.77–2.47). They reported a high on‑clopidogrel platelet reactivity in 40.4% of patients, which was associated with increased cardiovascular event risk (RR 2.80; 95% CI 2.40–3.27). Moreover, ten studies identified an increased cardiovascular event risk in patients with high‑on dual platelet reactivity (RR 2.77; 95% CI 1.87–4.12). In our study, although patients resistant to either aspirin or clopidogrel showed more cardiovascular events, this was not statistically significant. This may be explained by our relatively small sample size. However, similar to the meta-analysis, poor response to dual therapy was found to be an independent predictor of MACE (RR 3.33; 95% CI 0.484–22.954). Furthermore, according to this meta-analysis, 7 the Multiplate test, the same method used in our study, is one of the most reliable methods to identify cardiovascular events. The effect of antiplatelet resistance on stent thrombosis as a clinical outcome was examined in some studies. Slottow et al. 12 compared 26 patients who admitted with stent thrombosis under dual antiplatelet therapy with a control group to determine the relationship between stent thrombosis and antiplatelet resistance. 12 In this study, aspirin and clopidogrel reaction units were significantly higher in patients with early drug-eluting stent thrombosis. Similar to these results, in two other studies evaluating clopidogrel resistance, stent thrombosis was seen more frequently after 6 months of follow-up. 13,14 In a study comparing clopidogrel response with phenotyping and genotyping, patients with poor response to clopidogrel detected bymultiple electrode aggregometry (MEA) had a higher risk of developing MACE or stent thrombosis than clopidogrel responders (12.5% vs. 0.3%, p < 0.001, and 18.5% vs. 11.3%, p = 0.022, respectively). 15 Although we did not evaluate any stent thrombosis parameter, the frequency of cardiac mortality and TVR was significantly higher in patients with poor response to dual therapy than responders to dual therapy. In the literature, we identified only one study with a similar grouping design, i.e., considering the response (responders vs. poor responders) to dual platelet therapy. Campo et al. 16 evaluated the responsiveness status of aspirin and clopidogrel in 1,277 patients after elective PCI. 16 In this study, at one‑year follow-up they found that poor response to clopidogrel is an independent predictor of periprocedural MI and cardiovascular events whereas poor response to aspirin failed to predict a worse outcome. A distinctive feature of this study was that aspirin and clopidogrel response of 207 patients were evaluated together in subgroups and 25 patients were identified as the dual poor responder. In this subgroup analysis, the one-year composite endpoint of overall mortality, MI, and stroke was higher for dual poor responders compared with responders largely driven by a higher rate of MI (20% vs. 8.6%; p = 0.007). It may be expected lower cardiac mortality rates in our study group due to their younger age; however, our study had a longer follow-up than the above-mentioned study, which may have compensated for this. As a result, similar to the above study, we found a significant difference between the groups of nonresponders and the responders in terms of cardiac mortality (18.8% vs. 5.0%, p = 0.002). 143