Lower Risk Of Recurrent Stroke Research Articles

Early statin use is associated with improved survival and cardiovascular outcomes in patients with atrial fibrillation and recent ischaemic stroke: A propensity-matched analysis of a global federated health database.

Statins reduce recurrent stroke and cardiovascular events in patients with non-cardioembolic stroke. The benefits of statins in patients with AF and recent IS remain unclear. We aimed to investigate the benefits of statins in patients with AF and recent IS. This retrospective, cohort study was conducted using deidentified electronic medical records within TriNetX platform. Patients with AF and recent IS, who received statins within 28 days of their index stroke were propensity score-matched with those who did not. Patients were followed up for up to 2 years. Primary outcomes were the 2-year risk of recurrent IS, all-cause mortality and the composite outcome of all-cause mortality, recurrent IS, transient ischaemic attack (TIA), and acute myocardial infarction (MI). Secondary outcomes were the 2-year risk of TIA, intracranial haemorrhage (ICH), acute MI, and hospital readmission. Cox regression analyses were used to calculate hazard ratios (HRs) with 95% confidence intervals (95%CI). Of 20,902 patients with AF and recent IS, 7500 (35.9%) received statins within 28 days of their stroke and 13,402 (64.1%) did not. 11,182 patients (mean age 73.7 ± 11.5; 5277 (47.2%) female) remained after propensity score matching. Patients who received early statins had significantly lower risk of recurrent IS (HR: 0.45, 95%CI: 0.41-0.48, p < 0.001), mortality (HR: 0.75, 95%CI: 0.66-0.84, p < 0.001), the composite outcome (HR: 0.48, 95%CI: 0.45-0.52, p < 0.001), TIA (HR: 0.37, 95%CI: 0.30-0.44, p < 0.001), ICH (HR: 0.59, 95%CI: 0.47-0.72, p < 0.001 ), acute MI (HR: 0.35, 95%CI: 0.30-0.42, p < 0.001) and hospital readmission (HR: 0.46, 95%CI: 0.42-0.50, <0.001). Beneficial effects of early statins were evident in the elderly, different ethnic groups, statin dose intensity, and AF subtypes, large vessel occlusion and embolic strokes and within the context of statin lipophilicity, optimal LDL-cholesterol levels, various cardiovascular comorbidities, treatment with intravenous thrombolysis or endovascular thrombectomy, and NIHSS 0-5 and NIHSS > 5 subgroups. Patients with AF and recent IS, who received early statins, had a lower risk of recurrent stroke, death, and other cardiovascular outcomes including ICH, compared to those who did not.

Treatment Strategies and Prognosis for Moderate Stroke Patients in China

Introduction: Moderate stroke patients with National Institutes of Health Stroke Scale (NIHSS) scores of 4–10 and without intravenous thrombolysis or endovascular treatment are basically excluded from current secondary prevention trials. We aimed to explore the effectiveness of mono- versus dual-antiplatelet treatment (DAPT) strategies against subsequent stroke for these patients in a nationwide cohort. Methods: Data were derived from the Third China National Stroke Registry (CNSR-III). In this prospective nationwide cohort, moderate ischemic stroke patients with NIHSS scores of 4–10 and without intravenous thrombolysis or endovascular treatment were included and categorized into mono- or dual-antiplatelet groups. Demographics, medical history, NIHSS score, imaging, and laboratory data were collected. The outcomes were stroke recurrence and all-cause mortality at 3 months and 1 year, respectively. Cox proportional hazards models were utilized to investigate the association of treatment strategies and prognosis. Results: Of a total of 2,414 patients enrolled in the study, 1,633 (67.6%) received clopidogrel or aspirin, and 781 (32.4%) received DAPT. Recurrent stroke occurred in 108 (6.6%) patients of the mono-antiplatelet group and 40 (5.1%) patients of the DAPT group (adjusted hazard ratio [aHR] 0.73, 95% confidential interval [CI] 0.47–1.13, p = 0.16) at 3 months, and the rate of stroke recurrence was 10.7% in the mono-antiplatelet group and 8.6% in the DAPT group (aHR 0.81, 95% CI 0.58–1.13, p = 0.22) at 12 months. The DAPT paradigm was not significantly associated with death at 3 months (0.6% vs. 0.3%, aHR 0.28, 95% CI: 0.04–2.25) but significantly reduced the mortality at 12 months (2.3% vs. 1.0%, aHR 0.41, 95% CI: 0.17–0.98, p = 0.046). Conclusions: In moderate stroke patients presenting within 24 h of symptom onset, the addition of clopidogrel 75 mg to aspirin might not be associated with lower risk of recurrent stroke than aspirin or clopidogrel alone.

Association Between Magnitude of Differential Blood Pressure Reduction and Secondary Stroke Prevention

The degree to which more intensive blood pressure reduction is better than less intensive for secondary stroke prevention has not been delineated. To perform a standard meta-analysis and a meta-regression of randomized clinical trials to evaluate the association of magnitude of differential blood pressure reduction and recurrent stroke in patients with stroke or transient ischemic attack (TIA). PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1, 1980, to June 30, 2022. Randomized clinical trials that compared more intensive vs less intensive blood pressure lowering and recorded the outcome of recurrent stroke in patients with stroke or TIA. The Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) reporting guideline was used for abstracting data and assessing data quality and validity. Risk ratio (RR) with 95% CI was used as a measure of the association of more intensive vs less intensive blood pressure lowering with primary and secondary outcomes. The univariate meta-regression analyses were conducted to evaluate a possible moderating effect of magnitude of differential systolic blood pressure (SBP) and diastolic blood pressure (DBP) reduction on the recurrent stroke and major cardiovascular events. The primary outcome was recurrent stroke and the lead secondary outcome was major cardiovascular events. Ten randomized clinical trials comprising 40 710 patients (13 752 women [34%]; mean age, 65 years) with stroke or TIA were included for analysis. The mean duration of follow-up was 2.8 years (range, 1-4 years). Pooled results showed that more intensive treatment compared with less intensive was associated with a reduced risk of recurrent stroke in patients with stroke or TIA (absolute risk, 8.4% vs 10.1%; RR, 0.83; 95% CI, 0.78-0.88). Meta-regression showed that the magnitude of differential SBP and DBP reduction was associated with a lower risk of recurrent stroke in patients with stroke or TIA in a log-linear fashion (SBP: regression slope, -0.06; 95% CI, -0.08 to -0.03; DBP: regression slope, -0.17; 95% CI, -0.26 to -0.08). Similar results were found in the association between differential blood pressure lowering and major cardiovascular events. More intensive blood pressure-lowering therapy might be associated with a reduced risk of recurrent stroke and major cardiovascular events. These results might support the use of more intensive blood pressure reduction for secondary prevention in patients with stroke or TIA.

Early Rhythm Control in Patients With Incident Atrial Fibrillation Who Had a Prior Stroke

BackgroundThere are limited data regarding the benefit of early rhythm control therapy for secondary prevention for stroke in patients with atrial fibrillation (AF). ObjectivesThis study aimed to compare the risk of recurrent stroke between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke. MethodsUsing the Korean nationwide claims database, the investigators identified patients who were newly diagnosed with AF and had a history of prior stroke. Patients who received rhythm control therapy, including antiarrhythmic drug, direct current cardioversion, or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, and the others were the usual care group. The propensity score weighting method was used to balance baseline characteristics between the 2 groups. Incident stroke was evaluated as a primary outcome. ResultsA total of 53,509 patients were included (12,455 in the early rhythm control group and 41,054 in the usual care group). All patients were prescribed oral anticoagulants. During a median 2.6 years of follow-up, 4,382 patients had an incident stroke (incidence rate: 2.6 per 100 person-years). Early rhythm control was associated with a lower risk of recurrent stroke compared to the risk associated with usual care (weighted HR: 0.720; 95% CI: 0.666-0.779; P < 0.001). ConclusionsEarly rhythm control within 1 year after AF diagnosis might be beneficial to prevent recurrent stroke in patients with incident AF and a history of stroke. Integrated care, including optimal rhythm control with appropriate anticoagulation, should be considered in this population.

Abstract TMP26: Effect Of Pioglitazone On Recurrent Stroke Risk In Patients With Post-stroke Cognitive Impairment And Insulin Resistance: Subgroup Analysis Of IRIS Trial

Patients with post-stroke cognitive impairment are at higher risk of recurrent stroke but the effect of pioglitazone on that risk has not been explored. The goal of this study was to determine the effect of pioglitazone on the risk of recurrent vascular events in patients with post-stroke cognitive impairment (PSCI) and insulin resistance (IR). We studied patients enrolled in Insulin Resistance Intervention after Stroke (IRIS) trial with a baseline Modified Mini-Mental State Examination (3MS) cognitive exam at median of 79 days after their stroke. We considered a baseline score of ≤ 88 on the 3MS to indicate global PSCI, and domain-specific summary scores in the lowest quartile to indicate language, attention, orientation, memory and visuospatial impairments. The primary endpoint of the study was recurrent stroke and MI. We studied n=3,338 patients. In fully adjusted Cox proportional hazards models for recurrent stroke, the hazard ratio (HR) for the effect of pioglitazone compared to placebo differed by post-stroke memory impiarment status (interaction p = 0.01). Pioglitazone was associated with 51% lower risk of recurrent stroke in patients with post-stroke memory impairment [HR = 0.49 (95% CI: 0.30 - 0.81); p = 0.005], but not in those without it [HR = 1.01 (95% CI: 0.75- 1.36); p = 0.942]. In fully adjusted Cox proportional hazards models for MI, the HR for the effect of pioglitazone compared to placebo differed by global PSCI status (interaction p = 0.03). Pioglitazone was associated with 77% lower risk of MI in patients with post-stroke global PSCI [HR = 0.23 (95% CI: 0.08, 0.71); p = 0.01], but not in those without it [HR = 0.88 (95% CI: 0.59, 1.31); p = 0.53]. These data indicate that simple cognitive testing after 3 months from stroke may serve as a precision medicine tool to identify patients at higher risk who may benefit from pioglitazone treatment. This approach can be tested in secondary stroke prevention clinical trials.

Ticagrelor Aspirin vs Clopidogrel Aspirin in CYP2C19 Loss-of-Function Carriers With Minor Stroke or TIA Stratified by Risk Profile.

Genotype data of the Clopidogrel with Aspirin in Acute Minor Stroke or Transient Ischemic Attack (CHANCE) trial showed that efficacy of clopidogrel aspirin depended on CYP2C19 genotype and risk profile. A stratification of patients who carried CYP2C19 loss-of-function (LOF) alleles according to the risk of recurrent stroke may be important for selecting optimal antiplatelet therapy. We aimed to compare the efficacy and safety of ticagrelor aspirin with clopidogrel aspirin in CYP2C19 LOF carriers with minor stroke or transient ischemic attack (TIA) stratified by risk profile. Data were obtained from Ticagrelor or Clopidogrel with Aspirin in High-Risk Patients with Acute Nondisabling Cerebrovascular Events II (CHANCE-2) trial. Low-risk and high-risk profiles were defined by Essen Stroke Risk Score (ESRS) (<3 [low risk] and ≥3 [high risk], respectively). A total of 6,412 CYP2C19 LOF carriers were enrolled; ticagrelor aspirin was associated with a reduced risk of primary outcome (new stroke within 90-day follow-up) in patients at low risk (hazard ratio [HR], 0.65; 95% CI, 0.48-0.82), but not in those at high risk (HR, 0.97; 95% CI, 0.73-1.29), compared with clopidogrel aspirin (p = 0.02 for interaction). Secondary outcomes generally went in the same direction as the primary outcome. The primary safety outcome of severe or moderate bleeding did not differ based on risk profile (p = 0.24 for interaction), although the incidence of total bleeding was greater with ticagrelor aspirin than with clopidogrel aspirin among patients at low risk (p < 0.01 for interaction). Analysis in the per-protocol population yielded similar results. This post hoc analysis of CHANCE-2 trial showed that CYP2C19 LOF carriers with minor stroke or TIA at low risk of recurrent stroke received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. This study provides Class II evidence that CYP2C19 LOF carriers with minor stroke or TIA at low risk, but not at high risk, of recurrent stroke (by the ESRS) received a greater benefit from ticagrelor aspirin than from clopidogrel aspirin. URL: www. gov. Unique identifier: NCT04078737.

The effect of rivaroxaban vs aspirin on stroke recurrence among patients with history of cryptogenic stroke and left atrial cardiomyopathy: An analytical cross-sectional study

Background: Stroke is defined as a lack of blood flow in the brain that can cause neurological deficits. Approximately 25% of all ischemic stroke patients are classified as cryptogenic strokes, most of which are caused by an embolic mechanism. Anticoagulant treatment with rivaroxaban may result in a lower risk of recurrent stroke than aspirin in patients with history of cryptogenic stroke and left atrial cardiomyopathy. Methods: In this cross-sectional study, we compared the efficacy and safety of rivaroxaban with aspirin for the prevention of recurrent stroke in patients with history of cryptogenic stroke and left atrial cardiomyopathy. Results: The results showed that assuming the other variables such as age, sex, hypertension, and diabetes be constant, stroke recurrence odds ratio in the Aspirin therapy was 11 times more than rivaroxaban therapy (OR=11.35, CI 95%: 1.39-113.08, P-value=0.038). Conclusion: Rivaroxaban was superior to aspirin with regard to the prevention of recurrent stroke among patients with history of cryptogenic stroke and left atrial cardiomyopathy.

Editors' Note: Prolonged Cardiac Monitoring and Stroke Recurrence: A Meta-analysis

The American Heart Association recommends extended cardiac monitoring for the diagnosis of subclinical atrial fibrillation (AF) among patients with acute ischemic stroke and no clear source of embolism. In this meta-analysis by Dr. Tsivgoulis and colleagues, investigators pooled high-quality observational cohort and randomized clinical trial data involving nearly 3,000 patients to evaluate the probability of identifying AF, initiation of anticoagulation, and stroke recurrence risk. Although all cardiac monitors increased the risk of AF detection and anticoagulation initiation, implantable loop recorders were associated with the highest probability of AF detection and anticoagulation initiation. Compared with patients who underwent conventional monitoring, those with prolonged monitoring were associated with a lower risk of recurrent stroke, although this risk was driven by patients monitored in observational (nontrial) cohort studies (relative risk [RR] 0.29, 95% CI 0.15–0.59 vs RR of stroke in randomized clinical trials 0.72, 95% CI 0.49–1.07). Dr. Meinel emphasizes that intracranial and systemic hemorrhages ought to be considered along with recurrent ischemic stroke in the decision to anticoagulate a patient with AF. The investigators acknowledge that intracranial hemorrhages are a highly fatal complication after anticoagulation, and although the risk of death due to major extracranial hemorrhage is also considerable, the mortality rate is far lower than what is seen among intracranial hemorrhages. Fortunately, most bleeding events and deaths due to such events are generally low (<5%). Owing to lack of available data on bleeding rates and mortality in many studies reported in this meta-analysis, the investigators cannot be certain of the low risks across all populations. That said, there were no significant differences in all-cause mortality with prolonged vs conventional cardiac monitoring in 2 of the included studies. Dr. Scharf also comments that the burden of subclinical AF and etiologies of recurrent stroke (e.g., small vessel or large vessel atherosclerosis) are also integral to evaluating the efficacy of anticoagulation in these patients. All authors eagerly await the results of randomized trials evaluating the potential benefit of anticoagulation after AF detection through prolonged cardiac monitoring. The American Heart Association recommends extended cardiac monitoring for the diagnosis of subclinical atrial fibrillation (AF) among patients with acute ischemic stroke and no clear source of embolism. In this meta-analysis by Dr. Tsivgoulis and colleagues, investigators pooled high-quality observational cohort and randomized clinical trial data involving nearly 3,000 patients to evaluate the probability of identifying AF, initiation of anticoagulation, and stroke recurrence risk. Although all cardiac monitors increased the risk of AF detection and anticoagulation initiation, implantable loop recorders were associated with the highest probability of AF detection and anticoagulation initiation. Compared with patients who underwent conventional monitoring, those with prolonged monitoring were associated with a lower risk of recurrent stroke, although this risk was driven by patients monitored in observational (nontrial) cohort studies (relative risk [RR] 0.29, 95% CI 0.15–0.59 vs RR of stroke in randomized clinical trials 0.72, 95% CI 0.49–1.07). Dr. Meinel emphasizes that intracranial and systemic hemorrhages ought to be considered along with recurrent ischemic stroke in the decision to anticoagulate a patient with AF. The investigators acknowledge that intracranial hemorrhages are a highly fatal complication after anticoagulation, and although the risk of death due to major extracranial hemorrhage is also considerable, the mortality rate is far lower than what is seen among intracranial hemorrhages. Fortunately, most bleeding events and deaths due to such events are generally low (<5%). Owing to lack of available data on bleeding rates and mortality in many studies reported in this meta-analysis, the investigators cannot be certain of the low risks across all populations. That said, there were no significant differences in all-cause mortality with prolonged vs conventional cardiac monitoring in 2 of the included studies. Dr. Scharf also comments that the burden of subclinical AF and etiologies of recurrent stroke (e.g., small vessel or large vessel atherosclerosis) are also integral to evaluating the efficacy of anticoagulation in these patients. All authors eagerly await the results of randomized trials evaluating the potential benefit of anticoagulation after AF detection through prolonged cardiac monitoring.

Effectiveness and Safety of Clopidogrel vs Aspirin in Elderly Patients With Ischemic Stroke

ObjectiveTo evaluate the risks of recurrent stroke and major bleeding events with clopidogrel and aspirin use among patients aged 80 years or older. Patients and MethodsThis retrospective cohort study was conducted using the Full Population Data of the Health and Welfare Database in Taiwan. Patients aged 80 years or older who received monotherapy with clopidogrel or aspirin following hospitalization for primary acute ischemic stroke between January 1, 2009, and December 31, 2018, were included. Inverse probability of treatment weighting was used to balance measured covariates between clopidogrel and aspirin users. Measured outcomes included recurrent acute ischemic stroke, acute myocardial infarction, composite cardiovascular events (recurrent stroke or acute myocardial infarction), intracranial hemorrhage, major gastrointestinal tract bleeding, and composite major bleeding events (intracranial hemorrhage or major gastrointestinal tract bleeding). ResultsA total of 15,045 patients were included in the study, 1979 of whom used clopidogrel and 13,066 who used aspirin following hospitalization for primary acute ischemic stroke. Clopidogrel use was associated with significantly lower risk of recurrent acute ischemic stroke (hazard ratio [HR], 0.89; 95% CI, 0.83 to 0.96; P=.002), composite cardiovascular events (HR, 0.88; 95% CI, 0.82 to 0.95; P<.001), intracranial hemorrhage (HR, 0.71; 95% CI, 0.56 to 0.90; P=.005), and composite major bleeding events (HR, 0.89; 95% CI, 0.80 to 0.99; P=.04) compared with aspirin use. ConclusionIn patients aged 80 years or older with primary acute ischemic stroke, clopidogrel users had lower risks of recurrent stroke and the composite cardiovascular events compared with aspirin users. Clopidogrel users also had lower risks of intracranial hemorrhage and the composite major bleeding events compared with aspirin users.

Non-Linear Association Between Serum Alkaline Phosphatase and 3-Month Outcomes in Patients With Acute Stroke: Results From the Xi'an Stroke Registry Study of China.

BackgroundAlkaline phosphatase (ALP) is associated with an increased risk of cardiovascular events and is closely related to adverse outcomes after stroke. However, the regional investigation into the associations of ALP with acute stroke (AS) outcomes is limited. This study aimed to identify the association between serum ALP levels and clinical outcomes 3 months after AS in the Xi'an district of China.MethodsWe enrolled all patients with AS from 4 hospitals in the Xi'an district from January to December 2015. ALP levels and related patient information were collected at admission, and the events of stroke outcomes were followed up 1 and 3 months after diagnosis. ALP levels were analyzed as continuous variables and quartiles (Q1–Q4). The outcomes included all-cause mortality, recurrent stroke, and poor functional outcomes (modified Rankin Scale score of 3–6) within 3 months. A multivariate logistic regression and interaction analyses were performed to evaluate the independent association between serum ALP level and 3-month stroke outcomes.ResultsOverall, 2,799 patients with AS were enrolled in this study. The mean age was 63.9 ± 12.5 years. In the Q4 (≥93.0 U/L) group, the incidences of all-cause mortality, recurrent stroke, and poor functional outcomes were 7.8, 2.7, and 24.9%, respectively. After being adjusted for confounding variables, patients in Q4 (≥93.0 U/L) were related to an increased risk of all-cause mortality [odds ratio (OR) = 2.17, 95% CI: 1.19–3.96; P = 0.011] and patients in Q3 (76.8–92.9 U/L) were related to a lower risk of recurrent stroke (OR = 0.37, 95% CI: 0.14–0.97; P = 0.043) at the 3-month time point, compared to those in Q2 (63.0–76.7 U/L). The optimal range of ALP for all-cause mortality was seen in Q2, with a nadir level of 70 U/L. However, differences were statistically insignificant between ALP levels and poor functional outcomes (P > 0.05). Moreover, there was no significant interaction between ALP levels and age, gender, drinking status, smoking status, or pneumonia (P > 0.05) for all outcomes.ConclusionNon-linear associations were observed between serum ALP levels and 3-month outcomes in patients with AS. It might be beneficial to reduce the risk of all-cause mortality and recurrent stroke by maintaining ALP at optimal ranges.

May 2022 Stroke Highlights

May 2022 <i>Stroke</i> Highlights

CE-543-03 EARLY RHYTHM CONTROL IN PATIENTS WITH INCIDENT ATRIAL FIBRILLATION WHO HAD A PRIOR HISTORY OF STROKE: A NATIONWIDE POPULATION-BASED COHORT STUDY

Early rhythm control therapy has been demonstrated to be associated with a lower risk of stroke compared to usual care in patients with atrial fibrillation (AF). However, there are limited data regarding the benefit of early rhythm control therapy for secondary prevention for stroke in patients with AF. To compare the risk of recurrent stroke between early rhythm control therapy and usual care in patients with new-onset AF and a history of prior stroke. Using the Korean nationwide claims database, we identified patients who were newly diagnosed as AF and had a history of prior stroke. Patients who received rhythm control therapy, including antiarrhythmic drug (AAD), direct current cardioversion (DCC), or AF catheter ablation, within 1 year after incident AF were defined as the early rhythm control group, otherwise as the usual care group. The propensity score weighting method was used to balance baseline characteristics between the two groups. Incident stroke was evaluated as a primary outcome. A total of 53,509 patients were included (mean age 72±11 years, 53% men; mean CHA2DS2-VASc score 5.5±1.6). All patients were prescribed oral anticoagulants. Among the total study population, 12,455 patients were assigned to the early rhythm control group (AAD, DCC, and AF catheter ablation in 99.4%, 8.6%, and 3.9%, respectively), and 41,054 patients were in the usual care group. During a median 2.6 years (IQR 1.5 to 4.5 years) of follow-up, 4382 patients had an incident stroke (IR, 2.6 per 100 person-years). Early rhythm control was associated with a lower risk of recurrent stroke compared to usual care (hazard ratio, 0.720, 95% confidence interval, 0.666-0.779, p<0.001) (Figure). Early rhythm control consistently showed a lower risk of stroke than usual care regardless of the characteristics of prior stroke, whether recent, severe, and disabling stroke or not. In this large-scale observational cohort study, early rhythm control within 1 year after AF diagnosis might be beneficial to prevent recurrent stroke in patients with incident AF and a history of prior stroke. Integrated care, including optimal rhythm control with appropriate anticoagulation, should be considered for patients who had incident AF and a history of stroke to reduce the risk of recurrent stroke.

Prolonged Cardiac Monitoring and Stroke Recurrence: A Meta-analysis.

Prolonged poststroke cardiac rhythm monitoring (PCM) reveals a substantial proportion of patients with ischemic stroke (IS) with atrial fibrillation (AF) not detected by conventional rhythm monitoring strategies. We evaluated the association between PCM and the institution of stroke preventive strategies and stroke recurrence. We searched MEDLINE and SCOPUS databases to identify studies reporting stroke recurrence rates in patients with history of recent IS or TIA receiving PCM compared with patients receiving conventional cardiac rhythm monitoring. Pairwise meta-analyses were performed under the random effects model. To explore for differences between the monitoring strategies, we combined direct and indirect evidence for any given pair of monitoring devices assessed within a randomized controlled trial (RCT). We included 8 studies (5 RCTs, 3 observational; 2,994 patients). Patients receiving PCM after their index event had a higher rate of AF detection and anticoagulant initiation in RCTs (risk ratio [RR] 3.91, 95% CI 2.54-6.03; RR 2.16, 95% CI 1.66-2.80, respectively) and observational studies (RR 2.06, 95% CI 1.57-2.70; RR 2.01, 95% CI 1.43-2.83, respectively). PCM was associated with a lower risk of recurrent stroke during follow-up in observational studies (RR 0.29, 95% CI 0.15-0.59), but not in RCTs (RR 0.72, 95% CI 0.49-1.07). In indirect analyses of RCTs, the likelihood of AF detection and anticoagulation initiation was higher for implantable loop recorders compared with Holter monitors and external loop recorders. PCM after an IS or TIA can lead to higher rates of AF detection and anticoagulant initiation. There is no solid RCT evidence supporting that PCM may be associated with lower stroke recurrence risk.

Antiplatelet regimens after ischemic stroke or transient ischemic attack: a systematic review and updated network meta-analysis.

BackgroundIt is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation.MethodsWe utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration.ResultsA total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion.ConclusionsThe efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.

Sex differences in the risk of recurrent ischemic stroke after ischemic stroke and transient ischemic attack.

Sex differences in stroke outcomes have been noted, but whether this extends to stroke recurrence is unclear. We examined sex differences in recurrent stroke using data from the Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke (POINT) trial. We assessed the risk of recurrent stroke in women compared to men using data from the POINT trial. Adults >18 years old were randomized within 12 hours of onset of minor ischemic stroke or transient ischemic attack (TIA), and followed for up to 90 days for ischemic stroke, our primary outcome. We used Cox proportional hazards model adjusted for demographics and stroke risk factors to evaluate the association between sex and stroke recurrence. We used interaction term testing and prespecified subgroup analyses to determine if the association between sex and recurrent stroke differed by age (<60 versus >60 years old), locale (US versus non-US), and index event type (stroke versus TIA). Last, we evaluated whether sex modified the effect of common stroke risk factors on stroke recurrence. Of 4,881 POINT trial participants with minor stroke or high-risk TIA, 2,195 (45%) were women. During the 90-day follow-up period, 267 ischemic strokes occurred; 121 were in women and 146 in men. The cumulative risk of recurrent ischemic stroke was not significantly different among women (5.76%; 95% CI, 4.84%-6.85%) compared to men (5.67%; 95% CI, 4.83%-6.63%). Women were not at a different risk of recurrent ischemic stroke compared to men (hazard ratio [HR], 1.02; 95% CI, 0.80-1.30) in unadjusted models or after adjusting for covariates. However, there was a significant interaction of age with sex (P=0.04). Among patients <60 years old, there was a non-significantly lower risk of recurrent stroke in women compared to men (HR 0.66; 95% CI 0.42-1.05). Last, sex did not modify the association between common stroke risk factors and recurrent stroke risk. Among patients with minor stroke or TIA, the risk of recurrent ischemic stroke and the impact of common stroke risk factors did not differ between men and women.

P2Y12 receptor inhibitor plus aspirin versus aspirin treated within 24 hours of acute noncardioembolic ischemic stroke or TIA: Meta-analysis

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24h after acute noncardioembolic ischemic stroke or TIA. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin. CRD42020203730.

Rates, Predictors, and Impact of Smoking Cessation after Stroke or Transient Ischemic Attack: A Systematic Review and Meta-Analysis

BackgroundSmoking cessation after a first cardiovascular event reduces the risk of recurrent vascular events and mortality. This systematic review and meta-analysis aimed to summarize data on the rates, predictors, and the impact of smoking cessation in patients after a stroke or transient ischemic attack (TIA). MethodsMEDLINE, EMBASE and Web of Science were searched to identify all published studies providing relevant data through May 20, 2021. Random-effects meta-analysis method was used to pool proportions. Some findings were summarized narratively. ResultsTwenty-five studies were included. The pooled smoking cessation rates were 51.0% (8 studies, n = 1738) at 3 months, 44.4% (7 studies, n = 1920) at 6 months, 43.7% (12 studies, n = 1604) at 12 months, and 49.8% (8 studies, n = 2549) at 24 months or more of follow-up. Increased disability and intensive smoking cessation support programs were associated with a higher likelihood of smoking cessation, whereas alcohol consumption and depression had an inverse effect. Two studies showed that patients who quit smoking after a stroke or a TIA had substantially lower risk of recurrent stroke, death, and a composite of stroke, myocardial infarction, and death. ConclusionSmoking cessation in stroke survivors is associated with reduced recurrent vascular events and death. About half of smokers who experience a stroke or a TIA stop smoking afterwards. Those with low post-stroke disability, who consume alcohol, or have depression are less likely to quit. Intensive support programs can increase the likelihood of smoking cessation.

Antiplatelet regimens for Asian patients with ischemic stroke or transient ischemic attack: a systematic review and network meta-analysis.

BackgroundThe optimal antiplatelet treatment for the secondary prevention of non-cardioembolic stroke or transient ischemic attack (TIA) remains uncertain in Asians.MethodsWe searched for eligible randomized control trials in Medline, Embase, and the Cochrane Library. A Bayesian network meta-analysis (NMA) was performed to assess the efficacy and safety of antiplatelet regimens with placebo as the control. Each therapy was compared using relative risk ratios (RR) and 95% credible intervals (CrI), and ranked according to the value of the surface under the cumulative ranking curve.ResultsA total of 84,103 patients from 32 studies were included: patients in used aspirin (n=26,834); cilostazol (n=3,303); clopidogrel (n=12,406); prasugrel (n=1,885); sarpogrelate (n=752); ticagrelor (n=1,933); ticlopidine (n=1,644); triflusal (n=391); aspirin plus cilostazol (n=1,120), aspirin plus clopidogrel (n=4,623); aspirin plus dipyridamole (n=10,853); aspirin plus ticagrelor (n=5,859); aspirin plus ticlopidine (n=132). Patients who used aspirin plus clopidogrel and cilostazol had a lower risk of recurrent stroke than those who used placebo. Patients administered with aspirin plus ticagrelor, aspirin plus clopidogrel, and cilostazol had a lower risk of composite vascular events than those administered placebo. Patients administered aspirin plus ticagrelor had a higher risk of major bleeding than those administered placebo. Clustered three-dimensional rank plots of recurrent stroke, major bleeding, and composite vascular events demonstrated that cilostazol had higher values of the surface under the cumulative ranking curve than other treatments.ConclusionsOf the antiplatelet regimens, cilostazol showed the best net clinical benefits than other antiplatelet regimens in Asians with non-cardioembolic stroke or TIA.

Abstract P1: Antiplatelet Therapy for Secondary Prevention After Ischemic Stroke: Systematic Review and a Network Meta-Analysis From Randomized Trials

Introduction: While various antiplatelet regimens are currently available for secondary prevention after ischemic stroke, data comparing their efficacy and safety are scarce. We conducted a network meta-analysis investigating the efficacy and risk profile of each antiplatelet regimen including combination therapies for secondary prevention of recurrent stroke. Methods: PubMed and EMBASE were searched for reports on randomized controlled trials published between January 1, 1985, and July 21, 2020. Random-effects model was used for meta-analysis. Primary outcome was recurrent stroke after ischemic stroke and secondary outcomes was major bleeding. Results: 39 trials enrolling a total of 158,507 patients were eligible for our network meta-analysis. Patients were randomly allocated to receive aspirin, cilostazol, clopidogrel, dipyridamole, ticagrelor, ticlopidine, or combination of these antiplatelet agents in each study. In comparison to those who received aspirin monotherapy, the risk of recurrent stroke was significantly lower in patients who received cilostazol (odds ratio (OR), 0.65; 95% confidence interval (CI), 0.51-0.83), aspirin + ticagrelor (OR, 0.72; 95% CI, 0.62-0.83), aspirin + clopidogrel (OR, 0.73; 95% CI, 0.54-0.98) without significant heterogeneity (I2=45.1). Ticagrelor monotherapy did not demonstrate a significant difference in risk of recurrent stroke compared to clopidogrel monotherapy (OR, 1.02; 95% CI, 0.70-1.48). Aspirin and ticagrelor combination therapy did not demonstrate a significant difference in risk of recurrent stroke compared to aspirin and clopidogrel combination therapy (OR, 1.01; 95% CI, 0.74-1.39). Combination therapy of aspirin with clopidogrel or ticagrelor showed a higher risk of major bleeding compared to aspirin monotherapy (OR, 1.54; 95% CI, 1.30-1.84; OR, 2.93; 95% CI, 1.53-5.41, respectively). Conclusions: Ticagrelor and clopidogrel demonstrated similar efficacy and risk of major bleeding—as monotherapy and in combination with aspirin—when used for secondary prevention of recurrent stroke. Ticagrelor or clopidogrel in combination with aspirin showed lower risk of recurrent stroke but higher risk of major bleeding than aspirin monotherapy.

Abstract MP53: Intensive Blood Pressure Reduction and Secondary Stroke Risk: A Posthoc Analysis of the Sps3 Trial

Introduction: The SPRINT trial demonstrated cardiovascular benefit for a target systolic blood pressure (SBP) &lt;120 mm Hg, but the effect on primary stroke was neutral. The Secondary Prevention of Small Subcortical Strokes (SPS3) trial did not reduce secondary stroke with a target SBP &lt;130 mm Hg. No trial has investigated the effect of the more intensive SPRINT target of &lt;120 mm Hg on secondary stroke risk. Methods: We performed a secondary analysis of SPS3 and included patients with at least 10 SBP readings. The primary predictor is mean SBP from day 30 (to avoid confounding from the initial study intervention) to 2 years. The primary outcome is recurrent ischemic stroke from day 30 to 2 years. We fit Cox models to our outcomes to derive hazard ratios for recurrent stroke events. Results: We included 2,859 patients, of which 121 (4.2%) had ischemic stroke during follow-up. There were 321 patients with SBP &lt;120 (mean=115.5 mm Hg) and 2,538 with SBP ≥120 (mean=134.6 mm Hg), with a respective recurrent stroke rate of 1.9% versus 4.5% (p=0.026). In the Cox model, the hazard ratio for stroke with mean SBP &lt;120 mm Hg was 0.40 (95% CI, 0.18-0.92) (Figure 1) and after adjustment for potential confounders (age, sex, race, education, smoking, prior stroke, prior myocardial infarction) the hazard ratio was 0.39 (95% CI, 0.16-0.96). Conclusion: In patients with lacunar stroke, achieving the SPRINT intensive blood pressure goal of &lt;120 mm Hg was associated with a lower risk of recurrent stroke. While the current study is underpowered and has bias, these preliminary results suggest that the SPRINT definition of intensive blood pressure reduction could be beneficial for secondary stroke prevention.