Effectiveness and Safety of Ticagrelor Implementation in Patients with Acute Coronary Syndrome undergoing Percutaneous Coronary Intervention: A Cohort Study in Western Denmark

Abstract

Summary Background Ticagrelor was introduced in Denmark in 2011 after randomised data showed its superiority over clopidogrel for patients with acute coronary syndrome (ACS). We assessed the effectiveness and safety of ticagrelor implementation in ACS patients undergoing percutaneous coronary intervention (PCI). Methods We identified PCI-treated ACS patients in Western Denmark who redeemed a P2Y12 inhibitor prescription within 14 days. Using Danish health registries, 1-year outcomes were compared before (2007-2010) and after (2012-2015) introduction of ticagrelor. Outcomes were MACE (death, myocardial infarction, and ischaemic stroke) and hospitalisation for bleeding. Inverse probability of treatment weights were used to estimate weighted incidence rate ratios (wIRRs). Findings We included 14,450 patients; 7,102 were treated in the earlier time period (99·9% clopidogrel) and 7,348 in the later time period (87·8% ticagrelor). Ticagrelor implementation was not associated with a clinically relevant difference in 1-year risk of MACE with 413 events in the ticagrelor period vs. 424 events in the clopidogrel period (cumulative incidence percentage [CIP] 5·6% vs. 6·0%; wIRR 1·06, 95% CI 0·92-1·22). The 1-year risk of bleeding was also similar between groups with 335 bleedings requiring hospitalisation in the ticagrelor period vs. 309 events in the clopidogrel period (CIP 4·6% vs. 4·4%; wIRR 1·05, 95% CI 0·89-1·23). Results were robust in patients above and below 70 years of age. Interpretation Implementation of ticagrelor was not associated with changes in risks of ischaemic or bleeding events in Danish PCI-treated ACS patients.

CYP2C19 Genotype Prevalence and Association With Recurrent Myocardial Infarction in British–South Asians Treated With Clopidogrel

“…Given the biogeographic cohort, it seems likely to have been overwhelmingly European. 47

Central Illustration The G&H South-Asian Ancestry Population Has a High Prevalence of CYP2C19 LOF Alleles, Leading to Poor Activation of Clopidogrel and Linked With a Gradient of Increased Risk of Recurrent Myocardial Infarction With Increased LOF Burden Due to the small number of ultra-rapid metabolizers present in the acute MI cohort, they were excluded from the graph showing recurrent MI risk. GOF = gain of function; IM = intermediate metabolizer; LOF = loss of function; MI = myocardial infarction; NM = normal metabolizer; PM = poor metabolizer; RM = rapid metabolizer; UM = ultra-rapid metabolizer.

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Validating the Prognostic Utility of the ABCD-GENE Score in Asian Patients with Acute Coronary Syndrome Patients on Clopidogrel

“…Compounded by the pharmacological and clinical complexities surrounding DAPT, the ischaemic-bleeding conundrum, characterised by the concurrent need to achieve anti-ischaemic activity without elevating bleeding risk, suggests that the use of ticagrelor over clopidogrel may not always be clinically feasible. 28,29 Instead, the need to individualise P2Y12 inhibitors for ACS patients raises interest in personalised DAPT. Currently, the applicability of platelet reactivity-guided DAPT remains apocryphal, and head-to-head trials on genotype-guided DAPT have produced mixed outcomes.…”

Effect of ticagrelor versus clopidogrel after implantation of drug-eluting stents guided by either intravascular ultrasound or angiography in patients with acute coronary syndrome——Propensity score matching analysis

“…Although the more potent P2Y12 inhibitor, ticagrelor, can signi cantly reduce the ischemic events in ACS patients compared to clopidogrel [1], the high bleeding risk and other side effects associated with ticagrelor have limited its clinical application [2,3]. The bene t between the two agents has remained controversial in real-world studies [4][5][6]. Thus, clopidogrel is still extensively prescribed.…”