P2Y12 Inhibitors Research Articles

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

The effect of different dual antiplatelet therapies on thrombotic events on the background of intravascular ultrasound (IVUS) guidance is unclear. We investigated whether ticagrelor can provide any additional benefit to clopidogrel in reducing thrombotic events in acute coronary syndrome (ACS) treated with drug- eluting stent (DES), when guided by IVUS or not. A total of 5,666 ACS patients who underwent DES implantation and who were discharged on dual antiplatelet therapy were enrolled and grouped according to the use of IVUS or not. Each group was subdivided into two subgroups according to the type of P2Y12 inhibitor used after discharge. Propensity score matching (PSM) was used between the IVUS and no-IVUS groups. Covariate adjustment of Cox proportional hazards model was used between the ticagrelor and clopidogrel groups. Thrombotic event at 12 months was compared in groups separately. After PSM, 12-month follow-up data were available for 1,174 patients. Major adverse cardiac events (MACE) were less frequent in the IVUS-guided group (2.2% vs. 4.3%, P = 0.081) with a trend toward statistical significance. Comparison of antiplatelet regimens revealed significantly fewer major adverse cardiac and cerebrovascular events (MACCE) with ticagrelor in the entire PSM cohort and angiography-guided subgroup (2.9% vs. 5.7%, P = 0.035; 3.1% vs. 6.4%, P = 0.020, respectively). Among patients in the IVUS-guided group the outcome was comparable (2.5% vs. 4.4%, P = 0.312). Ticagrelor was associated with increasing bleeding incidence in the entire PSM cohort (1.3% vs. 3.3%, P = 0.030), mainly due to Bleeding Academic Research Consortium type 2 bleeding (0.7% vs. 2.6%, P = 0.010). The results were consistent after covariate adjustment of Cox proportional hazards model. The comparison of ischemic benefit between ticagrelor and clopidogrel was similar in patients receiving IVUS guidance during stent implantation, probably due to the precise implantation of IVUS. Multicenter, randomized studies should be performed to validate this conclusion.

Association of Periprocedural Inflammatory Activation With Increased Risk for Early Coronary Stent Thrombosis.

Stent thrombosis is a rare but deleterious event. Routine coronary angiography with percutaneous coronary intervention (PCI) is often deferred in the presence of laboratory markers of acute inflammation to prevent complications. The aim of this study was to investigate whether an acute inflammatory state is associated with an increased risk of early stent thrombosis. Within a prospective single-center registry, the association between preprocedural acute inflammatory activation, defined as C-reactive protein plasma levels >50 mg/L or a leukocyte count >12 g/L, and occurrence of early (≤30 days) stent thrombosis was evaluated. In total, 11 327 patients underwent PCI and of those, 6880 patients had laboratory results available. 49.6% of the study population received PCI for an acute coronary syndrome and 50.4% for stable ischemic heart disease. In patients with signs of acute inflammatory activation (24.9%), PCI was associated with a significantly increased risk for stent thrombosis (hazard ratio, 2.89; P<0.00001), independent of age, sex, kidney function, number and type of stents, presence of multivessel disease, choice of P2Y12 inhibitor, and clinical presentation. Elevated laboratory markers of acute inflammation were associated with the occurrence of stent thrombosis in both patients with acute coronary syndrome (hazard ratio, 2.63; P<0.001) and in patients with stable ischemic heart disease (hazard ratio, 3.57; P<0.001). An acute inflammatory state at the time of PCI was associated with a significantly increased risk of early stent thrombosis. Evidence of acute inflammation should result in deferred PCI in elective patients, while future studies are needed for patients with acute coronary syndrome.

The Impact of CYP2C19 Genotype on the Platelet Reactivity Index (PRI) among Chronic Coronary Syndromes (CCS) Patients Undergoing Percutaneous Coronary Intervention (PCI): Affectability of Rapid Genetic Testing.

In the Asian population, the presence of the CYP2C19 loss-of-function (LOF) allele is a known genetic variation. This allele is associated with a reduced capacity to metabolize clopidogrel into its active forms through the CYP2C19 enzyme, resulting in diminished platelet inhibition and an elevated risk of recurrent cardiovascular events. Regulatory authorities have recommended an alternative P2Y12 inhibitor, ticagrelor, for individuals carrying the LOF allele. Consequently, this study seeks to assess the impact of the CYP2C19 genotype on the Platelet reactivity index (PRI) using a rapid genetic testing approach in Asian patients with chronic coronary syndromes (CCS) who undergo percutaneous coronary intervention (PCI). This prospective study employed a parallel design, single-center design, and randomized approach. Genotyping for the CYP2C19*2 and *3 polymorphisms was conducted using the Nested Allele-Specific Multiplex PCR (NASM-PCR) technique. Patients meeting the inclusion criteria underwent genotyping for CYP2C19 polymorphisms. Following PCI, patients were randomly assigned to receive either ticagrelor or clopidogrel. PRI assessments were performed four hours after loading dose administration. The trial was registered with ClinicalTrials.gov under the identifier NCT05516784. Among the 94 patients recruited for the study, 40 (42.55%) were identified as carriers of the LOF allele for CYP2C19*2 and *3 (*1/*2, *2/*2, *1/*3). Out of the 84 patients evaluated for PRI (44 receiving clopidogrel and 40 receiving ticagrelor), 21 (47.7%) of the clopidogrel group and 39 (97.5%) of the ticagrelor group exhibited a favorable response to antiplatelet therapy (PRI < 50). Patients treated with ticagrelor demonstrated superior antiplatelet responses compared to those receiving clopidogrel, regardless of LOF carrier status (P = 0.005 and < 0.001 for non-LOF and LOF carriers, respectively). NASM-PCR as a rapid genetic test holds promise for personalizing antiplatelet therapy in Asian CCS patients.

Duration of DAPT After Stent Implantation, How Low Can We Go?

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the main actor in secondary prevention of recurrent coronary ischemic events and stent thrombosis. For this exact purpose the combination of two antiplatelet molecules have proven efficacy and superiority compared to monotherapy, aspirin alone, but this comes with an increased risk of major and potentially fatal bleedings, making the choice of the molecules and especially the duration of treatment a true challenge for every cardiologist. We are going to discuss some of the main factors that play a role in the decision, and the most important trials that studied the subject.

Synthesis and Biological Evaluation of Novel Thiadiazole Derivatives as Antiplatelet Agents.

A novel series of thiadiazole compounds was synthesized through the reaction of thiosemicarbazone intermediates with 2, 3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ). The antiplatelet activity of the synthesized compounds was evaluated using an aggregation test with adenosine diphosphate (ADP) and arachidonic acid (AA) as platelet aggregation inducers. Among the synthesized analogs, compound 3b exhibited the most potent inhibition of platelet aggregation induced by ADP (half maximal inhibitory concentration [IC50] = 39 ± 11 µM). Molecular docking studies of 3b revealed hydrogen bonds between the nitrogen of the thiadiazole ring and Lys280. The tolyl ring exhibited hydrophobic interactions with Tyr105, similar to the antagonist co-crystallized with P2Y12 (PDB ID: 4NTJ). These compounds have the potential to serve as lead molecules for designing P2Y12 inhibitors.

Pretreatment With P2Y12 Inhibitors in ST-Segment Elevation Myocardial Infarction: Insights From the Bern-PCI Registry

BackgroundEvidence to support immediate P2Y12 inhibitor loading in ST-segment elevation myocardial infarction (STEMI) is limited. ObjectivesThis study sought to compare outcomes of STEMI patients receiving immediate or delayed P2Y12 inhibitor treatment. MethodsUsing data from the prospective Bern-PCI registry between 2016 and 2020, we stratified STEMI patients undergoing percutaneous coronary intervention according to time periods with different institutional recommendations regarding P2Y12 inhibitor pretreatment. In cohort 1 (October 2016-September 2018), immediate P2Y12 inhibitor treatment was recommended. In cohort 2 (October 2018-September 2020), P2Y12 inhibitor treatment was recommended after coronary anatomy was confirmed. The primary endpoint was a composite of major adverse cardiac or cerebrovascular events (MACCEs) defined as all-cause death, recurrent myocardial infarction, stroke, or definite stent thrombosis at 30 days. Sensitivity analysis included only patients in whom these recommendations were followed. ResultsCohort 1 included 1,116 patients; pretreatment was actually given in 708 (63.4%). Cohort 2 included 847 patients; pretreatment was withheld in 798 (94.2%). The mean age was 65 ± 13 years, and 24% were female. Baseline characteristics were well-balanced between groups. The median difference for P2Y12 loading to angiography was 52 minutes between cohort 1 and 2 and 100 minutes between patients receiving vs not receiving pretreatment. Rates of MACCEs were similar between cohort 1 and cohort 2 (10.1% vs 8.1%; adjusted HR: 0.91; 95% CI: 0.65-1.28; P = 0.59) and between patients receiving vs not receiving pretreatment (7.1% vs 8.4%; adjusted HR: 1.17; 95% CI: 0.78-1.74; P = 0.45). ConclusionsIn this cohort study of patients with STEMI undergoing primary percutaneous coronary intervention, P2Y12 inhibitor pretreatment was not associated with improved MACCEs.

Efficacy and Safety of Long-Term Dual Antiplatelet Therapy: A Systematic Review and Meta-Analysis.

Dual antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is a standard therapy in patients with ischemic vascular diseases (IVD) including coronary artery, cerebrovascular and peripheral arterial diseases, although the optimal duration of this treatment is still debated. Previous meta-analyses reported conflicting results about the effects of long-term and short-term as well as non-DAPT use in various clinical settings. Herein, we conducted a comprehensive meta-analysis to assess the efficacy and safety of different durations of DAPT. We reviewed relevant articles and references from database, which were published prior to April 2023. Data from prospective studies were processed using RevMan5.0 software, provided by Cochrane Collaboration and transformed using relevant formulas. The inclusion criteria involved randomization to long-term versus short-term or no DAPT; the endpoints included at least one of total or cardiovascular (CV) mortalities, IVD recurrence, and bleeding. A total of 34 randomized studies involving 141 455 patients were finally included. In comparison with no or short-term DAPT, long-term DAPT reduced MI and stroke, but did not reduce the total and CV mortalities. Meanwhile, bleeding events were increased, even though intracranial and fatal bleedings were not affected. Besides, the reduction of MI and stroke recurrence showed no statistical significance between long-term and short-term DAPT groups. Long-term DAPT may not reduce the mortality of IVD besides increasing bleeding events, although reduced the incidences of MI and stroke early recurrence to a certain extent and did not increase the risk of fatal intracranial bleeding.

Efficacy and Safety of Extended Antithrombotic Therapy in Stable Coronary Artery Disease: Systematic Review of the Literature

Extended dual antithrombotic therapy, which entails the concurrent administration of acetylsalicylic acid and a P2Y12 inhibitor or anticoagulant beyond the initial 12 months of presenting with acute coronary syndrome, has been the subject of considerable research in recent years. The objective of this study was to evaluate the impact of dual antithrombotic therapy in stable coronary artery disease. We conducted a registered (PROSPERO CRD42023394771) assessing the safety and efficacy of antithrombotic therapy published over the past 20 years up to May 2021 in four databases (PubMed, EMBASE, BVSalud /LILACS, Cochrane Reviews). Using the RoB2 tool, we evaluated the risk of bias. We performed a literature search using keywords and identified 95 eligible articles, of which 23 were excluded as duplicates. After applying the inclusion and exclusion criteria, we found 29 articles for a detailed review and assessment of bias by applying the ROB2 toll, and we found that five articles had a low risk of bias. Our analysis found that extended dual antithrombotic therapy reduces ischemic cardiovascular outcomes, but it comes at the cost of an increased risk of bleeding when compared with acetylsalicylic acid monotherapy.

Factors of mortality in patients with cardiac implantable electronic device: 5-year experience.

The use of cardiac implantable electronic devices has increased in recent years. It has also brought some issues. Among these, the complications of cardiac implantable electronic devices infection and pocket hematoma are difficult to manage. It can be fatal with the contribution of patient-related risk factors. In this study, we aimed to find mortality rates in patients who developed cardiac implantable electronic devices infection and pocket hematoma over 5 years. We also investigated the risk factors affecting mortality in patients with cardiac implantable electronic devices. A total of 288 cardiac implantable electronic devices patients were evaluated. Demographic details, history, and clinical data of all patients were recorded. Cardiac implantable electronic devices infection was defined according to the modified Duke criteria. The national registry was used to ascertain the mortality status of the patients. The patients were divided into two groups (exitus and survival groups). In addition, the pocket hematoma was defined as significant bleeding at the pocket site after cardiac implantable electronic devices placement. The cardiac implantable electronic devices infection was similar in both groups (p=0.919), and the pocket hematoma was higher in the exitus group (p=0.019). The exitus group had higher usage of P2Y12 inhibitors (p≤0.001) and novel oral anticoagulants (p=0.031). The Cox regression analysis, including mortality-related factors, revealed that renal failure is the most significant risk factor for mortality. Renal failure was linked to a 2.78-fold higher risk of death. No correlation was observed between cardiac implantable electronic devices infection and mortality, whereas pocket hematoma was associated with mortality. Furthermore, renal failure was the cause of the highest mortality rate in patients with cardiac implantable electronic devices.

Platelet Function Testing to Guide Cangrelor Dosing in Patients with Temporary Mechanical Circulatory Support or as a Bridge to Procedure.

Cangrelor is a rapid-acting, intravenous P2Y12 inhibitor that can be used in patients after percutaneous coronary intervention who require mechanical circulatory support or as a bridge to procedure. We retrospectively reviewed adult patients who received platelet function testing (PFT) with the VerifyNow P2Y12 assay while on cangrelor from March 2021 through November 2022. All patients were initiated on 0.75 mcg/kg/min of cangrelor with P2Y12 reaction unit (PRU) values collected 12-24 h after initiation. Cangrelor doses were adjusted per protocol to maintain PRU values of 85-208. A total of 42 patients were included. Thirty-eight patients (90.5%) required temporary mechanical circulatory support while on cangrelor, and 4 patients (9.5%) received cangrelor as a bridge to procedure. The median cangrelor maintenance dose was 0.5 (interquartile range [IQR]: 0.375-0.75) mcg/kg/min, and the median time in therapeutic range with a PRU value between 85 and 208 was 66.6% (IQR: 39.6%-100%). No patients experienced stent thrombosis. A composite major adverse cardiovascular event occurred in 4 patients (9.5%), and major bleeding occurred in 16 patients (38.1%). Compared to empiric cangrelor dosing of 0.75 mcg/kg/min, PFT-guided cangrelor dose adjustment was associated with a median drug cost savings of $1605.60 (IQR: $0-4281.56). Utilizing PFT with cangrelor may allow for lower, individualized dosing while preventing stent thrombosis.

Risk of Bleeding and Ischemia in Elderly East Asian Patients with Diabetes Mellitus Treated with either Clopidogrel or Ticagrelor: From the Korean Acute Myocardial Infarction Registry-V.

Prescribing a P2Y12 inhibitor for patients with diabetes mellitus (DM) and acute myocardial infarction (AMI) who have undergone percutaneous coronary intervention (PCI) is challenging because of the risk of bleeding and ischemia. We compared the risk of ischemia and bleeding between clopidogrel and ticagrelor in elderly East Asian patients with diabetes using the Korea Acute Myocardial Infarction Registry (KAMIR)-V data. This study included 838 patients enrolled in the KAMIR-V who were >75 years, had DM, AMI, and had undergone PCI. The patients were divided into two groups based on the treatment drug. After propensity score matching, 466 patients (ticagrelor: clopidogrel= 233:233) were included in the Cox regression analyses to determine the risk of bleeding and ischemia. The baseline characteristics were not different. The type of antiplatelet therapy did not affect the incidence of Bleeding Academic Research Consortium type ≥2 bleeding. There was no significant difference between ticagrelor and clopidogrel treatment outcomes with respect to ischemia risk. This prospective study of a Korean patient cohort (elderly Korean patients with DM) showed no differences in bleeding and ischemia risks based on the use of either ticagrelor or clopidogrel. Large scale randomized controlled trials are warranted to determine the optimal antiplatelet agents for these patients.

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y12 Inhibitors and Their Association with Platelet Function.

Patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI) require dual antiplatelet therapy (DAPT). However, the response to treatment can vary considerably. Certain platelet microRNAs (miRs) are suspected to predict DAPT response and influence platelet function. This study aimed to analyze selected miRs' expressions and compare them among patients treated with different P2Y12 inhibitors while assessing their association with platelet activity and turnover parameters. We recruited 79 ACS patients post-PCI treated with clopidogrel, ticagrelor, or prasugrel, along with 18 healthy volunteers. Expression levels of miR-126-3p, miR223-3p, miR-21-5p, miR-197-3p, and miR-24-3p, as well as immature platelet fraction (IPF) and ADP-induced platelet reactivity, were measured and compared between groups. Analyses revealed significantly lower expressions of miR-126-3p, miR-223-3p, miR-21-5p, and miR-197-3p in patients treated with ticagrelor, compared to clopidogrel (fold changes from -1.43 to -1.27, p-values from 0.028 to 0.048). Positive correlations were observed between platelet function and the expressions of miR-223-3p (r = 0.400, p = 0.019) and miR-21-5p (r = 0.423, p = 0.013) in patients treated with potent drugs. Additionally, miR-24-3p (r = 0.411, p = 0.012) and miR-197-3p (r = 0.333, p = 0.044) showed correlations with IPF. The identified platelet miRs hold potential as biomarkers for antiplatelet therapy. (ClinicalTrials.gov number, NCT06177587).

P2Y12 inhibitor loading time before elective PCI and the prevention of myocardial necrosis

P2Y12 inhibitor loading time before elective PCI and the prevention of myocardial necrosis

Efficacy of eHealth Technologies on Medication Adherence in Patients With Acute Coronary Syndrome: Systematic Review and Meta-Analysis.

Suboptimal adherence to cardiac pharmacotherapy, recommended by the guidelines after acute coronary syndrome (ACS) has been recognized and is associated with adverse outcomes. Several randomized controlled trials (RCTs) have shown that eHealth technologies are useful in reducing cardiovascular risk factors. However, little is known about the effect of eHealth interventions on medication adherence in patients following ACS. The aim of this study is to examine the efficacy of the eHealth interventions on medication adherence to selected 5 cardioprotective medication classes in patients with ACS. A systematic literature search of PubMed, Embase, Scopus, and Web of Science was conducted between May and October 2022, with an update in October 2023 to identify RCTs that evaluated the effectiveness of eHealth technologies, including texting, smartphone apps, or web-based apps, to improve medication adherence in patients after ACS. The risk of bias was evaluated using the modified Cochrane risk-of-bias tool for RCTs. A pooled meta-analysis was performed using a fixed-effect Mantel-Haenszel model and assessed the medication adherence to the medications of statins, aspirin, P2Y12 inhibitors, angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and β-blockers. We identified 5 RCTs, applicable to 4100 participants (2093 intervention vs 2007 control), for inclusion in the meta-analysis. In patients who recently had an ACS, compared to the control group, the use of eHealth intervention was not associated with improved adherence to statins at different time points (risk difference [RD] -0.01, 95% CI -0.03 to 0.03 at 6 months and RD -0.02, 95% CI -0.05 to 0.02 at 12 months), P2Y12 inhibitors (RD -0.01, 95% CI -0.04 to 0.02 and RD -0.01, 95% CI -0.03 to 0.02), aspirin (RD 0.00, 95% CI -0.06 to 0.07 and RD -0.00, 95% CI -0.07 to 0.06), angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (RD -0.01, 95% CI -0.04 to 0.02 and RD 0.01, 95% CI -0.04 to 0.05), and β-blockers (RD 0.00, 95% CI -0.03 to 0.03 and RD -0.01, 95% CI -0.05 to 0.03). The intervention was also not associated with improved adherence irrespective of the adherence assessment method used (self-report or objective). This review identified limited evidence on the effectiveness of eHealth interventions on adherence to guideline-recommended medications after ACS. While the pooled analyses suggested a lack of effectiveness of such interventions on adherence improvement, further studies are warranted to better understand the role of different eHealth approaches in the post-ACS context.

The Utilization of Protamine during Peripheral Vascular Interventions in the VQI

ObjectiveProtamine administration was shown to reduce bleeding after carotid surgery but the role of protamine during peripheral vascular interventions (PVI) remains unknown. This study evaluates the trend and outcomes of protamine use in the VQI. Our hypothesis is that the use of protamine is associated with decreased bleeding after PVI. MethodsPatients undergoing elective PVI in the VQI (2016-2020) for peripheral arterial disease were reviewed and the utilization trend for protamine was described. The characteristics of patients undergoing PVI with and without protamine use were compared. After propensity score matching based on the patient's comorbidities, access site and procedural characteristics, the perioperative outcomes of both groups were compared using multivariable Poisson regression to estimate adjusted rate ratios (aRRs) and 95% confidence intervals (95% CIs). ResultsThe total number of patients was 131,618 and patients who received protamine constituted 29.8% of the sample (N=38,191). After propensity matching, the total number of patients was 94,582, and patients who received protamine constituted 28.8% of the sample (N=27,275). Protamine use significantly increased during the study period from 5.2% to 22.9%. Before propensity score matching, patients who received protamine were more likely to be white (79% vs 76.8, P=<.001), smokers (80.5% vs 78.5%, P=<.001), with medical comorbidities including hypertension (88.9% vs 88.5%, P=0.074), congestive heart failure (20.5% vs 19.8%, P=0.006), and chronic obstructive pulmonary disease (28.2% vs 26.5%). They were also more likely to be on perioperative medications such as P2Y12 Inhibitors (44.3% vs 45, P=0.013%), and statin (77.4% vs 76.5%, P=0.001) compared to patients who didn’t receive protamine. After propensity matching, there were no significant differences between the two groups. There was a significant decrease in bleeding during procedures where protamine was administered compared to no protamine (2.0% vs. 2.2%), (aRR, 0.89 [95% CI 0.80, 0.98]). Protamine was more likely to be given in procedures complicated by perforation (0.8% vs. 0.5%), (aRR, 1.48 [95% CI 1.24, 1.76]) and less likely to be given during procedures with distal embolization (0.4% vs. 0.7%), (aRR, 0.59 [95% CI 0.49, 0.73]). However, patients receiving protamine had significantly higher cardiac complications (1.4% vs. 1.1%), (aRR, 1.27 [95% CI 1.12, 1.43]). There was no significant difference in mortality between the two groups. ConclusionProtamine use is associated with decreased perioperative bleeding but increased cardiac complications. Protamine should be selectively administered to patients at high risk of bleeding during PVI.

Off-Target Effects of P2Y12 Receptor Inhibitors: Focus on Early Myocardial Fibrosis Modulation.

Several studies have demonstrated that, beyond their antithrombotic effects, P2Y12 receptor inhibitors may provide additional off-target effects through different mechanisms. These effects range from the preservation of endothelial barrier function to the modulation of inflammation or stabilization of atherosclerotic plaques, with an impact on different cell types, including endothelial and immune cells. Many P2Y12 inhibitors have been developed, from ticlopidine, the first thienopyridine, to the more potent non-thienopyridine derivatives such as ticagrelor which may promote cardioprotective effects following myocardial infarction (MI) by inhibiting adenosine reuptake through sodium-independent equilibrative nucleoside transporter 1 (ENT1). Adenosine may affect different molecular pathways involved in cardiac fibrosis, such as the Wnt (wingless-type)/beta (β)-catenin signaling. An early pro-fibrotic response of the epicardium and activation of cardiac fibroblasts with the involvement of Wnt1 (wingless-type family member 1)/β-catenin, are critically required for preserving cardiac function after acute ischemic cardiac injury. This review discusses molecular signaling pathways involved in cardiac fibrosis post MI, focusing on the Wnt/β-catenin pathway, and the off-target effect of P2Y12 receptor inhibition. A potential role of ticagrelor was speculated in the early modulation of cardiac fibrosis, thanks to its off-target effect.

Efficacy and Safety of Ticagrelor Monotherapy Versus Dual-Antiplatelet Therapy After Percutaneous Coronary Intervention With Drug-Eluting Stent in Patients With Diabetes Mellitus: A Systematic Review and Meta- analysis

BACKGROUND: Dual-antiplatelet therapy (DAPT) with aspirin and a P2Y12 inhibitor is the standard for the prevention of thrombotic events in patients undergoing percutaneous coronary intervention (PCI). Type 2 diabetes mellitus (DM) patients are a subgroup with a higher risk of bleeding and thrombotic events after PCI. OBJECTIVES: This meta-analysis aimed to determine whether ticagrelor monotherapy after an initial short-course DAPT is an effective and safe option in preventing thrombotic events among DM patients undergoing PC. METHODS: A systematic review and meta-analysis was done on randomized controlled trials (RCT) comparing ticagrelor monotherapy following short-course DAPT versus conventional DAPT in T2DM patients who underwent PCI. Outcome measures for major bleeding, myocardial infarction, and all-cause mortality were extracted and analyzed using a random-effects model via RevMan version 5.3. RESULTS: A total of three RCTs, with 7482 patients, were analyzed. There were no significant differences in major bleeding (P = 0.26) and myocardial infarction (P = 0.66) events between the ticagrelor and DAPT groups. However, there was a higher rate of all-cause mortality in the DAPT group, which was statistically significant (risk ratio, 0.76; 95% confidence interval, 0.59–0.98; P = 0.03). CONCLUSION: Ticagrelor monotherapy following short-course DAPT and conventional DAPT have similar rates of major bleeding and myocardial infarction among DM patients undergoing PCI with DES. However, conventional DAPT has a higher incidence of all-cause mortality, which suggests that ticagrelor monotherapy after short-course DAPT may be a preferable antiplatelet strategy in DM patients undergoing PCI. KEYWORDS: bleeding, diabetes mellitus, dual-antiplatelet therapy, percutaneous coronary intervention, thrombosis, ticagrelor

Ácido acetilsalicílico versus inibidores dos receptores P2Y12 para prevenção secundária em pacientes tratados por meio de intervenção coronária percutânea

Currently, percutaneous coronary intervention with a drug-eluting stent implantation is the main method of myocardial revascularization in tertiary care hospitals, regardless of the clinical presentation of coronary artery disease. It is well known that to be effective, it requires the use of a dual antiplatelet therapy, which is a combination of acetylsalicylic acid and a P2Y12 platelet receptor inhibitor, which plays a key role in preventing thromboses after endoprosthesis implantation and is also indicated to prevent atherothrombotic events in the late clinical course, regardless of the stent model used. After a variable period of time, depending on some factors, such as the clinical presentation of coronary artery disease and the type of stent implanted, this therapy is discontinued, and the main current guidelines recommend interrupting the P2Y12 receptor inhibitor and maintaining acetylsalicylic acid in the long term, as one of the main pharmacological measures for secondary prevention of atherosclerosis. However, recently, due to their greater antiplatelet potency and probable lower potential for significant bleeding, especially in the digestive tract, P2Y12 inhibitors have been considered a valid and attractive option as an antiplatelet agent for long-term use; but this alternative has not been endorsed by guidelines yet. This review discusses the details related to this important decision that must be made by cardiologists when discontinuing the different antithrombotic therapies initially used after percutaneous coronary intervention. In principle, the scarcity of conclusive and normative clinical studies, especially in the population treated by percutaneous intervention, means that acetylsalicylic acid is the only antiplatelet agent with class I indication for secondary prevention of atherosclerosis.

Ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation undergoing percutaneous coronary intervention for myocardial infarction.

The efficacy and safety of ticagrelor or prasugrel vs. clopidogrel in patients with atrial fibrillation (AF) on oral anticoagulation (OAC) undergoing percutaneous coronary intervention (PCI) for myocardial infarction (MI) have not been established. This was a nationwide cohort study of patients on OAC for AF who underwent PCI for MI from 2011 through 2019 and were prescribed a P2Y12 inhibitor at discharge. The primary efficacy outcome was major adverse cardiovascular events (MACE), defined as a composite of death from any cause, stroke, recurrent MI, or repeat revascularization. The primary safety outcome was cerebral, gastrointestinal, or urogenital bleeding requiring hospitalization. Absolute and relative risks for outcomes at 1 year were calculated through multivariable logistic regression with average treatment effect modelling. Outcomes were standardized for the individual components of the CHA2DS2-VASc and HAS-BLED scores as well as type of OAC, aspirin, and proton pump inhibitor use. We included 2259 patients of whom 1918 (84.9%) were prescribed clopidogrel and 341 (15.1%) ticagrelor or prasugrel. The standardized risk of MACE was significantly lower in the ticagrelor or prasugrel group compared with the clopidogrel group (standardized absolute risk, 16.3% vs. 19.4%; relative risk, 0.84, 95% confidence interval, 0.70-0.98; P = 0.02), while the risk of bleeding did not differ (standardized absolute risk, 5.5% vs. 5.1%; relative risk, 1.07, 95% confidence interval, 0.73-1.41; P = 0.69). In patients with AF on OAC who underwent PCI for MI, treatment with ticagrelor or prasugrel vs. clopidogrel was associated with reduced ischaemic risk, without a concomitantly increased bleeding risk.

Early in-hospital discontinuation of aspirin on the first post-procedural day after percutaneous coronary stent implantation in patients on direct oral anticoagulation.

Previous trials investigating antithrombotic therapy with a direct oral anticoagulant (DOAC) and a P2Y12 inhibitor after percutaneous coronary intervention (PCI), termed dual therapy, allowed a short period of triple therapy including a DOAC, a P2Y12 inhibitor, and aspirin. This study aimed to determine whether discontinuation of aspirin on the first post-procedural day is safe or causes ischemic events. Ischemic and bleeding events during hospitalization were investigated retrospectively in all patients treated with dual therapy (DOAC + P2Y12 inhibitor, designated as group 1) or triple therapy (DOAC + P2Y12 inhibitor+aspirin, designated as group 2) from day 1 after PCI at our center. Of 4,564 consecutive PCI procedures, 1,059 (23.2%) had an indication for OAC. Of these, 322 met the inclusion criteria for group 1 and 62 for group 2. Baseline characteristics, CHA2DS2-VASc and HAS-BLED scores showed no relevant differences between the two groups, and the main indication for DOAC therapy was atrial fibrillation in both groups. Approximately ¼ of patients were treated for acute coronary syndrome. The mean length of post-procedural hospitalization was 2.1 ± 2.5 and 2.2 ± 3.0 days in group 1 and 2, respectively (p = 0.305). One patient per group suffered a TIA (p = 0.297). There were no other ischemic events and no statistically significant differences in bleeding events. A subgroup analysis of cases hospitalized for ≥2 post-procedural days (group 1: 100 cases, mean 4.4 ± 3.4 days vs. group 2: 25 cases, mean 4.0 ± 4.1 days) confirmed these results. The initiation of dual therapy and thus discontinuation of aspirin on the first postprocedural day appears to be safe with respect to short-term ischemic events in a real-world population. Almost ¼ of patients undergoing PCI have an indication for OAC, highlighting the relevance of this issue.