Development and validation of QRISK3 risk prediction algorithms to estimate future risk of cardiovascular disease: prospective cohort study

Objectives: To develop and validate updated QRISK3 prediction algorithms to estimate the 10 year risk of cardiovascular disease in women and men accounting for potential new risk factors. Design: Prospective open cohort study. Setting: General practices in England providing data for the QResearch database. Participants: 1309 QResearch general practices in England: 981 practices were used to develop the scores and a separate set of 328 practices were used to validate the scores. 7.89 million patients aged 25-84 years were in the derivation cohort and 2.67 million patients in the validation cohort. Patients were free of cardiovascular disease and not prescribed statins at baseline. Methods: Cox proportional hazards models in the derivation cohort to derive separate risk equations in men and women for evaluation at 10 years. Risk factors considered included those already in QRISK2 (age, ethnicity, deprivation, systolic blood pressure, body mass index, total cholesterol: high density lipoprotein cholesterol ratio, smoking, family history of coronary heart disease in a first degree relative aged less than 60 years, type 1 diabetes, type 2 diabetes, treated hypertension, rheumatoid arthritis, atrial fibrillation, chronic kidney disease (stage 4 or 5)) and new risk factors (chronic kidney disease (stage 3, 4, or 5), a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, systemic lupus erythematosus (SLE), atypical antipsychotics, severe mental illness, and HIV/AIDs). We also considered erectile dysfunction diagnosis or treatment in men. Measures of calibration and discrimination were determined in the validation cohort for men and women separately and for individual subgroups by age group, ethnicity, and baseline disease status. Main outcome measures: Incident cardiovascular disease recorded on any of the following three linked data sources: general practice, mortality, or hospital admission records. Results: 363 565 incident cases of cardiovascular disease were identified in the derivation cohort during follow-up arising from 50.8 million person years of observation. All new risk factors considered met the model inclusion criteria except for HIV/AIDS, which was not statistically significant. The models had good calibration and high levels of explained variation and discrimination. In women, the algorithm explained 59.6% of the variation in time to diagnosis of cardiovascular disease (R2, with higher values indicating more variation), and the D statistic was 2.48 and Harrell’s C statistic was 0.88 (both measures of discrimination, with higher values indicating better discrimination). The corresponding values for men were 54.8%, 2.26, and 0.86. Overall performance of the updated QRISK3 algorithms was similar to the QRISK2 algorithms. Conclusion: Updated QRISK3 risk prediction models were developed and validated. The inclusion of additional clinical variables in QRISK3 (chronic kidney disease, a measure of systolic blood pressure variability (standard deviation of repeated measures), migraine, corticosteroids, SLE, atypical antipsychotics, severe mental illness, and erectile dysfunction) can help enable doctors to identify those at most risk of heart disease and stroke

Discontinuation and restarting in patients on statin therapy: a cohort study using a primary care database

Objectives: To estimate rates of discontinuation and restarting of statins, and to identify patient characteristics associated with either discontinuation or restarting. Design: Prospective open cohort study. Setting: 664 general practices contributing to the Clinical Practice Research Datalink in the United Kingdom. Data extracted in October 2014. Participants: Incident statin users aged 25-84 years identified between January 2002 and September 2013. Patients with statin prescriptions divided into two groups: primary prevention and secondary prevention (those already diagnosed with cardiovascular disease). Patients with statin prescriptions in the 12 months before study entry were excluded. Main outcome measures: Discontinuation of statin treatment (first 90 day gap after the estimated end date of a statin prescription), and restarting statin treatment for those who discontinued (defined as any subsequent prescription between discontinuation and study end). Results: Of 431 023 patients prescribed statins as primary prevention with a median follow-up time of 137 weeks, 47% (n=204 622) discontinued treatment and 72% (n=147 305) of those who discontinued restarted. Of 139 314 patients prescribed statins as secondary prevention with median follow-up time of 182 weeks, 41% (n=57 791) discontinued treatment and 75% (43 211) of those who discontinued restarted. Younger patients (aged ≤50 years), older patients (≥75 years), women, and patients with chronic liver disease were more likely to discontinue statins and less likely to restart. However, patients in ethnic minority groups, current smokers, and patients with type 1 diabetes were more likely to discontinue treatment but then were more likely to restart, whereas patients with hypertension and type 2 diabetes were less likely to discontinue treatment and more likely to restart if they did discontinue. These results were mainly consistent in the primary prevention and secondary prevention groups. Conclusions: Although a large proportion of statin users discontinue, many of them restart. For many patient groups previously considered as “stoppers,” the problem of statin treatment “stopping” could be part of the wider issue of poor adherence. Identification of patient groups associated with completely stopping or stop-starting behaviour has positive implications for patients and doctors as well as suggesting areas for future research

Predicting risk of type 2 diabetes in England and Wales: prospective derivation and validation of QDScore

Objective To develop and validate a new diabetes risk algorithm (the QDScore) for estimating 10 year risk of acquiring diagnosed type 2 diabetes over a 10 year time period in an ethnically and socioeconomically diverse population

Derivation, validation, and evaluation of a new QRISK model to estimate lifetime risk of cardiovascular disease: cohort study using QResearch database

Objective To develop, validate, and evaluate a new QRISK model to estimate lifetime risk of cardiovascular disease

Patients who discontinued statin treatment: a protocol for cohort study using primary care data

Introduction: Risk thresholds for using statins to prevent cardiovascular disease (CVD) have recently been lowered, so an increasing number of patients are now prescribed these drugs. Although the safety of long-term statin use has been generally established, concerns about the balance of risks and benefits of statins still exist for some medical professionals and patients, and issues concerning their side effects are occasionally widely publicised. This study will report the rates of stopping for statins and also identify any patient groups more likely to stop using statins, so possibly increasing their risk of cardiovascular events.Methods and analysis: A prospective open cohort study between 1 January 2002 and 30 September 2014 will be based on the general population of people prescribed statins, using records from UK general practices contributing to the Clinical Practice Research Database (CPRD). Participants aged 25–84 years will enter the cohort on the date of their first prescription for a statin and leave on the earliest date of: a cardiovascular event; death; leaving the practice; the last practice upload date or the study end date. If there are no prescriptions within 90 days after the expected finishing date of a prescription, a patient will be defined as a stopper with the discontinuation outcome date as the expected finishing date. Rates of statin discontinuation will be calculated by calendar year, type and dose of statin, age, and morbidities. Cox proportional regression analyses will be run to identify the most important factors associated with discontinuation. Analyses will be run separately for patients without CVD (primary prevention) and with diagnosed CVD (secondary prevention).Ethics and dissemination: The protocol has been reviewed and approved by Independent Scientific Advisory Committee for MHRA Database Research. The results will be published in a peer-reviewed journal

Patients who discontinued statin treatment: a protocol for cohort study using primary care data

Introduction: Risk thresholds for using statins to prevent cardiovascular disease (CVD) have recently been lowered, so an increasing number of patients are now prescribed these drugs. Although the safety of long-term statin use has been generally established, concerns about the balance of risks and benefits of statins still exist for some medical professionals and patients, and issues concerning their side effects are occasionally widely publicised. This study will report the rates of stopping for statins and also identify any patient groups more likely to stop using statins, so possibly increasing their risk of cardiovascular events.Methods and analysis: A prospective open cohort study between 1 January 2002 and 30 September 2014 will be based on the general population of people prescribed statins, using records from UK general practices contributing to the Clinical Practice Research Database (CPRD). Participants aged 25–84 years will enter the cohort on the date of their first prescription for a statin and leave on the earliest date of: a cardiovascular event; death; leaving the practice; the last practice upload date or the study end date. If there are no prescriptions within 90 days after the expected finishing date of a prescription, a patient will be defined as a stopper with the discontinuation outcome date as the expected finishing date. Rates of statin discontinuation will be calculated by calendar year, type and dose of statin, age, and morbidities. Cox proportional regression analyses will be run to identify the most important factors associated with discontinuation. Analyses will be run separately for patients without CVD (primary prevention) and with diagnosed CVD (secondary prevention).Ethics and dissemination: The protocol has been reviewed and approved by Independent Scientific Advisory Committee for MHRA Database Research. The results will be published in a peer-reviewed journal