Background: Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) induces a prothrombotic state, but long-term effects of COVID-19 on incidence of vascular diseases are unclear. Methods: We studied vascular diseases after COVID-19 diagnosis in population-wide anonymized linked English and Welsh electronic health records from January 1 to December 7, 2020. We estimated adjusted hazard ratios comparing the incidence of arterial thromboses and venous thromboembolic events (VTEs) after diagnosis of COVID-19 with the incidence in people without a COVID-19 diagnosis. We conducted subgroup analyses by COVID-19 severity, demographic characteristics, and previous history. Results: Among 48 million adults, 125 985 were hospitalized and 1 319 789 were not hospitalized within 28 days of COVID-19 diagnosis. In England, there were 260 279 first arterial thromboses and 59 421 first VTEs during 41.6 million person-years of follow-up. Adjusted hazard ratios for first arterial thrombosis after COVID-19 diagnosis compared with no COVID-19 diagnosis declined from 21.7 (95% CI, 21.0–22.4) in week 1 after COVID-19 diagnosis to 1.34 (95% CI, 1.21–1.48) during weeks 27 to 49. Adjusted hazard ratios for first VTE after COVID-19 diagnosis declined from 33.2 (95% CI, 31.3–35.2) in week 1 to 1.80 (95% CI, 1.50–2.17) during weeks 27 to 49. Adjusted hazard ratios were higher, for longer after diagnosis, after hospitalized versus nonhospitalized COVID-19, among Black or Asian versus White people, and among people without versus with a previous event. The estimated whole-population increases in risk of arterial thromboses and VTEs 49 weeks after COVID-19 diagnosis were 0.5% and 0.25%, respectively, corresponding to 7200 and 3500 additional events, respectively, after 1.4 million COVID-19 diagnoses. Conclusions: High relative incidence of vascular events soon after COVID-19 diagnosis declines more rapidly for arterial thromboses than VTEs. However, incidence remains elevated up to 49 weeks after COVID-19 diagnosis. These results support policies to prevent severe COVID-19 by means of COVID-19 vaccines, early review after discharge, risk factor control, and use of secondary preventive agents in high-risk patients.
ImportanceThe long-term effects of COVID-19 on the incidence of vascular diseases are unclear.ObjectiveTo quantify the association between time since diagnosis of COVID-19 and vascular disease, overall and by age, sex, ethnicity, and pre-existing disease.DesignCohort study based on population-wide linked electronic health records, with follow up from January 1st to December 7th 2020.Setting and participantsAdults registered with an NHS general practice in England or Wales and alive on January 1st 2020.ExposuresTime since diagnosis of COVID-19 (categorised as 0-6 days, 1-2 weeks, 3-4, 5-8, 9-12, 13-26 and 27-49 weeks since diagnosis), with and without hospitalisation within 28 days of diagnosis.Main outcomes and measuresPrimary outcomes were arterial thromboses (mainly acute myocardial infarction and ischaemic stroke) and venous thromboembolic events (VTE, mainly pulmonary embolism and lower limb deep vein thrombosis). We also studied other vascular events (transient ischaemic attack, haemorrhagic stroke, heart failure and angina). Hazard ratios were adjusted for demographic characteristics, previous disease diagnoses, comorbidities and medications.ResultsAmong 48 million adults, 130,930 were and 1,315,471 were not hospitalised within 28 days of COVID-19. In England, there were 259,742 first arterial thromboses and 60,066 first VTE during 41.6 million person-years follow-up. Adjusted hazard ratios (aHRs) for first arterial thrombosis compared with no COVID-19 declined rapidly from 21.7 (95% CI 21.0-22.4) to 3.87 (3.58-4.19) in weeks 1 and 2 after COVID-19, 2.80 (2.61-3.01) during weeks 3-4 then to 1.34 (1.21-1.48) during weeks 27-49. aHRs for first VTE declined from 33.2 (31.3-35.2) and 8.52 (7.59-9.58) in weeks 1 and 2 to 7.95 (7.28-8.68) and 4.26 (3.86-4.69) during weeks 3-4 and 5-8, then 2.20 (1.99-2.44) and 1.80 (1.50-2.17) during weeks 13-26 and 27-49 respectively. aHRs were higher, for longer after diagnosis, after hospitalised than non-hospitalised COVID-19. aHRs were also higher among people of Black and Asian than White ethnicity and among people without than with a previous event. Across the whole population estimated increases in risk of arterial thromboses and VTEs were 2.5% and 0.6% respectively 49 weeks after COVID-19, corresponding to 7,197 and 3,517 additional events respectively after 1.4 million COVID-19 diagnoses.Conclusions and RelevanceHigh rates of vascular disease early after COVID-19 diagnosis decline more rapidly for arterial thromboses than VTEs but rates remain elevated up to 49 weeks after COVID_19. These results support continued policies to avoid COVID-19 infection with effective COVID-19 vaccines and use of secondary preventive agents in high-risk patients.Key pointsQuestionIs COVID-19 associated with higher long-term incidence of vascular diseases?FindingsIn this cohort study of 48 million adults in England and Wales, COVID-19 was associated with higher incidence, that declined with time since diagnosis, of both arterial thromboses [week 1: adjusted HR [aHR] 21.7 (95% CI 21.0-22.4) weeks 27-49: aHR 1.34 (1.21-1.48)] and venous thromboembolism [week 1: aHR 33.2 (31.3-35.2), weeks 27–49 1.80 (1.50-2.17)]. aHRs were higher, for longer, after hospitalised than non-hospitalised COVID-19. The estimated excess number of arterial thromboses and venous thromboembolisms was 10,500.MeaningAvoidance of COVID-19 infection through vaccination, and use of secondary preventive agents after infection in high-risk patients, may reduce post-COVID-19 acute vascular diseases.
The UK's national health services are unique in having a well established programme of national clinical audits and databases across medical, surgical and mental health conditions. The Royal College of Physicians' (RCP) Clinical Effectivess and Evaluation Unit leads many of the largest and most mature audits in partnership with specialist societies, other colleges, patient groups and academic institutions. In this paper, we shall trace the development of national audit over the last 2 decades, explore the mechanisms by which this has helped improve care and discuss how national clinical audits and databases can best support quality improvement in the NHS of the future.
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