Clopidogrel In Acute Coronary Syndromes Research Articles

Frailty and Clinical Outcomes of Ticagrelor Versus Clopidogrel in Older Adults With Acute Myocardial Infarction.

Ticagrelor is recommended over clopidogrel in acute coronary syndrome based on the results of the PLATO (Study of Platelet Inhibition and Patient Outcomes) trial. We aimed to emulate PLATO in older adults with and without frailty and with acute coronary syndrome treated with percutaneous coronary intervention. We created a new-user cohort of Medicare fee-for-service beneficiaries aged ≥65 years hospitalized for acute coronary syndrome from 2014 to 2018 and initiated ticagrelor or clopidogrel following percutaneous coronary intervention. Frailty was defined using a validated claims-based frailty index ≥0.25. Coprimary outcomes were major adverse cardiovascular events and major bleeding. Follow-up began on the date of first outpatient prescription for ticagrelor or clopidogrel and ended on the earliest date for an outcome event, death, discontinuation of the index drug, or disenrollment from Medicare. The study included 42 843 older adults; 23% were frail. After propensity score matching, the rates of major adverse cardiovascular events per 100 person-years comparing ticagrelor versus clopidogrel groups were 7.8 and 7.3 in the frail cohort (hazard ratio [HR], 1.07 [95% CI, 0.84-1.36]) and 3.7 and 4.2 in the nonfrail cohort (HR, 0.87 [95% CI, 0.75-1.02]). The corresponding rates of major bleeding were 4.3 and 3.8 in the frail cohort (HR, 1.12 95% CI, [0.80-1.56]) and 2.2 and 1.8 in the nonfrail cohort (HR, 1.22 [95% CI, 0.98-1.51]). There was a trend toward a modest reduction in risk of major adverse cardiovascular events and a trend toward a modest increase in risk of major bleeding with ticagrelor compared with clopidogrel in the nonfrail cohort. There was insufficient evidence for the benefit of ticagrelor in frail older adults.

Cost-Effectiveness Comparison between Ticagrelor and Clopidogrel in Acute Coronary Syndrome in Iran.

The present study aimed to determine the cost-effectiveness of ticagrelor compared with clopidogrel in Iranian patients with acute coronary syndrome (ACS). A 1-year decision tree model combined with a 20-year Markov transition model was used to simulate the long-term cost and effectiveness of both ticagrelor and clopidogrel in Iran based on an Iranian payer's perspective. Clinical efficacy data were extracted from the PLATO trial and other published studies. Costs were estimated based on local prices in public sectors. Deterministic and probabilistic sensitivity analyses were used to test the robustness of base-case results over the uncertainties of model inputs. All calculations, analyses, and modeling were done in TreeAge 2011 and Microsoft Excel 2013. Compared with clopidogrel, the treatment of Iranian ACS patients with ticagrelor for 20 years resulted in an additional cost of US$ 2.39 in a hypothetical cohort of 1000 patients. However, ticagrelor led to 7.2 quality-adjusted life-years (QALYs) gained per 1000 hypothetical patients. Accordingly, the estimated incremental cost-effectiveness ratio for this analysis was US$ 332.032 per 1 QALY gained. Ticagrelor was a cost-effective antiplatelet medicine compared with clopidogrel in Iranian patients with ACS. This could help Iran's policymakers to allocate resources more efficiently to ACS.

Ticagrelor or prasugrel versus clopidogrel in patients undergoing percutaneous coronary intervention for chronic coronary syndromes.

Potent P2Y12 inhibitors such as ticagrelor and prasugrel are superior to clopidogrel in acute coronary syndrome (ACS) patients treated with percutaneous coronary intervention (PCI). Whether this benefit extends to a patient population with chronic coronary syndromes (CCS) is unclear. We sought to compare the safety and efficacy of prasugrel and ticagrelor versus clopidogrel in patients undergoing PCI for CCS. Consecutive patients undergoing PCI for CCS at a tertiary centre between 2014 and 2019 who were discharged on prasugrel or ticagrelor were compared with those on clopidogrel. The primary endpoint was the composite of death and myocardial infarction (MI), with secondary outcomes including rates of bleeding, stroke, and target vessel revascularisation at 1 year. Overall, 11,508 patients were included in the study (ticagrelor/prasugrel n=2,860 [24.9%], clopidogrel n=8,648 [75.1%]) with an increasing frequency of potent P2Y12 inhibitor use over the study period (ptrend<0.001). Clopidogrel was used more frequently in patients with multimorbid risk factors, whereas anatomical or procedural complexity was associated with ticagrelor/prasugrel use (left main PCI, bifurcation PCI, number of lesions, rotational atherectomy). No difference in the incidence of death or MI was noted across the groups (ticagrelor/prasugrel vs clopidogrel: 2.7% vs 3.1%, adjusted hazard ratio [adjHR] 0.86, 95% confidence interval [CI]: 0.62-1.17; p=0.33) or secondary outcomes including bleeding (adjHR 0.75, 95% CI: 0.46-1.21; p=0.23) on propensity score stratification analysis. Additionally, no difference in the primary outcome was observed across subgroups, including those undergoing complex PCI. Ticagrelor and prasugrel are increasingly used in patients with CCS undergoing PCI with similar 1-year efficacy and safety when compared to clopidogrel. Whether use of these agents can be beneficial in patients undergoing PCI for CCS with a high thrombotic and low bleeding risk warrants further study.

Antiplatelet efficacy of ticagrelor versus clopidogrel in Mediterranean patients with diabetes mellitus and chronic coronary syndromes: A crossover pharmacodynamic investigation.

Patients with diabetes mellitus (DM) have augmented platelet reactivity and diminished responsiveness to clopidogrel. Ticagrelor, a more potent P2Y12 inhibitor, is clinically superior to clopidogrel in acute coronary syndromes, although its role in chronic coronary syndromes (CCS) is still the subject of debate. The aim of this investigation was to compare the pharmacodynamic effectiveness of ticagrelor and clopidogrel in Mediterranean DM patients with CCS. In this prospective, randomized, crossover study, patients (n = 20) were randomized (1:1) to receive, on top of aspirin therapy, either ticagrelor 180 mg loading dose (LD)/90 mg maintenance dose (MD) b.i.d. or clopidogrel 600 mg LD/75 mg MD o.d. for 1 week in a crossover fashion with a 2-4 week washout period between regimens. Platelet function measurements were performed at 4 timepoints in each period (baseline, 2 h and 24 h after LD, and 1 week), including light transmission aggregometry (LTA, primary endpoint), VASP assay, Multiplate and VerifyNow P2Y12. The ticagrelor LD achieved greater platelet inhibitory effect than clopidogrel LD, assessed with LTA (20 μM ADP as agonist), at 2 h (34.9 ± 3.9% vs. 63.6 ± 3.9%; p < 0.001) and 24 h (39.4 ± 3.5% vs. 52.3 ± 3.8%; p = 0.014). After 1 week of therapy, platelet reactivity was again significantly inferior with ticagrelor compared to clopidogrel (30.7 ± 3.0% vs. 54.3 ± 3.0%; p < 0.001). The results were consistent with the other platelet function assays employed. In Mediterranean patients with DM and CCS, ticagrelor provides a more potent antiplatelet effect than clopidogrel after the LD and during the maintenance phase of therapy. [ClinicalTrials.gov], identifier [NCT02457130].

Abstract 14255: Effectiveness and Safety of Ticagrelor versus Clopidogrel in Acute Coronary Syndrome: A Meta-Analysis of Real - World Data

Background: Ticagrelor, a potent P2Y12 inhibitor, was superior to clopidogrel in preventing mortality post acute coronary syndrome (ACS) without a major safety concern in the PLATO trial. Nevertheless, the real-world evidence of ticagrelor post ACS is conflicting and inconclusive. Therefore, we conducted a meta-analysis to assess the effectiveness and safety of ticagrelor versus clopidogrel post ACS using real-world data. Methods: We performed a meta-analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We searched PubMed to identify observational studies exploring the effectiveness and safety of ticagrelor and versus clopidogrel in ACS until 12/01/2022. Two independent reviewers assessed the quality and risk of bias of the included studies. A random-effect model was used to combine data. Effectiveness outcomes were all-cause mortality, cardiovascular mortality, myocardial infarction (MI), and stent thrombosis. Safety outcomes included major bleeding, gastrointestinal (GI) bleeding, and dyspnea. Results: A total of 26 observational studies comparing ticagrelor to clopidogrel post ACS were included. Compared to clopidogrel, ticagrelor significantly reduced all-cause mortality (odds ratio [OR], 0.68 [95% CI, 0.58-0.81], I 2 = 78%)) and cardiovascular mortality (OR, 0.64 [95% CI, 0.48-0.85], I 2 = 78%). Whereas there was no statically significant difference between ticagrelor and clopidogrel in MI and stent thrombosis (OR, 0.92 [95% CI, 0.81-1.05] I 2 =56%) and (OR, 0.61 [95% CI, 0.23-1.66], I 2 = 89%), respectively. Ticagrelor was associated with significantly higher major bleeding incidence (OR, 1.21 [95% CI, 1.06-1.39], I 2 =52%). However, GI bleeding and dyspnea were not significantly increased with ticagrelor use. Conclusions: Real-world data of ticagrelor use post ACS demonstrated that ticagrelor reduced all-cause mortality and cardiovascular mortality in comparison to clopidogrel. However, it was associated with increased major bleeding. Real-world evidence with long follow-up confirming the safety of ticagrelor in comparison to clopidogrel post ACS demonstrated in controlled trials is warranted.

Is there an inter-manufacturer difference in generic clopidogrel response?

Abstract Background Differences in platelet aggregation response to generic clopidogrel by manufacturer has not been investigated. Purpose Compare rates of clopidogrel response among patients receiving medication produced by two different manufacturers after acute coronary syndrome and/or percutaneous coronary intervention. Methods This quality improvement project included 515 adult patients receiving clopidogrel for acute coronary syndrome or ischemic heart disease and referred for coronary angiography/percutaneous coronary intervention at a large, public hospital. The project was divided into two phases: 1. retrospective collection of baseline data; 2. two 12-week, prospective phases in which all clopidogrel in the hospital was restricted to a single manufacturer at a time. The primary outcome was clopidogrel response measured by platelet function testing defined as ADP response &amp;lt;40% on light transmission aggregometry between two manufacturer groups. Aspirin response defined as arachidonic acid response &amp;lt;20% was also measured. Results Of 515 total patients included in both phases (mean [SD] age, 64.5 [11.4] years; 351 [68.2%] men; 450 [87.4%] ACS), 52% were found to be clopidogrel responders based on results of platelet function testing (Table 1 – select variables). Among 135 patients in the prospective phase, there was a significantly lower proportion of patients who were clopidogrel responders in the Manufacturer 1 group compared to the Manufacturer 2 group (34.8% vs. 55.1%, p=0.03) (Table 2 – select variables). After adjustment for age, sex, BMI, aspirin response, therapeutic hypothermia, LHC indication, clopidogrel loading dose, time between loading dose and lab measurement, and manufacturer, aspirin response (OR [95% CI]: 0.96 [0.95–0.97], p&amp;lt;0.001) and manufacturer (OR [95% CI]: 2.45 [1.18–5.22], p=0.02) were associated with clopidogrel response. Conclusions In a large public hospital, we observed that pharmacodynamic response to clopidogrel varied by drug manufacturer. Further investigation and/or regulation is needed to minimize inter-manufacturer variability. Funding Acknowledgement Type of funding sources: None.

Low-dose and standard-dose ticagrelor compared with clopidogrel in patients with acute coronary syndromes: A cohort study from china.

PurposePrevious trials have demonstrated that ticagrelor was superior to clopidogrel in acute coronary syndrome (ACS) patients. However, several recent studies showed that ticagrelor was associated with a significantly higher risk of bleeding compared with clopidogrel, especially in East Asian patients. Low-dose ticagrelor might improve the safety of ACS patients in the Chinese population. Therefore, this study mainly explored the low-dose ticagrelor in Chinese ACS patients.MethodsA total of 199 ACS patients were enrolled in this study. The maximum platelet aggregation rate induced by adenosine-5-diphosphate (ADP) was detected by light transmittance aggregometry (LTA). Platelet aggregation rate induced by ADP of more than or equal to 42.9% was defined as high on-treatment platelet reactivity (HPR) to P2Y12 inhibitors. All patients were followed up for at least 12 months. Clinical outcomes, changes of antiplatelet regimen, medication compliance and adverse reactions were collected.ResultsPatients were divided into three groups according to the P2Y12 inhibitors, including 87 cases in clopidogrel (75 mg once a day) group, 41 cases in ticagrelor 60 mg (twice a day) group, and 71 cases in ticagrelor 90 mg (twice a day) group. ADP-induced platelet aggregation rates in ticagrelor 60 mg group and 90 mg group were 28.4 (19.6, 42.9) and 22.33 (15.1, 34.7) respectively, which were significantly lower than those in clopidogrel group 49.3 (36.5, 61.0) with adjusted P < 0.001. At the same time, there was no significant difference in ADP-induced platelet aggregation rate between ticagrelor 60 mg and 90 mg group (adjusted P = 0.105). Compared with clopidogrel, the proportion of normal on-treatment platelet reactivity (NPR) of ticagrelor 60 mg and ticagrelor 90 mg were significantly higher than that of clopidogrel, and the proportion of NPR of ticagrelor 90 mg group was significantly higher than that of ticagrelor 60 mg group.ConclusionsPatients of ticagrelor 60 mg and ticagrelor 90 mg had comparable platelet aggregation rates induced by ADP, and both of them had significantly more potent antiplatelet aggregation activity detected by LTA than clopidogrel.

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.

Comparative Safety and Effectiveness of Ticagrelor versus Clopidogrel in Patients With Acute Coronary Syndrome: An On-Treatment Analysis From a Multicenter Registry.

Background:The net clinical benefit of ticagrelor over clopidogrel in acute coronary syndrome (ACS) has recently been questioned by observational studies which did not account for time-dependent confounders. We aimed to assess the comparative safety and effectiveness of ticagrelor vs. clopidogrel accounting for non-adherence in a real-life setting.MethodsThis is a prospective, multicenter cohort study of patients with ACS discharged on ticagrelor or clopidogrel between 2015 and 2019. Major exclusions were previous intracranial bleeding, and the use of prasugrel or oral anticoagulation. Association of P2Y12 inhibitor therapy with 1-year risk of Bleeding Academic Research Consortium Type 3 or 5 bleeding; major adverse cardiac events (MACEs), a composite endpoint of all-cause death, nonfatal myocardial infarction (MI), nonfatal stroke, or urgent target lesion revascularization; definite/probable stent thrombosis; vascular death; and net adverse clinical event (a composite endpoint of major bleeding and MACE) were analyzed according to the “on-treatment” principle, using fully adjusted Cox and Fine-Gray regression models with doubly robust inverse probability of censoring weighted estimators.ResultsAmong 2,070 patients (mean age 63 years, 27% women, 62.5% ST-elevation MI), 1,035 were discharged on ticagrelor and clopidogrel, respectively. Ticagrelor-treated patients were younger and had few comorbidities, but high rates of medication non-compliance, compared with clopidogrel users. After comprehensive multivariate adjustments, ticagrelor did not increase the risk of major bleeding compared with clopidogrel [subhazard ratio, 1.40; 95% confidence interval (CI), 0.96–2.05], while proved superior in reducing MACE (hazard ratio 0.62; 95% CI, 0.43–0.90), vascular death (subhazard ratio, 0.71; 95% CI, 0.52–0.97) and definite/probable stent thrombosis (subhazard ratio, 0.54; 95% CI, 0.30-0.79); thereby resulting in a favorable net clinical benefit (hazard ratio 0.78; 95% CI, 0.60–0.98) compared with clopidogrel. Results from sensitivity analyses were consistent with those from the primary analysis, whereas those from the intention-to-treat (ITT) analysis went in the opposite direction.ConclusionAmong all-comers with ACS, ticagrelor did not significantly increase the risk of major bleeding, while resulting in a net clinical benefit compared with clopidogrel. Further research is warranted to confirm these findings in high bleeding risk populations.CREA-ARIAM Andalucía(ClinicalTrials.gov Identifier: NCT02500290); Current pre-specified analysis (ClinicalTrials.gov Identifier: NCT04630288).

Factors predicting the occurrence of net adverse clinical and cerebral events in patients with acute coronary syndrome treated with clopidogrel or ticagrelor in combination with aspirin: a real-world study.

BackgroundThis study aimed to establish the factors influencing the clinical benefits of ticagrelor and clopidogrel for acute coronary syndrome (ACS) patients undergoing percutaneous coronary intervention (PCI) surgery.MethodsA multicenter, retrospective, real-world study was conducted on patients with ACS whose data were sourced from 3 databases, namely the BRIC-ACS(I) study, COSTIC study, and 301 Hospital PCI patient database from January 2014 to October 2017. The primary endpoint was net adverse clinical and cerebral events (NACCE).ResultsA total of 7,236 ACS patients were included, of which 4,444 patients (61.4%) and 2,792 patients (38.6%) were in the clopidogrel dual antiplatelet therapy (DAPT) group and ticagrelor DAPT group, respectively. The hazard ratio (HR) for NACCE was significantly higher in patients aged ≥65 years than those aged ≤65 years in the clopidogrel DAPT group (HR: 2.15, 95% CI: 1.68–2.76) and ticagrelor DAPT group (HR: 1.75, 95% CI: 1.34–2.29). In patients treated with clopidogrel DAPT, patients with unstable angina had a significantly lower HR for NACCE than patients with ST-elevation myocardial infarction. Use of beta blockers (HR: 0.77, 95% CI: 0.60–0.99) was an influencing factor in patients treated with clopidogrel DAPT, whereas in patients treated with ticagrelor DAPT, only smoking status (HR: 0.75, 95% CI: 0.57–0.99) was a significant influencing factor.ConclusionsAge, hypertension status, and presence or absence of unstable angina were factors influencing the composite outcome of NACCE. The selection of patients to be treated with either clopidogrel DAPT or ticagrelor DAPT depending on the presence or absence of factors influencing treatment outcome may improve therapeutic management.

АНТИАГРЕГАНТНАЯ ТЕРАПИЯ И ВТОРИЧНАЯ ПРОФИЛАКТИКА ПОСЛЕ КОРОНАРНОГО ШУНТИРОВАНИЯ ПРИ ОСТРЫМ КОРОНАРНЫМ СИНДРОМЕ

Antiplatelet therapy with aspirin and clopidogrel has clear advantages in reducing serious adverse cardiovascular events and mortality following acute coronary syndrome. Although these drugs may pose an additional risk of bleeding in the small percentage of acute coronary syndrome patients who will undergo coronary artery bypass grafting, the benefits are vastly superior, and most bleeding can be reduced, if possible, by delaying coronary artery bypass grafting. Short-acting anticoagulants can be administered flexibly, allowing platelet function to be restored after clopidogrel is discontinued. The postoperative bleeding time may clarify the need for platelet transfusion in case of bleeding. Coronary artery bypass grafting without the use of a heart-lung machine may offer some benefits by avoiding heparinization and the inflammatory response associated with bypass surgery. Secondary prophylaxis with antiplatelet therapy, beta-blockers, lipid-lowering therapy, and ACE inhibitors or angiotensin-converting enzyme inhibitors is critical to the long-term success of revascularization. In this regard, it should be borne in mind that regardless of the method of revascularization, patients with acute coronary syndrome are characterized by the clinical benefit of taking antiplatelet agents such as aspirin and clopidogrel, since these drugs reduce the risk of serious adverse events. On the other hand, antiplatelet agents also increase the risk of bleeding in patients who will eventually undergo coronary artery bypass grafting. However, scientists indicate that in most cases, the benefits of early initiation of antiplatelet therapy outweigh the potential risks [1]. In addition, the beneficial effects of aspirin and clopidogrel in acute coronary syndrome are additive. In the study of clopidogrel, indicated for the prevention of recurrence of unstable angina and non-ST-segment elevation myocardial infarction, patients taking both clopidogrel and aspirin were less likely to die of cardiac death, non-fatal myocardial infarction, or stroke at 30 days and 1 year compared with patients who took only aspirin [22]. All these studies confirm that antiplatelet therapy with aspirin and clopidogrel should be carried out in the early stages of acute coronary syndrome. In patients with ST-segment elevation myocardial infarction, clopidogrel improves outcomes in addition to aspirin. In a trial of clopidogrel and metoprolol for myocardial infarction, clopidogrel, in addition to aspirin, was associated with a significant reduction in death, re-heart attack, or stroke compared with aspirin alone [14].

Efficacy and safety of ticagrelor versus clopidogrel in Chinese patients with acute coronary syndrome treated with glycoprotein Ⅱb/Ⅲa receptor antagonist

Objective: To explore the efficacy and safety of ticagrelor versus clopidogrel in acute coronary syndrome (ACS) Chinese patients using glycoprotein Ⅱb/Ⅲa inhibitor (GPI). Methods: The data from CCC-ACS (Improving Care for Cardiovascular Disease in China-ACS) project were systematically reviewed in ACS patients with GPI. The patients were divided into ticagrelor and clopidogrel groups. A logistic analysis and propensity score matching (PSM) were performed to compare occurrences of major cardiovascular events (MACE) and bleeding events between the two groups during hospitalization. Results: A total of 63 641 ACS patients were collected from 150 hospitals. Logistic regression analyses showed that there was no statistically significant difference in the reduction of MACE between ticagrelor and clopidogrel when using GPI (OR=0.881, 95%CI 0.599-1.296; P=0.521). However, major bleeding rate was higher in the ticagrelor group than that in the clopidogrel group (OR=1.401, 95%CI 1.075-1.852; P=0.013). Similar results were observed after PSM. No statistic difference in MACE between the ticagrelor and clopidogrel group (OR=0.919, 95%CI 0.613-1.376; P=0.681). Major bleeding rate was higher in the ticagrelor group (OR=1.559, 95%CI 1.130-2.150; P=0.007). Conclusion: In ACS patients with GPI, ticagrelor did not reduce MACE, but increased the major bleeding risk compared with clopidogrel.

PCV18 Implementation of Pharmacogenomic Clinical Decision Support Alerts in Learning Health Systems: A Cost-Utility Analysis

Pharmacogenomic (PGx) test results delivered by clinical decision support (CDS) alerts guide drug therapy, however, evidence of its value is lacking. Thus, we estimated the value of developing and implementing PGx-CDS alerts over a 20-year time horizon, using a cost-utility analysis from the perspective of Learning Health Systems (LHSs). To generate customizable estimates, we present modifiable parameters in a R Shiny app to guide development of alerts. We compared PGx-CDS alerts to no alerts in an age-based cohort of 500,000 individuals who had received preemptive PGx testing for four pharmacogenes (CYP2C19, CYP2C9, CYP4F2 and VKORC1) to guide potential therapy with clopidogrel for acute coronary syndrome (ACS) or warfarin for atrial fibrillation (AF). We identified literature-based payoffs for PGx testing, including incremental costs, incremental quality-adjusted life-years (QALYs), and risk differences for adverse events. Incident prescription use by age was estimated from IBM® MarketScan Research Databases 2015-2019. To mirror real-world practice, alert fatigue, start-up- and maintenance costs were included. A 3% annual discount was applied, and one-way and probabilistic sensitivity analyses were conducted. Over 20 years, 3,173 alerts would be fired, at an average cost of $92/alert fired. The incremental cost of PGx-CDS alerts was $292,029, and the incremental QALYs were 10.29, producing an incremental cost effectiveness ratio (ICER) of $28,381/QALY gained in favor of alerting. For every two alerts fired for clopidogrel, one adverse event of non-fatal MI and one cardiovascular death would be averted; for every two alerts fired for warfarin, three events of bleeding and one event of clotting would be averted. The most influential parameter was the risk of initiating clopidogrel or warfarin therapy. Estimated ICERs were below $50,000/QALY in 99% of 1,000 probabilistic simulations. Our results suggest that implementing PGx-CDS alerts reduces the number of drug-related adverse events in a cost-effective manner.

Intravenous glycoprotein IIbIIIa inhibitor bridging for urgent coronary artery bypass graft after acute coronary syndrome

Abstract Background Previous studies have shown the safety of intravenous glycoprotein (GP) IIbIIIa inhibitors used as a bridging after ADP receptor blocker withdrawal in patients with stable coronary artery disease and previous percutaneous coronary interventions (PCI) undergoing cardiac or non-cardiac surgeries. However, there are few data analyzing GP IIbIIIa inhibitor bridging among patients with acute coronary syndromes (ACS) scheduled for coronary artery bypass graft (CABG) during the same hospitalization. Purpose To evaluate the safety of tirofiban bridging after clopidogrel withdraw in post-ACS patients schedule for CABG during the same hospitalization. Methods Fifty-six patients who underwent CABG after tirofiban bridging post-ACS (bridge group - BG) were compared to 56 sex and age-matched controls also submitted to same-hospitalization CABG post-ACS without bridging (control group - CG). All patients received aspirin plus clopidogrel for ACS; clopidogrel was withdrawn 5 to 7 days before CABG and aspirin was maintained during the whole perioperative period. The primary endpoint was chest tube output in the first 24h after CABG (CTO24h). We hypothesized that BG would be non-inferior to CG, with a non-inferiority margin of 25% in excess of CTO24h in the BG compared to the CG, based on prior literature data. Other exploratory analyses were: blood transfusions, number of red blood cells/patient and re-thoracotomy 24h after surgery. A multivariable linear regression model was developed considering CTO24h as dependent variable and adjusted for other eight co-variates, described in the figure. Results From the 112 patients included (75% men; mean age 60.2±9.3 years), in comparison with CG, BG had higher proportion of STEMI (80.0% vs. 28.6%, p&amp;lt;0.01), fibrinolytic utilization (25% vs. 7.1%, p&amp;lt;0.05), PCI in the acute phase (92.9% vs. 0%, p&amp;lt;0.01) and LMCA stenosis (30.4% vs. 7.1% p&amp;lt;0.01). Tirofiban was utilized by clinician discretion due to PCI in the same hospitalization previously to CABG (n=52), previous PCI up to 3 months before index event (n=3) or severe LMCA stenosis (n=1). BG patients received tirofiban for a mean of 4.3±2.1 days and it was withdrawn at a mean of 6.6±4.3 hours before CABG. After adjustments, BG was non-inferior to CG regarding CTO24h (figure) There were no significant differences between BG and CG regarding need for blood transfusion (26.8% vs. 26.8%, p&amp;gt;0.99), mean number of red blood cells/patient (0.3±0.8 vs 0.5±1.2, p=0.35) or re-thoracotomy due to bleeding (5.4% vs 0%, p=0.24). Conclusion Among ACS patients submitted to urgent CABG after clopidogrel withdrawal, tirofiban bridging, compared to no bridging, was not associated with higher risk of bleeding in the first 24 hours after surgery. Our study suggests that tirofiban may be a safe therapy to patients with high risk of thrombotic complication (such as stent thrombosis or re-infarction) after clopidogrel withdraw. Figure 1 Funding Acknowledgement Type of funding source: None

Impact of antiplatelet therapy on tissue prolapse at super acute phase after stenting: serial OCT study in acute coronary syndrome patients.

Although drug-eluting stents have improved clinical outcomes, percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) remains a challenging procedure in terms of thrombus management. A new-generation P2Y12 receptor inhibitor, prasugrel, provides more rapid and potent antiplatelet action compared with clopidogrel. Prasugrel achieved significant reduction of ischemic events compared with clopidogrel in ACS. The aim of this optical coherence tomography (OCT) study was to evaluate temporal changes in tissue prolapse after stenting under different antiplatelet regimens (aspirin plus prasugrel or clopidogrel) in ACS patients. A total of 119 ACS patients were randomized to either prasugrel or clopidogrel at the time of PCI. OCT analysis was available in 119 patients at baseline (just after stenting), 77 patients at 2weeks, and 62 patients at 4months after stenting. Cross-sectional analysis for every 1mm was performed at in-stent and adjacent reference segment. Tissue prolapse area was calculated by lumen area minus stent area within the stented segment. Baseline patient and procedural characteristics were not different between the prasugrel and clopidogrel groups. Tissue prolapse area was significantly lower in the prasugrel compared with the clopidogrel group after stenting (0.24 ± 0.23 vs. 0.36 ± 0.23 mm2, p = 0.003) and at 2weeks (0.11 ± 0.13 vs. 0.19 ± 0.16 mm2, p = 0.005). However, there was no significant difference at 4months. In conclusion, our study suggests prasugrel was effective in reducing tissue prolapse in the super acute phase in ACS patients compared with clopidogrel. However, the effect of tissue prolapse reduction was not different up to 4months follow-up.

Evaluation of a Novel Antiplatelet Therapy Strategy in Patients Undergoing Elective Percutaneous Coronary Intervention

Background Ticagrelor presents less thrombotic risk compared to clopidogrel in acute coronary syndromes. However, its role in dual antiplatelet therapy (DAPT)-naive patients with stable ischemic heart disease (SIHD) undergoing elective percutaneous intervention (PCI) remains unclear, including uncertainty in the method of conversion to clopidogrel for adequate coverage without increased bleeding risk. Objective Determine the safety and efficacy of ticagrelor loading and transitioning to clopidogrel in patients with SIHD undergoing elective PCI. Methods This is a retrospective cohort review of patients with SIHD who underwent elective PCI. The Switch Rx patients were treated with ticagrelor immediately before PCI, converted to clopidogrel 300 mg the day after, and discharged with clopidogrel 75 mg daily. Standard Rx patients, who received a clopidogrel load and received clopidogrel 75 mg daily after the procedure, were analyzed as a matched comparator cohort. The safety outcomes were any bleeding event at 24 hours and 30 days. The efficacy outcomes included major adverse cardiac events (MACE) at 24 hours and 30 days. Results Five Switch Rx patients (n = 54) experienced bleeding academic research consortium type I bleeding within 24 hours, with no subsequent bleeding observed out to 30 days. When comparing the Switch Rx patients (n = 39) to their matched Standard Rx cohort (n = 39), no MACEs occurred within 30 days and there were no significant differences in safety and efficacy outcomes. Conclusion In DAPT-naive patients undergoing elective PCI for SIHD, a strategy of in-lab ticagrelor transitioning to clopidogrel with a 300-mg load was not associated with increased bleeding or other adverse events.

Does concurrent use of clopidogrel and PPIs increase CV risk in patients with ACS?

No. Adding a proton pump inhibitor (PPI) in patients taking antiplatelet medications such as clopidogrel for acute coronary syndrome (ACS) doesn't increase the composite risk of cardiovascular (CV) events: CV death, myocardial infarction (MI), and cerebrovascular accident (CVA) (strength of recommendation: B, randomized, controlled trial [RCT] and prepon-derance of posthoc analyses of large RCTs).

Clinical Utility of CYP2C19 Genotype-Guided Antiplatelet Therapy in Patients at Risk of Adverse Cardiovascular and Cerebrovascular Events: A Review of Emerging Evidence.

In patients undergoing percutaneous coronary intervention (PCI), the standard of care is dual antiplatelet therapy with a P2Y12 inhibitor (clopidogrel, prasugrel, or ticagrelor) and aspirin. Current clinical practice guidelines now recommend more potent P2Y12 inhibitors (prasugrel or ticagrelor) over clopidogrel in acute coronary syndrome (ACS). However, clopidogrel remains the most commonly prescribed P2Y12 inhibitor in the setting of PCI and is also the preferred agent in the treatment and secondary prevention of stroke. Clopidogrel is a prodrug that requires bioactivation by the CYP2C19 enzyme. It has been shown that clopidogrel use in patients who are CYP2C19 no function allele carriers are associated with impaired antiplatelet inhibition and a higher risk of major adverse cardiovascular and cerebrovascular events. Compared to clopidogrel, prasugrel and ticagrelor clinical response is not impacted by CYP2C19 genotype. Even with a demonstrated increased risk of adverse outcomes in CYP2C19 no function allele carriers treated with clopidogrel, routine implementation of CYP2C19 genotyping to guide antiplatelet therapy selection has remained controversial and has not been widely adopted. Recent results from multiple prospective randomized and nonrandomized clinical trials investigating the use of CYP2C19 genotype-guided antiplatelet therapy following PCI have advanced the evidence base demonstrating the clinical utility of this strategy. Multiple recent studies have examined the effects of CYP2C19 genotype on clopidogrel outcomes in the setting of stroke and neurointerventional procedures. In this review, we discern the clinical utility of using CYP2C19 genotype testing to guide antiplatelet therapy prescribing by evaluating the impact of CYP2C19 genotype-guided selection of antiplatelet therapy on clinical outcomes, summarizing emerging data from cardiovascular and neurology clinical studies, and discussing implications for clinical practice guidelines, remaining knowledge gaps and future research directions.

The role of clopidogrel in the current treatment of acute coronary syndrome

In the article, a review is given of the facts that determined contemporary views of the role of clopidogrel in the treatment of acute coronary syndrome. The author described a history of the clinical studies of clopidogrel in acute coronary syndrome (ACS), analysed its role in the current approaches to the treatment of the disease during the widespread use of other platelet P2Y 12 receptor antagonists (ticagrelor and prasugrel). The article discusses circumstances, when clopidogrel may have additional advantages, particularly the role of adherence to prolonged double antiplatelet therapy, as well as situations, when sever suppression of platelet function can be decreased (treatment de-escalation). According to a prospective randomized open-label PoPular Age study, clopidogrel combined with acetylsalicylic acid in patients with ACS without persistent ST segment elevations at the age of ≥70 years showed better adherence to treatment over the coming year as compared with clopidogrel combined with ticagrelor or prasugrel. As a result, these two approaches had comparable efficacy. Today, treatment de-escalation is a necessary measure to extend the double antiplatelet therapy in cases, when continued administration of prasugrel or ticagrelor appears unacceptable. There is insufficient evidence for the routine implementation of de-escalation in stented patients with ACS, although a small prospective, one-centre randomized open-label ToPIC study shows that this approach is safe. The author provides a review of the results of recently presented prospective studies on the choice of a platelet P2Y 12 receptor antagonist for long-term treatment of acute coronary syndrome, taking into account the residual platelet reactivity and cytochrome p450 2c19 genetic polymorphisms. Among them are multicenter open randomized clinical TRoPICAL-ACS study, multicenter randomized open-label PoPular Genetics and TAILoR PCI studies. According to the study results, the long-term outcomes in stented patients with ACS with a good response to clopidogrel assessed by the residual functional activity of platelets or by studying cytochrome p450 2c19 genetic polymorphisms may not be worse than those during use of prasugrel or ticagrelor.

Comparative Efficacy and Safety of Oral P2Y12 Inhibitors in Acute Coronary Syndrome: Network Meta-Analysis of 52 816 Patients From 12 Randomized Trials.

New randomized, controlled trials have become available on oral P2Y12 inhibitors in acute coronary syndrome. We aimed to evaluate current evidence comparing the efficacy and safety profile of prasugrel, ticagrelor, and clopidogrel in acute coronary syndrome by a meta-analysis of randomized controlled trials. We performed a network meta-analysis and direct pairwise comparison analysis of efficacy and safety outcomes from 12 randomized controlled trials including a total of 52 816 patients with acute coronary syndrome. In comparison with clopidogrel, ticagrelor significantly reduced cardiovascular mortality (hazard ratio [HR], 0.82 [95% CI, 0.72-0.92]) and all-cause mortality (HR, 0.83 [95% CI, 0.75-0.92]), whereas there was no statistically significant mortality reduction with prasugrel (HR, 0.90 [95% CI, 0.80-1.01] and HR, 0.92 [95% CI, 0.84-1.02], respectively). In comparison with each other, there were no significant differences in mortality (HR prasugrel versus ticagrelor, 1.10 [95% CI, 0.94-1.29] and 1.12 [95% CI, 0.98-1.28]). In comparison with clopidogrel, prasugrel reduced myocardial infarction (HR, 0.81 [95% CI, 0.67-0.98]), whereas ticagrelor showed no risk reduction (HR, 0.97 [95% CI, 0.78-1.22]). Differences between prasugrel and ticagrelor were not statistically significant. Stent thrombosis risk was significantly reduced by both ticagrelor and prasugrel versus clopidogrel (28%-50% range of reduction). In comparison with clopidogrel, both prasugrel (HR, 1.26 [95% CI, 1.01-1.56]) and ticagrelor (HR, 1.27 [95% CI, 1.04-1.55]) significantly increased major bleeding. There were no significant differences between prasugrel and ticagrelor for all outcomes explored. Prasugrel and ticagrelor reduced ischemic events and increased bleeding in comparison with clopidogrel. A significant mortality reduction was observed with ticagrelor only. There was no efficacy and safety difference between prasugrel and ticagrelor. Registration: URL: https://www.crd.york.ac.uk/PROSPERO/; Unique identifier: CRD42019155648.