Lower Risk Of Composite Outcome Research Articles

Effect of catheter ablation vs medical therapy on cardiovascular outcomes in hypertrophic cardiomyopathy with atrial fibrillation

Abstract Background Atrial fibrillation (AF) increases the risks of stroke and mortality. AF ablation in patients with heart failure (HF) was associated with a lower risk of death and hospitalisation for worsening HF. Whether AF ablation is beneficial to improve cardiovascular outcomes in patients with concomitant hypertrophic cardiomyopathy (HCM) and AF remains unclear. Objective To investigate whether AF ablation is more effective than conventional medical therapy for improving outcomes in HCM. Methods 2,281 patients with HCM and AF undergoing catheter ablation or medical therapy (antiarrhythmic drugs or rate control drugs) in 2005–2015 were identified from the Korean National Health Insurance Service database. The primary composite outcome of death from cardiovascular causes, ischaemic stroke, hospitalization for worsening HF, or acute myocardial infarction was compared between catheter ablation and medical therapy using propensity score overlap weighting. The time-at-risk was counted from the first medical therapy, and catheter ablation was analysed as a time-varying exposure. Results Of the included (41.1% female; median age: 66 years), 145 (6.1%) underwent catheter ablation for AF during the study period. During a mean follow-up of 3.1 (IQR 1.3–5.8) years, a total of 831 composite outcomes occurred including 292 cardiovascular deaths and 401 strokes. Catheter ablation, compared with medical therapy, was associated with lower risks of the primary composite outcome (weighted incidence rate: 3.84 vs. 6.43 per 100 person-years; weighted HR 0.61, 95% CI 0.38–0.96) and ischaemic stroke (weighted HR 0.43, 95% CI 0.19–0.97). The association between ablation and a lower risk of composite outcome was more pronounced in cases of ablation success whereas no significant difference was observed in cases of ablation failure. Conclusions In patients with AF and HCM, catheter ablation was associated with a lower risk of adverse cardiovascular outcomes than medical therapy.

Associations of built environment characteristic using NEWS questionnaires with major cardiovascular diseases and all-cause mortality

Abstract Background The WHO of 2016 reports that cardiovascular diseases (CVDs) represent the leading cause of death in most countries and China has one of the highest prevalence of CVDs[1-2]. In order to reduce the burden of CVD risk factors, environmental interventions have become increasingly recognized as necessary approaches to health promotion and diseases prevention[3]. Pervious evidence mainly from the western countries, examined the effects of built environment on health (i.e. physical activity, mental health, self-reported health scale and CVD risk factors) , while the potential impact on CVDs has not been fully explored[4]. Thus, the aim of this study is to evaluate the longitudinal relationships between perceived built environment attributes using neighborhood environment walkability scale (NEWS) questionnaire and the CVDs in Chinese adults, to explore the different between urban and rural areas, and to provide a logical foundation for both research and policy making. Methods PURE-China is a prospective cohort study, recruiting participants aged 35–70 years from 115 urban and rural communities in 12 provinces of China between 2005 and 2009[5]. Baseline including NEWS information was collected using standardized questionnaires. Participants without any NEWS data and with baseline CVDs were excluded. The primary outcome is the composite of major CVD events and all-cause mortality. The main exposure variables including land use mix-diversity, land use-access, streets connectivity, infrastructure for walking and cycling, aesthetics, safety from traffic, safety from crime, and community satisfaction. Cox frailty model with random intercepts to account for cluster were used to assess the association between total built environment score/ subscales score and the time to occurrence of events. Based and fully-adjusted model were estimated and presented as HR and 95%CI. Interactions and stratified subgroup analysis were also tested. Results A total of 32,534 PURE participants were included with averaged 51 years old and 59.9% females. During a median follow-up period of 11.7 years (IQR 9.4 – 12.2), we documented 3298 (10.2%) new CVD events and 1639 (5.1%) all cause deaths. Table 1 summarizes based models and adjusted models results. For composite outcomes, higher level of land use access (HR, 1.06; 95%CI, 1.01-1.11), aesthetics (HR, 1.07; 95%CI, 1.02-1.12), safety from crime (HR, 1.06; 95%CI, 1.01-1.10), community satisfaction (HR, 1.04; 95%CI, 1.00-1.09), combined BE metrics (HR, 1.05; 95%CI, 1.01-1.10) were associated with a lower risk of composite outcome in adjusted model. For major CVD events more statistically significant differences were observed. Conclusions and Relevance High level of specific BE characteristics were associated with lower risk of all-cause mortality and CVD in China. Our findings may guide policy makers on how to implement BE measures to easing the burden of CVDs and premature deaths.Table 1

ABC (Atrial fibrillation Better Care) pathway in asian patients: an analysis from the prospective Asia-Pacific Heart Rhythm Society Atrial Fibrillation Registry

Abstract Introduction The "Atrial fibrillation Better Care" (ABC) has been proposed as an integrated approach to improve management in patients with atrial fibrillation (AF) based on 3 pillars: "A" Avoid stroke with Anticoagulation; "B" Better symptom optimisation through rate or rhythm control; "C" Cardiovascular risk factor management. There are limited prospective data on the clinical outcomes associated with ABC pathway adherence from Asian countries. Purpose To investigate the beneficial effect of ABC pathway adherence in the prospective multi-country Asia-Pacific Heart Rhythm Society (APHRS) Atrial Fibrillation registry. Method We investigated 4013 AF patients prospectively enrolled in the APHRS registry. Cox-regression analyses were performed to investigate the association between ABC adherence and clinical outcomes. Primary outcome was a composite of all-cause death, any thromboembolic events, acute coronary syndrome or percutaneous interventional procedures and new/worsening heart failure. Secondary outcomes were each component of the composite outcome and major bleeding. Results In the whole population, 1549 (38.6%) patients were ABC adherent (mean age 66±12 years; 33% female). After 1-year of follow-up, ABC pathway adherent patients had a lower incidence of composite outcome (4.0% vs 8.5%, p<0.001), all-cause death (1.4% vs 4.0%, p<0.001), cardiovascular death (0.3% vs 0.9%, p=0.013) and new/worsening heart failure (1.7% vs 2.7%, p=0.010), when compared to those ABC non-adherent. On multivariable Cox regression ABC pathway adherence was associated with a lower risk for composite outcome (Hazard Ratio 0.72, 95% Confidence Interval 0.53-0.97) and the reduction of the risk increased progressively with the number of the ABC criteria fulfilled. There was no statistically significant interaction in the clinical benefit seen between the different participating countries in the APHRS registry (pint=0.217). Conclusion In a large contemporary cohort of Asian AF patients, ABC pathway adherence was associated with a reduction of the risk for the composite outcome of all-cause death and cardiovascular events. This benefit was seen irrespective of enrolling country.

Prognostic implications of left ventricular ejection fraction trajectory changes in heart failure.

The latest guidelines recommended to assess the trajectory of left ventricular ejection fraction (LVEF) in patients with heart failure (HF). However, there is limited data on the trajectory of LVEF in real-world settings. In this study, we investigated the frequency and prognostic implications of changes in LVEF trajectory. Patients were divided into intensified LVEF, static LVEF, and worsening LVEF groups based on the transitions of HF types from baseline to follow-up. The intensified and worsening LVEF groups were further subdivided into mild (≤10% absolute changes of LVEF) and significant (>10% absolute changes of LVEF) increase or decrease groups according to the magnitude of change. The incidences and associations of changes in LVEF with patient outcomes were analyzed. Among the 2,429 patients in the study cohort, 38.3% of HF with reduced ejection fraction (HFrEF) and 37.6% of HF with mildly reduced ejection fraction (HFmrEF) showed an improvement in their LVEF. In contrast, a decline in LVEF was observed in 19.3% of HF patients with preserved ejection fraction (HFpEF) and 34.9% of those with HFmrEF. Cox regression analysis showed that the intensified LVEF group was associated with a lower risk of composite endpoints, while the worsening LVEF group yielded opposite findings. Subgroup analysis revealed that compared to those with mild changes in LVEF, baseline HFrEF patients with significant increase showed a lower risk of composite outcome, while baseline HFpEF patients were the opposite. The trajectories of LVEF changes are strongly correlated with outcomes in patients with HF who had prior history of HF admission. The most significant prognostic implications observed in patients with significant LVEF changes. Trajectory LVEF and type of HF changes are useful tools recommended for prognostication.

328 IMPACT OF INTEGRATED CARE WITH ABC PATHWAY IN PATIENTS WITH ATRIAL FIBRILLATION AND HEART FAILURE: DATA FROM MORE THAN 11000 PATIENTS ENROLLED IN A EUROPEAN REGISTRY

Abstract Background and aim Heart failure (HF) is closely associated with atrial fibrillation (AF). The Atrial fibrillation Better Care (ABC) pathway is recommended in guidelines as a holistic or integrated care approach to AF management. However, few data are specifically available on ABC pathway adherence in AF patients with HF, especially according to HF phenotypes. Therefore, we aimed to retrospectively investigate the effect of ABC management in a large contemporary cohort of AF patients with HF and the impact on the clinical outcomes. Methods We analyzed patients enrolled in the ESC-EHRA EORP-AF General Long-Term Registry. According to the availability of HF status and ejection fraction (EF) values, patients were categorized as follows: i) non-HF; ii) HF EF>40% iii) HF EF≤40%. The primary outcome was a composite outcome of all-cause death and major adverse cardiac events. Results Among the original 11 096 AF patients enrolled, 9175 (82.7%) were included in this analysis (median age 71 years, interquartile range [IQR 63-77], 40.1% were female, with median EF 55% [IQR 45-61%] and median CHA2DS2-VASc 3 [2-4]). In this cohort, 5935 (64.7%) were non-HF patients, and 3240 (35.3%) had HF patients. According to the EF values, 2005 (65%) were categorized as HF EF>40%, and 1235 (35%) were HF EF≤40%. Overall, ABC pathway adherence in HF patients was 23.3% [95% CI: 21.6-25.2], being higher in HF EF≤40% patients (28.0%) and lower in HF EF>40% ones (21.9%). After a median follow-up of 731[IQR 690-748] days, ABC adherence was associated with a lower risk for the composite outcome compared to non-ABC adherent patients in each HF group (HF EF>40%: ABC 15.4% vs no ABC 20.9%; HF EF≤40%: ABC 20.3% vs no ABC 33.9%; both p<0.001). Cox regression analysis showed that ABC adherence was associated with a lower risk of composite outcome in each HF category (HF EF>40%: HR 0.66 [95% CI: 0.46-0.96], p=0.030; HF EF≤40%: HR 0.60 [95% CI: 0.40-0.90], p=0.013). ABC adherence was associated with a consistent risk reduction for the composite outcome across the entire EF spectrum [Figure]. Conclusions In this large contemporary cohort of AF-HF patients, adherence to the ABC pathway was associated with a lower occurrence of the primary outcome, irrespective of baseline EF. ABC pathway is consistently associated with a lower risk for adverse outcomes across the entire spectrum of EF.

Programmed Cell Death 1 (PD-1) and Programmed Cell Death Ligand 1 (PD-L1) inhibitors and adverse cardiovascular events: a population-based study

Abstract Funding Acknowledgements Type of funding sources: None. OnBehalf Cardiovascular Analytics Group Background Programmed death-1 (PD-1) and programmed death-ligand 1 (PD-L1) inhibitors are major classes of immune checkpoint inhibitors that are increasingly used for cancer treatment. However, they are associated with adverse cardiovascular events. Purpose To evaluate the cardiotoxicity of PD-1 and PD-L1 inhibitors, the present study aims to examine the incidence of new-onset cardiac complications in patients receiving PD-1 or PD-L1 inhibitors. Methods Patients receiving PD-1 or PD-L1 inhibitors since their launch up to December 31st, 2019 without pre-existing cardiac complications were included. Patient data were obtained using a territory-wide electronic health record database. The primary outcome was a composite of incident heart failure (HF), acute myocardial infarction (AMI), atrial fibrillation (AF) or atrial flutter followed up to August 31st, 2020. Propensity score matching between PD-L1 and PD-1 inhibitor use with a 1:1 ratio for patient demographics and comorbidities was performed. Results A total of 1925 patients were included. Over a median follow-up of 136 days (interquartile range [IQR]: 42-279), 318 (16.51%) patients met the primary outcome after PD-1/PD-L1 treatment: 242 (incidence rate [IR]: 12.57%) with HF, 38 (IR: 1.97%) with AMI, 53 (IR: 2.75%) with AF, 6 (IR: 0.31%) with atrial flutter. Compared with PD-1 inhibitor treatment, PD-L1 inhibitor treatment was significantly associated with a lower risk of composite outcome after matching (HR: 0.78, 95% CI: [0.62-0.99], P value = 0.0417). Patients who developed cardiovascular complications had shorter average readmission intervals and more hospitalization episodes after treatment with PD-1/PD-L1 inhibitors both before and after matching (P value < 0.0001). Conclusions Compared with PD-1 inhibitor users, PD-L1 inhibitor users had a significantly lower risk of new-onset composite cardiovascular complications. Abstract Figure. Kaplan-Meier survival curve

Integrated care and outcomes in patients with atrial fibrillation and comorbidities.

Integrated care for management of atrial fibrillation (AF) patients has been associated with a reduction in adverse events. The 'Atrial fibrillation Better Care (ABC) pathway' has been proposed to streamline such integrated management. In this paper, we analysed the impact of ABC pathway adherent clinical management on outcomes in AF patients with high-risk 'metabolic' comorbidities (i.e. diabetes mellitus [DM], chronic kidney disease [CKD], metabolic syndrome [MetS]. Patients from the SPORTIF III and V trials and with available data to evaluate ABC criteria were analysed. DM, CKD and MetS were evaluated according to baseline data. A composite of major adverse cardiovascular events and all-cause death was the study outcome. A total of 3637 patients (median age 72 [IQR 66-77], 30.3% female) were analysed. DM was evident in 23.4%, CKD in 25.8% and MetS in 31.5% among the overall cohort. Respectively, 23.2% were ABC pathway adherent in the DM subgroup, 21.2% in CKD and 23.7% in MetS subgroups. Composite outcome occurred less frequently in patients managed adherent to ABC pathway than those nonadherents, in all three groups. In the final multivariate model, ABC adherent care was inversely associated with a lower risk of composite outcome in the DM (HR 0.45, 95% CI 0.23-0.88), CKD (HR 0.60, 95% CI 0.36-0.98) and MetS (HR 0.37, 95% CI 0.19-0.71) subgroups. In high-risk AF patients with DM, CKD and MetS, ABC pathway adherent management was associated with a lowered risk of the composite outcome of cardiovascular events, cardiovascular and all-cause death.

Bupi Yishen Formula Versus Losartan for Non-Diabetic Stage 4 Chronic Kidney Disease: A Randomized Controlled Trial.

Chinese herbal medicine (CHM) might have benefits in patients with non-diabetic chronic kidney disease (CKD), but there is a lack of high-quality evidence, especially in CKD4. This study aimed to assess the efficacy and safety of Bupi Yishen Formula (BYF) vs. losartan in patients with non-diabetic CKD4. This trial was a multicenter, double-blind, double-dummy, randomized controlled trial that was carried out from 11-08-2011 to 07-20-2015. Patients were assigned (1:1) to receive either BYF or losartan for 48 weeks. The primary outcome was the change in the slope of the estimated glomerular filtration rate (eGFR) over 48 weeks. The secondary outcomes were the composite of end-stage kidney disease, death, doubling of serum creatinine, stroke, and cardiovascular events. A total of 567 patients were randomized to BYF (n = 283) or losartan (n = 284); of these, 549 (97%) patients were included in the final analysis. The BYF group had a slower renal function decline particularly prior to 12 weeks over the 48-week duration (between-group mean difference of eGFR slopes: −2.25 ml/min/1.73 m2/year, 95% confidence interval [CI]: −4.03,−0.47), and a lower risk of composite outcome of death from any cause, doubling of serum creatinine level, end-stage kidney disease (ESKD), stroke, or cardiovascular events (adjusted hazard ratio = 0.61, 95%CI: 0.44,0.85). No significant between-group differences were observed in the incidence of adverse events. We conclude that BYF might have renoprotective effects among non-diabetic patients with CKD4 in the first 12 weeks and over 48 weeks, but longer follow-up is required to evaluate the long-term effects. Clinical Trial Registration: http://www.chictr.org.cn, identifier ChiCTR-TRC-10001518.

Heart failure events in a clinical trial of arterial hypertension. The acquittal of the SPRINT trial

Abstract Introduction The Systolic Blood Pressure Intervention Trial (SPRINT) was a randomized trial showing that intensive lowering of systolic blood pressure (BP), as compared to standard treatment (i.e. <120 vs <140 mm Hg) was associated with a reduced risk (HR 0.75 [95% CI 0.64–0.79], p<0.001) for the primary composite outcome (CE), defined as myocardial infarction, an acute coronary syndrome other than myocardial infarction, stroke, acute exacerbation of heart failure and cardiovascular death. primary outcome event in subjects at high cardiovascular risk. However, the primary endpoint events in the intensive treatment arm were only 76 fewer than in the standard treatment arm (243 vs 319 events), and he reduction in heart failure events was responsible for half of the effect (62 vs 100 events, i.e. 38 events fewer). Thus, several experts in hypertension argued that these results were mainly driven by a reduction of heart failure events, and questioned the main conclusion of the study. Aim To assess the effect of SPRINT intervention on a redefined CE: the primary SPRINT endpoint with HF events excluded. Material and methods We used limited SPRINT data, available from the NHLBI Biologic Specimen and Data Repository to assess the impact of BP intervention in SPRINT on a redefined CE excluding HF events. The Chi-square test, Cox proportional model and survival analysis were applied. Results Among 9361 SPRINT participants (mean age 67.9±9.5 years, 35.6% female, 20% with previous cardiovascular disease), there was 461 CE events. There were fewer CE events in the intensive treatment arm than in the standard treatment arm (204 [4.4%] vs 257 [5.5%], p=0.0117, respectively). Intensive systolic BP lowering was associated with lower risk for CE than standard treatment (HR 0.79 [95% CI 0.66–0.95], p=0.0115). Kaplan-Meier curves show that intensive treatment was associated with better outcome (Figure 1). Analyses in subgroups (age >75 vs <75 years, female vs male, black vs non-black, prior cardiovascular disease vs no cardiovascular disease, prior chronic kidney disease vs no chronic kidney disease) showed no difference in benefit of intensive treatment (p for interaction >0.05 in all subgroup). Conclusion The reduction in cardiovascular events by intensive BP lowering in SPRINT was not explained by a difference in heart failure events. This supports the concept that more intensive BP reduction may provide benefit in reducing cardiovascular event risk. Figure 1. Kaplan-Meier curves Funding Acknowledgement Type of funding source: None

Long-term efficacy after closure of patent foramen ovale for ischemic neurological events in young adults: A systematic review and meta-analysis.

Background:The efficacy of patent foramen ovale (PFO) closure remains controversial, and it is unclear which patient groups are best benefited. We performed this meta-analysis to clarify the efficacy of PFO closure of younger patients for prevention of recurrent ischemic neurological events.Methods:We systematically searched for studies of PFO closure for younger patients under the age of 55, and pooled available data on PFO closure of younger vs older patients and on PFO closure of younger patients vs medical therapy. The primary endpoints were the composite outcome of recurrent ischemic neurological events [stroke and/or transient ischemic attack (TIA)]. The secondary endpoints included recurrent stroke, TIA, atrial fibrillation (AF) and bleeding events. We calculated the odds ratios (OR) and 95% confidence interval (CI) using fixed-effect and random-effect models.Results:Three randomized controlled trials (RCT) and 13 observational studies were eligible. Compared with older patients undergoing PFO closure, younger patients undergoing closure had a lower risk of composite outcome (OR: 0.40, 95% CI: 0.28 to .56; P < .001) and AF (OR: 0.25, 95% CI: 0.10–0.61; P = .003). Compared with medical therapy, PFO closure of younger patients reduced the risk of composite outcome (OR: 0.50, 95% CI: 0.33–0.75; P<.001); there was no statistical difference in total complications of AF and bleeding events (OR: 2.15, 95% CI: 0.15–30.37; P = .57). Separate analysis of stroke and TIA showed that PFO closure in younger patients was more effective in preventing stroke (OR: 0.45, 95% CI: 0.28–0.72; P < .001) and TIA (OR: 0.35, 95% CI: 0.21–0.58); P < .001) compared with older patients. Compared with medical therapy, PFO closure of younger patients reduced the risk of stroke (OR: 0.26, 95% CI: 0.13–0.51; P < .001); but there was no difference in the risk of TIA (OR: 1.07, 95% CI: 0.16–7.01; P = .94).Conclusions:Compared with PFO closure of older patients and medical therapy, PFO closure of younger patients can benefit more for the prevention of recurrent ischemic neurological events. Our results indicate that PFO closure is the best treatment strategy for younger patients under the age of 55.

Ablation Versus Medical Therapy for Atrial Fibrillation in the Elderly: A Propensity Score-Matched Comparison.

BackgroundWhether ablation therapy reduces the risk of death and embolic events in elderly patients with atrial fibrillation (AF) remains unclear.Material/MethodsAF patients ≥65 years old receiving either catheter ablation or non-ablation therapy at 2 tertiary and 2 non-tertiary hospitals in Beijing from November 2009 to December 2012 were enrolled. Patients were followed up every 6 months for information on treatment and clinical event occurrence. A propensity score matching algorithm produced comparable 2 groups of patients treated with ablation or non-ablation. Rates of a composite of all-cause death, non-fatal stroke, and peripheral embolism were the primary outcomes. Each composite component and major bleeding were the secondary outcomes.ResultsThere were 596 ablated patients and 1144 patients with non-ablation therapy enrolled. Propensity score algorithm matched 347 comparable pairs of patients. Patient characteristics variables were well balanced. During 523.5 and 497.5 patient-years follow-up, respectively, ablation therapy was associated with a significant lower risk of experiencing the primary composite outcome (hazard ratio [HR]=0.40; 95% confidence interval [CI]: 0.19–0.85), all-cause death (HR=0.13 95% CI: 0.04–0.43), and major bleeding (HR=0.23; 95% CI: 0.12–0.67), without apparent heterogeneity by age, sex, and AF type, and for risk score subgroups.ConclusionsIn this propensity-matched elderly sample, ablation therapy was associated with lower risk of composite outcome consisting of all-cause death, non-fatal stroke, and peripheral embolism, and therefore might be an alternative to conservative therapy.

Secondary prevention of acute coronary events with antiplatelet agents (SPACE-AA): One-year real-world effectiveness and safety cohort study in the French nationwide claims database

Background and aimsWe aimed to compare the effectiveness of ticagrelor vs. clopidogrel or prasugrel on recurrence of acute coronary syndromes (ACS) in real-life conditions, as requested by regulatory authorities at the time of marketing. MethodsWe performed a cohort study in SNDS, the French national healthcare database. All patients with a hospital admission for ACS in 2013 were followed one year. Patients on ticagrelor, clopidogrel or prasugrel were matched 1:1 using age, gender, index ACS type, and high-dimensional propensity scores (hdPS). Outcomes were ACS, stroke, all-cause death, and major bleeding, compared within matched groups using Cox proportional hazards models analysis during treatment. Results54,048 ACS were hospitalized in 2013. At discharge, 19,796 were dispensed clopidogrel, 8242 prasugrel, and 13,916 ticagrelor. Per group, 9224 ticagrelor vs. clopidogrel, 6752 ticagrelor vs. prasugrel, and 4676 prasugrel vs. clopidogrel patients were matched. Compared to clopidogrel, ticagrelor was associated with a lower hazard ratio of death 0.73 [0.59–0.90] and composite criterion (0.88, 95% CI [0.79–0.99] but not ACS 0.92 [0.80–1.06], stroke (0.96 [017-5.53]) or major bleeding (1.02 [0.82–1.26]). Prasugrel was not different from ticagrelor or clopidogrel for any outcome, in matched patients. ConclusionsTicagrelor in real-life conditions in matched populations was associated with a lower risk of all-cause death than clopidogrel, and a lower risk of composite outcome, as in the main pivotal clinical trial. Ticagrelor and prasugrel were not different, nor were prasugrel and clopidogrel.

Cilostazol versus aspirin for secondary prevention of vascular events after stroke of arterial origin.

Aspirin is widely used for secondary prevention after stroke. Cilostazol has shown promise as an alternative to aspirin in Asian people with stroke. To determine the relative effectiveness and safety of cilostazol compared directly with aspirin in the prevention of stroke and other serious vascular events in patients at high vascular risk for subsequent stroke, those with previous transient ischaemic attack (TIA) or ischaemic stroke of arterial origin. We searched the Cochrane Stroke Group Trials Register (last searched September 2010), the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2009, Issue 4), MEDLINE (1950 to May 2010) and EMBASE (1980 to May 2010). In an effort to identify further published, ongoing and unpublished studies we searched journals, conference proceedings and ongoing trial registers, scanned reference lists from relevant studies and contacted trialists and Otsuka Pharmaceutical Co Ltd. We selected all randomised controlled trials (RCTs) comparing cilostazol with aspirin where participants were treated for at least one month and followed systematically for development of vascular events. Data extracted from eligible studies included: (1) a composite outcome of vascular events (stroke, myocardial infarction or vascular death) during follow up (primary outcome); (2) separate outcomes of stroke (ischaemic or haemorrhagic, fatal or non-fatal), myocardial infarction (MI) (fatal or non-fatal), vascular death and death from all causes; and (3) main outcomes of safety including any intracranial, extracranial or gastrointestinal (GI) haemorrhage and other outcomes during treatment follow up (secondary outcomes). We computed an estimate of treatment effect and performed a test for heterogeneity between trials. We analysed data on an intention-to-treat basis and assessed bias for all included studies. We included two RCTs with 3477 Asian participants. Compared with aspirin, cilostazol was associated with a significantly lower risk of composite outcome of vascular events (6.77% versus 9.39%, risk ratio (RR) 0.72, 95% confidence interval (CI) 0.57 to 0.91), and lower risk of haemorrhagic stroke (0.53% versus 2.01%, RR 0.26, 95% CI 0.13 to 0.55). In terms of outcome of safety compared with aspirin, cilostazol was significantly associated with minor adverse effects (8.22% versus 4.95%, RR 1.66, 95% CI 1.51 to 1.83). Cilostazol is more effective than aspirin in the prevention of vascular events secondary to stroke. Cilostazol has more minor adverse effects, although there is evidence of fewer bleeds.