Association of Prestroke Glycemic Control With Vascular Events During 1-Year Follow-up

ObjectiveWe evaluated the association between admission HbA1c and subsequent risk of composite vascular events, including stroke, myocardial infarction, and vascular death, in patients with acute ischemic stroke and diabetes.MethodsPatients who had a transient ischemic attack or an acute ischemic stroke within 7 days of symptom onset, and diabetes were included in a retrospective cohort design using the stroke registry of the Clinical Research Center for Stroke in Korea. The association between admission HbA1c and composite vascular events, including stroke, myocardial infarction (MI), and vascular death, during one-year follow-up was estimated using the Fine-Gray model. The risk of composite vascular events according to the ischemic stroke subtype was explored using fractional polynomial and linear-quadratic models.ResultsOf the 18567 patients, 1437 developed composite vascular events during follow-up. In multivariable analysis using HbA1c as a categorical variable, the risk significantly increased at a threshold of 6.8%–7.0%. The influence of admission HbA1c level on the risk of composite vascular events was pronounced particularly among those in whom fasting glucose at admission was ≤130 mg/dL. The optimal ranges of the HbA1c associated with minimal risks for composite vascular events was the lowest for the small vessel occlusion subtype (6.6, [95% confidence internal [CI], 6.3–6.9]), compared to the large artery atherosclerosis (7.3 [95% CI, 6.8–7.9]) or the cardioembolic subtype (7.4[95% CI, 6.3–8.5]).ConclusionIn patients with ischemic stroke and diabetes, the risks of composite vascular events were significantly associated with admission HbA1c. The optimal range of the admission HbA1c was below 6.8%–7.0%, and were different according to the ischemic stroke subtype.

Misreported Cancer Deaths in PLATO Trial

The potential link between antiplatelet agents and anticoagulants with excess cancer deaths (CD) was reported first for prasugrel (TRITON, DAPT), clopidogrel (DAPT), vorapaxar (TRACER), apixaban (APPRAISE-2), and later ticagrelor (PEGASUS). However, verified CD in the ticagrelor indication-seeking PLATO were not public. We obtained the complete list of deaths and their primary causes in PLATO, matched that dataset against local site records, and analyzed the patterns of CD reporting. The FDA-issued spreadsheet contains 31 precisely detailed CD (PLATO code 12-3). We obtained local site evidence for four CD and matched them with FDA-reported. We also assessed the patterns of how CD were reported among non-vascular death database column “S” by scrolling the FDA Excel file down among 938 PLATO entries. Clopidogrel CD (n = 17) were reported exclusively by sponsor, while independent CRO’s reported only ticagrelor CD (3 out of 14 PLATO total). Among four matched verified outcomes, one ticagrelor CD was correct, second ticagrelor CD was unreported, and two (ticagrelor and clopidogrel) CD were reported inaccurately. Of the remaining 16 clopidogrel CD six were reported as three separate next in line paired entries in Denmark (236–237), Poland (597–598), Romania (679–680), and as two more fatalities in South Africa (786) and Spain (789), while patients 787 and 788 received ticagrelor out of 938 records suggesting possible late addition of incorrect clopidogrel CD reports. We conclude that some CD were misreported in PLATO, favoring ticagrelor. Such mismatch may require reevaluation of this critical outcome in the trial focusing on the exact death cause reported by site investigators.

509 POTENTIALLY INAPPROPRIATE MEDICATION USE AND MORTALITY IN PATIENTS WITH COGNITIVE IMPAIRMENT

Introduction Potentially inappropriate medications (PIMsare associated with falls, hospitalisation, and cognitive decline. Few studies have investigated the association between PIMsrelated to cognitive impairment (PIMCog) and mortality in dementia or mild cognitive impairment (MCI). Methods This was a retrospective observational study. Patients diagnosed with MCI or dementia (DSM-IV criteria) presenting to a tertiary-referral memory clinic from 2013–2019 were eligible. The primary outcome was all-cause death. Secondary outcomes were vascular death and non-vascular death defined according to formal certification. The primary exposure variable of interest was PIMCog, defined as any medication in the Beers 2015 or STOPP criteria, classified as potentially inappropriate for patients with cognitive impairment. Anticholinergic burden was measured using the anticholinergic cognitive burden (ACB) scale. Polypharmacy was defined as ≥5 medications. Cox proportional hazard models were used to calculate hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results There were 418 patients included (n = 261 dementia, n = 157 MCI). The median age was 79 (interquartile range {IQR} 74–82) and median follow-up was 809 days (IQR 552–1,571). One or more PIMCog was prescribed in 141 patients (33.4%). PIMCog use was associated with all-cause mortality after adjustment for age, sex, dementia severity, Charlson Co-morbidity Index, chronic obstructive pulmonary disease, congestive cardiac failure, and peripheral vascular disease. (HR 1.96, 95% CI 1.24–3.09). PIMCog use was associated with vascular death (HR 3.28, 95% CI 1.51–7.11) but not with non-vascular death (HR 1.40 95% CI: 0.78–2.52). Neither an ACB ≥3 (HR 0.87, 95% CI: 0.46–1.64) or polypharmacy (HR 1.87, 95% CI: 0.67–5.24) were associated with death. Conclusion The burden of PIMCog use in patients with cognitive impairment is high. PIMCog use is independently associated with all-cause mortality and vascular death. This is a potential modifiable risk factor for death in patients with neurocognitive disorders. Further research is required to independently validate this finding.

Thromboembolism, bleeding and vascular death in nonvalvular atrial fibrillation patients with type 2 diabetes receiving rivaroxaban or warfarin

Background Diabetes increases a patient’s risk of developing atrial fibrillation by 49%. Patients with nonvalvular atrial fibrillation are at a fivefold increased risk of stroke and die more frequently from vascular causes. We sought to evaluate the effectiveness and safety of rivaroxaban versus warfarin in nonvalvular atrial fibrillation patients with type 2 diabetes. Methods This was an analysis of Optum® De-Identified electronic health record data from 11/2010 to 12/2019. We included adults with nonvalvular atrial fibrillation and type 2 diabetes, newly started on rivaroxaban or warfarin and with ≥ 12-months of prior electronic health record activity. Patients who were pregnant, had alternative indications for oral anticoagulation or valvular heart disease were excluded. We evaluated the incidence rate (%/year) of developing the composite outcome of stroke/systemic embolism or vascular death and major or clinically relevant nonmajor bleeding as well as each endpoint individually. Hazard ratios with 95% confidence intervals were calculated using propensity score-overlap weighted proportional hazards regression. Results We included 32,078 rivaroxaban (31% initiated on 15 mg dose) and 83,971warfarin users (time-in-therapeutic range = 47 ± 28%). Rivaroxaban was associated with a reduced risk of stroke/systemic embolism or vascular death (3.79 vs. 4.19; hazard ratio = 0.91, 95% confdience interval = 0.88–0.95), driven mostly by reductions in vascular death (2.81 vs 3.18, hazard ratio = 0.90, 95% confidence interval = 0.86–0.95) and systemic embolism (0.13 vs. 0.16; hazard ratio = 0.82, 95% confidence interval = 0.66–1.02). Major/clinically relevant nonmajor bleeding was less frequent with rivaroxaban versus warfarin (2.17 vs. 2.31; hazard ratio = 0.94, 95% confidence interval = 0.89–0.99) due to decreased critical organ bleeding (including intracranial hemorrhage) (0.35 vs. 0.54; hazard ratio = 0.63, 95% confidence interval = 0.55–0.72). Conclusions In nonvalvular atrial fibrillation patients with type 2 diabetes, rivaroxaban was associated with an ~ 10% relative reduction in vascular mortality and fewer bleeding-related hospitalizations versus warfarin.

Abstract 17278: Mid-Term Clinical Outcomes of Functionally-Guided Treatment of Coronary Bifurcation Lesions

Background: Rates of major adverse cardiac events (MACE) after functionally guided percutaneous coronary intervention (PCI) of coronary bifurcation lesions have not been specifically analysed. Methods: Patients from FIESTA registry (ClinicalTrials.govNCT01724957) with stable angina, bifurcation lesions in a coronary artery with diameter ≥ 2.5 mm and ≤ 4.5 mm and SB diameter≥2.0 mm were included in the analysis. Subjects with ST-segment elevation myocardial infarction, left main disease, hemodynamic instability were excluded. Provisional stenting was the default strategy in all patients. Fractional flow reserve (FFR) was performed using the PrimeWire or PrimeWire Prestige (Volcano Corp., USA). Bifurcation lesion with FFR above 0.80 were deferred from PCI. Follow-up for vital status at every 3-month period was performed and rates of MACE, including cardio-vascular death, nonfatal myocardial infarction and stroke, were analyzed. Results: Overall 165 patients were included, mean age was 67±10 years, 66% males, 72 (44%) had functionally significant bifurcation lesions (FSL) and 93 (56%) were with non-significant lesions (nFSL). There were no differences (FSL vs. nFSL) regarding: dyslipidemia (88% vs 96%), diabetes (44% vs. 32%), smoking (52% vs 40%), previous MI (24% vs 15%), previous PCI (54% vs 49%), atrial fibrillation (17% vs 29%), PAD (10% vs. 9%), renal failure (29% vs 31%) – all p>0.05. On a median follow-up of 34±14 months there were no differences between FSL and nFSL regarding rates of cardio-vascular death -12.5% (n=9/72) vs. 7.5% (n=7/93), p=0.4, MACEs - 13.9% (n=10/72)vs 8.6 (8/93), p=0.512. On multivariate Cox-regression analysis factors associated with occurrence of MACE were: presence of cancer OR 3.692, (CI 0.955-14.269); renal failure OR 2.550, (CI 0.961-6.767) SYNTAX ≥9 OR 1.836, (CI 0.490-6.874); SB RVD ≥ 2.4mm OR 2.546, (CI 0.708-9.160); SB BARI 13.5% OR 2.013, (CI 0.652-6.211); WBC≥7OR 3.647, (CI 0.824-16.134); Platelet count ≥ 256.106/ml OR 3.814, (CI 1.220-11.925). Conclusion: Less than a half of angiographically significant coronary bifurcation lesions were functionally significant requiring stent implantation. The rates of MACE were not-significantly different in deferred and treated stenoses up to 3 years follow-up.

Trends and predictors of myocardial infarction or vascular death after ischaemic stroke or TIA in China, 2007–2018: insights from China National Stroke Registries

BackgroundAlthough stroke management, primary and secondary preventions have been improved in China last decades, the trends and predictors of major vascular events after ischaemic stroke or transient ischaemic attack (TIA) at national scale are less known.MethodsData were obtained from the three phases of China National Stroke Registry (CNSR), including CNSR-Ⅰ (years 2007–2008), CNSR-Ⅱ (years 2012–2013) and CNSR-III (years 2015–2018). For comparison, patients who were diagnosed as ischaemic stroke or TIA were included. Kaplan-Meier estimates of myocardial infarction (MI) or vascular death were calculated at 1 year. Independent predictors were further assessed with a Cox proportional hazards regression.ResultsFrom 2007 to 2018, a total of 50 284 patients with ischaemic stroke or TIA were enrolled in this study. A declining trend was found in 1-year MI or vascular death (p for trend <0.001), while recurrent stroke depicted a U-shape curve with a nadir in 2012–2013 cohort. A similar trend was also observed in patients who were admitted to 26 hospitals in all three CNSRs. In 2015–2018 cohort, only 251 (1.7%; 95% CI 1.5% to 1.9%) MI or vascular death had occurred at 1 year. Older age, previous stroke or TIA, history of coronary artery disease and the National Institutes of Health Stroke Scale >6 were associated with both an increased risk of MI or vascular death and recurrent stroke. While early antiplatelet therapy and lipid-lowering agents at discharge predicted a reduced risk.ConclusionA declining trend and current low incidence of MI or vascular death, rather than recurrent stroke, after ischaemic stroke or TIA were observed in China. Traditional factors were found as independent predictors. These findings suggested there is still much room to improve for stroke management.

Statin therapy in acute cardioembolic stroke with no guidance-based indication

ObjectiveIt is uncertain whether patients with cardioembolic stroke and without a guidance-based indication for statin therapy should be administered a statin for prevention of subsequent vascular events. This study was performed to determine whether the statin therapy is beneficial in preventing major vascular events in this population.MethodsUsing a prospective multicenter stroke registry database, we identified patients with acute cardioembolic stroke who were hospitalized between 2008 and 2015. Patients who had other established indications for statin therapy according to current guidelines were excluded. Major vascular event was defined as a composite of stroke recurrence, myocardial infarction, and vascular death. We performed frailty model analysis with the robust sandwich variance estimator using the stabilized inverse probability of treatment weighting method to estimate hazard ratios of statin therapy on outcomes.ResultsOf 6,124 patients with cardioembolic stroke, 2,888 (male 44.6%, mean age 75.3 years, 95% confidence interval [CI] 74.8–75.8) were eligible, and 1,863 (64.5%) were on statin therapy during hospitalization. After a median follow-up of 359 days, cumulative incidences of major vascular events were 9.3% in the statin users and 20.5% in the nonusers (p < 0.001 by log-rank test). The adjusted hazard ratios of statin therapy were 0.39 (95% CI 0.31–0.48) for major vascular events, 0.81 (95% CI 0.57–1.16) for stroke recurrence, 0.28 (95% CI 0.21–0.36) for vascular death, and 0.53 (95% CI 0.45–0.61) for all-cause death.ConclusionStarting statin during the acute stage of ischemic stroke may reduce the risk of major vascular events, vascular death, and all-cause death in patients with cardioembolic stroke with no guidance-based indication for statin.

Abstract TP421: Cardiovascular Risk in Patients With Symptomatic Intracranial Atherosclerosis: A Post-Hoc Analysis of the SAMMPRIS Trial

Introduction: Previous studies have shown an elevated risk of MI (MI) in patients with symptomatic intracranial atherosclerotic disease (sICAD), but the mediators of increased risk of MI or death in these patients remain uncertain. We aim to determine risk factors associated with MI or death in patients with symptomatic ICAD. Methods: Patients enrolled in SAMMPRIS had sICAD and were randomized to aggressive medical management (AMM) vs. stenting and AMM. The primary outcome of this post-hoc analysis is MI or vascular death within 2 years of follow-up. We excluded patients who were lost to follow up, had a stroke during follow up, had non-vascular death or death within 30 days of stenting. Patients meeting the inclusion criteria were divided into two groups: those with vs. those without the primary outcome. We used binary logistic regression to determine predictors of incident MI or death within 2 years. Results: Of the 451 patients enrolled in SAMMPRIS, 350 patients met the inclusion criteria (reasons for exclusion: 4 deaths occurring within 30 days of stenting, 63 with ischemic stroke, 6 with symptomatic hemorrhage, 7 patients with non-cardiovascular death within 2 years, and 21 lost to follow up). At 2 years, 17 patients (4.9%) had MI/death; 10 patients had MI and 7 had cardiovascular deaths. In a multivariable model, factors associated with MI/death were: history of coronary artery disease (adjusted OR 3.19, 95% CI 1.14 - 8.93, p = 0.027) and systolic blood pressure (adjusted OR per 10 mm increase 1.20, 95% CI 0.98 - 1.44, p = 0.080). This risk was abut 24% with both predictors present and 2.8% with them absent (Figure). Conclusion: Higher systolic blood pressure and pre-existing cardiovascular disease were independently associated with incident MI or vascular death in patients with sICAD, despite medical management. Further studies are needed to confirm this association and test interventions to reduce this risk.