Ticagrelor Prescription Research Articles

Implementation of prasugrel and prognostic outcomes after percutaneous coronary intervention for myocardial infarction: a nationwide observational study

Abstract Background Prasugrel has shown superior efficacy and similar safety compared to ticagrelor for patients with acute coronary syndrome treated with percutaneous coronary intervention (PCI) in a randomised setting. Since 2020, prasugrel has been recommended over ticagrelor in our country. It remains unknown if these recommendations have been implemented, and if the findings from the randomised trial can be expanded to an all-comer population. Purpose To assess the implementation of prasugrel and compare effectiveness and safety between prasugrel and ticagrelor in PCI-treated, all-comer patients with myocardial infarction (MI). Methods From January 1st, 2019, to December 31st, 2021 patients with MI treated with PCI were identified by use of nationwide health registries. We included patients who were alive and claimed a prescription of prasugrel or ticagrelor within 7 days from discharge. Incidence rates per 100 person-years (IRs) 6 months from discharge were calculated for a composite outcome of all-cause mortality, recurrent MI (>28 days after index MI), and stroke (MACE), all-cause mortality alone, ischaemic events (a composite of recurrent MI and stroke) and bleeding leading to hospitalisation. We illustrated a Kaplan Meier curve with log-rank test and a cumulative incidence curve with Gray’s test and performed Cox models to assess adjusted comparative differences of the outcomes between prasugrel and ticagrelor after adjusting for age, sex, relevant comorbidities, and calendar year. Results We identified 14,365 PCI-treated patients with MI, of whom 13,887 (96.7%) were alive 7 days from discharge. After excluding patients who did not collect a P2Y12 inhibitor (n=1097 [7.9%]) or collected clopidogrel within 7 days from discharge (n=2696 [21.1%]), the final study population counted 10,094 patients of whom 2045 (20.3%) patients collected prasugrel and 8049 (79.7%) ticagrelor. Figure 1 shows the temporal use of P2Y12 inhibitors. The mean age was 64.4 (±11.7) years and 23.9% were female. Patients with prasugrel were less often ≥75 years old (16.3% vs. 23.2%), female (22.1% vs. 24.3%), and had fewer comorbidities (hypertension, hypercholesterolemia, diabetes, stroke or transient ischaemic attack, bleeding, and prior PCI) than ticagrelor-treated patients. Figure 2 illustrates IRs of the outcomes and Kaplan Meier and cumulative incidence curves. Prasugrel treatment was associated with reduced risk of MACE (HR 0.67 [95% CI 0.47-0.95]) and ischaemic events (HR 0.68 [0.47-0.97]) compared with ticagrelor after adjustment, and there were no differences in all-cause mortality or bleeding (Figure 2). Conclusion Prasugrel use increased from 1% to 44% from 2019 to 2021, but most all-comer patients with MI were treated with ticagrelor after PCI. Prasugrel showed lower risk of MACE and ischaemic events without excess in bleeding 6 months post-discharge compared to ticagrelor, consistent with the findings of a previous randomised trial.Temporal use of potent P2Y12 inhibitorsSix-months outcomes of potent P2Y12i

Racial/Ethnic Disparities in Outcomes After Percutaneous Coronary Intervention

Asian American/Pacific Islanders (AAPIs) and Hispanics are growing minority United States populations, but are poorly represented in the cardiovascular literature. This study examines guideline adherence and outcomes in AAPIs and Hispanics compared with non-Hispanic Whites (NHWs) in a quaternary care center after inpatient percutaneous coronary intervention (PCI). The primary end points were inpatient post-PCI bleed, heart failure, cardiogenic shock, and all-cause mortality, whereas the secondary end point was the prescription rate of post-PCI guideline-directed medical therapy including aspirin, statins, P2Y12 receptor blockers, and cardiopulmonary rehabilitation. Intergroup differences were assessed through analysis of variance or two-way chi-square tests, and the association of race with binary outcomes was examined through logistic regression with NHW as the reference group. Compared with NHW, AAPIs, and Hispanics had higher odds of diabetes mellitus, and AAPIs had higher odds of hypertension and being on dialysis. Hispanics had higher odds of post-PCI mortality versus NHW, both in acute coronary syndrome (odds ratio [OR] 2.04, p=0.03) and elective PCI (OR2.51, p=0.04). AAPI also trended toward higher mortality than NHW in both categories. AAPIs were found to have higher odds of statin prescription (OR1.91, p=0.04). Hispanics had lower odds of ticagrelor prescription versus NHW (OR0.65, p=0.04), and AAPIs trended toward such. No differences were found for cardiopulmonary rehabilitation prescriptions in groups. This study suggests that despite quality improvement efforts, disparities remain in postprocedural outcomes in minority groups in comparison with NHW.

Is the duration of dual antiplatelet therapy (DAPT) excessive in post-angioplasty in chronic coronary syndrome? Data from the France-PCI registry (2014-2019).

while the duration of dual antiplatelet therapy (DAPT) following coronary angioplasty for chronic coronary syndrome (CCS) recommended by the European Society of Cardiology has decreased over the last decade, little is known about the adherence to those guidelines in clinical practice in France. To analyze the real duration of DAPT post coronary angioplasty in CCS, as well as the factors affecting this duration. Between 2014 and 2019, 8.836 percutaneous coronary interventions for CCS from the France-PCI registry were evaluated, with 1 year follow up, after exclusion of patients receiving oral anticoagulants, procedures performed within one year of an acute coronary syndrome, and repeat angioplasty. Post-percutaneous coronary intervention (PCI) DAPT duration was > 12 months for 53.1% of patients treated for CCS; 30.5% had a DAPT between 7 and 12 months, and 16.4% a DAPT ≤ 6 months. Patients with L-DAPT (>12 months) were at higher ischemic risk [25.0% of DAPT score ≥2 vs. 18.8% DAPT score ≥2 in S&I-DAPT group (≤12 months)]. The most commonly used P2Y12 inhibitor was clopidogrel (82.2%). The prescription of ticagrelor increased over the period. post-PCI DAPT duration in CCS was higher than international recommendations in the France PCI registry between 2014 and 2019. More than half of the angioplasty performed for CCS are followed by a DAPT > 12 months. Ischemic risk assessment influences the duration of DAPT. This risk is probably overestimated nowadays, leading to a prolongation of DAPT beyond the recommended durations, thus increasing the bleeding risk.

Abstract 13910: Racial/Ethnic Outcomes Following Percutaneous Coronary Intervention

Introduction: Asian-American/Pacific Islanders (AAPIs) and Hispanics are two of the most rapidly growing minorities, but both are poorly represented in the cardiovascular literature. In light of national quality improvement efforts to ensure adherence to cardiovascular therapy guidelines, this study examines guideline adherence and outcomes in AAPIs and Hispanics compared to non-Hispanic Whites (NHW) in a quaternary care center after percutaneous coronary intervention (PCI). Methods: 1,896 AAPI, Hispanics, and NHW adults from February 28, 2012 to December 30, 2020 who underwent emergent or elective PCI were included. The primary endpoint was the prescription of post-PCI guideline-directed medical therapy including aspirin, statins, P2Y12 receptor blockers, and cardiopulmonary rehabilitation. Secondary endpoints included comorbidity burden, post-PCI morbidity and mortality, and prior PCI. Analyses were adjusted for age, sex, and insurance type. Results: Hispanics had the lowest median age and the highest rates of government insurance. Hispanics had lower odds of either ACE inhibitor or ARB prescription versus NHW (OR = 0.75, p = 0.03). Odds of ticagrelor prescriptions were lower for both Hispanics (OR = 0.56, p = 0.01) and AAPIs (OR = 0.62, p = 0.02) versus NHW. However, odds of clopidogrel prescriptions were higher for Hispanics than NHW (OR = 1.57, p = 0.01), while AAPIs trended towards the same (OR = 1.42, p = 0.05). No differences were found for statin or cardiopulmonary rehabilitation prescriptions. AAPIs and Hispanics had significantly higher risks of diabetes (OR = 2.28 and 1.8 respectively, p < 0.01) and of being on dialysis (OR = 2.25 and 2.52 respectively, p < 0.01) than NHW. AAPIs also had higher odds of hypertension than NHW (OR = 1.51, p = 0.01). Hispanics had significantly higher risk of post-PCI mortality versus NHW (OR = 2.12, p < 0.01). Conclusions: AAPIs and Hispanics had lower odds of ticagrelor prescription than NHW, and Hispanics had higher odds of clopidogrel prescription. Hispanics also had higher odds of mortality post-PCI. Further, AAPIs and Hispanics had higher comorbidity burdens. This study suggests that despite quality improvement efforts, work remains to be done to narrow health disparities.

Abstract 11269: Comparing Measures of Adherence and Persistence to Ticagrelor Therapy in Patients With Acute Coronary Syndromes

Introduction: There have been efforts to accurately measure adherence to ticagrelor to identify suboptimal medication therapy in the first year post-ACS as nonadherence during this crucial period is a major obstacle to optimizing clinical outcomes. Our study aims to examine ticagrelor adherence and persistence using different methods to better understand adherence patterns. Methods: We conducted a retrospective cohort study of patients aged ≥65 years who had filled a ticagrelor prescription within 7 days post-ACS discharge in Ontario, Canada between 4/2014-3/2018. We estimated mean proportion of days covered [PDC], the proportion of patients with “good” adherence of PDC≥80%, both at 1 year and the proportion of patients who were persistently taking ticagrelor at 1-year, using permissible gaps between prescriptions of 3, 7, 14 and 30 days. Results: There were 9,763 ticagrelor users (mean age 73.6; 65.4% men). The mean 1-year PDC (±SD) was 80.8±29.2, while only 73.0% of the cohort showed good adherence (PDC≥80%). Using a permissible gap definition of 14 days, only 55.7% of patients were persistent with ticagrelor in the year post-ACS. The 1-year persistence rates were as high as 62.6% with an allowable gap of 30 days and as low as 49.7% for a 7-day gap and 39.3% for a 3-day gap. Conclusions: Adherence and persistence estimates varied widely based on the definition used. While the PDC estimates implied reasonable 1-year ticagrelor adherence, PDC methods overestimated continuous use of ticagrelor, yet persistence methods with small gaps were likely too stringent. Readers of adherence and persistence studies should pay close attention to the methods and definitions used.

Hospital-Level Variation in Ticagrelor Use in Patients With Acute Coronary Syndrome.

BackgroundDespite improved outcomes associated with ticagrelor compared with clopidogrel in acute coronary syndrome (ACS), many studies have demonstrated slow adoption of ticagrelor in the United States because of its increased cost. Less is known about how ticagrelor is adopted when there is no added cost consideration. Our objectives were to determine patterns of use of ticagrelor, hospital‐level adoption of ticagrelor use, and factors associated with its use after ACS in a publicly funded health care system.Methods and ResultsWe conducted a population‐based cohort study including patients (≥65 years) hospitalized with their first ACS from April 2014 to March 2018 in Ontario, Canada. We determined temporal trends in ticagrelor use and hospital‐level adoption of its use post‐ACS discharge. Using hierarchical regression models, we identified significant predictors of ticagrelor use. There were 23 962 patients with ACS (mean age 76.3 years, 59.7% men) hospitalized in 156 hospitals. Overall ticagrelor use increased from 32.6% in 2014/2015 to 51.8% in 2017/2018. There was substantial variation in ticagrelor use post‐ACS across hospitals, with hospital‐specific prescribing rates ranging from 0% to 83.6%. Lower odds of ticagrelor use was associated with advanced age and the presence of comorbidities. Besides patient factors, being admitted to a rurally located hospital more than halved the odds of being prescribed ticagrelor (odds ratio [OR], 0.49; 95% CI, 0.32–0.77). Being managed by a cardiologist during the index ACS hospitalization was associated with higher odds of having a ticagrelor prescription after ACS (OR, 2.80; 95% CI, 2.36–3.33).ConclusionsTicagrelor use rates varied substantially across hospitals and were strongly associated with physician and hospital factors independent of patient characteristics.

Effect of Genotype-Guided Oral P2Y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

BackgroundClopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment. MethodsA comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. ResultsSeven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE), improved cardiovascular (CV) mortality, and reduced incidence of myocardial infarction (MI) in the genotype arm, and a similar stroke incidence in the two arms. Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm. ConclusionOur analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

Abstract 11621: Effect of Genotype Guided Oral P2y12 Inhibitor Selection After Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis of Randomized Clinical Trials

Introduction: Clopidogrel is the most frequently used P2Y12 inhibitor as a component of the dual antiplatelet regimen in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Prior studies have shown the variable efficacy of clopidogrel due to genotypic differences in the CYP2C19 enzyme function, which converts clopidogrel to its active metabolite. Hypothesis: The aim of this meta-analysis is to evaluate the effectiveness of genotype testing-guided P2Y12 inhibitor prescription therapy to patients after PCI for ACS compared to non-genotype guided conventional treatment. Methods: A comprehensive literature search was performed in PubMed, Embase, and Cochrane to identify relevant trials. Summary effects were calculated using a DerSimonian and Laird random-effects model as odds ratio with 95% confidence intervals for all the clinical endpoints. Results: Seven studies with 9617 patients were included. Genotype-guided strategy arm included prasugrel or ticagrelor prescription to patients with loss of function (LOF) of CYP219 alleles (most commonly alleles being *2 and *3) and clopidogrel prescription to those without the LOF allele. The conventional arm included patients treated with clopidogrel without genotype testing. Comparison of genotype arm with conventional arm showed decreased major adverse cardiovascular events (MACE) (RR 0.72, 95% CI 0.55-0.95; p=0.02, I 2 =23), improved cardiovascular (CV) mortality (RR 0.62, 95% CI 0.43-0.90; p=0.01, I 2 =0) and reduced incidence of myocardial infarction (MI) (RR 0.57, 95% CI 0.41-0.97; p< 0.01), and a similar stroke incidence (RR 0.65, 95% CI 0.35-1.21; p= 0.18). Regarding adverse events, the incidence of stent thrombosis was lower in the genotype arm than the conventional arm (RR 0.52, 95% CI 0.28-0.96; p=0.04). Conclusions: Our analysis illustrates the possible advantages of genotype-guided P2Y12 inhibitor prescription strategy compared to non-genotype-guided strategy with reductions in MACE, CV mortality, MI, and stent thrombosis. This analysis can be used as a stepping stone to conducting further trials determining the efficacy of this treatment strategy in various ACS subtypes.

Use of Clopidogrel, Prasugrel, or Ticagrelor and Patient Outcome after Acute Coronary Syndrome in Austria from 2015 to 2017.

Background: Dual antiplatelet therapy improves patient outcome after acute coronary syndrome (ACS), but prescription differences of P2Y12 inhibitor treatments exist. The aim of the present investigation was to study the long-term utilization and patient outcomes of clopidogrel, prasugrel, and ticagrelor in patients with ACS from 2015 to 2017 in Austria. Methods: Data from 13 Austrian health insurance funds of patients with a hospital discharge diagnosis of ACS for the years 2015 to 2017 were analyzed. The primary end point was to investigate the recurrence of ACS or death. Results: Of 49,124 P2Y12 inhibitor-naive patients with a hospital discharge diagnosis of ACS, 25,147 subjects filled a P2Y12 inhibitor prescription within 30 days after the index event. Of these patients, 10,626 (42.9%) subjects had a prescription for clopidogrel, 4788 (19.3%) for prasugrel, and 9383 (37.8%) for ticagrelor. Ticagrelor was the most frequently prescribed P2Y12 inhibitor among patients below 70 years old, and clopidogrel in those aged ≥70 years. Occurrence of an endpoint was highest in elderly patients. After adjustment for age, sex, and pre-existing medication as proxy for comorbidity, the hazard ratio for ACS or death for prasugrel vs. clopidogrel of 0.70 (95% CI: 0.61; 0.79) was similar to that of ticagrelor vs. clopidogrel (0.70; 95% CI: 0.64; 0.77). Conclusion: Prescription of ticagrelor or prasugrel after ACS were associated with a lower risk of ACS recurrence or death compared to clopidogrel.

Sex-specific differences in antithrombotic therapy and prognosis in patients with acute coronary syndrome treated with stent.

Impact of sex-related differences in patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention and treated with new P2Y12 inhibitors is not adequately characterised. We aimed to analyse gender-based differences in dual antiplatelet therapy, and adverse cardiovascular events and bleeding. Prospective-observational study of the consecutive ACS patients treated with stent from July 2016 to January 2016, with a follow-up of 1 year. We examined 283 patients, 75 (26.5%) women and 208 (73.5%) men. Women were older than men (71 ± 13 vs. 66,5 ± 13 years). There were 44% of women and 52% of men presenting with ST-elevation ACS (p = 0.21). Women had a higher bleeding risk (CRUSADE), without differences in the ischaemic risk (GRACE and TIMI). More women were treated with drug-eluting stent (88.9 vs. 75.5%, p = 0.04). There was a lower rate of ticagrelor prescription in women (42.6 vs. 50.9%, p = 0.29), in favour of clopidogrel. No differences were observed in prasugrel prescription. No significant differences were observed after a year of follow up, but women had a tendency towards lower mortality (1.4 vs. 6.7%, p = 0.19) and higher bleeding rates (23.3 vs. 17.4%, p = 0.27). In our study of patients presenting with ACS treated with stent, clopidogrel was preferred in women, whereas ticagrelor was the most frequent prescription in men. No significant differences were noted in clinical outcomes, but women experienced a tendency towards less mortality and more bleeding events.

P939Cardiovascular outcomes in patients with Acute Coronary Syndrome and previous cardiovascular disease. An analysis from ACHILLES Registry

Abstract Background Patients with acute coronary syndrome (ACS) and previous cardiovascular disease (CVD) [stroke, peripheral arterial disease (PAD) or coronary artery disease (CAD)] are at high risk of serious events and mortality. Current clinical guidelines recommend new antiplatelet drugs (NAD) for high cardiovascular risk patients with ACS; however, these drugs are underused in different scenarios. Purpose The aim of this study was to analyze the use of NAD and advese events in patients with ACS an previous CVD. Methods ACHILLES registry is and observational, multicenter and prospective registry of ACS patients. 1717 ACS patients were consecutively included in this study from 3 tertiary Hospitals. Of them, 641 (37.33%) suffered from previous CVD: 149 patients with stroke, 154 patients with PAD and 541 patients with CAD. Bleeding, mortality and major adverse cardiac events (MACE) at 1 year of follow-up after hospital discharge were analyzed. Results NADs administration during hospital stay and at discharge was less frequent in patients with previous CVDs. Cox analysis in this cohort of patients showed that clopidogrel prescription at discharge was independently associated with MACEs [HR: 1.59 (95% CI 1.03–2.45); p=0.036] and with death [HR: 1.99 (95% CI 1.00–3.98); p=0.049] in multivariate analysis. More specifically, when ticagrelor prescription at discharge was compared with clopidogrel prescription, a significant death reduction was found in both, the univariate and the multivariate Cox analysis [HR: 4.54 (95% CI 2.26–9.13); p<0.001 and HR: 2.61 (95% CI 1.16–5.90); p=0.021, respectively]. KM curves according NAD and CVD disease Conclusion New antiplatelet drugs, especially ticagrelor, showed lower rates of mortality in patients with CVD without differences for bleeding. Despite the recommendations of current clinical guidelines for high risk patients with ACS, the use of NADs is very low in “real-life” patients with previous CVD.

The choice of the P2Y12 receptors blocker in the treatment of a patient with acute coronary syndrome: practice of N.I. Pirogov city clinical hospital №1

Ticagrelor is known to prefer clopidigrel except in cases of high risk of bleeding, but according to the literature, clopidogrel still remains the most frequent second component of dual antiplatelet therapy (DAPT) in the world. The aim of the study was to conduct comparative description of patient groups with the acid acetilsalicilic (ACS), taken depending on a prescription of clopidogrel or ticagrelor as the second component of DAPT according to data of the year’s work of the Pirogov City Clinical Hospital №1. Materials and methods: clinical data of 854 patients with ACS who undergone treatment in of Pirogov City Clinical Hospital №1 in 2017 were analyzed. Clopidogrel was prescribed to 623 patients (73%) – the I group, ticagrelor 231 (27%) – the II group. Patients in the I group compared to the II group were significantly older (70 and 62 years accordingly), women accounted for 43% in I group and 27% in II group. Arterial hypertension (96 and 89%), diabetes (34 and 26%), post-acute myocardial infarction (38 and 19%), chronic kidney disease (26 and 12%), anemia (15 and 7%). Among patients of II group final diagnosis of ST-elevation myocardial infarction (STEMI) was more often (64 and 31%), coronary angiography (CAG) and percutaneous coronary intervention (PCI) were more frequent – 98/94% and 88/75%, accordingly. Clopidogrel is prescribed to the patients more often in comparison with ticagrelor. Doctors make a choice in favor of clopidogrel for elderly patients, more often women and more comorbid patients. The presence of STEMI, as well as the performance of CAG / PCI in any definitive diagnosis, is associated with a relatively more frequent prescription of ticagrelor, and in elderly patients, the implementation of PCI is the only factor that significantly influences the choice of more active antiaggregant in DAPT.

Increase in ticagrelor use over time is associated with lower rates of ischemic stroke following myocardial infarction

ObjectivesTo evaluate the impact of a rapid change in preferred treatment from clopidogrel to ticagrelor on the risk of ischemic stroke following acute myocardial infarction (AMI).MethodsData for AMI patients treated with either clopidogrel or ticagrelor were obtained from the Swedish Register of Information and Knowledge about Swedish Heart Intensive Care Admissions (RIKS-HIA). Patients were divided into two cohorts, each covering a two-year time period; the initial prescription of ticagrelor (20 Dec 2011) was used as a cut-off point. Patients in the early cohort (n = 23,447) were treated with clopidogrel, while those in the later cohort (n = 24,227), were treated with either clopidogrel (47.9%) or ticagrelor (52.1%). Kaplan-Meier analyses were used to assess the risk of ischemic stroke over time, with multivariable Cox regression analyses used to identify predictors of ischemic stroke.ResultsOf 47,674 patients, there were 1203 cases of ischemic stroke. Cumulative Kaplan-Meier incidence estimates of ischemic stroke after one year were 2.8% vs. 2.4% for the early and late cohorts, respectively (p = 0.001). Older age, hypertension, diabetes, previous stroke, congestive heart failure, atrial fibrillation, and ST-elevation myocardial infarction were associated with an increased risk of ischemic stroke. Percutaneous coronary intervention and statins at discharge were associated with a decreased risk of ischemic stroke, as was higher estimated glomerular filtration rate. Membership of the late cohort correlated with a 13% reduction in the relative risk of ischemic stroke.ConclusionsThe introduction of ticagrelor as well as an improved management of AMI was associated with a lower rate of ischemic stroke in a relatively unselected AMI population.

Ticagrelor and Acetylsalicylic Acid after Placement of Pipeline Embolization Device for Cerebral Aneurysm: A Case Series

Dual antiplatelet therapy with acetylsalicylic acid (ASA) and a P2Y12-receptor antagonist is often used to prevent thrombotic complications after placement of a Pipeline embolization device (PED) for cerebral aneurysm. Although clopidogrel is common in this setting, high rates of nonresponse to this drug have made ticagrelor a potentially attractive alternative. To describe safety and efficacy outcomes for ticagrelor following PED placement, including measurement of platelet function. A retrospective analysis of data was completed for patients who underwent PED placement for cerebral aneurysm at a single centre between November 2015 and March 2017, with subsequent prescription of ticagrelor and ASA as dual antiplatelet therapy. The primary end point was any ischemic stroke or death within 1 year after the procedure. Intracranial hemorrhage was a secondary end point. Additionally, measurement of and values for platelet reactivity units (PRUs) during receipt of ticagrelor and ASA were evaluated. A total of 29 patients were included in this retrospective study. One patient experienced ischemic stroke 226 days after placement of the PED. In addition, 3 patients died during the 1-year follow-up period for causes unrelated to stroke or bleeding complications. No cases of intracranial hemorrhage were observed. Samples for measurement of P2Y12 levels were drawn at the discretion of the neurointerventionalists, and the PRU value was measured at least once for 28 (97%) of the 29 patients. The mean number of PRU measurements per patient after initiation of ticagrelor was 2.1 (standard deviation [SD] 1). Mean PRU value after initiation of ticagrelor was 65 (SD 57). In this case series describing the use of ticagrelor and ASA as dual antiplatelet therapy after PED placement for cerebral aneurysm, there was just one ischemic stroke, which occurred after the dual antiplatelet therapy had been discontinued. Further prospective trials are needed to describe the utility of ticagrelor use after PED placement, as well as its dosing and monitoring.

Appropriateness of Ticagrelor Use at Initiation: A Population-Based Cohort Study.

Ticagrelor is recommended following an acute coronary syndrome if used appropriately. Its use has not yet been well described in the context of ambulatory clinical practice. The objective of this study was to assess the proportion of ticagrelor new users who initiated this medication appropriately and explore associated factors. A retrospective population-based inception cohort study was conducted using Quebec administrative databases. The study population included all Quebec residents aged ≥18 years who had a first ticagrelor prescription claim between 1 January, 2012, and 31 March, 2015, and had been continuously eligible in the Quebec public drug plan during the 365 days preceding the first ticagrelor claim. The initial ticagrelor prescription was considered appropriate if:1) it met the indication for use criterion, 2) the prescribed daily dose was 90 mg twice a day, and 3) there was a concomitant use of acetylsalicylic acid (ASA) 80-81 mg daily. Factors potentially associated with the ticagrelor appropriateness of use were included in a logistic log-binomial regression model. A total of 7,073 patients were included in the study, 6,013 (85.0%) had an appropriate indication, 6,895 (97.5%) were prescribed ticagrelor 90 mg twice a day, and 6,385 (90.3%) had a concomitant prescription of ASA. A total of 5,371 (75.9%) patients were prescribed ticagrelor in accordance with all criteria. Twelve factors were associated with prescription appropriateness. A large majority of patients initiated ticagrelor appropriately. Further improvement in appropriateness may come at targeting indication for use.

Increased Use of Ticagrelor After Myocardial Infarction Is Not Associated With Intracranial Hemorrhage.

Background and Purpose- Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction. Methods- Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH. Results- The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period ( P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH. Conclusions- The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

Trends in cardiovascular and bleeding outcomes in acute coronary syndrome patients treated with or without proton-pump inhibitors during the introduction of novel P2Y12 inhibitors: a five-year experience from a single-centre observational registry.

Proton-pump inhibitors (PPIs) are commonly prescribed in acute coronary syndrome (ACS) patients on antiplatelet therapy. We studied PPI prescription in ACS patients in the era of novel P2Y12 inhibitors and assessed the association between PPI use and clinical outcomes. Between 2010 and 2014, we included all consecutive ACS patients admitted to a Dutch tertiary hospital. The main outcome was PPI prescription at discharge. Additionally, we present 1-year mortality and 30-day cardiovascular and bleeding outcomes. Of 4595 ACS patients with known discharge medication, 63.9% received a PPI. PPI-treated patients were older (67.1 ± 12.5 vs. 63.0 ± 13.3, P < 0.001). PPI treatment at discharge increased from 34.7% in 2010 to 88.7% in 2014 (P < 0.001). Concurrently, ticagrelor prescription at discharge increased from 0.0% to 48.6% in 2014 (P < 0.001), while clopidogrel prescription decreased from 78.6% in 2010 to 28.7% in 2014 (P < 0.001). PPI treatment was associated with reductions in death or myocardial infarction (MI) [adjusted hazard ratio (HR) 0.27, 95% confidence interval (CI) 0.10-0.76] and death, MI or stroke (adjusted HR 0.33, 95% CI 0.14-0.81) at 30-days post-discharge. However, this association was not present in subgroup analyses of patients treated with clopidogrel or ticagrelor. In this single-centre registry, PPI prescription in ACS patients doubled between 2010 and 2014. PPI treatment at discharge was associated with a reduction in death, MI, or stroke at 30-days post-discharge, mainly driven by a reduction in MI. There were no differences gastrointestinal bleeding between patients treated with or without a PPI. PPI treatment may serve as a marker of improved therapies and outcome, rather than causing a reduction in cardiovascular events.

Ischemic stroke rates decrease with increased ticagrelor use after acute myocardial infarction in patients treated with percutaneous coronary intervention.

Aims It is unknown whether dual antiplatelet therapy with ticagrelor instead of clopidogrel reduces the risk of ischaemic stroke in acute myocardial infarction patients that undergo percutaneous coronary intervention. This study investigated whether the introduction of dual antiplatelet therapy with ticagrelor was associated with reduced ischaemic stroke risk in a real-world population. Methods and results Patients with ischaemic stroke after acute myocardial infarction from 8 December 2009-31 December 2013 were identified using the Register for Information and Knowledge on Swedish Heart Intensive Care Admissions and the Swedish National Patient Register. The study period was divided into two similar periods using the date of the first prescription of ticagrelor as the cut-off. The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients during the first period (100% clopidogrel treatment) versus the second period (60.7% ticagrelor treatment) was assessed using Kaplan-Meier analysis. Variables associated with ischaemic stroke were identified using a multivariable Cox proportional hazards model. There were 686 ischaemic stroke events (2.0%) among 34931 percutaneous coronary intervention-treated acute myocardial infarction patients within one year, 366 (2.2%) during the first period and 320 (1.8%) during the second period ( p = 0.004). The Cox model showed a 21% relative risk reduction in ischaemic stroke in the second period versus the first one (hazard ratio 0.79, 95% confidence interval, 0.68-0.92; p = 0.003). The independent predictors of increased stroke risk were older age, hypertension, diabetes mellitus, atrial fibrillation, heart failure during hospitalization, previous ischaemic stroke, and ST-segment elevation myocardial infarction. Conclusion The risk of ischaemic stroke in percutaneous coronary intervention-treated acute myocardial infarction patients decreased after the introduction of ticagrelor in Sweden.

Ticagrelor Use in Acute Myocardial Infarction: Insights From the National Cardiovascular Data Registry.

BackgroundTicagrelor is a P2Y12 receptor inhibitor with superior clinical efficacy compared with clopidogrel. However, it is associated with reduced efficacy when combined with a high‐dose aspirin.Methods and ResultsPatients in the acute coronary treatment and intervention outcomes network (ACTION) Registry‐Get With The Guidelines (GWTG) with acute myocardial infarction from October 2013 through December 2014 were included in the study (167 455 patients; 622 sites). We evaluated temporal trends in the prescription of P2Y12 inhibitors, and identified factors associated with ticagrelor use at discharge. Among patients discharged on ticagrelor and aspirin (21 262 patients), we evaluated the temporal trends and independent factors associated with high‐dose aspirin prescription at discharge. Ticagrelor prescription at discharge increased significantly from 12% to 16.7% (P<0.0001). Decreases in prasugrel and clopidogrel use at discharge (15.7%–13.9% and 54.2%–51.1%, respectively, P<0.0001) were also observed. Independent factors associated with preferential ticagrelor prescription at discharge over clopidogrel included younger age, white race, home ticagrelor use, invasive management, and in‐hospital re‐infarction and stroke (P<0.0001 for all), whereas older age, female sex, prior stroke, home ticagrelor use, and in‐hospital stroke (P<0.0001 for all) were associated with preferential ticagrelor prescription at discharge over prasugrel. High‐dose aspirin was used in 3.1% of patients discharged on ticagrelor. Independent factors associated with high‐dose aspirin prescription at discharge included home aspirin use, diabetes mellitus, previous myocardial infarction, previous coronary artery bypass graft, ST‐segment–elevation myocardial infarction, cardiogenic shock, and geographic region (P=0.01).ConclusionsOur contemporary analysis shows a modest but significant increase in the use of ticagrelor and a high rate of adherence to the use of low‐dose aspirin at discharge.

Ticagrelor-related late-onset dyspnea as cause of emergency department visit: a 3-year outpatient study.

The aim of the current study was to define the rate of emergency department visits for late-onset dyspnea in acute coronary syndrome patients treated with ticagrelor. We conducted a population-based study on about 850 000 residents of Florence metropolitan area, by using data from healthcare records. Between 2012 and 2014, 1073 subjects in Florence metropolitan area had at least one prescription of ticagrelor. Two-hundred and thirty-four patients were diagnosed with 'respiratory system or other chest symptoms' or 'other diseases of lung', and among them we identified 20 subjects with ticagrelor-related late-onset dyspnea. These, and the 979 nonevent subjects (receiving ticagrelor but not developing dyspnea), contributed to 413 person-years overall. The dyspnea rate was 4.84 per 100 person-years (95% confidence interval: 3.12-7.51). Late-onset dyspnea rate is notably lower than early-onset one; nevertheless prescribing clinicians should be aware that about one in 20 outpatients with a stabilized ticagrelor treatment might develop a dyspnea leading to an emergency department visit, and they should consider ticagrelor replacement only in patients who cannot tolerate dyspnea.