Antiplatelet Therapy For Secondary Prevention Research Articles

Strategies for management of patients with elevated lipoprotein(a).

There is growing literature that supports the testing of Lp(a). However, few patients are tested, including those with a personal or family history of cardiovascular disease (CVD). One often noted barrier to more widespread testing is uncertainty regarding what to do with an elevated Lp(a) level. Although guidelines vary, there is agreement on the use of Lp(a) as a risk enhancer to guide medical care and shared decision-making. This review will discuss a clinical approach with supporting evidence for management of patients with elevated Lp(a). At the minimum, elevated Lp(a) increases cardiovascular risk and can be incorporated into existing risk stratification paradigms. The cornerstone of management is aggressive management of traditional cardiovascular risk factors, including LDL-cholesterol (LDL-C). More recent studies have highlighted the potential role for proprotein convertase subtilisin/kexin type 9 inhibitors (PCSK9i), aspirin in primary prevention, and prolonged dual antiplatelet therapy in secondary prevention. Although there is optimism for Lp(a)-targeted therapies in the near future, an elevated Lp(a) level is actionable today, and uncertainty regarding the management of patients with elevated Lp(a) should not be a barrier to more widespread testing.

Beyond RCTs: Short-term dual antiplatelet therapy in secondary prevention of ischemic stroke and transient ischemic attack.

Randomized controlled trials (RCTs) proved the efficacy of short-term dual antiplatelet therapy (DAPT) in secondary prevention of minor ischemic stroke or high-risk transient ischemic attack (TIA). We aimed at evaluating effectiveness and safety of short-term DAPT in real-world, where treatment use is broader than in RCTs. READAPT (REAl-life study on short-term Dual Antiplatelet treatment in Patients with ischemic stroke or Transient ischemic attack) (NCT05476081) was an observational multicenter real-world study with a 90-day follow-up. We included patients aged 18+ receiving short-term DAPT soon after ischemic stroke or TIA. No stringent NIHSS and ABCD2 score cut-offs were applied but adherence to guidelines was recommended. Primary effectiveness outcome was stroke (ischemic or hemorrhagic) or death due to vascular causes, primary safety outcome was moderate-to-severe bleeding. Secondary outcomes were the type of ischemic and hemorrhagic events, disability, cause of death, and compliance to treatment. We included 1920 patients; 69.9% started DAPT after an ischemic stroke; only 8.9% strictly followed entry criteria or procedures of RCTs. Primary effectiveness outcome occurred in 3.9% and primary safety outcome in 0.6% of cases. In total, 3.3% cerebrovascular ischemic recurrences occurred, 0.2% intracerebral hemorrhages, and 2.7% bleedings; 0.2% of patients died due to vascular causes. Patients with NIHSS score ⩽5 and those without acute lesions at neuroimaging had significantly higher primary effectiveness outcomes than their counterparts. Additionally, DAPT start >24 h after symptom onset was associated with a lower likelihood of bleeding. In real-world, most of the patients who receive DAPT after an ischemic stroke or a TIA do not follow RCTs entry criteria and procedures. Nevertheless, short-term DAPT remains effective and safe in this population. No safety concerns are raised in patients with low-risk TIA, more severe stroke, and delayed treatment start.

Long-term combined antiplatelet therapy for secondary prevention of noncardioembolic stroke

Introduction. The high risk of recurrent ischemic events after non-cardioembolic ischemic stroke(IS), the prevalence of which is 25% of all strokes in the Russian Federation, determines the need to search for effective and safe secondary prevention strategies.Аim. The study was to evaluate the efficacy and safety of a combination of ADP receptor inhibitors (dipyridamole) with acetylsalicylic acid in patients with ischemic stroke (IS) in the secondary prevention of noncardioembolic stroke.Materials and methods. 229 patients in the early recovery period of noncardioembolic IS (139 women, 90 men), with an average age of 59.0 ± 5.7 years were included in the study. The duration of IS was 54.4 ± 6.1 days. All patients received a multimodal medical rehabilitation (MMR) program. Long-term double antiplatelet therapy with acetylsalicylic acid (ASA) 75 mg per day and dipyridamole at a daily dose of 225 mg divided into 3 doses were prescribed to all the patients. The neurological and neuropsychological status of the patient, quality of life and hemorheological parameters were assessed initially (T0), after MMR (T1, 6 weeks) and 12 months after IS(T2).Results. Motor and coordination indicators of patients as well as the cognitive and emotional parameters were significantly (p < 0,05) improved due to MMR technology. These were confirmed by the dynamics of the corresponding scales. The prescribed double antiplatelet therapy did not cause significant adverse events and worsening of the patients’ well-being both during the MMR process and during the observation period. The combination of ASA with dipyridamole was well tolerated. At the end of the study, recurrent IS, myocardial infarctions, and fatal bleeding were not recorded. In 5.2% patients with severe risks of cardiovascular complications there was occurred TIA. The effectiveness of the dual antiplatelet therapy was confirmed by a decrease in the level of platelet aggregation (p < 0,05).Conclusions. The high effectiveness of secondary prevention of IS with a combination of ASA and dipyridamole with good tolerability and safety in patients after IS has been shown.

A Study on the Effectiveness of Mono and Dual Antiplatelet Therapy in Secondary Prevention of Vascular Events

A Study on the Effectiveness of Mono and Dual Antiplatelet Therapy in Secondary Prevention of Vascular Events

Antiplatelet Therapy for Secondary Prevention in Patients with Ischaemic Stroke and Transient Ischaemic Attack: A Retrospective Cohort Study in Malaysia

In this study, we evaluated clinical outcomes of antiplatelet therapy for secondary prevention in ischaemic stroke and transient ischaemic attack (TIA) patients. This was a retrospective cohort study that included patients with newly diagnosed ischaemic stroke or TIA between 2014 and 2017 using data from routine practice in Malaysia. Patients were grouped into single antiplatelet therapy (SAPT) and dual antiplatelet therapy (DAPT) users. Primary outcome was composite of stroke, myocardial infarction, and all-cause death in 90 days and 1 year. Safety outcome was major bleeding events. Among 3344 stroke patients, 8.1% received DAPT and 91.2% received SAPT. The 1-year cumulative incidence of composite events was 16.0 and 7.2 per 100 person-years for SAPT and DAPT, respectively. Propensity score-matched analysis of Cox hazard model showed DAPT reduced the risk of composite event (hazard ratio (HR) 0.48; 95% CI 0.25-0.91) and recurrent stroke (HR 0.38; 95% CI 0.16-0.92) in 1-year follow-up. Results were not significant for myocardial infarction, all-cause death, and 90-day outcomes. The risks of bleeding were not significantly different between SAPT and DAPT. Treatment with DAPT after an ischaemic stroke/TIA was associated with reduced risk of the composite events (stroke, myocardial infarction, or death) and recurrent stroke at 1 year.

307 An audit of dual antiplatelet prescribing after minor ischaemic stroke

Abstract Background The American Heart Association make class 1A recommendation for dual antiplatelet therapy for secondary prevention in patients with minor ischemic stroke (National Institutes of Health Stroke Scale score ≤ 3) or high risk TIA on the basis of evidence from randomised controlled trials, such as POINT and CHANCE, which have demonstrated a lower rate of subsequent stroke compared with single antiplatelet therapy. A number of clinical factors have been shown to influence effectiveness, including time from symptom onset to initiation of dual antiplatelet therapy. We aim to evaluate the rate of dual antiplatelet prescribing in this cohort and whether the rationale not to prescribe was clearly documented. Methods We reviewed the electronic records of all stroke patients aged 18 and above, admitted to University Hospital Galway within June 1st to September 29th 2022. Patients who either had a minor ischaemic stroke with a clearly documented NIHSS score of ≤3 were included in the analysis. These records were then assessed for the rate of dual antiplatelet prescribing versus single antiplatelet prescribing and if the rationale was documented. Results Of 29 patients admitted with minor ischaemic stroke, 8 were commenced on dual antiplatelet therapy. The mean number of days from symptom onset to presentation was 1.92 for those who were prescribed DAPT and 2.42 for those who were prescribed SAPT. Of those prescribed SAPT, the rationale for not commencing DAPT was documented. Rationale included delay to presentation (>72 hours) and atrial fibrillation. Conclusion 48.3% (n = 14) DAPT was either prescribed or a documented rationale for SAPT was provided. Our findings are consistent with DAPT prescribing patterns in other studies [1].

Antiplatelet Therapy for Secondary Prevention of Stroke in Hypertensive Elderly Patients with History of Peptic Ulcer Disease: A Multicenter Cohort Study

<p>背景/目的：阿斯匹林(Aspirin)被用來當作心血管疾病的次級預防治療，但目前特別針對老人族群的阿斯匹林使用實證和指引並未完全建立。若產生消化性潰瘍之高血壓長者，尚未有研究去探討出血後繼續使用阿斯匹林之適切性，本研究將探討上消化道出血後，高血壓長者若持續使用阿斯匹林後續產生主要心腦血管事件及上消化道出血住院的相關性。</p> <p>方法：本研究設計擬以回溯性世代研究的方式，於台大醫院及其分院資料庫作為研究資料來源。申請臺大醫療體系醫療整合資料庫，日期自2014年1月1日至2018年12月31日，當中有使用阿斯匹林且做胃鏡之65歲以上高血壓病人。分三組進行前瞻性追蹤（病歷回溯日期範圍自2014年1月1日至2020年12月31日），分別為停止使用阿斯匹林組、續用阿斯匹林組、轉換成Clopidogrel組，主要預後為主要腦心血管事件、上消化道出血住院。分析方式包括Cox比例風險模型、治療權重倒數機率。</p> <p>結果：共735位病人納入分析，平均追蹤時間為39.7個月，共140人發生腦心血管事件。轉換成Clopidogrel組(n=88)並未發現減少主要腦心血管事件(adjusted HR 1.09, 95% CI 0.63-1.87)，且續用阿斯匹林組(n=210)增加主要腦心血管事件發生(adjusted HR 1.58, 95% CI 1.04-2.38)，相對於停止使用阿斯匹林組(n=172)。在後續上消化道出血住院的風險，轉換成Clopidogrel組(adjusted HR 1.07, 95% CI 0.48-2.37)和續用阿斯匹林組(adjusted HR 1.14, 95% CI 0.61-2.10)都沒有增加，但在次族群分析當中，慢性腎病病人有較高風險產生後續上消化道出血住院(adjusted HR 2.41, 95% CI 1.30-4.47)。</p> <p>結論：此研究發現使用阿斯匹林之老年高血壓病人若因消化道潰瘍出血，後續續用阿斯匹林作為次級預防，並未減少心血管事件發生。抗血小板藥物作為老年高血壓病人之次級預防的適切性在消化道潰瘍發生後更應小心評估，尤其是在慢性腎病的共病下，可能會增加後續產生上消化道出血住院之風險。</p> <p> </p><p>Objectives: The cardiovascular and bleeding outcomes of antiplatelet therapy continuation in older hypertensive adults with peptic ulcer disease (PUD) are uncertain. We aimed to investigate the appropriateness of maintaining antiplatelet therapy in older hypertensive aspirin users with PUD by determining the risks of major adverse cardiac events (MACEs) and hospitalizations for upper gastrointestinal bleeding (hUGIBs). </p> <p> Methods: This multicenter cohort study screened patients with panendoscopy-proven PUD and hypertension aged 65 years or older between 2014 and 2018. Subsequent antiplatelet strategies were categorized as aspirin discontinuation (AD), aspirin continuation (AC), and switch to clopidogrel (SC) groups. Inverse probability of treatment weighting was applied. The main outcomes were incident MACEs and hUGIBs, followed through 31 December 2020. </p> <p> Results: 735 eligible patients were analyzed. During a median follow-up of 39.7 months, 140 MACEs occurred. Compared with AD, AC increased the risk of incident MACEs (adjusted HR 1.58, 95% CI 1.04-2.38) in secondary prevention patients. On the other hand, 102 hUGIBs occurred during a median follow-up of 43.4 months. Compared with AD, neither AC nor SC affected the risk of hUGIBs in secondary prevention patients. However, secondary prevention patients with chronic kidney disease were at increased risk of hUGIBs (adjusted HR 2.41, 95% CI 1.30-4.47). </p> <p> Conclusions: AC did not reduce MACEs in older hypertensive adults with PUD previously taking aspirin for secondary prevention. We do not advocate continuing antiplatelet therapy in older hypertensive adults once with PUD, despite its neutral association with hUGIBs.</p> <p> </p>

Antiplatelet Therapy for Secondary Prevention After Myocardial Infarction in Antiplatelet-Naive High Cardiovascular Risk Patients with Non-Obstructive Coronary Artery Disease

Antiplatelet Therapy for Secondary Prevention After Myocardial Infarction in Antiplatelet-Naive High Cardiovascular Risk Patients with Non-Obstructive Coronary Artery Disease

The Increased Ischemic Risk During the Early Period After Clopidogrel Noncompliance in Patients with Acute Coronary Syndrome: A Meta-Analysis.

Although dual antiplatelet therapy for secondary prevention in acute coronary syndrome (ACS) is highly recommended by current guidelines, P2Y12 inhibitor non-adherence often occurs and devastates prognosis. To evaluate whether the ischemic risk during the early period of clopidogrel noncompliance was increased among ACS patients, a comprehensive search of PubMed, Embase, and Web of Science was conducted to identify studies reporting early ischemic risk after clopidogrel noncompliance in ACS patients. The primary endpoint was a composite of death or myocardial infarction (MI). Effect sizes were synthesized in patients with or without revascularization. A total of 7 observational studies focusing on clopidogrel noncompliance were included in this meta-analysis, whereas no studies involving ticagrelor or prasugrel were retrieved. A significantly increased risk of death or MI 0 to 90 days after clopidogrel noncompliance was found compared with that during 90 to 180 or 90 to 360 days regardless of revascularization (incidence rate ratio [IRR]: 2.01, 95% confidence interval (CI): 1.62-2.49, P < .001, I2 = 9%) or not (IRR: 1.61, 95% CI: 1.05-2.48, P < .001, I2 = 74%). Patients undergoing percutaneous coronary intervention had a higher risk of death or MI 0 to 90 days after clopidogrel noncompliance compared with 90-180 or 90-360 days irrespective of drug-eluting stent or bare metal stent implantation (P < .05 for both). The early ischemic risk after clopidogrel noncompliance is significantly higher than the late risk in ACS patients. Antiplatelet noncompliance remains a serious concern.

Antiplatelet therapy for secondary prevention of lacunar stroke: a systematic review and network meta-analysis.

To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0. Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study. This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.

S2340 Massive Upper Gastrointestinal Hemorrhage Following Radiofrequency Ablation for Barrett’s Esophagus

Introduction: Radiofrequency ablation (RFA) is an established endoscopic technique for the management of Barrett’s esophagus (BE) with low grade dysplasia (LGD). Bleeding risk after RFA treatment has been reported to be around 1%. We present a case of massive upper GI bleeding following RFA treatment resulting in death as an adverse event. Case Description/Methods: A 79-year-old male with history of BE with LGD underwent esophagogastroduodenoscopy (EGD) with RFA treatment. The patient had a history of coronary artery disease for which he was taking aspirin and prasugrel. His prasugrel was held 7 days prior to the procedure. During the procedure, the esophagus was carefully examined using white light and narrow band imaging. No esophageal nodules were found; however, mucosal changes secondary to established short-segment Barrett's were seen. The Barrx 90 ultra RFA catheter was used to ablate the Barrett’s mucosa and the procedure was uneventful. Aspirin was resumed the following day, but prasugrel was held for 1 week post procedure. Ten days post procedure, the patient presented to an outside hospital with hematemesis and chest pain. An emergent EGD was performed that revealed massive bleeding in the esophagus with no obvious source. A mesenteric angiogram with embolization of left phrenic and gastric arteries was performed by interventional radiology. A subsequent EGD revealed multiple large, deep ulcerations in the distal esophagus. The patient stabilized and was downgraded from the ICU. However, 2 days later, the patient developed acute respiratory failure with multi-organ failure, thought to be due to aspiration. The patient was transitioned to comfort care and passed away. Discussion: RFA is considered a safe and effective technique for the treatment of patients with BE with either low- or high-grade dysplasia as it is associated with an increased risk of developing esophageal adenocarcinoma. The most frequent adverse events following RFA treatment are esophageal stricture (8-10%), chest pain, bleeding (1%) and perforation (0.6%). Current guidelines for patients on dual antiplatelet therapy for secondary prevention who are undergoing elective procedures suggest temporary interruption of the P2Y12 inhibitor while continuing aspirin. These guidelines were followed in our patient. However, no clear guidance for when to resume newer anticoagulants exists. After extensive literature review, we did not find any case reports of massive upper GI bleed resulting in death following RFA treatment.Figure 1.: A) Barret's esophagus under narrow band imaging B) RFA treatment.

Impact of body size on platelet function in patients with acute coronary syndrome on dual antiplatelet therapy

IntroductionPatients undergoing acute percutaneous coronary intervention receive dual antiplatelet therapy for secondary prevention. Recurrent myocardial infarction or bleedings are possibly due to under- or overdosing of antiplatelet therapy in relation to body size. MethodsWe correlated residual platelet aggregation with body mass index, body surface area, lean body mass and blood volume in 220 patients on prasugrel (n = 121) or ticagrelor (n = 99). ResultsPlatelet aggregation outside the recommended window was recorded in 85 patients, but not correlated with any of the body indices. ConclusionBody size does not affect platelet response to prasugrel or ticagrelor at the guideline-recommended fixed dosages.

Evaluation of Evidence-Based Dual Antiplatelet Therapy for Secondary Prevention in US Patients With Acute Ischemic Stroke

Evaluation of Evidence-Based Dual Antiplatelet Therapy for Secondary Prevention in US Patients With Acute Ischemic Stroke

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1-7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1-7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

American College of Gastroenterology-Canadian Association of Gastroenterology Clinical Practice Guideline: Management of Anticoagulants and Antiplatelets During Acute Gastrointestinal Bleeding and the Periendoscopic Period.

We conducted systematic reviews of predefined clinical questions and used the Grading of Recommendations, Assessment, Development and Evaluations approach to develop recommendations for the periendoscopic management of anticoagulant and antiplatelet drugs during acute gastrointestinal (GI) bleeding and the elective endoscopic setting. The following recommendations target patients presenting with acute GI bleeding: For patients on warfarin, we suggest against giving fresh frozen plasma or vitamin K; if needed, we suggest prothrombin complex concentrate (PCC) compared with fresh frozen plasma administration; for patients on direct oral anticoagulants (DOACs), we suggest against PCC administration; if on dabigatran, we suggest against the administration of idarucizumab, and if on rivaroxaban or apixaban, we suggest against andexanet alfa administration; for patients on antiplatelet agents, we suggest against platelet transfusions; and for patients on cardiac acetylsalicylic acid (ASA) for secondary prevention, we suggest against holding it, but if the ASA has been interrupted, we suggest resumption on the day hemostasis is endoscopically confirmed. The following recommendations target patients in the elective (planned) endoscopy setting: For patients on warfarin, we suggest continuation as opposed to temporary interruption (1–7 days), but if it is held for procedures with high risk of GI bleeding, we suggest against bridging anticoagulation unless the patient has a mechanical heart valve; for patients on DOACs, we suggest temporarily interrupting rather than continuing these; for patients on dual antiplatelet therapy for secondary prevention, we suggest temporary interruption of the P2Y12 receptor inhibitor while continuing ASA; and if on cardiac ASA monotherapy for secondary prevention, we suggest against its interruption. Evidence was insufficient in the following settings to permit recommendations. With acute GI bleeding in patients on warfarin, we could not recommend for or against PCC administration when compared with placebo. In the elective periprocedural endoscopy setting, we could not recommend for or against temporary interruption of the P2Y12 receptor inhibitor for patients on a single P2Y12 inhibiting agent. We were also unable to make a recommendation regarding same-day resumption of the drug vs 1–7 days after the procedure among patients prescribed anticoagulants (warfarin or DOACs) or P2Y12 receptor inhibitor drugs because of insufficient evidence.

Dual anti-platelet therapy for secondary prevention in intracranial atherosclerotic disease: a network meta-analysis

Background:Intracranial arterial stenosis (ICAS) is a non-marginal cause of stroke/transient ischemic attacks (TIAs) and is associated with high stroke recurrence rate. Some studies have investigated the best secondary prevention ranging from antithrombotic therapy to endovascular treatment (ET). However, no direct comparison between all the possible treatments is currently available especially between single and dual anti-platelet therapies (SAPT and DAPT).Aim:To establish whether DAPT is more effective than SAPT in preventing the recurrence of ICAS-related stroke, by means of a network meta-analysis (NMA).Design:Systematic review and NMA in accordance to PRISMA guidelines.Data sources and methods:We performed a systematic review of trials investigating secondary prevention (SAPT or DAPT, anticoagulant treatment or ET) in patients with symptomatic ICAS available in MEDLINE, Scopus and Web of Science from January 1989 to May 2021. We defined our primary efficacy outcome as the recurrence of ischemic stroke/TIA. We analysed the extracted data with Bayesian NMA approach.Results:We identified 815 studies and included 5 trials in the NMA. Sequence generation was adequate in all the selected studies while the allocation concealment method was described in one study. All the included studies reported the pre-specified primary outcomes, and outcome assessment was blinded in all the studies. We used the fixed-effect approach as the heterogeneity was not significant (p > 0.1) according to the Cochran’s Q statistic. DAPT was superior to SAPT and DAPT + ET in preventing stroke/TIA recurrence [respectively, odds ratio (OR), 0.59; confidence interval (CI), 0.39–0.9; and OR, 0.49, CI, 0.26–0.88], while no difference was found between DAPT and oral anticoagulant therapy (OAC). DAPT was safer than OAC (OR, 0.48; CI, 0.26–0.89) and DAPT + ET (OR, 0.50; CI, 0.35–0.71), while no difference was found between DAPT and SAPT.Conclusion:DAPT is more effective than SAPT for secondary stroke prevention in patients with symptomatic ICAS, without increasing the risk of haemorrhage.Registration:Prospero/CRD42019140033.

Pleiotropic Effects of the Protease-Activated Receptor 1 (PAR1) Inhibitor, Vorapaxar, on Atherosclerosis and Vascular Inflammation

Background: Protease-activated receptor 1 (PAR1) and toll-like receptors (TLRs) are inflammatory mediators contributing to atherogenesis and atherothrombosis. Vorapaxar, which selectively antagonizes PAR1-signaling, is an approved, add-on antiplatelet therapy for secondary prevention. The non-hemostatic, platelet-independent, pleiotropic effects of vorapaxar have not yet been studied. Methods and Results: Cellular targets of PAR1 signaling in the vasculature were identified in three patient cohorts with atherosclerotic disease. Evaluation of plasma biomarkers (n = 190) and gene expression in endomyocardial biopsies (EMBs) (n = 12) revealed that PAR1 expression correlated with endothelial activation and vascular inflammation. PAR1 colocalized with TLR2/4 in human carotid plaques and was associated with TLR2/4 gene transcription in EMBs. In addition, vorapaxar reduced atherosclerotic lesion size in apolipoprotein E–knock out (ApoEko) mice. This reduction was associated with reduced expression of vascular adhesion molecules and TLR2/4 presence, both in isolated murine endothelial cells and the aorta. Thrombin-induced uptake of oxLDL was augmented by additional TLR2/4 stimulation and abrogated by vorapaxar. Plaque-infiltrating pro-inflammatory cells were reduced in vorapaxar-treated ApoEko mice. A shift toward M2 macrophages paralleled a decreased transcription of pro-inflammatory cytokines and chemokines. Conclusions: PAR1 inhibition with vorapaxar may be effective in reducing residual thrombo-inflammatory event risk in patients with atherosclerosis independent of its effect on platelets.

Prior intracerebral hemorrhage and white matter hyperintensity burden on recurrent stroke risk

Prior intracerebral hemorrhage (ICH) is associated with increased risk of ischemic stroke. Since white matter hyperintensity (WMH) is associated with ischemic stroke and ICH, this study aimed to evaluate the relationship between ICH and the risk of recurrent stroke by WMH severity. From a prospective multicenter database comprising 1454 noncardioembolic stroke patients with cerebral small-vessel disease, patients were categorized by presence or absence of prior ICH and WMH severity: mild-moderate WMH (reference); advanced WMH; ICH with mild-moderate WMH; and ICH with advanced WMH. Among patients with ICH, the association with stroke outcomes by WMH burden was further assessed. The primary endpoint was ischemic stroke and hemorrhagic stroke. The secondary endpoint was major adverse cardiovascular events (MACE): stroke/coronary heart disease/vascular death. During the mean 1.9-year follow-up period, the ischemic stroke incidence rate per 100 person-years was 2.7, 4.0, 2.5, and 8.1 in increasing severity, and the rate of hemorrhagic stroke was 0.7, 1.3, 0.6, and 2.1, respectively. The risk of ischemic stroke was higher in ICH with advanced WMH (adjusted HR 2.62; 95% CI 1.22−5.60) than the reference group, while the risk of hemorrhagic stroke trended higher (3.75, 0.85–16.53). The risk of MACE showed a similar pattern in ICH with advanced WMH. Among ICH patients, compared with mild WMH, the risk of ischemic stroke trended to be higher in advanced WMH (HR 3.37; 95% CI 0.90‒12.61). Advanced WMH was independently associated with an increased risk of hemorrhagic stroke (HR 33.96; 95% CI 1.52−760.95). Given the fewer rate of hemorrhagic stroke, the risk of hemorrhagic stroke might not outweigh the benefits of antiplatelet therapy for secondary prevention.

A Clinical Update on Antiplatelet Therapy in Secondary Prevention of Ischemic Stroke.

Antiplatelet therapy remains the standard of care in secondary stroke prevention for non-cardioembolic ischemic stroke and transient ischemic attack. We aim to examine the use of antiplatelet agents in secondary prevention through highlighting relevant clinical trials and meta-analyses as well as providing commentary regarding our practice. In the POINT and CHANCE trials, dual antiplatelet therapy reduced recurrent stroke compared to aspirin monotherapy. Sub-analyses of these trials suggest that genetic polymorphisms could play a role in diminishing the effectiveness of clopidogrel. Similarly, THALES demonstrated better outcomes with ticagrelor-aspirin combination therapy over aspirin monotherapy. Combination antiplatelet therapy with aspirin and the P2Y12 inhibitors, clopidogrel and ticagrelor, reduced stroke recurrence in those presenting with mild ischemic stroke or high risk TIA. Genetic polymorphisms may play a role in determining the appropriate regimen. Questions remain regarding the optimal duration of combination antiplatelet therapy for various stroke etiologies.

Antiplatelet therapy for secondary prevention of cardiovascular disease: challenging the certainties

Antiplatelet therapy for secondary prevention of cardiovascular disease: challenging the certainties