Real-World Bleeding and Ischemic Events in Asian Patients on P2Y12-Inhibitors After Percutaneous Coronary Intervention: A National Claims Data Analysis

Abstract

Introduction The safety and effectiveness of potent P2Y12 inhibitors in East Asians have been questioned because of the higher bleeding tendency and lower thrombotic risk in this population. We comparatively evaluated the safety, effectiveness and treatment persistence of the dual antiplatelet therapies (DAPT) with clopidogrel (CDAPT), ticagrelor (TDAPT) and prasugrel (PDAPT) after percutaneous coronary intervention (PCI) in the Korean population. Methods A retrospective cohort study was conducted using Korean National Health Insurance claims data. In 57,197 patients treated with DAPT after PCI, the risk of bleeding events, risk of major adverse cardiac and cerebral events (MACCE: a composite of all-cause death, myocardial infarction [MI], stroke and revascularization), risk of net adverse clinical events (NACE) and persistence and adherence rates were assessed with stabilized inverse probability of treatment weighting. Results TDAPT was associated with higher risks of bleeding (1 year: hazard ratio [HR], 1.37; 95% confidence interval [CI] 1.28–1.46; prolonged: HR 1.39, 95% CI 1.31–1.47), MACCE (1 year: HR 1.10, 95% CI 1.03–1.18; prolonged: HR 1.24, 95% CI 1.16–1.31) and NACE (1 year: HR 1.23, 95% CI 1.18–1.29; prolonged: HR 1.31, 95% CI 1.25–1.36) than CDAPT both at 1 year and in the prolonged periods, whereas there were no significant differences between PDAPT and CDAPT. Similar results were also observed in a subgroup analysis of patients with baseline MI. CDAPT was associated with higher persistence and adherence rates than TDAPT and PDAPT. Conclusions CDAPT was associated with clinical outcomes that were more favorable than those in TDAPT and comparable to those in PDAPT and drug persistence and adherence that were higher than in TDAPT or PDAPT. Clopidogrel may remain a viable first option for post-PCI DAPT in East Asian patients with a low thrombotic risk and a high bleeding tendency. Electronic Supplementary Material The online version of this article (10.1007/s12325-020-01526-4) contains supplementary material, which is available to authorized users.

The value of evaluating and implementing pharmaceuticals

“…A Swedish based observational study supported the effectiveness of ticagrelor; 174 however, more recent studies have questioned the effectiveness of ticagrelor when used in clinical practice. [175][176][177][178][179] This is clearly relevant for the results of our case study since effectiveness estimates are central to the value that ticagrelor provide. Paper 4 investigates this particular issue.…”

“…189,190 Because ticagrelor treatment is generally initiated during hospitalisation, conditioning on surviving hospitalisation or having a ticagrelor prescription at or after discharge can introduce bias. Many previous observational studies on ticagrelor restricted study populations to those surviving hospitalisation, those treated with P2Y12-inhibitors, or both, [174][175][176]179,[181][182][183][184] which could explain part of the variation in the study results. Using prescription data after hospital discharge to estimate the effectiveness of treatments initiated during hospitalisation, bring to mind the analogy of looking for keys under the streetlight rather than where the keys were lost (the so called streetlight effect).…”

“…The impact of patient selection was investigated using inclusion and exclusion criteria from past observational studies [174][175][176]179,[182][183][184] : 1) patients surviving the index hospitalisation; 2) patients treated with a P2Y12-inhibitor; and 3) patients surviving hospitalisation and treated with a P2Y12inhibotor.…”

“…160,163 However, observational studies on ticagrelor use in clinical practice has produced varying and conflicting evidence on ticagrelor effectiveness. [175][176][177][178][179][181][182][183][184] Some studies have found positive effects from ticagrelor when used in clinical practice, including a study by Sahlén et al (2016) who analysed data collected as part of Swedish routine clinical practice. 174 Other studies have found zero and even negative effects of ticagrelor use in clinical practice, including a recent study by Szummer et al (2020) who found an increased risk of mortality associated with ticagrelor in patients above 80 years of age.…”

“…174 Other studies have found zero and even negative effects of ticagrelor use in clinical practice, including a recent study by Szummer et al (2020) who found an increased risk of mortality associated with ticagrelor in patients above 80 years of age. [175][176][177][178][179] The studies by Sahlén et al (2016) and Szummer et al (2020) both used data from the SWEDEHEART registry collecting information on patients hospitalised for acute coronary syndrome or receiving vascular or coronary interventions for other reasons.…”