stroke

Background: Studies have suggested that evening dosing with antihypertensive therapy might have better outcomes than morning dosing. The Treatment in Morning versus Evening (TIME) study aimed to investigate whether evening dosing of usual antihypertensive medication improves major cardiovascular outcomes compared with morning dosing in patients with hypertension.

Methods: The TIME study is a prospective, pragmatic, decentralised, parallel-group study in the UK, that recruited adults (aged ≥18 years) with hypertension and taking at least one antihypertensive medication. Eligible participants were randomly assigned (1:1), without restriction, stratification, or minimisation, to take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the evening (2000-0000 h). Participants were followed up for the composite primary endpoint of vascular death or hospitalisation for non-fatal myocardial infarction or non-fatal stroke. Endpoints were identified by participant report or record linkage to National Health Service datasets and were adjudicated by a committee masked to treatment allocation. The primary endpoint was assessed as the time to first occurrence of an event in the intention-to-treat population (ie, all participants randomly assigned to a treatment group). Safety was assessed in all participants who submitted at least one follow-up questionnaire. The study is registered with EudraCT (2011-001968-21) and ISRCTN (18157641), and is now complete.

Findings: Between Dec 17, 2011, and June 5, 2018, 24 610 individuals were screened and 21 104 were randomly assigned to evening (n=10 503) or morning (n=10 601) dosing groups. Mean age at study entry was 65·1 years (SD 9·3); 12 136 (57·5%) participants were men; 8968 (42·5%) were women; 19 101 (90·5%) were White; 98 (0·5%) were Black, African, Caribbean, or Black British (ethnicity was not reported by 1637 [7·8%] participants); and 2725 (13·0%) had a previous cardiovascular disease. By the end of study follow-up (March 31, 2021), median follow-up was 5·2 years (IQR 4·9-5·7), and 529 (5·0%) of 10 503 participants assigned to evening treatment and 318 (3·0%) of 10 601 assigned to morning treatment had withdrawn from all follow-up. A primary endpoint event occurred in 362 (3·4%) participants assigned to evening treatment (0·69 events [95% CI 0·62-0·76] per 100 patient-years) and 390 (3·7%) assigned to morning treatment (0·72 events [95% CI 0·65-0·79] per 100 patient-years; unadjusted hazard ratio 0·95 [95% CI 0·83-1·10]; p=0·53). No safety concerns were identified.

Interpretation: Evening dosing of usual antihypertensive medication was not different from morning dosing in terms of major cardiovascular outcomes. Patients can be advised that they can take their regular antihypertensive medications at a convenient time that minimises any undesirable effects.

Funding: British Heart Foundation.

Background: In a previously reported randomized trial of standard and intensive systolic blood-pressure control, data on some outcome events had yet to be adjudicated and post-trial follow-up data had not yet been collected.

Methods: We randomly assigned 9361 participants who were at increased risk for cardiovascular disease but did not have diabetes or previous stroke to adhere to an intensive treatment target (systolic blood pressure, <120 mm Hg) or a standard treatment target (systolic blood pressure, <140 mm Hg). The primary outcome was a composite of myocardial infarction, other acute coronary syndromes, stroke, acute decompensated heart failure, or death from cardiovascular causes. Additional primary outcome events occurring through the end of the intervention period (August 20, 2015) were adjudicated after data lock for the primary analysis. We also analyzed post-trial observational follow-up data through July 29, 2016.

Results: At a median of 3.33 years of follow-up, the rate of the primary outcome and all-cause mortality during the trial were significantly lower in the intensive-treatment group than in the standard-treatment group (rate of the primary outcome, 1.77% per year vs. 2.40% per year; hazard ratio, 0.73; 95% confidence interval [CI], 0.63 to 0.86; all-cause mortality, 1.06% per year vs. 1.41% per year; hazard ratio, 0.75; 95% CI, 0.61 to 0.92). Serious adverse events of hypotension, electrolyte abnormalities, acute kidney injury or failure, and syncope were significantly more frequent in the intensive-treatment group. When trial and post-trial follow-up data were combined (3.88 years in total), similar patterns were found for treatment benefit and adverse events; however, rates of heart failure no longer differed between the groups.

Conclusions: Among patients who were at increased cardiovascular risk, targeting a systolic blood pressure of less than 120 mm Hg resulted in lower rates of major adverse cardiovascular events and lower all-cause mortality than targeting a systolic blood pressure of less than 140 mm Hg, both during receipt of the randomly assigned therapy and after the trial. Rates of some adverse events were higher in the intensive-treatment group. (Funded by the National Institutes of Health; SPRINT ClinicalTrials.gov number, NCT01206062.).

Importance: Carotid artery stenosis is atherosclerotic disease that affects extracranial carotid arteries. Asymptomatic carotid artery stenosis refers to stenosis in persons without a history of ischemic stroke, transient ischemic attack, or other neurologic symptoms referable to the carotid arteries. The prevalence of asymptomatic carotid artery stenosis is low in the general population but increases with age.

Objective: To determine if its 2014 recommendation should be reaffirmed, the US Preventive Services Task Force (USPSTF) commissioned a reaffirmation evidence review. The reaffirmation update focused on the targeted key questions on the potential benefits and harms of screening and interventions, including revascularization procedures designed to improve carotid artery blood flow, in persons with asymptomatic carotid artery stenosis.

Population: This recommendation statement applies to adults without a history of transient ischemic attack, stroke, or other neurologic signs or symptoms referable to the carotid arteries.

Evidence assessment: The USPSTF found no new substantial evidence that could change its recommendation and therefore concludes with moderate certainty that the harms of screening for asymptomatic carotid artery stenosis outweigh the benefits.

Recommendation: The USPSTF recommends against screening for asymptomatic carotid artery stenosis in the general adult population. (

Background

Aspirin is often prescribed for the primary prevention of atherosclerotic cardiovascular disease (ASCVD) however, recent randomized trials (RCTs) have challenged this practice. Despite this, aspirin is commonly recommended for high risk primary prevention. We tested the hypothesis that aspirin is more efficacious for the primary prevention of ASCVD, as the baseline risk increases.

Methods

RCTs that compared aspirin to control for primary prevention and evaluated ASCVD (composite of myocardial infarction and ischemic stroke) and major bleeding were included. Rate ratios (RR) and 95% confidence intervals (CI) were calculated. A regression analysis was performed using the ASCVD event rate in the control arm of each RCT as the moderator.

Results

Twelve RCTs were identified with 963,829 patient years of follow-up. Aspirin was associated with a reduction in ASCVD (4.7 versus 5.3 events per 1,000 patient years; RR 0.86; 95% CI 0.79-0.92). There was increased major bleeding among aspirin users (2.5 versus 1.8 events per 1000 patient years, RR 1.41 95% CI, 1.29-1.54). Regression analysis found no relationship between the log rate ratio of ASCVD or major bleeding and incidence of ASCVD in the control arm of each RCT.

Conclusion

Aspirin is associated with a reduction in ASCVD when used for primary prevention; however, it is unlikely to be clinically significant given the increase in bleeding. More importantly, aspirin's treatment effect does not increase as ASCVD risk increases as many hypothesize. There is no suggestion from this data that use of aspirin for higher risk primary prevention patients is beneficial.