Multiple Antiplatelet Therapy in Ischemic Stroke Already on Antiplatelet Agents Based on the Linked Big Data for Stroke.

BACKGROUND: Optimal antiplatelet strategy for patients with ischemic stroke who were already on single antiplatelet therapy (SAPT) remains to be elucidated. This study aimed to evaluate the effect of different antiplatelet regimens on vascular and safety outcomes at 1 year after non-cardioembolic stroke in patients previously on SAPT. METHODS: We identified 9,284 patients with acute non-cardioembolic ischemic stroke that occurred on SAPT using linked data. Patients were categorized into three groups according to antiplatelet strategy at discharge: 1) SAPT; 2) dual antiplatelet therapy (DAPT); and 3) triple antiplatelet therapy (TAPT). One-year outcomes included recurrent ischemic stroke, composite outcomes (recurrent ischemic stroke, myocardial infarction, intracerebral hemorrhage, and death), and major bleeding. RESULTS: Of 9,284 patients, 5,565 (59.9%) maintained SAPT, 3,638 (39.2%) were treated with DAPT, and 81 (0.9%) were treated with TAPT. Multiple antiplatelet therapy did not reduce the risks of 1-year recurrent stroke (DAPT, hazard ratio [HR], 1.08, 95% confidence interval [CI], 0.92-1.27, P = 0.339; TAPT, HR, 0.71, 95% CI, 0.27-1.91, P = 0.500) and 1-year composite outcome (DAPT, HR, 1.09, 95% CI, 0.68-1.97, P = 0.592; TAPT, HR, 1.46, 95% CI, 0.68-1.97, P = 0.592). However, the TAPT groups showed an increased risk of major bleeding complications (DAPT, HR, 1.23, 95% CI, 0.89-1.71, P = 0.208; TAPT, HR, 4.65, 95% CI, 2.01-10.74, P < 0.001). CONCLUSION: Additional use of antiplatelet agents in patients with non-cardioembolic ischemic stroke who were already on SAPT did not reduce the 1-year incidence of vascular outcomes, although it increased the risk of bleeding complications.

Relationship of functional disability after a recent stroke with recurrent stroke risk.

BACKGROUND AND PURPOSE: Post-stroke disability status is primarily focused on recovery prognostication but the influence of post-stroke disability on future vascular risk is unknown. The relationship between functional disability after an index stroke and risk of recurrent vascular events was examined. METHODS: A cohort analysis of 3680 recent non-cardioembolic, non-to-moderate disabled [modified Rankin Scale (mRS) ≤3] stroke patients aged ≥35 years and followed for 2 years was reviewed. The mRS measured at a median of 35 days after the index stroke was analyzed as a dichotomous variable (mRS 3 vs. ≤2) and in a stepwise manner. Independent associations of post-stroke disability by mRS score with ischaemic stroke (primary outcome), stroke/coronary heart disease/vascular death as major vascular events (secondary outcome) and all-cause death (tertiary outcome) were analyzed. RESULTS: Amongst study participants, 435 (11.8%) had an mRS of 3. Compared with mRS ≤2 as no/slight disability, mRS 3 as moderate disability was associated with a higher risk of stroke (adjusted hazard ratio 1.45, 95% confidence interval 1.06-1.99). Compared with mRS 0, there was a progressively higher independent risk for each of the study outcomes: stroke, mRS 1 (1.42, 0.97-2.08), mRS 2 (1.46, 0.97-2.20), mRS 3 (1.89, 1.20-2.97); major vascular events, mRS 1 (1.31, 1.01-1.70), mRS 2 (1.31, 0.99-1.74), mRS 3 (1.46, 1.06-2.01); and all-cause death, mRS 1 (1.75, 1.03-2.98), mRS 2 (2.49, 1.44-4.31), mRS 3 (2.72, 1.43-5.19). CONCLUSION: Compared with no/slight disability, moderate disability after a recent stroke is linked to a higher risk of recurrent stroke.

Heart failure, recurrent vascular events and death in patients with ischemic stroke-results of the MonDAFIS study.

Heart failure (HF) is associated with poor outcome after stroke, but data from large prospective trials are sparse.We assessed the impact of HF on clinical endpoints in patients hospitalized with acute ischemic stroke or transient ischemic attack (TIA) enrolled in the prospective, multicenter Systematic Monitoring for Detection of Atrial Fibrillation in Patients with Acute Ischemic Stroke (MonDAFIS) trial. HF was defined as left ventricular ejection fraction (LVEF) < 55% or a history of HF on admission. The composite of recurrent stroke, major bleeding, myocardial infarction, and all-cause death, and its components during the subsequent 24 months were assessed. We used estimated hazard ratios in confounder-adjusted models. Overall, 410/2562 (16.0%) stroke patients fulfilled the HF criteria (i.e. 381 [14.9%] with LVEF < 55% and 29 [1.9%] based on medical history). Patients with HF had more often diabetes, coronary and peripheral arterial disease and presented with more severe strokes on admission. HF at baseline correlated with myocardial infarction (HR 2.21; 95% CI 1.02-4.79), and all-cause death (HR 1.67; 95% CI 1.12-2.50), but not with major bleed (HR 1.93; 95% CI 0.73-5.06) or recurrent stroke/TIA (HR 1.08; 95% CI 0.75-1.57). The data were adjusted for age, stroke severity, cardiovascular risk factors, and randomization. Patients with ischemic stroke or TIA and comorbid HF have a higher risk of myocardial infarction and death compared with non-HF patients whereas the risk of recurrent stroke or major hemorrhage was similar. Trial registration number Clinicaltrials.gov NCT02204267.

Differential impacts of admission LDL-cholesterol on early vascular outcomes by ischemic stroke subtypes.

BACKGROUND: Because ischemic stroke is heterogeneous, the associations between low-density lipoprotein (LDL)-cholesterol levels and early vascular outcomes might be different according to the stroke subtype in acute ischemic stroke patients. METHODS: This study was an analysis of a prospective, multicenter, stroke registry. Acute ischemic stroke patients previously not treated with statins were included. Admission LDL-cholesterol levels were divided into 7 groups at 20 mg/dl intervals for comparison. The primary early vascular outcome was a composite of stroke, myocardial infarction (MI) and all-cause mortality within 3 months. RESULTS: A total of 38,531 patients (age, 68.5 ± 12.8 yrs; male, 59.6%) were analyzed for this study. The 3-month cumulative incidences of the composite of stroke, MI, and all-cause mortality significantly differed among the LDL-cholesterol level groups, with the highest event rate (11.11%) in the lowest LDL-cholesterol group (<70 mg/dl). After adjustment, the U-shaped associations of LDL-cholesterol levels with primary outcome and all-cause mortality were observed. For the stroke subtypes, there were substantial interactions between the LDL-cholesterol groups and stroke subtype and all-cause mortality (Pinteraction=0.07). Different patterns, with higher risks of all-cause mortality in the lower LDL-cholesterol in the large artery atherosclerosis subtype (adjusted hazard ratio [aHR] 1.29, 95% confidence interval [CI] 0.98-1.69), but in the higher LDL-cholesterol in the cardioembolism subtype (aHR 1.71 95% CI [1.28-2.29]), were observed among stroke subtypes. CONCLUSION: We found that there were differential associations of admission LDL-cholesterol levels with all-cause mortality within 3 months among stroke subtypes. These results suggest that admission LDL-cholesterol and early vascular outcomes had complex relationships in patients with ischemic stroke according to the stroke subtypes.

Impact of non-traditional lipid profiles on 1-year vascular outcomes in ischemic stroke patients with prior statin therapy and LDL-C < 100 mg/dL.

This study aimed to investigate the association between non-traditional lipid profiles and the risk of 1-year vascular events in patients who were already using statins before stroke and had admission LDL-C < 100 mg/dL. This study was an analysis of a prospective, multicenter, nationwide registry of consecutive patients with acute ischemic stroke patients who treated with statin before index stroke and LDL-C < 100 mg/dL on admission. Non-traditional lipid profiles including non-HDL, TC/HDL ratio, LDL/HDL ratio, and TG/HDL ratio were analyzed as a continuous or categorical variable. The primary vascular outcome within one year was a composite of recurrent stroke (either hemorrhagic or ischemic), myocardial infarction (MI) and all-cause mortality. Hazard ratios (95% Cis) for 1-year vascular outcomes were analyzed using the Cox PH model for each non-traditional lipid profiles groups. A total of 7028 patients (age 70.3 ± 10.8years, male 59.8%) were finally analyzed for the study. In unadjusted analysis, no significant associations were observed in the quartiles of LDL/HDL ratio and 1-year primary outcome. However, after adjustment of relevant variables, compared with Q1 of the LDL/HDL ratio, Q4 was significantly associated with increasing the risk of 1-year primary outcome (HR 1.48 [1.19-1.83]). For the LDL/HDL ratio, a linear relationship was observed (P for linearity < 0.001). Higher quartiles of the LDL/HDL ratio were significantly and linearly associated with increasing the risk of 1-year primary vascular outcomes. These findings suggest that even during statin therapy with LDL-C < 100 mg/dl on admission, there should be consideration for residual risk based on the LDL/HDL ratio, following stroke.

Long-Term Effectiveness of Cilostazol in Patients with Hemodialysis with Peripheral Artery Disease.

AIM: The aim of this study was to investigate the effects of continuous cilostazol use on emergency department (ED) visits, hospitalizations, and vascular outcomes in patients with hemodialysis (HD) with peripheral artery disease (PAD). METHODS: This retrospective cohort study recruited 558 adult patients, who had received chronic HD for at least 90 days between January 1, 2008 and December 31, 2012, from the National Health Insurance Research Database. Eligible patients were divided into two groups based on continuing or discontinuing cilostazol treatment. Outcome measures were ED visits, hospitalizations, mortality, and vascular outcomes such as percutaneous transluminal angioplasty, surgical bypass, lower leg amputation, ischemic stroke, hemorrhagic stroke, and cardiovascular events. RESULTS: Patients with continuous cilostazol use had significantly higher prevalence of stroke, cancer, vintage, and the use of angiotensin receptor blocker and ß-blocker, but significantly lower incidence of ischemic stroke and cardiovascular events, as well as lower mortality, than those without continuous cilostazol use (all p＜.05). Continuous cilostazol use was independently associated with lower risk of ED visits, hemorrhagic stroke, and cardiovascular events (adjusted hazard ratios: 0.79, 0.29, and 0.67; 95% confidence intervals: 0.62-0.98, 0.10-0.84, and 0.48-0.96, respectively; all p＜.05). Continuous cilostazol use was significantly associated with higher ED visit-free and cardiovascular event-free rates (log-rank test; p＜.05). CONCLUSION: Continuous treatment of cilostazol in patients with HD with PAD significantly decreases the risk of ED visits, hemorrhagic stroke, and cardiovascular events and improves ED visit-free and cardiovascular event-free rates during long-term follow-up.

Admission LDL-cholesterol, statin pretreatment and early outcomes in acute ischemic stroke.

BACKGROUND: Lipid paradox of low LDL-C may cause physicians to be reluctant to use statins in acute ischemic stroke (AIS) patients with low LDL-C levels at admission. OBJECTIVE: This study investigated the association between LDL-C levels and early vascular outcomes and assessed the potential interaction effect between LDL-C and statin pretreatment on early outcomes. PATIENTS AND METHODS: This was a study of a prospective, multicenter, registry of AIS patients with admission LDL-C. The subjects were divided into 3 groups according to LDL-C levels: low LDL-C (≤100 mg/dL); intermediate LDL-C (>100, <130 mg/dL); and high LDL-C (≥130 mg/dL). The primary early vascular outcome was a composite of stroke (ischemic or hemorrhagic), myocardial infarction and all-cause mortality within 3 months. The associations of LDL-C levels as a continuous variable and the risks of primary outcome using Cox proportional hazards models with restricted cubic splines were explored. RESULTS: A total of 32,505 patients (age, 69 ± 12; male, 58.6%) were analyzed. The 3 groups showed significant differences in the 3-month primary outcome, with highest events in the low LDL-C group; after adjustment, no significant associations with the 3-month primary outcome remained. U-shaped nonlinear relationships of LDL-C levels with the 3-month primary outcome were observed (Pnon-linearity<0.001), with substantial relationships in the no pretreatment subgroup. CONCLUSIONS: The relationships between admission LDL-C levels and early outcomes are complex but appear to be paradoxical in patients with low LDL-C and no statin pretreatment. The results suggest that statin pretreatment might offset the paradoxical response of low LDL-C on early vascular outcomes. Further study would be warranted.

Admission hyperglycemia, stroke subtypes, outcomes in acute ischemic stroke.

AIMS: Whether admission hyperglycemia is differentially associated with early vascular outcomes in acute ischemic stroke (AIS) depending on stroke subtype has been incompletely delineated. METHODS: In a multicenter, prospective stroke registry, patients with AIS were categorized based on admission glucose levels into normoglycemia, moderate hyperglycemia, and severe hyperglycemia (<140mg/dl, 140-179mg/dl, and ≥180mg/dl, respectively) groups. Multivariate analysis assessed the interaction between the hyperglycemia and ischemic stroke subtypes of large artery atherothrombosis (LAA), cardioembolism (CE), and small vessel occlusion (SVO) and early vascular outcomes (3-month stroke, all-cause mortality, and composite of stroke, MI, and all-cause mortality). RESULTS: Among the 32,772 patients (age:69.0±12.6yrs, male:58.4%) meeting eligibility criteria, 61.9% were in the normoglycemia group, 19.5% were in the moderate hyperglycemia group, and 18.7% were in the severe hyperglycemia group. Substantial interactions between hyperglycemia groups and stroke subtypes were observed for 3-month stroke (Pinteraction = 0.003) and composite of stroke, MI, and all-cause mortality (Pinteraction = 0.001), with differential recurrence strongest among CE, intermediate among LAA, and least among SVO. CONCLUSIONS: Hyperglycemia was differently associated with the risk of 3-month stroke by ischemic stroke subtype. The associations of hyperglycemia with 3-month stroke were greatest in CE subtype but not in SVO subtype. These results suggest that the effect of glucose-lowering treatment after AIS may differ according to stroke subtype.

Cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in Asians with type 2 diabetes: A systematic review and meta-analysis of cardiovascular outcome trials.

BACKGROUND AND AIMS: Both type 2 diabetes and cardiovascular (CV) disease develops at a younger age in Asians and often have a higher risk of mortality. Both sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) have shown a significant reduction in CV end-points in CV outcome trials (CVOTs). Whether similar CV benefit exists in Asians, is not yet clearly known. METHODS: We systematically searched relevant medical database up to January 31, 2020 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs. Subsequently, we meta-analyzed the pooled data of hazard ratio (HR) of major adverse cardiac events (MACE) in Asians. We additionally analyzed the data of heart failure hospitalization (HHF) or CV-death with SGLT-2Is in Asians. RESULTS: The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 4987), did not find any significant reduction in MACE (HR, 0.88; 95% CI, 0.67 to 1.15; P = 0.35) and HHF or CV-death (HR, 0.86; 95% CI, 0.55 to 1.36; P = 0.53) in Asians, compared to the placebo. In contrast, the meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 4298) demonstrated a significant reduction in MACE, compared to the placebo (HR, 0.71; 95% CI, 0.59 to 0.86; P < 0.0001). CONCLUSIONS: This meta-analysis found a significant reduction in MACE with GLP-1RAs but not with SGLT-2Is in Asians. No significant reduction in HHF or CV-death demonstrated either with SGLT-2Is in Asians. Whether these results are related to an inadequate statistical power, or due to underrepresentation of Asians, or a true ethnic difference, remains to be established.

Gender difference in cardiovascular outcomes with SGLT-2 inhibitors and GLP-1 receptor agonist in type 2 diabetes: A systematic review and meta-analysis of cardio-vascular outcome trials.

BACKGROUND AND AIMS: Type 2 diabetes confers a differential risk of cardiovascular (CV) disease according to the gender. Whether newly approved anti-diabetic drugs like sodium-glucose co-transport-2 inhibitors (SGLT-2Is) and glucagon-like peptide-1 receptor agonists (GLP-1RAs) that have shown a significant reduction in the CV end-points in CV outcome trials (CVOTs) also have a differential impact gender-wise, is still not clearly known. METHODS: We systematically searched the medical database up to December 31, 2019 and retrieved all the dedicated CVOTs conducted with SGLT-2Is and GLP-1RAs that explicitly reported the outcome of major adverse cardiac events (MACE). Subsequently, we pooled the hazard ratio (HR) of MACE in both sexes separately and meta-analyzed the result gender-wise. RESULTS: The meta-analysis of three CVOTs conducted with SGLT-2Is (N = 34,322), demonstrated a significant reduction in MACE in men but not in women (Men - HR, 0.90; 95% CI, 0.83 to 0.97; P = 0.006; Women - HR, 0.88; 95% CI, 0.77 to 1.00; P = 0.06) compared to placebo. The meta-analysis of seven CVOTs conducted with GLP-1RAs (N = 56,004) demonstrated a significant reduction in MACE in both sex (Men - HR, 0.88; 95% CI, 0.82 to 0.93; P < 0.0001; Women - HR, 0.88; 95% CI, 0.79 to 0.99; P = 0.03), against the placebo. CONCLUSIONS: The reduction in MACE with SGLT-2Is appears to be significantly less in women with diabetes vs men, while GLP-1RAs confers a similar reduction in MACE, irrespective of the gender. Whether these results are related to inadequate statistical power (underrepresentation of women) in CVOT, or it reflects a true gender difference, still remains to be established.

A 7-Year Single-Center Experience of Transfemoral TAVI: Evolution of Surgical Activity and Impact on Vascular Outcome.

Transcatheter aortic valve implantation (TAVI) has become a well-established alternative to open surgery to treat aortic stenosis. We describe our 7-year TAVI experience using transfemoral access and identity changes in surgical activity and evaluate its impact on postoperative vascular outcomes. Consecutive patients (N = 340) who underwent TAVI with percutaneous transfemoral access were retrospectively included and divided into 4 quartiles according to the date of intervention. Vascular outcomes were classified according to the Valve Academic Research Consortium 2 classification. The number of patients who underwent transfemoral TAVI increased over time and their clinical characteristics evolved, with a lower Society of Thoracic Surgeons score and less comorbidities. The material used evolved and TAVI could be performed despite higher iliac calcification and tortuosity scores. With experience, the procedural time, the postoperative length of stay at hospital, and the 30-day postoperative mortality significantly decreased. No significant change was observed for vascular outcome, except for minor hematoma. We witnessed an increase in transfemoral TAVI procedure, with changes in clinical and procedural characteristics associated with an improvement in postoperative outcomes.

Association of obstructive sleep apnoea with the risk of vascular outcomes and all-cause mortality: a meta-analysis.

OBJECTIVE: This study aimed to conduct a meta-analysis to explore and summarise the evidence regarding the association between obstructive sleep apnoea (OSA) and the subsequent risk of vascular outcomes and all-cause mortality. METHODS: Electronic databases PubMed, Embase and the Cochrane Library were searched to identify studies conducted through May 2016. Prospective cohort studies that reported effect estimates with 95% CIs of major adverse cardiac events (MACEs), coronary heart disease (CHD), stroke, cardiac death, all-cause mortality and heart failure for different levels versus the lowest level of OSA were included. RESULTS: A total of 16 cohort studies reporting data on 24 308 individuals were included. Of these, 11 studies reported healthy participants, and the remaining five studies reported participants with different diseases. Severe OSA was associated with an increased risk of MACEs (relative risk (RR): 2.04; 95% CI 1.56 to 2.66; P<0.001), CHD (RR: 1.63; 95% CI 1.18 to 2.26; P=0.003), stroke (RR: 2.15; 95% CI 1.42 to 3.24; P<0.001), cardiac death (RR: 2.96; 95% CI 1.45 to 6.01; P=0.003) and all-cause mortality (RR: 1.54; 95% CI 1.21 to 1.97; P<0.001). Moderate OSA was also significantly associated with increased risk of MACEs (RR: 1.16; 95% CI 1.01 to 1.33; P=0.034) and CHD (RR: 1.38; 95% CI 1.04 to 1.83; P=0.026). No significant association was found between mild OSA and the risk of vascular outcomes or all-cause mortality (P>0.05). Finally, no evidence of a factor-specific difference in the risk ratio for MACEs among participants with different levels of OSA compared with those with the lowest level of OSA was found. CONCLUSIONS: Severe and moderate OSAs were associated with an increased risk of vascular outcomes and all-cause mortality. This relationship might differ between genders. Therefore, further large-scale prospective studies are needed to verify this difference.

Association of heme oxygenase-1 gene rs2071746 polymorphism with vascular outcomes in patients with atherosclerotic stroke.

As an inducible isoform of heme oxygenase (HO), HO-1 was suggested to have an anti-oxidative stress, anti-inflammatory, anti-apoptotic and anti-proliferative effect. It was regarded as an important cytoprotective enzyme. We undertook this study to investigate whether HO-1 gene rs2071746 polymorphism was associated with clinical outcomes in atherosclerosis ischemic stroke patients. Between December 2009 and October 2012, consecutive atherosclerosis ischemic stroke patients were enrolled. The primary endpoint was the composite of vascular death, nonfatal ischemic stroke and myocardial infarct. A total of 961 patients were enrolled. After an average follow-up of 15.13 (SD=7.42) months, 89 patients (9.26%) had the primary endpoint. The cumulative incidence of the primary endpoint was significantly lower in A carriers (AT+AA) than TT genotype (7.9% vs. 12.2%, HR=0.648, 95% CI: 0.425-0.988, P=0.044). After adjustment for age, sex and other cardiovascular risk factors, we found that A carrier was an independent protective factor for atherosclerosis ischemic stroke (HR=0.646, 95% CI: 0.420-0.994, P=0.047). Age (HR=1.023, P=0.028) and low level of HDL (HR=1.772, P=0.012) were independent risk factors for the primary endpoint. In conclusion, HO-1 gene rs2071746 A allele carrier might be a protective factor for patients with atherosclerotic stroke.