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      Statins After Ischemic Stroke in the Oldest : A Cohort Study Using the Clinical Practice Research Datalink Database

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          Abstract

          Background and Purpose:

          Statins are frequently initiated in patients aged 80 years and older after an ischemic stroke, even though evidence on prevention of recurrent cardiovascular disease is scarce. In this study, we seek evidence for statin prescription in the oldest old.

          Methods:

          We performed a retrospective cohort study in patients aged 65 years and older hospitalized for a first ischemic stroke between 1999 and 2016 without statin prescriptions in the year before hospitalization using the Clinical Practice Research Datalink. The age group 65 to 80 years was included to compare our results to current evidence on statin efficacy. The primary outcome was a composite of recurrent stroke, myocardial infarction, and cardiovascular mortality. The secondary outcome was all-cause mortality. A time-varying Cox model was used to account for statin prescription over time. We compared at least 2 years of statin prescription time with untreated and <2 years of prescription time. Analyses were adjusted for potential confounders. The number needed to treat was calculated based on the adjusted hazard ratios and corrected for deaths during the first 2 years of follow-up.

          Results:

          Five thousand nine hundred ten patients, aged 65 years and older were included, of whom 3157 were 80 years and older. Two years of statin prescription in patients aged 80 years and older resulted in both a lower risk of the composite end point (adjusted hazard ratio, 0.80 [95% CI, 0.62–1.02]) and all-cause mortality (adjusted hazard ratio, 0.67 [95% CI, 0.57–0.80]). After correction for the mortality of 23.9% of the patients during the first 2 years, the number needed to treat was 64 for the primary outcome during a median follow-up of 3.9 years and 19 for all-cause mortality.

          Conclusions:

          Statins initiated in patients aged 80 and older, discharged home after hospitalization for an ischemic stroke are associated with a reduction in cardiovascular events.

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          Is Open Access

          Data Resource Profile: Clinical Practice Research Datalink (CPRD)

          Emily Herrett, Arlene M. Gallagher, Krishnan Bhaskaran … (2015)
          The Clinical Practice Research Datalink (CPRD) is an ongoing primary care database of anonymised medical records from general practitioners, with coverage of over 11.3 million patients from 674 practices in the UK. With 4.4 million active (alive, currently registered) patients meeting quality criteria, approximately 6.9% of the UK population are included and patients are broadly representative of the UK general population in terms of age, sex and ethnicity. General practitioners are the gatekeepers of primary care and specialist referrals in the UK. The CPRD primary care database is therefore a rich source of health data for research, including data on demographics, symptoms, tests, diagnoses, therapies, health-related behaviours and referrals to secondary care. For over half of patients, linkage with datasets from secondary care, disease-specific cohorts and mortality records enhance the range of data available for research. The CPRD is very widely used internationally for epidemiological research and has been used to produce over 1000 research studies, published in peer-reviewed journals across a broad range of health outcomes. However, researchers must be aware of the complexity of routinely collected electronic health records, including ways to manage variable completeness, misclassification and development of disease definitions for research.
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            Rosuvastatin to prevent vascular events in men and women with elevated C-reactive protein.

            Paul Ridker, Eleanor Danielson, Francisco A.H. Fonseca … (2008)
            Increased levels of the inflammatory biomarker high-sensitivity C-reactive protein predict cardiovascular events. Since statins lower levels of high-sensitivity C-reactive protein as well as cholesterol, we hypothesized that people with elevated high-sensitivity C-reactive protein levels but without hyperlipidemia might benefit from statin treatment. We randomly assigned 17,802 apparently healthy men and women with low-density lipoprotein (LDL) cholesterol levels of less than 130 mg per deciliter (3.4 mmol per liter) and high-sensitivity C-reactive protein levels of 2.0 mg per liter or higher to rosuvastatin, 20 mg daily, or placebo and followed them for the occurrence of the combined primary end point of myocardial infarction, stroke, arterial revascularization, hospitalization for unstable angina, or death from cardiovascular causes. The trial was stopped after a median follow-up of 1.9 years (maximum, 5.0). Rosuvastatin reduced LDL cholesterol levels by 50% and high-sensitivity C-reactive protein levels by 37%. The rates of the primary end point were 0.77 and 1.36 per 100 person-years of follow-up in the rosuvastatin and placebo groups, respectively (hazard ratio for rosuvastatin, 0.56; 95% confidence interval [CI], 0.46 to 0.69; P<0.00001), with corresponding rates of 0.17 and 0.37 for myocardial infarction (hazard ratio, 0.46; 95% CI, 0.30 to 0.70; P=0.0002), 0.18 and 0.34 for stroke (hazard ratio, 0.52; 95% CI, 0.34 to 0.79; P=0.002), 0.41 and 0.77 for revascularization or unstable angina (hazard ratio, 0.53; 95% CI, 0.40 to 0.70; P<0.00001), 0.45 and 0.85 for the combined end point of myocardial infarction, stroke, or death from cardiovascular causes (hazard ratio, 0.53; 95% CI, 0.40 to 0.69; P<0.00001), and 1.00 and 1.25 for death from any cause (hazard ratio, 0.80; 95% CI, 0.67 to 0.97; P=0.02). Consistent effects were observed in all subgroups evaluated. The rosuvastatin group did not have a significant increase in myopathy or cancer but did have a higher incidence of physician-reported diabetes. In this trial of apparently healthy persons without hyperlipidemia but with elevated high-sensitivity C-reactive protein levels, rosuvastatin significantly reduced the incidence of major cardiovascular events. (ClinicalTrials.gov number, NCT00239681.) 2008 Massachusetts Medical Society
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              Development and validation of an electronic frailty index using routine primary care electronic health record data

              Andrew W. Clegg, Chris Bates, John Young … (2016)
              Background: frailty is an especially problematic expression of population ageing. International guidelines recommend routine identification of frailty to provide evidence-based treatment, but currently available tools require additional resource. Objectives: to develop and validate an electronic frailty index (eFI) using routinely available primary care electronic health record data. Study design and setting: retrospective cohort study. Development and internal validation cohorts were established using a randomly split sample of the ResearchOne primary care database. External validation cohort established using THIN database. Participants: patients aged 65–95, registered with a ResearchOne or THIN practice on 14 October 2008. Predictors: we constructed the eFI using the cumulative deficit frailty model as our theoretical framework. The eFI score is calculated by the presence or absence of individual deficits as a proportion of the total possible. Categories of fit, mild, moderate and severe frailty were defined using population quartiles. Outcomes: outcomes were 1-, 3- and 5-year mortality, hospitalisation and nursing home admission. Statistical analysis: hazard ratios (HRs) were estimated using bivariate and multivariate Cox regression analyses. Discrimination was assessed using receiver operating characteristic (ROC) curves. Calibration was assessed using pseudo-R 2 estimates. Results: we include data from a total of 931,541 patients. The eFI incorporates 36 deficits constructed using 2,171 CTV3 codes. One-year adjusted HR for mortality was 1.92 (95% CI 1.81–2.04) for mild frailty, 3.10 (95% CI 2.91–3.31) for moderate frailty and 4.52 (95% CI 4.16–4.91) for severe frailty. Corresponding estimates for hospitalisation were 1.93 (95% CI 1.86–2.01), 3.04 (95% CI 2.90–3.19) and 4.73 (95% CI 4.43–5.06) and for nursing home admission were 1.89 (95% CI 1.63–2.15), 3.19 (95% CI 2.73–3.73) and 4.76 (95% CI 3.92–5.77), with good to moderate discrimination but low calibration estimates. Conclusions: the eFI uses routine data to identify older people with mild, moderate and severe frailty, with robust predictive validity for outcomes of mortality, hospitalisation and nursing home admission. Routine implementation of the eFI could enable delivery of evidence-based interventions to improve outcomes for this vulnerable group.
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                Author and article information

                Contributors
                Geert J. Lefeber: (View ORCID Profile)
                Wilma Knol: (View ORCID Profile)
                Patrick C. Souverein: (View ORCID Profile)
                Marcel L. Bouvy: (View ORCID Profile)
                Anthonius de Boer: (View ORCID Profile)
                Huiberdina L. Koek: (View ORCID Profile)
                Journal
                Title: Stroke
                Abbreviated Title: Stroke
                Publisher: Ovid Technologies (Wolters Kluwer Health)
                ISSN (Print): 0039-2499
                ISSN (Electronic): 1524-4628
                Publication date (Electronic): February 10 2021
                Affiliations
                [1 ]Department of Geriatrics, University Medical Center Utrecht, Utrecht University, the Netherlands. (G.J.L., W.K., H.L.K.)
                [2 ]Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, the Netherlands. (P.C.S., M.L.B., A.d.B.)
                [3 ]Expertise Centre Pharmacotherapy in Old Persons (EPHOR), Utrecht, the Netherlands (G.J.L., W.K., H.L.K.).
                Article
                DOI: 10.1161/STROKEAHA.120.030755
                PubMed ID: 33563018
                SO-VID: b921c657-0a24-4f13-ae29-6945031132f3
                Copyright © © 2021
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