Alexander, Karen P

Abstract Whether initiation of statins could increase survival free of dementia and disability in adults aged ≥75 years is unknown. PREVENTABLE, a double‐blind, placebo‐controlled randomized pragmatic clinical trial, will compare high‐intensity statin therapy (atorvastatin 40 mg) with placebo in 20,000 community‐dwelling adults aged ≥75 years without cardiovascular disease, disability, or dementia at baseline. Exclusion criteria include statin use in the prior year or for >5 years and inability to take a statin. Potential participants are identified using computable phenotypes derived from the electronic health record and local referrals from the community. Participants will undergo baseline cognitive testing, with physical testing and a blinded lipid panel if feasible. Cognitive testing and disability screening will be conducted annually. Multiple data sources will be queried for cardiovascular events, dementia, and disability; survival is site‐reported and supplemented by a National Death Index search. The primary outcome is survival free of new dementia or persisting disability. Co‐secondary outcomes are a composite of cardiovascular death, hospitalization for unstable angina or myocardial infarction, heart failure, stroke, or coronary revascularization; and a composite of mild cognitive impairment or dementia. Ancillary studies will offer mechanistic insights into the effects of statins on key outcomes. Biorepository samples are obtained and stored for future study. These results will inform the benefit of statins for increasing survival free of dementia and disability among older adults. This is a pioneering pragmatic study testing important questions with low participant burden to align with the needs of the growing population of older adults.

Background: Patients evaluated for coronary artery disease have a range of symptoms and underlying risk. The relationships between patient-described symptoms, clinician conclusions, and subsequent clinical management and outcomes remain incompletely described. Methods: In this secondary analysis, we examined the association between 4 types of presenting symptoms (substernal/left-sided chest pain, other chest/neck/arm pain, dyspnea, and other symptoms) and patient risk, noninvasive test results, clinical management, and outcomes for stable outpatients randomized in the PROMISE (Prospective Multicenter Imaging Study for Evaluation of Chest Pain) trial. Multivariable regression models were used to evaluate differences in noninvasive test result, all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/myocardial infarction by symptom type. Results: Among 9996 patients, most presented with chest pain (47.2% substernal, 29.2% other), followed by dyspnea (14.9%), and other symptoms (8.7%). Patients with dyspnea were older (median age 63 versus 60, P ≤0.02) with higher baseline risk (78.2% with atherosclerotic cardiovascular disease >7.5% versus 67.6%, P ≤0.02). Using patients with substernal chest pain as a reference, there was no difference in noninvasive test positivity across symptom groups (all P >0.05), but test-positive patients with dyspnea (adjusted odds ratio, 0.66 [95% CI, 0.51–0.85]) or other symptoms (adjusted odds ratio, 0.65 [95% CI, 0.47–0.90]) were less likely to be referred for cardiac catheterization. While symptom type alone was not associated with outcomes, symptom presentation with chest pain or dyspnea did modify the association between a positive noninvasive test and clinical outcome (interaction P =0.025 for both all-cause death/myocardial infarction/unstable angina hospitalization and cardiovascular death/MI). Conclusions: Among low-risk outpatients evaluated for coronary artery disease, typicality of symptoms was not closely associated with higher baseline risk but was related to differences in processes of care and the prognostic value of a positive test. Adverse events were not associated with clinician risk estimates or symptoms alone. These unexpected findings highlight the limitation of relying solely on symptom presentation or clinician risk estimation to evaluate patients for suspected coronary artery disease. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01174550.