Antiplatelet Regimens In Patients Research Articles

Abstract 136: Antiplatelet Regimens for Secondary Prevention in Minor Ischemic Stroke or TIA: A Network Meta‐Analysis

Introduction There is increased risk of major cardiovascular events among patients with minor ischemic stroke or transient ischemic attack (TIA) [1]. Antiplatelet drugs have been proven to reduce the risk of major cardiovascular events and highly recommended for secondary stroke prevention in this population [2]. However, using antiplatelets has shown an increase in the risk of bleeding events. Hence there are multiple antiplatelet regimens, we aim to investigate the efficacy and safety of these different regimens in minor ischemic stroke defined as National Institutes of Health Stroke Scale (NIHSS) score of 5 or less and high‐ risk TIA). Methods A comprehensive literature search of (PubMed, Cochrane, Scopus, and WOS) was conducted to identify randomized controlled trials comparing different antiplatelet regimens in patients with minor ischemic stroke or TIA. Frequentist NMA was conducted to estimate relative risks (RR) and 95% confidence intervals (CI) for the outcomes of interest using R statistical programming language [3]. The primary outcome measure was recurrent stroke while secondary outcomes included, any bleeding events, serious adverse events (SAEs), hemorrhagic stroke, myocardial infarction (MI), cardiovascular mortality, and all‐cause mortality. Results Five RCTs with 34,941 participants were included. Compared to SAPT (aspirin alone), both DAPT regimens (aspirin + clopidogrel and aspirin + ticagrelor) demonstrated a significant reduction in stroke recurrence (RR: 0.72 with 95% CI [0.63, 0.82], P < 0.01) and (RR: 0.75 with 95% CI [0.64, 0.87], P < 0.01), respectively. However, both DAPT regimens were associated with a higher risk of bleeding events (RR: 1.95 with 95% CI [1.09, 3.50], P = 0.02), (RR: 3.07 with 95% CI [1.16, 8.15], P = 0.02), respectively. In contrast, no significant differences were observed among various antiplatelet modalities regarding all‐cause mortality, cardiovascular mortality, hemorrhagic stroke, myocardial infarction, and serious adverse events. In contrast, no significant differences were observed among various antiplatelet modalities regarding all‐cause mortality, cardiovascular mortality, hemorrhagic stroke, myocardial infarction, and serious adverse events. Conclusion Our findings indicate that DAPT regimens were effective in reducing stroke recurrence compared to SAPT. However, caution is warranted as both DAPT regimens were associated with a higher risk of bleeding events. Clinicians should weigh the potential benefits of reduced stroke recurrence with DAPT against the increased risk of bleeding events. Further research and clinical trials assessing both safety and efficacy are warranted to better understand the optimal prevention approach for this specific patient population.

Abstract Number ‐ 157: Effect of Antiplatelet Therapy in Acute Ischemic Stroke with Tandem Lesions

Introduction Recent studies have shown beneficial effects of Carotid artery stenting (CAS) in acute ischemic stroke patients with tandem lesions (TL). However, stent placement requires the use of antiplatelet medications to prevent in‐stent thrombosis and re‐occlusion of the artery. This must be balanced with the risk of intracerebral hemorrhage. In this multicenter study, we aimed to investigate the safety and feasibility of using antiplatelet regimens in patients with anterior circulation stroke with TLs. Methods Patient level data were pooled from 17 centers and included patients with intracranial occlusion of ICA or M1/M2 segment of MCA with a concomitant extracranial ICA occlusion or stenosis ≥ 50%. Inclusion criteria were; age ≥ 18 years, EVT for intracranial occlusion, and underwent treatment for extracranial ICA lesions demonstrated on CTA and/or DSA. Patients were divided into groups according to the number of antiplatelets administered at the time of endovascular therapy (EVT) procedure into four groups including; 1) no antiplatelets, 2) single oral antiplatelet, 3) dual antiplatelets, and 4) intravenous antiplatelets (in combination of single or dual antiplatelets). Multivariable logistic regression models with multiple imputations were built to assess the association of primary outcome; symptomatic intracranial hemorrhage (sICH), and secondary outcomes including; modified Rankin Score (mRS) 0–2 at 90 days, and successful reperfusion (mTICI score ≥ 2b). Results A total of 682 patients were included. Of these, 138 (20.2%) did not receive any antiplatelet therapy, while 143 (20.97%) were treated with single oral, 207 (30.35%) with dual oral, and 194 (28.5%) with intravenous combined with single or dual antiplatelets. The rate of favorable outcome was non‐significantly higher in the dual (53%) and IV‐combination (54.4%) antiplatelets, as compared with single (38.9%) and without antiplatelet (38.6%) medications. In the multivariable model, after adjusting, there was no significant differences in the sICH (single: aOR: 1.07, CI: 0.62‐1.84, p = 0.8, dual: aOR: 1.18, CI: 0.70‐1.99, p = 0.55, IV‐combination: aOR: 1.01, CI: 0.57‐1.78, p = 0.98) and functional outcome at 90 days (single: aOR: 1.15, CI: 0.63‐2.12, p = 0.64, dual: aOR: 1.03, CI: 0.55‐1.9, p = 0.9, IV‐combination: aOR: 0.83, CI: 0.42‐1.64, p = 0.59) among the study groups. Interestingly, successful reperfusion (mTICI score ≥ 2b) was significantly higher in dual oral and IV‐combination antiplatelets (single: aOR: 1.14, CI: 0.61‐2.14, p = 0.69, dual: aOR: 4.82, CI: 2.23‐10.42, p = < 0.001, IV‐combination: aOR: 3.65, CI: 1.71‐7.79, p = 0.001). Conclusions Administration of antiplatelet medications during EVT was associated with successful reperfusion without increasing the rate of symptomatic hemorrhage in patients with anterior circulation LVO with TLs. Further large‐scale randomized studies are warranted to validate the optimal antiplatelet regimens during acute carotid artery stenting in patients with TLs.

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

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

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

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

P2Y12 Inhibitor Monotherapy Versus Conventional Dual Antiplatelet Therapy or Aspirin Monotherapy in Acute Coronary Syndrome: A Pooled Analysis of the SMART-DATE and SMART-CHOICE Trials

Controversy remains regarding the optimal antiplatelet regimen in patients with acute coronary syndrome (ACS). This study sought to investigate the efficacy and safety of P2Y12 inhibitor monotherapy compared with conventional dual antiplatelet therapy (DAPT) and aspirin monotherapy in patients with ACS undergoing percutaneous coronary intervention. Data on 4,453 patients were pooled from SMART-DATE and SMART-CHOICE randomized trials. Antiplatelet therapy regimens were categorized as P2Y12 inhibitor monotherapy (P2Y12 inhibitor monotherapy after 3-month DAPT), conventional DAPT (12-month or longer DAPT), and aspirin monotherapy (aspirin monotherapy after 6-month DAPT). The primary endpoint was major adverse cardiac and cerebrovascular events (MACCE, a composite of all-cause death, myocardial infarction, and stroke). Inverse-probability of treatment-weighted (IPTW) analysis was performed. At 1 year, patients in the P2Y12 inhibitor monotherapy had a comparable risk of MACCE compared with those in the conventional DAPT (IPTW-adjusted hazard ratio [HR], 0.655; 95% confidence interval [CI] 0.393 to 1.094; p = 0.106), and tended to have a lower risk of MACCE than those in the aspirin monotherapy (IPTW-adjusted HR, 0.606; 95% CI, 0.347 to 1.058; p = 0.078). The adjusted hazard for the Bleeding Academic Research Consortium (BARC) type 2 to 5 bleeding was significantly lower in P2Y12 inhibitor monotherapy than in conventional DAPT (IPTW-adjusted HR, 0.341; 95% CI, 0.190 to 0.614; p < 0.001) and in aspirin monotherapy (IPTW-adjusted HR, 0.359; 95% CI, 0.182 to 0.708; p = 0.003). In conclusion, among patients with ACS undergoing PCI, P2Y12 inhibitor monotherapy after 3-month DAPT reduced risk of bleeding compared with conventional DAPT and aspirin monotherapy after 6-month DAPT without increasing MACCE.

Antiplatelet therapy in percutaneous coronary intervention: latest evidence from randomized controlled trials.

Antiplatelet therapy is key to reduce systemic and local thrombotic events among patients undergoing percutaneous coronary interventions (PCI). Antiplatelet treatment regimens have been subject to continuous changes over the years, with a dual antiplatelet therapy (DAPT), consisting of aspirin and a P2Y12 inhibitor representing the cornerstone of treatment in these patients. The need for less aggressive antithrombotic drugs to prevent local ischemic events with newer generation drug-eluting stent together with the increased understanding of the prognostic relevance of bleeding events in PCI patients, have prompted investigations aimed at identifying antiplatelet treatment regimens associated with a more favorable balance between ischemic and bleeding risks. Several key randomized controlled trials (RCTs) on antiplatelet regimens in patients undergoing PCI have been recently reported resulting in updates in practice guidelines. This manuscript provides an overview of the advancements in the field deriving from key RCTs on antiplatelet regimens in patients undergoing PCI.

NSTE-ACS ESC Guidelines Recommend Prasugrel as the Preferred P2Y12 Inhibitor: A Contrarian View.

In the 2020 European Society of Cardiology guidelines on non-ST-segment elevation acute coronary syndromes (NSTE-ACS), the experts proposed to put an end to the equipoise of ticagrelor and prasugrel in addition to aspirin in patients with NSTE-ACS who proceed to percutaneous coronary intervention (PCI). They gave a strong level of recommendation (IIa) in favor of prasugrel over ticagrelor in these patients. We challenge this proposition, which was mainly driven by the results of ISAR-REACT 5, an open-label prospective head-to-head study of a prasugrel-based strategy compared with a ticagrelor-based strategy in patients with ACS undergoing PCI. In addition to the methodological concerns regarding the ISAR-REACT 5 study, we also question this decision in light of the ISAR-REACT 5 diabetes mellitus subgroup analysis and previous studies and meta-analysis that showed no difference between ticagrelor and prasugrel in patients with ACS. Although we agree with the “one size does not fit all” concept for antiplatelet regimens in patients with ACS who proceed to PCI, we believe that the decision to strongly favor prasugrel was premature and not supported enough by the ISAR-REACT 5 results. In our opinion, equipoise remains between the ticagrelor- and prasugrel-based strategies and more data are needed to settle the debate.

Association of Mortality with Antiplatelet Treatment in Patients with Stent Placement or Angioplasty: A Population-Based Nested Case-Control Study

PurposeAntiplatelet drugs are essential in patients with cardiovascular disease who undergo stent placement. We hypothesized that risks of mortality would differ according to adherence to antiplatelet agents, number of antiplatelet agents, and antiplatelet regimens in patients undergoing stent placement or angioplasty.Materials and MethodsBetween 2002 and 2013, we initially enrolled 8671 subjects who underwent stent placement or angioplasty in the National Health Insurance Service-National Sample Cohort in Korea. Using the International Classification of Diseases, 10th revision, the incidence of all-cause death, including cardiovascular disease, cerebrovascular disease, and cancer, was defined. Using a nested case-control study design, controls were matched to cases at a ratio of 4:1, and a total of 5415 subjects were eligible for this study.ResultsDuring a median follow-up period of 3.51 years, the incidence rate of all-cause death was 40 per 1000 person-years. We found that adherence to antiplatelet monotherapy significantly decreased risk of death by cerebro-cardiovascular disease, compared with discontinuation of antiplatelets [adjusted odds ratio (OR) 0.62, 95% confidence interval (CI) (0.41–0.96)]. Compared with dual antiplatelet therapy (DAPT), aspirin and clopidogrel monotherapy significantly reduced death by cerebro-cardiovascular disease [adjusted OR 0.65, 95% CI (0.44–0.95) and adjusted OR 0.58, 95% CI (0.35–0.96), respectively]. There was no significant difference of mortality between aspirin monotherapy and clopidogrel monotherapy.ConclusionOur study demonstrated that adherence to antiplatelet therapy and antiplatelet monotherapy, compared with DAPT, in patients with stent placement or angioplasty may have a beneficial effect on mortality in cerebro-cardiovascular disease.

Ticagrelor-based antiplatelet regimens in patients treated with coronary artery bypass grafting: a meta-analysis of randomized controlled trials

The optimal antiplatelet strategy in patients undergoing CABG remains unclear. This is the first meta-analysis investigating the clinical outcomes associated with ticagrelor-based antiplatelet regimens in patients receiving CABG. Relevant scientific databases were searched for studies investigating antiplatelet regimens after CABG from inception until April 1, 2019. Studies which randomly assigned CABG patients to either ticagrelor-based or control antiplatelet regimens were eligible. The primary outcome of this analysis was all-cause death. The main secondary outcome was MI. Other outcomes of interest were cardiac death, major adverse cardiac events, stroke and bleeding. This study is registered with PROSPERO, number CRD42019122192. Five trials comprising 3996 patients (2002 assigned to ticagrelor-based and 1994 to control antiplatelet regimens) were eligible for quantitative synthesis. The median follow-up was 12 months. Control antiplatelet regimens consisted of either aspirin or clopidogrel or both. As compared to control, ticagrelor-based regimens reduced the risk of all-cause death [0.61 (0.43-0.87); P = 0.007], cardiac death [0.58 (0.39-0.86); P = 0.007] and major adverse cardiac events [0.79 (0.63-0.98); P = 0.03], without difference in the risk of MI [0.76 (0.50-1.18); P = 0.22], stroke [0.99 (0.56-1.78); P = 0.98] or bleeding [1.04 (0.95-1.14); P = 0.41]. There was a treatment effect modification for the primary outcome associated with trials enrolling predominantly patients with acute coronary syndrome (P for interaction = 0.038). In patients receiving CABG, ticagrelor-based regimens reduce mortality and major adverse cardiac events without excess bleeding risk as compared with aspirin monotherapy or the combination of aspirin and clopidogrel. The benefit of ticagrelor-based regimens is more relevant in those studies enrolling predominantly patients with acute coronary syndrome. These findings require further confirmation in randomized trials focused on this subset of patients and powered for clinical outcomes.

Impact of ticagrelor monotherapy on two-year clinical outcomes in patients with long stenting: a post hoc analysis of the GLOBAL LEADERS trial.

The aim of this study was to evaluate the impact of a novel antiplatelet regimen in patients with increasing total stent length (TSL). This is a post hoc analysis of the GLOBAL LEADERS trial, a prospective, multicentre, open-label, randomised trial, investigating the impact of the experimental strategy (one-month dual antiplatelet therapy [DAPT] followed by 23-month ticagrelor monotherapy) versus the reference regimen (12-month DAPT followed by 12-month aspirin monotherapy) in patients with a Biolimus A9-eluting stent (BES). The primary endpoint was the composite of all-cause death and new Q-wave myocardial infarction (MI), and the secondary endpoint was Bleeding Academic Research Consortium (BARC) type 3 or 5 bleeding at two years. To investigate the association between total stent length and outcomes, groups were compared in quartiles according to TSL; the fourth quartile group was at significantly higher ischaemic risk at two years. In that stratum (TSL ≥46 mm), the experimental strategy significantly reduced the risk of the primary endpoint (hazard ratio [HR] 0.67, 95% confidence interval [CI]: 0.49-0.90; pinteraction=0.043), while demonstrating a similar risk of BARC type 3 or 5 bleeding (HR 0.99, 95% CI: 0.66-1.49; pinteraction=0.975). Ticagrelor monotherapy could potentially balance ischaemic and bleeding risks, thereby achieving a net clinical benefit in patients with a TSL ≥46 mm with a BES.

Ticagrelor-based antiplatelet regimens in patients with atherosclerotic artery disease—A meta-analysis of randomized clinical trials

Randomized trials did not consistently support superiority of ticagrelor, as monotherapy or in combination with aspirin, in terms of efficacy or safety, in patients with atherosclerotic artery disease. Medline, EMBASE, the Cochrane Central Register of Controlled Trials, and scientific session abstracts were searched for trials of patients with coronary or peripheral artery disease (with >1,000 participants and a follow-up ≥3 months) randomly assigned to ticagrelor-based or conventional antiplatelet therapies. Trial-level hazard ratios (HRs) were pooled using a fixed- or random-effect model (in case of significant heterogeneity) with the inverse variance weighting. The primary outcome was all-cause mortality. Other outcomes were myocardial infarction (MI), stroke, and major bleeding. Overall 77,489 patients received either ticagrelor-based (n = 38,721) or conventional antiplatelet regimens (n = 38,768) in 6 trials. The primary outcome occurred in 4.5% of patients treated with experimental therapy and 4.9% of patients treated with control therapy (HR = 0.91, 95% CI 0.81-1.01; P = .07). Overall, patients treated with ticagrelor-based versus conventional antiplatelet regimens showed no significant difference in terms of all-cause death, MI, stroke, or major bleeding after 20 months. However, in trials of patients with coronary artery disease as primary diagnosis, the risk for all-cause death (HR = 0.84 [0.77-0.91], P < .001) and MI (HR = 0.87 [0.80-0.94], P = .007) was significantly reduced by experimental therapy. In patients with atherosclerotic artery disease, the benefit of ticagrelor-based therapies was confined to patients treated for coronary artery disease. The drug significantly reduced the risk for all-cause death and MI without excess risk of bleeding in these patients. In consideration of limitations of subgroup analyses, these results need further validation.

Ticagrelor in the prevention of coronary and non-coronary atherothrombotic events: A comprehensive meta-analysis of 10 randomized trials

Background and aimsMore potent antithrombotic strategies have significantly reduced the rate of recurrent ischemic events in cardiovascular disease. Ticagrelor, in particular, has significantly improved the outcome in patients with acute coronary syndromes, offering potential benefits also in terms of survival. In addition, more recent data have suggested that the advantages of ticagrelor could be extended also to non-coronary atherothrombotic disease, although with contrasting results, especially for mortality reduction. The aim of the present meta-analysis was to investigate the safety and effectiveness of a newer antiplatelet strategy with ticagrelor as compared to traditional antiplatelet regimens in patients with coronary or non-coronary atherothrombotic disease. MethodsLiterature and main scientific session abstracts were searched for studies comparing a ticagrelor-based antiplatelet regimen vs. different antiplatelet agents in the secondary prevention of cardiac, cerebral or vascular atherothrombotic events. The primary efficacy endpoint was mortality, primary safety endpoint was the occurrence of major bleedings. Secondary endpoints were myocardial infarction and stroke. ResultsWe included 10 randomized clinical trials, for a total population of 73,121 patients, 54.9% randomized to ticagrelor. At a mean follow-up of 13.4 ± 12.6 months, a newer antiplatelet strategy based on ticagrelor was associated with a significant reduction in mortality as compared to a traditional therapy (OR[95%CI] = 0.92[0.86,0.99], p=0.02; phet = 0.14), however, such benefits were more evident in patients with coronary artery disease, while not in non-coronary trials, with a significant interaction between patients’ setting and the prognostic impact of ticagrelor (p int = 0.03). A similar result was achieved for cardiovascular mortality, recurrent myocardial infarction, while for the risk of stroke, the largest advantages were observed in patients with a previous cerebrovascular accident. Major bleeding events were increased in ticagrelor treated patients (OR [95%CI] = 1.11 [1.02, 1.20], p=0.01; phet = 0.0003), although not affecting overall mortality, as confirmed by meta-regression analysis. ConclusionsBased on the current meta-analysis, a newer antiplatelet strategy based on ticagrelor is associated with a significant reduction in mortality and recurrent cardiovascular events, as compared to a traditional treatment, among patients treated for coronary disease but not among those with non-coronary atherothrombotic disease. However, ticagrelor therapy was associated with a significant increase in major bleeding complications.

Efficacy and safety of more potent antiplatelet therapy with vorapaxar in patients with impaired renal function.

Patients with renal disease are often undertreated with antiplatelet therapy due to concerns about bleeding. Vorapaxar blocks platelet activation via the PAR-1 receptor and reduces cardiovascular events in patients with stable atherosclerosis, but with increased bleeding. We examined the efficacy and safety of vorapaxar in patients with impaired renal function. TRA2°P-TIMI 50 randomized patients with stable atherosclerosis to vorapaxar or. We analyzed patients with eGFR assessed who qualified with a history of MI or PAD (without stroke or TIA) (n = 19,932). Cox models assessed the risk of CV events and bleeding by quartile of baseline eGFR in the placebo arm and then by randomized assignment. Net clinical outcome (NCO) was predefined as CV death, MI, stroke, or GUSTO severe bleeding. Patients with lower eGFR tended to be older, female, have hypertension, hyperlipidemia or prior PAD. In the placebo arm, baseline eGFR in the lowest quartile was associated with a 26% higher risk of CV death, MI or stroke (Q1:Q4 HRadj 1.26, 1.03-1.55) and 73% higher risk of GUSTO moderate or severe bleeding (HRadj 1.73, 1.12-2.65). Vorapaxar reduced the risk of MACE to a similar extent (14-26%) across quartiles of baseline eGFR (P interaction = 0.70) and increased the relative risk of GUSTO moderate or severe bleeding (P interaction = 0.54). NCO was similar across quartiles of eGFR (P interaction = 0.65). Intensification of antiplatelet therapy with vorapaxar offers comparable net clinical benefit regardless of baseline renal function. These data support the use of more potent antiplatelet regimens in patients with renal dysfunction.

Adverse clinical outcomes associated with double dose clopidogrel compared to the other antiplatelet regimens in patients with coronary artery disease: a systematic review and meta-analysis

BackgroundRecently, several newer antiplatelet treatment strategies have been used in patients with coronary artery disease (CAD). Apart from the dual antiplatelet therapy (DAPT) consisting of aspirin and clopidogrel, double dose clopidogrel (DDC), triple antiplatelet therapy (TAPT) consisting of aspirin, clopidogrel and cilostazol and other newer antiplatelet agents have shown to be effective in different ways. In this analysis, we aimed to systematically compare the adverse clinical outcomes and the bleeding events which were observed when DDC was compared to the other antiplatelet regimens in patients with CAD.MethodsEnglish publications comparing DDC with other antiplatelet regimens were searched from MEDLARS/MEDLINE, EMBASE, www.ClinicalTrials.gov and Google Scholar. Adverse cardiovascular outcomes and bleeding events were the study endpoints. Statistical analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) with 95% confidence intervals (CIs) were calculated.ResultsA total number of 23,065 participants were included. Results of this analysis showed major adverse cardiac events (MACEs), all-cause mortality, cardiac death, stroke, stent thrombosis, revascularization and myocardial infarction (MI) to have been similarly manifested in patients who were treated with DDC versus the control group with OR: 0.98, 95% CI: 0.78–1.22; p = 0.83, OR: 0.95, 95% CI: 0.77–1.17; p = 0.62, OR: 0.97, 95% CI: 0.79–1.20; p = 0.81, OR: 0.98, 95% CI: 0.65–1.48; p = 0.94, OR: 0.84, 95% CI: 0.40–1.75; p = 0.64, OR: 0.88, 95% CI: 0.52–1.49; p = 0.63, and OR: 0.89, 95% CI: 0.65–1.21; p = 0.45 respectively. Any minor and major bleedings were also similarly manifested.When DDC was compared to DAPT, no significant difference was observed in any bleeding event with OR: 1.58, 95% CI: 0.86–2.91; p = 0.14. Even when DDC was compared with either ticagrelor or prasugrel or TAPT, still no significant difference was observed in terms of bleeding outcomes.ConclusionsIn patients with CAD, adverse clinical outcomes were not significantly different when DDC was compared to the other antiplatelet regimens. In addition, bleeding events were also similarly manifested when DDC was compared to DAPT, TAPT or ticagrelor/prasugrel.

Efficacy and safety of adding rivaroxaban to the anti-platelet regimen in patients with coronary artery disease: a systematic review and meta-analysis of randomized controlled trials

BackgroundRivaroxaban, a direct factor Xa inhibitor, has seldom been used in patients with coronary artery disease. In this analysis, we aimed to systematically compare the efficacy and safety of rivaroxaban in addition to the anti-platelet regimen in patients with coronary artery disease.MethodsOnline databases (MEDLINE, EMBASE, Cochrane database, www.ClinicalTrials.gov and Google scholar were searched for randomized controlled trials which were exclusively based on patients with coronary artery disease; and which compared efficacy (cardiovascular outcomes) and safety (bleeding outcomes) outcomes with the addition of rivaroxaban to the other anti-platelet agents. Analysis was carried out by the RevMan 5.3 software whereby odds ratios (OR) and 95% confidence intervals (CI) were generated following data input.ResultsFour trials with a total number of 40,148 patients were included (23,231 participants were treated with rivaroxaban whereas 16,919 participants were treated with placebo) in this analysis. Patients’ enrollment period varied from years 2006 to 2016. The current results showed addition of rivaroxaban to significantly lower composite endpoints (OR: 0.81, 95% CI: 0.74–0.88; P = 0.00001). In addition, all-cause death, cardiac death, myocardial infarction, and stent thrombosis were also significantly reduced (OR: 0.82, 95% CI: 0.72–0.92; P = 0.0009), (OR: 0.80, 95% CI: 0.69–0.92; P = 0.002), (OR: 0.87, 95% CI: 0.77–0.98; P = 0.03) and (OR: 0.73, 95% CI: 0.55–0.97; P = 0.03) respectively. However, stroke was not significantly different.However, TIMI defined minor and major bleeding were significantly higher with rivaroxaban (OR: 2.27, 95% CI: 1.47–3.49; P = 0.0002) and (OR: 3.44, 95% CI: 1.13–10.52; P = 0.03) respectively. In addition, intracranial hemorrhage and bleeding which was defined according to the International Society on Thrombosis and Hemostasis criteria were also significantly higher with rivaroxaban (OR: 1.63, 95% CI: 1.04–2.56; P = 0.03) and (OR: 1.80, 95% CI: 1.45–2.22; P = 0.00001) respectively. Nevertheless, fatal bleeding was not significantly different.ConclusionsAddition of rivaroxaban to the anti-platelet regimen was effective in patients with coronary artery disease, but the safety outcomes were doubtful. Further future trials will be able to completely solve this issue.

GW28-e0255 Safety and Efficacy of different antiplatelet regimens in Patients With Acute Coronary Syndrome Treated With Elective Percutaneous Coronary Intervention

GW28-e0255 Safety and Efficacy of different antiplatelet regimens in Patients With Acute Coronary Syndrome Treated With Elective Percutaneous Coronary Intervention

Antiplatelet regimens in the long-term secondary prevention of transient ischaemic attack and ischaemic stroke: an updated network meta-analysis

ObjectiveTo examine the comparative efficacy and safety of different antiplatelet regimens in patients with prior non-cardioembolic ischaemic stroke or transient ischaemic attack.DesignSystematic review and network meta-analysis.Data sourcesAs on 31 March...

Abstract 209: Intracranial Wall Irregularity and Recurrent Stroke: the SPS3 Trial

Background and Purpose: Intracranial atherosclerosis is an important cause of ischemic stroke and even mild stenosis or subtle wall changes may be a marker for subsequent stroke risk. We tested whether any arterial wall irregularity was predictive of recurrent stroke in participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial. Methods: SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in patients with recent, symptomatic, MRI-confirmed lacunar stroke patients. Magnetic resonance angiography (MRA) proximate to study entry was adequate and available for 2169 of 3020 study patients. Seven intracranial arteries (basilar [BA], vertebral [VA], internal carotid [ICA], and middle cerebral artery [MCA]) were assessed on time-of-flight MRA for wall irregularities including stenosis and changes of arterial diameter. Cox Proportional Hazards models adjusted for assigned treatments and clinical risk factors were used to estimate risk for recurrent stroke associated with any wall irregularity overall and in specific arteries. Results: Mean age of the 2169 patients was 63 yr with 63% male; hypertension, diabetes, and prior lacunar stroke were present in 75%, 36%, and 10%, respectively. Wall irregularities in ≥1 artery (325 one artery, 250 &gt; 1 artery) were observed in 575 patients (27%). Recurrent stroke occurred in 195 patients during mean follow-up of 3.5 years (annualized rate 2.5% per patient-year). Patients with at least one wall irregularity had an increased risk of recurrent stroke (adjusted HR 1.4, 95% CI 1.0-1.9). There was no interaction between either randomized treatment arm (antiplatelet therapy or blood pressure control target) and wall irregularities. Irregularity by any individual artery (BA, n = 115, 14 strokes; VA, n = 150, 17 strokes; ICA, n = 268, 31 strokes; or MCA, n = 316, 37 strokes) was not predictive of recurrent stroke (each p &gt;0.1). Conclusion: In this large well characterized cohort of lacunar stroke patients, any wall irregularity in at least one artery was associated with recurrent stroke independent of clinical risk factors and assigned treatment groups.

Abstract 137: Noninvasive Fractional Flow on MRA and Recurrent Stroke: SPS3 Trial

Background and Purpose: Noninvasive fractional flow reserve (FFR) on time-of-flight magnetic resonance angiography (TOF-MRA) may be used to identify high-risk intracranial lesions. We tested whether FFR was associated with vascular territory of the qualifying lacunar stroke in participants of the Secondary Prevention of Small Subcortical Strokes (SPS3) trial and the utility of FFR for predicting recurrent stroke during the trial. Methods: SPS3 was a randomized trial investigating optimal blood pressure target and antiplatelet regimen in patients with recent, symptomatic, MRI-confirmed lacunar stroke patients TOF-MRA proximate to study entry was adequate and available for 2169 of 3020 study patients. Signal intensity (SI) was measured in the background, and proximal and distal aspects of 7 intracranial arteries (internal carotid, middle cerebral, basilar, and vertebral). Adjusted FFR was then calculated in each artery: FFR = [distal SI - background SI] / [proximal SI - background SI] and divided into quartiles by artery. Associations between the vascular territory of the qualifying infarct and the FFR quartile of the relevant artery were investigated using contingency tables and chi-square tests. Risks for recurrent stroke associated with FFR quartiles were evaluated using Cox Proportional Hazards models (model adjusted for assigned treatment groups). Results: Mean age of the 2169 patients included was 63 yr with 63% male; hypertension, diabetes, and prior lacunar stroke were present in 75%, 36%, and 10% respectively. Median FFRs varied by artery with the lowest in the basilar (0.793) and highest in the middle cerebral arteries (left 1.154; right 1.176). A recurrent stroke occurred in 195 patients during a mean follow-up of 3.5 years (annualized rate 2.5% per patient-year).No significant association was found between the FFR tertiles and the vascular territory of the qualifying infarct. Quartiles of adjusted FFR in any of the 7 arteries were not found to be predictive of recurrent stroke. Conclusion: In this large well-characterized cohort of lacunar stroke patients, FFR was not associated with the location of the qualifying subcortical infarct and did not predict the risk of recurrent stroke.

Adequate antiplatelet regimen in patients on chronic anti-vitamin K treatment undergoing percutaneous coronary intervention

To investigate the impact of dual antiplatelet therapy (DAT) in patients on anti-vitamin K (AVK) regimen requiring percutaneous coronary intervention (PCI). Between February 2006 and February 2008, 138 consecutive patients under chronic AVK treatment were enrolled in this registry. Of them, 122 received bare metal stent implantation and 16 received drug eluting stent implantation. The duration of DAT, on top of AVK treatment, was decided at the discretion of the clinician. Adequate duration of DAT was defined according to type of stent implanted and to its clinical indication. The baseline clinical characteristics of patients reflect their high risk, with high incidence of comorbid conditions (Charlson score ≥ 3 in 89% of the patients). At a mean follow-up of 17 ± 11 mo, 22.9% of patients developed a major adverse cardiac event (MACE): 12.6% died from cardiovascular disease and almost 6% had an acute myocardial infarction. Major hemorrhagic events were observed in 7.4%. Adequate DAT was obtained in only 44% of patients. In the multivariate analysis, no adequate DAT and Charlson score were the only independent predictors of MACE (both P = 0.02). Patients on chronic AVK therapy represent a high risk population and suffer from a high MACE rate after PCI. An adequate DAT regimen and absence of comorbid conditions are strongly associated with better clinical outcomes.