SummaryBackgroundResults of small trials indicate that fluoxetine might improve functional outcomes after stroke. The FOCUS trial aimed to provide a precise estimate of these effects.MethodsFOCUS was a pragmatic, multicentre, parallel group, double-blind, randomised, placebo-controlled trial done at 103 hospitals in the UK. Patients were eligible if they were aged 18 years or older, had a clinical stroke diagnosis, were enrolled and randomly assigned between 2 days and 15 days after onset, and had focal neurological deficits. Patients were randomly allocated fluoxetine 20 mg or matching placebo orally once daily for 6 months via a web-based system by use of a minimisation algorithm. The primary outcome was functional status, measured with the modified Rankin Scale (mRS), at 6 months. Patients, carers, health-care staff, and the trial team were masked to treatment allocation. Functional status was assessed at 6 months and 12 months after randomisation. Patients were analysed according to their treatment allocation. This trial is registered with the ISRCTN registry, number ISRCTN83290762.FindingsBetween Sept 10, 2012, and March 31, 2017, 3127 patients were recruited. 1564 patients were allocated fluoxetine and 1563 allocated placebo. mRS data at 6 months were available for 1553 (99·3%) patients in each treatment group. The distribution across mRS categories at 6 months was similar in the fluoxetine and placebo groups (common odds ratio adjusted for minimisation variables 0·951 [95% CI 0·839–1·079]; p=0·439). Patients allocated fluoxetine were less likely than those allocated placebo to develop new depression by 6 months (210 [13·43%] patients vs 269 [17·21%]; difference 3·78% [95% CI 1·26–6·30]; p=0·0033), but they had more bone fractures (45 [2·88%] vs 23 [1·47%]; difference 1·41% [95% CI 0·38–2·43]; p=0·0070). There were no significant differences in any other event at 6 or 12 months.InterpretationFluoxetine 20 mg given daily for 6 months after acute stroke does not seem to improve functional outcomes. Although the treatment reduced the occurrence of depression, it increased the frequency of bone fractures. These results do not support the routine use of fluoxetine either for the prevention of post-stroke depression or to promote recovery of function.FundingUK Stroke Association and NIHR Health Technology Assessment Programme.

IMPORTANCEThe prevalence and short-term outcomes of hypertensive urgency (systolic blood pressure Ն180 mm Hg and/or diastolic blood pressure Ն110 mm Hg) are unknown. Guidelines recommend achieving blood pressure control within 24 to 48 hours. However, some patients are referred to the emergency department (ED) or directly admitted to the hospital, and whether hospital management is associated with better outcomes is unknown.OBJECTIVES To describe the prevalence of hypertensive urgency and the characteristics and short-term outcomes of these patients, and to determine whether referral to the hospital is associated with better outcomes than outpatient management. DESIGN, SETTING, AND PARTICIPANTSThis retrospective cohort study with propensity matching included all patients presenting with hypertensive urgency to an office in the Cleveland Clinic Healthcare system from January 1, 2008, to December 31, 2013. Pregnant women and patients referred to the hospital for symptoms or treatment of other conditions were excluded. Final follow-up was completed on June 30, 2014, and data were assessed from October 31, 2014, to May 31, 2015.EXPOSURES Hospital vs ambulatory blood pressure management. MAIN OUTCOMES AND MEASURESMajor adverse cardiovascular events (MACE) consisting of acute coronary syndrome and stroke or transient ischemic attack, uncontrolled hypertension (Ն140/90 mm Hg), and hospital admissions. RESULTSOf 2 199 019 unique patient office visits, 59 836 (4.6%) met the definition of hypertensive urgency. After excluding 851 patients, 58 535 were included. Mean (SD) age was 63.1 (15.4) years; 57.7% were women; and 76.0% were white. Mean (SD) body mass index (calculated as weight in kilograms divided by height in meters squared) was 31.1 (7.6); mean (SD) systolic blood pressure, 182.5 (16.6) mm Hg; and mean (SD) diastolic blood pressure, 96.4 (15.8) mm Hg. In the propensity-matched analysis, the 852 patients sent home were compared with the 426 patients referred to the hospital, with no significant difference in MACE at 7 days (0 vs 2 [0.5%]; P = .11), 8 to 30 days (0 vs 2 [0.5%]; P = .11), or 6 months (8 [0.9%] vs 4 [0.9%]; P > .99). Patients sent home were more likely to have uncontrolled hypertension at 1 month (735 of 852 [86.3%] vs 349 of 426 [81.9%]; P = .04) but not at 6 months (393 of 608 [64.6%] vs 213 of 320 [66.6%]; P = .56). Patients sent home had lower hospital admission rates at 7 days (40 [4.7%] vs 35 [8.2%]; P = .01) and at 8 to 30 days (59 [6.9%] vs 48 [11.3%]; P = .009). CONCLUSIONS AND RELEVANCEHypertensive urgency is common, but the rate of MACE in asymptomatic patients is very low. Visits to the ED were associated with more hospitalizations, but not improved outcomes. Most patients still had uncontrolled hypertension 6 months later.

Summary Background Antiplatelet therapy reduces the risk of major vascular events for people with occlusive vascular disease, although it might increase the risk of intracranial haemorrhage. Patients surviving the commonest subtype of intracranial haemorrhage, intracerebral haemorrhage, are at risk of both haemorrhagic and occlusive vascular events, but whether antiplatelet therapy can be used safely is unclear. We aimed to estimate the relative and absolute effects of antiplatelet therapy on recurrent intracerebral haemorrhage and whether this risk might exceed any reduction of occlusive vascular events. Methods The REstart or STop Antithrombotics Randomised Trial (RESTART) was a prospective, randomised, open-label, blinded endpoint, parallel-group trial at 122 hospitals in the UK. We recruited adults (≥18 years) who were taking antithrombotic (antiplatelet or anticoagulant) therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage, discontinued antithrombotic therapy, and survived for 24 h. Computerised randomisation incorporating minimisation allocated participants (1:1) to start or avoid antiplatelet therapy. We followed participants for the primary outcome (recurrent symptomatic intracerebral haemorrhage) for up to 5 years. We analysed data from all randomised participants using Cox proportional hazards regression, adjusted for minimisation covariates. This trial is registered with ISRCTN (number ISRCTN71907627). Findings Between May 22, 2013, and May 31, 2018, 537 participants were recruited a median of 76 days (IQR 29–146) after intracerebral haemorrhage onset: 268 were assigned to start and 269 (one withdrew) to avoid antiplatelet therapy. Participants were followed for a median of 2·0 years (IQR [1·0– 3·0]; completeness 99·3%). 12 (4%) of 268 participants allocated to antiplatelet therapy had recurrence of intracerebral haemorrhage compared with 23 (9%) of 268 participants allocated to avoid antiplatelet therapy (adjusted hazard ratio 0·51 [95% CI 0·25–1·03]; p=0·060). 18 (7%) participants allocated to antiplatelet therapy experienced major haemorrhagic events compared with 25 (9%) participants allocated to avoid antiplatelet therapy (0·71 [0·39–1·30]; p=0·27), and 39 [15%] participants allocated to antiplatelet therapy had major occlusive vascular events compared with 38 [14%] allocated to avoid antiplatelet therapy (1·02 [0·65–1·60]; p=0·92). Interpretation These results exclude all but a very modest increase in the risk of recurrent intracerebral haemorrhage with antiplatelet therapy for patients on antithrombotic therapy for the prevention of occlusive vascular disease when they developed intracerebral haemorrhage. The risk of recurrent intracerebral haemorrhage is probably too small to exceed the established benefits of antiplatelet therapy for secondary prevention. Funding British Heart Foundation.

Aims Positron emission tomography (PET) myocardial perfusion imaging (MPI) can non-invasively measure myocardial blood flow reserve (MBFR). We aimed to examine whether MBFR identifies patients with a survival benefit after revascularization, helping to guide post-test management. Methods and results We examined all-cause mortality in 12 594 consecutive patients undergoing Rb82 rest/stress PET MPI from January 2010 to December 2016, after excluding those with cardiomyopathy, prior coronary artery bypass surgery (CABG), and missing MBFR. Myocardial blood flow reserve was calculated as the ratio of stress to rest absolute myocardial blood flow. A Cox model adjusted for patient and test characteristics, early revascularization (percutaneous coronary intervention or CABG ≤90 days of MPI), and the interaction between MBFR and early revascularization was developed to identify predictors of all-cause mortality. After a median follow-up of 3.2 years, 897 patients (7.1%) underwent early revascularization and 1699 patients (13.5%) died. Ischaemia was present in 4051 (32.3%) patients, with 1413 (11.2%) having ≥10% ischaemia. Mean MBFR was 2.0 ± 1.3, with MBFR <1.8 in 4836 (38.5%). After multivariable adjustment, every 0.1 unit decrease in MBFR was associated with 9% greater hazard of all-cause death (hazard ratio 1.09, 95% confidence interval 1.08–1.10; P < 0.001). There was a significant interaction between MBFR and early revascularization (P < 0.001); such that patients with MBFR ≤1.8 had a survival benefit with early revascularization, regardless of type of revascularization or level of ischaemia. Conclusion Myocardial blood flow reserve on PET MPI is associated with all-cause mortality and can identify patients who receive a survival benefit with early revascularization compared to medical therapy. This may be used to guide revascularization, and prospective validation is needed.