Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study
Objective To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.Design Target trial and modelling study.Setting North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-AC...
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BMJ Publishing Group
2025-07-01
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| Series: | BMJ Medicine |
| Online Access: | https://bmjmedicine.bmj.com/content/4/1/e001132.full |
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| author | Sarah R Haile Oliver Senn Nicola Serra Eva A Rehfuess Milo A Puhan Mona Loutfy Jennifer E Thorne Greer A Burkholder Michael J Silverberg Raynell Lang Timothy R Sterling Vincent C Marconi Huldrych F Günthard Sally B Coburn Gregory M Lucas Henock G Yebyo Oliver Langselius Jonathan A Colasanti Sonia Napravnik Maile Karris Keri N Althoff |
| author_facet | Sarah R Haile Oliver Senn Nicola Serra Eva A Rehfuess Milo A Puhan Mona Loutfy Jennifer E Thorne Greer A Burkholder Michael J Silverberg Raynell Lang Timothy R Sterling Vincent C Marconi Huldrych F Günthard Sally B Coburn Gregory M Lucas Henock G Yebyo Oliver Langselius Jonathan A Colasanti Sonia Napravnik Maile Karris Keri N Althoff |
| author_sort | Sarah R Haile |
| collection | DOAJ |
| description | Objective To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.Design Target trial and modelling study.Setting North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-ACCORD integrates individual level data from >20 HIV cohorts across the US and Canada from people with HIV who have successfully linked into care.Participants 157 699 people with HIV enrolled in one of the cohorts of NA-ACCORD. 54 165 eligible individuals, aged 40-75 years, were enrolled in the target trial.Main outcome measures The primary outcomes for the target trial were the 10 year effects of statins on cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcomes (type 2 diabetes, mild cognitive impairment, rhabdomyolysis, and myopathy). The secondary outcome was the 10 year risk threshold where the reduction in cardiovascular disease outweighed the increased risk of harm outcomes, showing an overall net benefit of statins.Results Participants who first started receiving treatment with statins (statin initiators) had a 21% reduction in cardiovascular disease events (hazard ratio 0.79, 95% confidence interval (CI) 0.72 to 0.87) and a 26% reduction in the combined risk of stroke and myocardial infarction (0.74, 0.56 to 0.98), but a 12% increase in the risk of type 2 diabetes (1.12, 1.01 to 1.25) compared with participants who developed the indication but did not take statins (non-initiators). The effects on cognitive impairment (hazard ratio 1.13, 95% CI 0.82 to 1.56), myopathy (1.10, 0.76 to 1.61), and rhabdomyolysis (1.09, 0.68 to 1.75) were not statistically significant. On average, the benefit of statins exceeded harms for individuals with a 10 year baseline risk of cardiovascular disease of ≥13.8%. Subgroup specific thresholds included men (14.2%), women (11.1%), ages 40-64 years (13.8%) versus 65-75 years (15.1%), and CD4 count >200 cells/mm³ (13.6%) versus <200 cells/mm³ (15.3%). Varying weights for cardiovascular disease yielded thresholds ranging from 11.6% to 54.0%, whereas weights for harm outcomes resulted in thresholds ranging from 5.0% to >30.0%.Conclusions In this study, statins benefitted individuals with HIV with a moderate or high risk of cardiovascular disease, but the threshold for net benefit varied by patient subgroup and preference, implying the need to customise statin treatment to individual risks, preferences, and treatment goals. Given the limitations of observational data, further controlled studies are needed to evaluate the efficacy and safety of statins in people with HIV receiving modern antiretroviral therapy. |
| format | Article |
| id | doaj-art-4f6f451e76354ee4a3ea8daab48624f2 |
| institution | DOAJ |
| issn | 2754-0413 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMJ Publishing Group |
| record_format | Article |
| series | BMJ Medicine |
| spelling | doaj-art-4f6f451e76354ee4a3ea8daab48624f22025-08-20T02:44:16ZengBMJ Publishing GroupBMJ Medicine2754-04132025-07-014110.1136/bmjmed-2024-001132Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling studySarah R Haile0Oliver Senn1Nicola Serra2Eva A Rehfuess3Milo A Puhan4Mona Loutfy5Jennifer E Thorne6Greer A Burkholder7Michael J Silverberg8Raynell Lang9Timothy R Sterling10Vincent C Marconi11Huldrych F Günthard12Sally B Coburn13Gregory M Lucas14Henock G Yebyo15Oliver Langselius16Jonathan A Colasanti17Sonia Napravnik18Maile Karris19Keri N Althoff20Epidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, SwitzerlandInstitute of Primary Care, University of Zurich and University Hospital Zurich, Zurich, SwitzerlandPhysics Institute, University of Zurich, Zurich, SwitzerlandInstitute for Medical Information Processing, Biometry, and Epidemiology, Ludwig-Maximilians-Universität München, Munich, GermanyEpidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, SwitzerlandMaple Leaf Medical Clinic, Women’s College Hospital, Toronto, Ontario, CanadaBloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USADivision of Infectious Diseases, University of Alabama at Birmingham, Birmingham, Alabama, USADivision of Research, Kaiser Permanente, Oakland, California, USADepartment of Medicine, University of Calgary, Calgary, Alberta, CanadaVanderbilt University Medical Center, Nashville, Tennessee, USASchool of Medicine and Rollins School of Public Health, Emory University, Atlanta, Georgia, USADepartment of Infectious Diseases and Hospital Epidemiology, University Hospital Zurich, Zurich, SwitzerlandDepartment of Epidemiology, Bloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USADivision of Infectious Diseases, Department of Medicine, School of Medicine, Johns Hopkins University, Baltimore, Maryland, USAEpidemiology, Biostatistics, and Prevention Institute, University of Zurich, Zurich, SwitzerlandPettenkofer School of Public Health, Ludwig-Maximilians-Universität München, Munich, GermanyDepartment of Medicine, Grady Health System, Emory University, Atlanta, Georgia, USADivision of Infectious Diseases, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USADepartment of Medicine, University of California San Diego, La Jolla, California, USABloomberg School of Public Health, Johns Hopkins University, Baltimore, Maryland, USAObjective To evaluate the effectiveness and benefit-harm balance of various statins for the primary prevention of cardiovascular disease in people with HIV.Design Target trial and modelling study.Setting North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD), 1995 to 2019. NA-ACCORD integrates individual level data from >20 HIV cohorts across the US and Canada from people with HIV who have successfully linked into care.Participants 157 699 people with HIV enrolled in one of the cohorts of NA-ACCORD. 54 165 eligible individuals, aged 40-75 years, were enrolled in the target trial.Main outcome measures The primary outcomes for the target trial were the 10 year effects of statins on cardiovascular disease events (fatal and non-fatal myocardial infarction, hospital admission for unstable angina, coronary or arterial revascularisation, fatal and non-fatal stroke, or transient ischaemic attack) and harm outcomes (type 2 diabetes, mild cognitive impairment, rhabdomyolysis, and myopathy). The secondary outcome was the 10 year risk threshold where the reduction in cardiovascular disease outweighed the increased risk of harm outcomes, showing an overall net benefit of statins.Results Participants who first started receiving treatment with statins (statin initiators) had a 21% reduction in cardiovascular disease events (hazard ratio 0.79, 95% confidence interval (CI) 0.72 to 0.87) and a 26% reduction in the combined risk of stroke and myocardial infarction (0.74, 0.56 to 0.98), but a 12% increase in the risk of type 2 diabetes (1.12, 1.01 to 1.25) compared with participants who developed the indication but did not take statins (non-initiators). The effects on cognitive impairment (hazard ratio 1.13, 95% CI 0.82 to 1.56), myopathy (1.10, 0.76 to 1.61), and rhabdomyolysis (1.09, 0.68 to 1.75) were not statistically significant. On average, the benefit of statins exceeded harms for individuals with a 10 year baseline risk of cardiovascular disease of ≥13.8%. Subgroup specific thresholds included men (14.2%), women (11.1%), ages 40-64 years (13.8%) versus 65-75 years (15.1%), and CD4 count >200 cells/mm³ (13.6%) versus <200 cells/mm³ (15.3%). Varying weights for cardiovascular disease yielded thresholds ranging from 11.6% to 54.0%, whereas weights for harm outcomes resulted in thresholds ranging from 5.0% to >30.0%.Conclusions In this study, statins benefitted individuals with HIV with a moderate or high risk of cardiovascular disease, but the threshold for net benefit varied by patient subgroup and preference, implying the need to customise statin treatment to individual risks, preferences, and treatment goals. Given the limitations of observational data, further controlled studies are needed to evaluate the efficacy and safety of statins in people with HIV receiving modern antiretroviral therapy.https://bmjmedicine.bmj.com/content/4/1/e001132.full |
| spellingShingle | Sarah R Haile Oliver Senn Nicola Serra Eva A Rehfuess Milo A Puhan Mona Loutfy Jennifer E Thorne Greer A Burkholder Michael J Silverberg Raynell Lang Timothy R Sterling Vincent C Marconi Huldrych F Günthard Sally B Coburn Gregory M Lucas Henock G Yebyo Oliver Langselius Jonathan A Colasanti Sonia Napravnik Maile Karris Keri N Althoff Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study BMJ Medicine |
| title | Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study |
| title_full | Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study |
| title_fullStr | Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study |
| title_full_unstemmed | Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study |
| title_short | Statins for primary prevention of cardiovascular events in people with HIV: target trial and modelling study |
| title_sort | statins for primary prevention of cardiovascular events in people with hiv target trial and modelling study |
| url | https://bmjmedicine.bmj.com/content/4/1/e001132.full |
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