Potent P2Y12 inhibitors versus clopidogrel to predict adherence to antiplatelet therapy after an acute coronary syndrome: insights from IDEAL-LDL.

BACKGROUND: Superiority of potent P2Y12 inhibitors over clopidogrel after an acute coronary syndrome (ACS) has been well established, however potent P2Y12 inhibition is responsible for more adverse events, which may influence patient adherence to treatment. Aim of the present study is to investigate the adherence to the prescribed P2Y12 inhibitor (P2Y12i) in patients on dual antiplatelet therapy (DAPT) after an ACS. METHODS: In an IDEAL-LDL trial substudy, we included 344 patients after ACS discharged on DAPT. The primary outcome was the difference between potent P2Y12i and clopidogrel in terms of adherence, as well as other predictors of adherence to the antiplatelet regimen. Secondary outcomes included the prevalence of DAPT continuation and its predictors and the antiplatelet regimen selection after DAPT. RESULTS: Adherence to the potent P2Y12i and to clopidogrel was observed in 140/178 (78.7%) and 111/166 (66.9%) patients (p = 0.016), respectively. In the multivariate model, after adjustment for P2Y12i switching during the first year of therapy, there was no difference observed in adherence between potent P2Y12i and clopidogrel (odds ratio [OR] = 0.98, 95% confidence interval [CI] = 0.55-1.74). Significant predictors included history of cardiovascular disease (CVD) (OR = 0.51, 95% CI = 0.31-0.86) and percutaneous coronary intervention (PCI) index event treatment (OR = 2.58, 95% CI = 1.38-4.82). Of patients, 72% continued DAPT >12 months and female gender was a negative predictor of DAPT prolongation (adjusted OR = 0.43, 95% CI = 0.21-0.90). DAPT was continued until the end of follow-up in 42.7%, while 54.6% resumed with single antiplatelet regimen. CONCLUSIONS: Adherence to DAPT was not affected by the P2Y12i potency, whereas history of CVD and PCI treatment were associated with reduced and increased adherence, respectively. CLINICAL TRIAL REGISTRATION: NCT02927808, https://clinicaltrials.gov/ct2/show/NCT02927808.

Comparative efficacy and safety of oral P2Y12 inhibitors for patients with chronic kidney disease and acute coronary syndrome: a network meta-analysis.

BACKGROUND: Currently, there is a paucity of data concerning the safety and effectiveness of P2Y12 inhibitors in the acute coronary syndrome (ACS) with chronic kidney disease (CKD) population. The aim of this study is to compare the different oral P2Y12 inhibitors in terms of efficacy and safety, focusing exclusively on patients with CKD who were treated for ACS. METHODS: We systematically searched PubMed, CENTRAL, and Web of Science to identify studies that compared different oral P2Y12 inhibitors (clopidogrel, prasugrel, and ticagrelor) in patients with ACS with CKD. Efficacy outcomes included the major adverse cardiovascular events composite outcome and safety outcomes included major bleedings and major or minor bleedings combined. We performed a frequentist network meta-analysis. RESULTS: Twelve studies were included in the systematic review, 7 CKD subgroup analyses of RCTs (8878 patients) and 5 observational studies (20175 patients). After the exclusion of studies with conservative management, prasugrel resulted in significant primary endpoint reduction versus clopidogrel (HR 0.80 and 95% CI 0.64 - 0.99), while ticagrelor did not (HR 0.88 and 95% CI 0.73 - 1.06). Major bleedings did not differ between the interventions. Ticagrelor resulted in more major or minor bleedings than clopidogrel (HR 1.21 and 95% CI 1.06 - 1.38), whereas prasugrel did not (HR 1.12 and 95% CI 0.84 - 1.49). CONCLUSION: In patients with ACS with underlying CKD, who are intended to receive invasive management, there may be a significant reduction of the primary efficacy outcome with prasugrel as compared to clopidogrel but not with ticagrelor as compared to clopidogrel. There probably exists no difference among interventions in the major bleedings. Dedicated RCTs are needed to confirm these results.

Predictive Role of Platelet-Associated Indices on Admission and Discharge in the Long-Term Prognosis of Acute Coronary Syndrome Patients.

Our study aimed to investigate the association between platelet indices and their in-hospital change and long-term prognosis in acute coronary syndrome (ACS). Data from a randomized controlled trial (NCT02927808) recruiting ACS patients were analyzed (survival analysis). The examined variables were platelet count (PC), mean platelet volume (MPV), platelet distribution width (PDW), and plateletcrit (PCT) on admission and discharge, as well as their alteration during hospitalization. The primary endpoint was major adverse cardiac events (MACE) (cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke or hospitalization for unstable angina) and all-cause mortality, while secondary endpoints were all-cause hospitalization and bleeding events. The study included 252 patients with a follow-up of 39 (28-45) months. In the univariate analysis, MACE was associated with discharge PC [hazard ratio (HR) 2.20, 95% confidence interval (CI) 1.10-4.40], discharge MPV (HR 0.48, 95% CI 0.25-0.94), and in-hospital PC difference (HR 0.25, 95% CI 0.13-0.51). In the multivariable analysis, only in-hospital PC decrease correlated with lower MACE incidence (adjusted HR .27, 95% CI 0.14-0.54) and lower all-cause hospitalization risk (adjusted HR 0.36, 95% CI 0.19-0.68). PC reduction during hospitalization for ACS is an independent predictor of better prognosis.