Part Of Dual Antiplatelet Therapy Research Articles

Clopidogrel resistance and its relevance: Current concepts

ABSTRACT Clopidogrel is the most widely used P2Y12 receptor inhibitor (P2Y12i) as a part of dual antiplatelet therapy along with aspirin. Clopidogrel is a pro-drug and is metabolized to its active metabolite by the hepatic enzyme cytochrome P4502C19 (CYP2C19). This active metabolite is responsible for the antiplatelet action of clopidogrel. Recent studies have demonstrated that single nucleotide polymorphisms in the CYP2C19 gene, including CYP2C19*2,*3,*4, and *5 alleles, result in reduced production of the active metabolite of clopidogrel, and hence reduced inhibition of platelet aggregation. This in turn enhances the incidence of stent thrombosis and recurrent cardiovascular (CV) events. We report a case of coronary stent thrombosis due to clopidogrel resistance proven by CYP2C19 genotyping. We then review the literature on clopidogrel resistance and its impact on CV outcomes. Subsequently, we discuss the methods of diagnosis of resistance, evidence from clinical trials for tailoring clopidogrel therapy, the role of potent P2Y12 inhibitors, the current guidelines, and future directions.

Ticagrelor versus Clopidogrel in diabetes patients afflicted with acute coronary syndrome stratified by renal function

Abstract Background Ticagrelor has been recommended in place of clopidogrel as part of dual antiplatelet therapy (DAPT) in diabetic patients with acute coronary syndrome (ACS). Chronic kidney disease (CKD) patients also have a worse prognosis in the setting of ACS, but the safety and efficacy data for the use of P2Y12 inhibitors in moderate to severe CKD patients (eGFR <60 mL/min/1.73m2) are insufficient. Purpose There has been limited data on the outcome of prescribing ticagrelor compared to clopidogrel in ACS-DM patients with chronic kidney disease (CKD). Methods This prospective, nationwide, multi-center, observational study, the Acute Coronary Syndrome-Diabetes Mellitus Registry (ACS-DM Registry) was compiled from consecutive patients between October 1, 2013 and September 30, 2016. The primary end point was repeated revascularisation and the composite outcome was CV death, repeat revascularisation and CV-related readmission, was stratified by renal function stages. The Cox proportional hazards models and propensity score models were applied to six-months, one-year, and two-year post ACS, respectively. Results There were 539 patients with moderate to severe CKD or on dialysis identified from ACS-DM Registry. There were 451 patients eligible for inclusion criteria of which 116 patients were taking ticagrelor and 335 patients were taking clopidogrel. At our two-year follow-up, the unadjusted incidence of primary end point resulted higher in Ticagrelor group (HR 2.09, 95% CI 1.37-3.18, p = 0.001). After adjustment, ticagrelor also had poor primary end point event and composite outcome as compared to clopidogrel (HR 2.24, 95% CI 1.36-3.68, p = 0.002; HR 1.63, 95% CI 1.06-2.48, p = 0.024, respectively). In regards to the repeated revascularisation issue, the clopidogrel was preferable within the eGFR strata (CKD stage III: HR 2.53, 95% CI 1.32-4.84, CKD stage IV: 1.06 (0.09-12.51), CKD stage V: 1.91 (0.80-4.59), P for interaction=0.684). Conclusions Cardiovascular benefits associated with ticagrelor may not be as significant as in the landmark trial. Our results show that patients taking ticagrelor was associated with increased CV events as compared to clopidogrel in ACS-DM patients with stage III-V CKD.propensity score matchingForest plots

Abstract 17654: Sarpogrelate versus Clopidogrel for Arterial Interventions Systematic Review and Meta Analysis

Background: Sarpogrelate has been used to alleviate ischemic changes by preventing thrombosis, vasoconstriction, and vascular smoothmuscle proliferation. The worldwide use of Sarpogrelate is arguable due to the lack of reliable data regarding its efficacy and safety.Accordingly, our meta-analysis aims to compare the complications after receiving Sarpogrelate with Aspirin (S&A) vs. Clopidogrel withAspirin (C&A) as part of dual anti-platelet therapy in patients with endovascular intervention. Methods: Multiple electronic databases weresearched to identify relevant articles, including MEDLINE, Cochrane CENTRAL, Scopus, Google Scholar, Web of Science, and EMBASE. Allclinical studies that investigated the complication after performing Sarpogrelate versus clopidogrel with Aspirin for arterial interventionswere included in the meta-analysis. Reviews, case reports, conference abstracts, editorials, and animal studies were all excluded. Data wereanalyzed by using comprehensive meta-analysis studies. A complete quality assessment was performed using the Cochrane Risk of Bias toolversion 2 for randomized clinical trials (RCTs). Results: A total of 2588 studies were screened, with three studies included. Two multicenterRCTs and one retrospective cohort study including 527 patients (251 S&A and 276 C&A) were included. The overall quality was high in 2studies and fair in one. No statistically significant difference in restenosis, mortality, and bleeding risk as follows, respectively: (RR:0.81, 95%CI:0.52-1.2, P-value:0.36), (RR:0.37, 95% CI:0.06-2, P-value:0.25) and (RR:0.4, 95% CI:0.13-1.19, P-value:0.1). Conclusion: The antithromboticeffects of Aspirin with Sarpogrelate after vascular intervention are comparable to those of Aspirin plus Clopidogrel. Further large clinicalstudies are required to identify the actual difference in early and late complications after using Sarpogrelate versus clopidogrel.

Usefulness of the PRECISE-DAPT score at differentiating between ticagrelor and prasugrel for dual antiplatelet therapy initiation.

As a part of dual antiplatelet therapy (DAPT), prasugrel or ticagrelor is prescribed along with aspirin to patients of acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). We aimed to assess if the PRECISE-DAPT score, which provides prediction of bleeding during DAPT, could be used to choose between prasugrel and ticagrelor for DAPT initiation. 181 patients out of which 71 received prasugrel and 110 received ticagrelor were enrolled in this prospective cohort study. PRECISE-DAPT score was calculated for everyone and was used to dichotomize patients into two subgroups (score <25 and ≥25). After balancing potential confounders in baseline characteristics of the subgroups using propensity scores, comparison of a composite outcome of 4-point major adverse cardiovascular events (4P-MACE) (i.e., cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or coronary revascularization due to stent thrombosis) and bleeding (any type as defined by the Bleeding Academic Research Consortium) within 1-year post-PCI was performed among the subgroups using Cox proportional hazards regression. Prasugrel was associated with lower and comparatively higher 4P-MACE events in subgroups with score ≥25 (HR: 0.17; 95% CI, 0.04-0.77) and score <25 (HR: 3.58; 95% CI, 0.62-20.70) respectively. For bleeding outcome, prasugrel trended towards more clinical benefit for scores ≥25 (HR: 0.44; 95% CI, 0.10-1.93) than <25 (HR: 0.93; 95% CI, 0.13-6.58). Therefore, prasugrel was associated with better clinical effectiveness and trended towards a lower bleeding risk compared to ticagrelor within 1-year post-PCI for those with a high PRECISE-DAPT score (≥25). This finding requires validation through larger studies.

Role of platelet function testing in acute coronary syndromes: a meta-analysis

ObjectiveThis meta-analysis aimed to evaluate whether using platelet function testing (PFT) in acute coronary syndromes (ACS) to personalise antiplatelet therapy including a P2Y12 antagonist offers any clinical benefits to indicate...

The Advantages of Dual Antiplatelet Therapy Combinations in Predicting Recurrent Cardiovascular Events in Obese Patients after Myocardial Infarction

The purpose of the study was to analyze the incidence of recurrent cardiovascular events in obese patients after a myocardial infarction during a 6-month follow-up period, depending on the combination of ticagrelor or clopidogrel with acetylsalicylic acid as a part of dual antiplatelet therapy. Materials and methods. The study involved 75 patients with acute myocardial infarction with ST segment elevation and concomitant obesity. The patients were divided into 2 subgroups: the first included 31 patients who received the combination of acetylsalicylic acid and ticaglelor, and the second – 44 patients treated with the combination of acetylsalicylic acid and clopidogrel in dual antiplatelet therapy. The GRACE scale was used to stratify the risk of hospital and 6-month mortality. Control of the recurrent cardiovascular events presence was carried out after 6 months. Results and discussion. Acute myocardial infarction with ST elevation is still the main cause of mortality and invalidisation of able-bodied population. Regardless of the primary percutaneous coronary intervention or thrombolysis, dual antiplatelet therapy remains the main therapeutic strategy, both in the acute ST-elevation myocardial infarction period and in the remote – for the secondary prevention of possible adverse cardiovascular events, and is a combination of acetylsalicylic acid and a P2Y12 receptor inhibitor. To date, the issue of the choice of a P2Y12 receptor inhibitor in the dual antiplatelet therapy that is used in the treatment of ST-elevation myocardial infarction is an urgent subject of scientific discussion. While observing patients after a myocardial infarction with concomitant obesity over a period of 6 months, it was found that 28 patients had a recurrent myocardial infarction and / or unstable angina, which was 37.56% of all patients. The analysis of the GRACE scale scores in a cohort of patients with recurrent cardiovascular events revealed that all patients were included in high risk group (&gt; 118 points). In the group of patients who received dual antiplatelet therapy with the involvement of acetylsalicylic acid and ticagrelor in 11 people recorded a repeated myocardial infarction and / or unstable angina, which was 14.76%. At the same time, in a group of patients receiving dual antiplatelet therapy in a combination of acetylsalicylic acid with clopidogrel, re-cardiovascular catastrophes were detected in 17 patients, which was 22.8% of all patients with ST-elevation myocardial infarction on the background of concomitant obesity. Conclusion. The patients with obesity after a myocardial infarction who are included in the GRACE high risk group are recommended to be treated with the combination of acetylsalicylic acid and ticagrelor as a result of a notable reduction in the risk of recurrent cardiovascular catastrophes compared with the combination of acetylsalicylic acid and clopidogrel

Efficacy and Safety of Clopidogrel Versus Ticagrelor as Part of Dual Antiplatelet Therapy in Acute Coronary Syndrome-A Systematic Review and Meta-analysis.

The efficacy and safety of clopidogrel compared with ticagrelor as part of dual antiplatelet therapy in patients, and in older patients, with acute coronary syndrome is reviewed. PubMed, Embase, the Cochrane Library, MEDLINE, and HTA databases were searched (September 2, 2020) for randomized controlled trials (RCTs). Pooled risk differences (clopidogrel minus ticagrelor) were estimated using random-effects meta-analyses, and certainty of evidence was assessed according to Grading of Recommendations Assessment, Development, and Evaluation. In all, 29 RCTs were identified. The risk difference for all-cause mortality was 0.6% (-0.03% to 1.3%), cardiovascular (CV) mortality: 0.6% (95% confidence interval: 0.01% to 1.1%), myocardial infarction (MI): 0.9% (0.4% to 1.3%), stent thrombosis: 0.7% (0.4 to 1.1%), clinically significant bleeding: -1.9% (-3.7% to -0.2%), major bleeding: -0.9% (-1.6% to -0.1%), and dyspnea: -5.8% (-7.7% to -3.8%). In older patients, there were no differences between the comparison groups regarding all-cause mortality, CV mortality, and MI, whereas the risk of clinically significant bleeding and major bleeding was lower in the clopidogrel group, -5.9% (-11 to -0.9%, 1 RCT) and -2.4% (-4.4% to -0.3%), respectively. Compared with ticagrelor, clopidogrel may result in little or no difference regarding all-cause mortality. Although not evident in older patients, it cannot be excluded that clopidogrel may be slightly less efficient in reducing the risk of CV mortality and MI, whereas ticagrelor is probably more efficacious in reducing the risk of stent thrombosis. Clopidogrel results in a reduced risk of dyspnea and clinically significant bleeding and in older people probably in a reduced risk of major bleeding.

TCT-471 ABSTRACT WITHDRAWN

TCT-471 ABSTRACT WITHDRAWN

Efficiency and safety of various dual antiplatelet therapy strategies in patients undergoing percutaneous coronary intervention due to myocardial infarction

Aim. To compare the efficacy and safety of prasugrel, ticagrelor, or clopidogrel as part of dual antiplatelet therapy (DAPT) in patients undergoing percutaneous coronary intervention (PCI) due to myocardial infarction (MI).Material and methods. The observational study included 74 patients who underwent PCI due to MI within the first 24 hours after the onset. The patients were devided into 3 groups: group 1 — patients who received ticagrelor as part of DAPT; group 2 — clopidogrel, group 3 — prasugrel. The follow-up period was 28 days. To assess the efficacy and safety of therapy, a composite endpoint was assessed (death + nonfatal recurrent MI (and/or stent rethrombosis) + nonfatal ischemic stroke (IS). Additional secondary endpoints were any moderate and severe (major) bleeding according to the GUSTO and/or TIMI scales. We assessed the incidence of reperfusion arrhythmias, an opening of an infarct-related coronary artery (IRCA), and non-ST elevation myocardial infarction (non-STEMI).Results. The analysis showed no significant differences in the cumulative incidence of adverse outcomes in the study groups within 28 days. The prevalence of secondary endpoints over a 28-day follow-up period was 3,1% in the ticagrelor group and 5,9% in the clopidogrel group, while no moderate and life-threatening bleeding was recorded in the prasugrel group during. There were no significant differences in the incidence of reperfusion arrhythmias, opening of an IRCA, and non-STEMI between the groups.Conclusion. The obtained results suggest the comparable efficacy and safety profiles of prasugrel, ticagrelor and clopidogrel as a part of DAPT in patients undergoing PCI due to MI. There were no significant differences in endpoint event rates. In particular, prasugrel has been shown to be as effective and safe as ticagrelor.

Anticoagulants and antiaggregants in the COVID-19 era

Review of the latest scientific data and the main provisions of clinical guidelines on the use of anticoagulants and antiaggregants in patients with COVID-19 is presented. A separate part of the paper focuses on the use of prasugrel in this group of patients. The main trend in the use of anticoagulants for the prevention of venous thromboembolism in COVID-19 infection can be considered as a decrease in drug activity. Thus, the experts of the American Hematological Society suggest using low doses of oral or parenteral anticoagulants for thromboprophylaxis in hospitalized patients, preferring them to intermediate or high doses. Virtually all experts agree that prophylactic anticoagulant use should be avoided in clinical practice in patients with COVID-19 who are on outpatient treatment (whether it was chosen as an initial tactic or was a continuation of inpatient treatment). The principles for the therapeutic use of anticoagulants in COVID-19 should be based on already existing clinical guidelines for the conditions that require anticoagulants (atrial fibrillation, venous thrombosis or thromboembolism, presence of mechanical valves, etc.). The use of antiaggregants in patients with COVID-19 outside their registered indications is currently continuing to be studied in several clinical trials. That said, as part of dual antiplatelet therapy after percutaneous coronary intervention for COVID-19, it is advisable to continue this treatment without cancelling any of its components without a specific indication. The same is true for prasugrel, which remains one of the first recommended potent P2Y12 inhibitors.

Efficacy and safety comparing prasugrel/ticagrelor and clopidogrel in Hong Kong post-acute coronary syndrome patients-A 10-year cohort study.

BackgroundClinical evidence of prasugrel/ticagrelor in dual antiplatelet therapy (DAPT) in Asian acute coronary syndrome (ACS) population remains inconclusive. We aimed to compare the clinical efficacy and safety of prasugrel/ticagrelor compared to clopidogrel as part of DAPT in Hong Kong ACS population for 10 years.HypothesisPrasugrel/ticagrelor, compared to clopidogrel, reduces risk of major adverse cardiovascular event (MACE) in Hong Kong ACS population.MethodsThe retrospective observational cohort study included patients admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008–2017. Risk of MACE, defined as composite of cardiovascular (CV) death, non‐fatal myocardial infarction (MI) and non‐fatal stroke, and risk of any bleeding leading to hospitalization were examined. Baseline characteristics difference was adjusted by propensity score (PS) matching. Adjusted Cox regression model was used to estimate hazard ratio of interested outcome.ResultsIn PS matched cohort including 944 patients in each group, MACE risk reduction of 40% from 1 year to 5 years after index ACS event was observed in prasugrel/ticagrelor group (HR 0.60, 95% CI 0.39–0.91, p = .015). The risk reduction was highly driven by MI reduction (HR 0.54, 95% CI 0.33–0.91, p = .019). Lower bleeding risk was observed in prasugrel/ticagrelor group compared to clopidogrel from 1 year to 5 years (HR 0.46, 95% CI 0.21–1.00, p = .051).ConclusionsPrasugrel/ticagrelor showed MACE risk reduction over clopidogrel as part of DAPT up to 5 years after index event, while prasugrel/ticagrelor was not associated with increased bleeding risk.

Prasugrel switching from clopidogrel after percutaneous coronary intervention for acute coronary syndrome in Taiwanese patients: an analysis of safety and efficacy

The recommended maintenance dose of prasugrel for East Asian populations (i.e., Japanese and Taiwanese) is 3.75 mg as part of dual antiplatelet therapy (DAPT) for the prevention of recurrent ischemia and stent thrombosis in acute coronary syndrome (ACS). This modified dosage regimen has been established in studies conducted in Japan; however, the efficacy and safety of switching from clopidogrel to prasugrel DAPT among Taiwanese patients remain to be explored. In this phase IV, multicenter, single-arm, open-label study, we evaluated the 4-week pharmacodynamic response, and the 48-week safety outcomes of prasugrel 3.75 mg after a switch from clopidogrel in Taiwanese ACS patients. A total of 203 prasugrel-naïve ACS patients (over 90% male) who had received post-PCI clopidogrel DAPT for at least 2 weeks were enrolled from ten medical centers in Taiwan and subsequently switched to prasugrel 3.75 mg DAPT. Four weeks after the switch, P2Y12 reaction unit (PRU) values were significantly decreased in the total cohort (mean − 18.2 ± 48.1; 95% confidence interval − 24.9 to − 11.5, p < 0.001), and there was an overall consistent antiplatelet response in the treated subjects. The proportion of patients with high on-treatment platelet reactivity (HPR; PRU > 208) dropped from 23.5 to 10% (p < 0.001). Female sex was associated with a greater PRU reduction with prasugrel, whereas HPR at baseline, age ≥ 65 years, and body mass index ≥ 25 best predicted HPR at Week 4. Throughout the 48-week treatment with prasugrel, the incidences of MACE (1.0%) and TIMI major bleeding (2.0%) were rather low, accompanying an acceptable safety profile of TIMI minor (6.4%) and non-major, non-minor clinically relevant bleeding (3.0%). Overall, switching to the maintenance dose of prasugrel (3.75 mg) was observed to be effective and well tolerated among post-PCI ACS patients in Taiwan. Clinical Trial Registration Number: NCT03672097.

Patients Living with HIV and Coronary Disease: Are we Using Appropriate Anti platelets as Part of Dual Antiplatelet Therapy?

Background: People living with HIV (PLHIV) have a higher incidence of cardiovascular disease and complications after intervention, including in-stent thrombosis. The frequency of potential drug-drug interactions in the setting of acute coronary syndrome (ACS) with antiretroviral therapy (ART) and dual-antiplatelet therapy (DAPT) regimens remains unclear. We sought to determine the frequency of potential drug-drug interactions in a cohort of people living with HIV who were investigated for coronary disease and initiated on DAPT as per Australian ACS Guidelines. Methods: A retrospective audit was performed in a single tertiary hospital in PLHIV presenting with symptomatic coronary artery disease (CAD) receiving DAPT. Patients were grouped based on exposure to a protease inhibitor or efavirenz and etravirine, given that these were found to have the greatest potential interactions with DAPT. Results: Fifty-three patients received DAPT, of which 31 (58%) had a potential drug-drug interaction. Clopidogrel was the most frequent P2Y12 inhibitor prescribed, accounting for 47 (87%) of the interactions. Twenty-six patients were on a protease inhibitor, of which 21 (81%) had a potential drug-drug interaction. There were 11 instances of efavirenz and 3 of etravirine use, of which all resulted in potential drug-drug interactions (100%, respectively). Conclusion: Potential drug-drug interactions were very common in PLHIV needing DAPT. The widespread use of clopidogrel in DAPT regimens resulted in a high rate of drug-drug interactions. An awareness of interactions and guidelines around P2Y12 inhibitor selection may help reduce the rate of in-stent thrombosis for PLHIV and improve clinical outcomes.

Effect of ticagrelor in patients with acute coronary syndrome on the achievement of the targets of federal project on the prevention of cardiovascular diseases: 3-year perspective estimates

Aim . To assess the additional effect of ticagrelor as part of dual antiplatelet therapy (DAPT) compared with DAPT with clopidogrel and acetylsalicylic acid (ASA) monotherapy on the achievement of goals of federal project on the prevention of cardiovascular diseases: “reduction of cardiovascular mortality” and “reduction of mortality from myocardial infarction (MI)”. Material and methods . In the first year of treatment, all adult Russian patients with documented acute coronary syndrome (ACS), who had indications for DAPT, were considered as the target population. In the second and third years, treat -ment was continued only by patients with a high risk of thrombotic events. The calculation of the number of deaths that can be prevented using DAPT with ti -cagrelor 90 mg + ASA instead of clopidogrel + ASA during the first year was based on the data of the PLATO trial. To calculate the number of deaths that can be prevented using DAPT with ticagrelor 60 mg + ASA instead of ASA monotherapy, we used the data of PEGASUS trial for patients with a history of MI within the past 2 years. Then the proportion of goals that can be achieved in 2021-2023 was calculated when using DAPT with ticagrelor instead of clopidogrel or ASA monotherapy. Results. The use of ticagrelor within DAPT for patients with ACS will allow (compared to DAPT with clopidogrel and ASA monotherapy): — to prevent an additional 5389, 5702 and 6009 deaths in 2021, 2022, and 2023, respectively, achieving the target of federal project on the prevention of cardiovascular diseases “reduction of cardiovascular mortality” by 18,4, 19,4 and 20,5%, respectively. In addition, the use of ticagrelor within DAPT for patients with ACS compared with clopidogrel or ASA monotherapy will also allow: — to prevent an additional 957, 1013 and 1067 deaths due to MI in 2021, 2022, and 2023, respectively, achieving the target of federal project on the prevention of cardiovascular diseases “reduction of mortality from MI” by 50,2%, 49,3% and 51,9%, respectively. Conclusion . The use of ticagrelor in patients with ACS will reduce cardiovascular mortality and contribute on the achievement of goals of federal project on the prevention of cardiovascular diseases.

Overlooked hepatotoxicity with Clopidogrel

Clopidogrel is an adenosine diphosphate receptor blocker. It is widely used as a part of dual antiplatelet therapy (DAPT) in patients with ischemic heart disease (IHD), regardless of the acute coronary syndrome (ACS). Although a rarely reported entity, clopidogrel-induced liver injury is commonly seen in clinical practice. It is widely overlooked by clinicians and is thus a potential hazard to patients with IHD.

PCV52 Cost Analysis on Prasugrel/Ticagrelor Versus Clopidogrel As PART of Dapt in Hong Kong Post-ACS Patients

Clinical benefit of prasugrel or ticagrelor over clopidogrel as part of dual antiplatelet therapy (DAPT) was inconclusive in Asian population. The study aimed to compare the direct medical cost of using prasugrel/ticagrelor versus clopidogrel as part of DAPT in Hong Kong acute coronary syndrome (ACS) patients. The retrospective observational cohort study included patients, aged 18 years old or above, admitted to seven institutions under Hospital Authority Hong Kong with diagnosis of ACS during 2008-2017. Cost analysis was conducted to evaluate direct medical cost related to ACS management using prasugrel/ticagrelor versus clopidogrel as part of DAPT at one year, two years and five years post-ACS episode. Cost of drugs, cost of hospitalization and procedures, as well as cost of cardiovascular (CV)-related clinic visit were considered. Association of cost difference and choice of P2Y12 receptor antagonist was investigated using adjusted linear regression or adjusted Poisson regression model. A total number of 7349, 6079 and 3611 ACS patients were included for one-year, two-year and five-year analyses respectively. Compared to clopidogrel, prasugrel/ticagrelor was associated with lower cost of hospitalization at one-year and two-year analysis, lower cost of CV-related clinic visit at one-year, two-year and five-year analysis and higher cost of drug at one-year, two-year and five-year analysis. Despite higher cost of drug, prasugrel/ticagrelor was associated with lower cost of CV-related clinic visit in five years and lower cost of hospitalization in two years after index event.

Outcomes and strategy of tailored antiplatelet therapy with ticagrelor in patients undergoing transcarotid artery revascularization

ObjectiveAntiplatelet drug resistance is associated with periprocedural ischemic complications in patients undergoing intravascular stent implantation. Nonresponders are subject to increased risk of stent thrombosis and in-stent stenosis, and high on-treatment platelet reactivity (HTPR) is present in up to 44% of patients taking clopidogrel, a widely used component of dual antiplatelet therapy (DAPT). Evidence points to ticagrelor as a viable alternative to overcome HTPR on clopidogrel. Studies have shown fewer thromboembolic events with ticagrelor therapy; however, results on bleeding risk are mixed, and its safety and efficacy in hybrid operative techniques have yet to be established. Transcarotid artery revascularization (TCAR) is a hybrid procedure to treat severe carotid stenosis. The objective of this study was to establish the safety and efficacy of ticagrelor as part of DAPT in patients undergoing TCAR and to develop a protocol to ensure adequate antithrombotic protection throughout the operative course. MethodsData were collected retrospectively for patients undergoing TCAR on DAPT of aspirin and ticagrelor for symptomatic (≥50%) or asymptomatic (≥80%) carotid stenosis. Preoperative platelet reactivity was determined using Thromboelastography with Platelet Mapping (Haemonetics Corporation, Braintree, Mass), with adequate platelet reactivity defined as maximal amplitude produced by adenosine diphosphate <50 mm. The primary safety end point was 30-day major bleeding event rate. Primary efficacy end points were 30-day incidence of ipsilateral cerebrovascular ischemic event (stroke or transient ischemic attack), myocardial infarction, and death. Secondary end points were postoperative length of hospital stay, procedure time, and clamp/flow reversal time. ResultsSixty-seven TCAR procedures with patients receiving periprocedural DAPT of ticagrelor and aspirin were performed during the study period. Patients had an average age of 79 years, and 28 (42%) were symptomatic. The mean procedure time was 45.8 ± 9.2 minutes, with a mean clamp/flow reversal time of 4.8 ± 1.5 minutes, and mean postoperative length of hospital stay of 3.1 ± 2.2 days for inpatients and 1.3 ± 0.8 days for outpatients. Technical success was achieved in all cases, with no 30-day major bleeding events and no occurrence of ipsilateral cerebrovascular ischemic event, myocardial infarction, or death. ConclusionsInitial experience with ticagrelor as part of DAPT in patients undergoing TCAR demonstrated its safety and efficacy in both symptomatic and asymptomatic disease. No bleeding events or thromboembolic complications occurred. Furthermore, a protocol to administer ticagrelor to assay for HTPR on ticagrelor and consequent medication and patient management is proposed. Ticagrelor may represent a safe and effective alternative to overcome clopidogrel nonresponsiveness in DAPT regimens for TCAR.

The Role of Clopidogrel in 2020: A Reappraisal.

Antiplatelet therapy is the mainstay of treatment and secondary prevention of cardiovascular disease (CVD), including acute coronary syndrome (ACS), transient ischemic attack (TIA) or minor stroke, and peripheral artery disease (PAD). The P2Y12 inhibitors, of which clopidogrel was the first, play an integral role in antiplatelet therapy and therefore in the treatment and secondary prevention of CVD. This review discusses the available evidence concerning antiplatelet therapy in patients with CVD, with a focus on the role of clopidogrel. In combination with aspirin, clopidogrel is often used as part of dual antiplatelet therapy (DAPT) for the secondary prevention of ACS. Although newer, more potent P2Y12 inhibitors (prasugrel and ticagrelor) show a greater reduction in ischemic risk compared with clopidogrel in randomized trials of ACS patients, these newer P2Y12 inhibitors are often associated with an increased risk of bleeding. Deescalation of DAPT by switching from prasugrel or ticagrelor to clopidogrel may be required in some patients with ACS. Furthermore, real-world studies of ACS patients have not confirmed the benefits of the newer P2Y12 inhibitors over clopidogrel. In patients with very high-risk TIA or stroke, short-term DAPT with clopidogrel plus aspirin for 21–28 days, followed by clopidogrel monotherapy for up to 90 days, is recommended. Clopidogrel monotherapy may also be used in patients with symptomatic PAD. In conclusion, there is strong evidence supporting the use of clopidogrel antiplatelet therapy in several clinical settings, which emphasizes the importance of this medication in clinical practice.

Meta-Analysis of Intraocular Bleeding With Dual Antiplatelet Therapy Using P2Y12 Inhibitors Prasugrel or Ticagrelor

Intraocular bleeding is a devastating clinical event due to its potentially blinding nature. It is not known if determine if dual antiplatelet therapy using aspirin and potent P2Y12 inhibitors increases this risk. We searched MEDLINE and ClinicalTrials.gov for randomized controlled trials that were phase III, randomly assigned patients to dual antiplatelet therapy with either aspirin and a potent P2Y12 inhibitor or aspirin and clopidogrel, had follow-up of 6 months, and at least 200 patients. Corresponding authors were contacted for intraocular bleeding data. Inverse-variance, weighted, fixed-effects meta-analysis was undertaken, with random-effects meta-analysis performed as a sensitivity analysis. Four trials enrolling 42,850 patients were included. The median follow-up ranged from 12 to 14 months. There was overall low risk of bias. Pooled analysis demonstrated no statistically significant increase in the risk of intraocular bleeding with dual antiplatelet therapy using potent P2Y12 inhibitors compared with clopidogrel (risk ratio 0.89, 95% confidence interval 0.58 to 1.36). There was no significant heterogeneity observed across trials (I2 statistic 0%, p = 0.98). The use of random-effects meta-analysis did not change the effect estimate or confidence intervals, and the results appeared similar when stratified by potent P2Y12 inhibitor (p = 0.97). In conclusion, this collaborative meta-analysis of dual antiplatelet trials does not suggest that the risk of intraocular bleeding is increased with the use of potent P2Y12 inhibitors compared with clopidogrel. Our results suggest that these potent P2Y12 inhibitors may continue to be used cautiously where indicated as part of dual antiplatelet therapy, even in those at high risk of spontaneous intraocular bleeding.

Prescription Patterns of Clopidogrel, Prasugrel, and Ticagrelor After Percutaneous Coronary Intervention With Stent Implantation (from the NCDR PINNACLE Registry)

The use of prasugrel and ticagrelor as part of dual antiplatelet therapy is increasing in patients after percutaneous coronary intervention (PCI). Accordingly, we aimed to evaluate their prescription patterns in the National Cardiovascular Data Registry (NCDR) Practice Innovation and Clinical Excellence (PINNACLE) registry. We analyzed patients enrolled in NCDR PINNACLE registry from January 2013 to March 2015 who underwent PCI with drug-eluting stent and were prescribed dual antiplatelet therapy. All patients received aspirin. The primary study outcome was a 3-level variable denoting the second antiplatelet agent prescribed: (1) clopidogrel, (2) prasugrel, or (3) ticagrelor. Baseline characteristics were compared among the 3 groups. Odds ratios and 95% credible intervals were calculated from a nested hierarchical Bayesian logistic regression models to identify independent predictors of prescription of antiplatelet medications, incorporating practice and provider as random effects. Our study cohort consisted of 26,710 patients during our study period January 2013 to March 2015. Seventy nine percent of patients were prescribed clopidogrel, 12% prasugrel, and 11% ticagrelor. Patients aged ≥75 years, women, history of tobacco use, Peripheral Arterial Disease (PAD), hypertension, diabetes, previous vascular complication, heart failure, and stroke/transient ischemic attack were more likely to be on clopidogrel than prasugrel or ticagrelor. The relative percentages of ticagrelor and prasugrel were higher in patients with history of myocardial infarction, compared with those without myocardial infarction. In summary, our study highlights the prescription patterns associated with prescription of antiplatelet agents after PCI. We found that both ticagrelor and prasugrel were mostly prescribed per the current practice guidelines, thus reflecting appropriate guideline adherence by practices in NCDR PINNACLE registry.