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Background and Purpose: Management of stroke risk factors might reduce later dementia. In ASCOT (Anglo-Scandinavian Outcome Trial), we determined whether dementia or stroke were associated with different blood pressure (BP)–lowering regimens; atorvastatin or placebo; and mean BP, BP variability, and mean cholesterol levels., Methods: Participants with hypertension and ≥3 cardiovascular disease risk factors were randomly allocated to amlodipine- or atenolol-based BP-lowering regimen targeting BP <140/90 mm Hg for 5.5 years. Participants with total cholesterol ≤6.5 mmol/L were also randomly allocated to atorvastatin 10 mg or placebo for 3.3 years. Mean and LDL (low-density lipoprotein) cholesterol, BP, and SD of BP were calculated from 6 months to end of trial. UK participants were linked to electronic health records to ascertain deaths and hospitalization in general and mental health hospitals. Dementia and stroke were ascertained by validated code lists and within-trial ascertainment., Results: Of 8580 UK participants, 7300 were followed up to 21 years from randomization. Atorvastatin for 3.3 years had no measurable effect on stroke (264 versus 272; adjusted hazard ratio [HR], 0.92 [95% CI, 0.78–1.09]; P=0.341) or dementia (238 versus 227; adjusted HR, 0.98 [95% CI, 0.82–1.18]; P=0.837) compared with placebo. Mean total cholesterol was not associated with later stroke or dementia. An amlodipine-based compared with an atenolol-based regimen for 5.5 years reduced stroke (443 versus 522; adjusted HR, 0.82 [95% CI, 0.72–0.93]; P=0.003) but not dementia (450 versus 465; adjusted HR, 0.94 [95% CI, 0.82–1.07]; P=0.334) over follow-up. BP variability (SD mean BP) was associated with a higher risk of dementia (per 5 mm Hg HR, 1.14 [95% CI, 1.06–1.24]; P<0.001) and stroke (HR, 1.21 [95% CI, 1.12–1.32]; P<0.001) adjusted for mean BP., Conclusions: An amlodipine-based BP regimen reduced the long-term incidence of stroke compared with an atenolol-based regimen but had no measurable effect on dementia. Atorvastatin had no effect on either stroke or dementia. Higher BP variability was associated with a higher incidence of later dementia and stroke.

Background: Despite current therapies, patients with vascular disease remain at high risk for major adverse cardiovascular events. Low-density lipoprotein cholesterol is a well-established modifiable cardiovascular risk factor. Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 that reduces low-density lipoprotein cholesterol by approximately 60% across various populations., Study Design: FOURIER is a randomized, placebo-controlled, double-blind, parallel-group, multinational trial testing the hypothesis that adding evolocumab to statin therapy will reduce the incidence of major adverse cardiovascular events in patients with clinically evident vascular disease. The study population consists of 27,564 patients who have had a myocardial infarction (MI), an ischemic stroke, or symptomatic peripheral artery disease and have a low-density lipoprotein ≥70 mg/dL or a non-high-density lipoprotein cholesterol ≥100 mg/dL on an optimized statin regimen. Patients were randomized in a 1:1 ratio to receive either evolocumab (either 140 mg subcutaneously every 2 weeks or 420 mg subcutaneously every month, according to patient preference) or matching placebo injections. The primary end point is major cardiovascular events defined as the composite of cardiovascular death, MI, stroke, hospitalization for unstable angina, or coronary revascularization. The key secondary end point is the composite of cardiovascular death, MI, or stroke. The trial is planned to continue until at least 1,630 patients experience the secondary end point, thereby providing 90% power to detect a relative reduction of ≥15% in this end point., Conclusions: FOURIER will determine whether the addition of evolocumab to statin therapy reduces cardiovascular morbidity and mortality in patients with vascular disease., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Background: Statins improve lipid profiles and reduce cardiovascular morbidity and mortality but there are few data on their relative effects in different ethnic groups., Methods: We used data from the randomised, placebo-controlled Anglo-Scandinavian Cardiac Outcomes Trial-Lipid Lowering Arm (ASCOT-LLA) to conduct a prespecified comparison of the lipid-lowering efficacy of statin therapy among hypertensive participants from different ethnic groups in the UK and Ireland. The effects of atorvastatin (10 mg daily) and placebo on fasting plasma lipid profiles were compared in matched groups of Whites and Blacks (of African-Caribbean or African origin) and Whites and South Asians (from the Indian subcontinent), adjusting for placebo effect., Results: In the active treatment group, 156 Blacks and 72 South Asians were compared with 419 and 198 Whites, respectively. In multivariable analyses adjusted for baseline lipid levels and other potential confounders, atorvastatin reduced total cholesterol, low-density lipoprotein (LDL)-cholesterol and triglycerides from baseline in all ethnic groups. There were no clinically or statistically significant differences in the effect between Whites and Blacks or between Whites and South Asians after adjusting for placebo effect; similar proportions in each group achieved lipid targets. There was no significant effect of atorvastatin on high-density lipoprotein (HDL)-cholesterol in any group., Conclusions: A standard dose of atorvastatin improved lipid profiles to a similar extent in Whites, Blacks and South Asians. Given the proven benefits of statins, these results suggest that, when used in standard doses, they are likely to be similarly effective for cardiovascular disease prevention in all ethnic groups.