Giulia Corn PhD , Marie Lund MD, PhD , Niklas W. Andersson MD , Tine L. Dohlmann MSc, PhD , Mark A. Hlatky MD , Jan Wohlfahrt MSc, DrMedSci , Mads Melbye MD, DrMedSci
{"title":"根据并发症和联合用药确定低密度脂蛋白胆固醇对他汀类药物的反应：一项基于人群的研究。","authors":"Giulia Corn PhD , Marie Lund MD, PhD , Niklas W. Andersson MD , Tine L. Dohlmann MSc, PhD , Mark A. Hlatky MD , Jan Wohlfahrt MSc, DrMedSci , Mads Melbye MD, DrMedSci","doi":"10.1016/j.ahj.2024.04.018","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.</p></div><div><h3>Methods</h3><p>This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (<em>P</em>-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.</p></div><div><h3>Results</h3><p>Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.</p></div><div><h3>Conclusion</h3><p>Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.</p></div>","PeriodicalId":7868,"journal":{"name":"American heart journal","volume":null,"pages":null},"PeriodicalIF":3.7000,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0002870324001054/pdfft?md5=389b47d88aa9cf0f546a6bb2530b5300&pid=1-s2.0-S0002870324001054-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study\",\"authors\":\"Giulia Corn PhD , Marie Lund MD, PhD , Niklas W. Andersson MD , Tine L. Dohlmann MSc, PhD , Mark A. Hlatky MD , Jan Wohlfahrt MSc, DrMedSci , Mads Melbye MD, DrMedSci\",\"doi\":\"10.1016/j.ahj.2024.04.018\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.</p></div><div><h3>Methods</h3><p>This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (<em>P</em>-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.</p></div><div><h3>Results</h3><p>Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.</p></div><div><h3>Conclusion</h3><p>Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. 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Low-density lipoprotein cholesterol response to statins according to comorbidities and co-medications: A population-based study
Background
The response of low-density lipoprotein cholesterol (LDL-C) to statin therapy is variable, and may be affected by the presence of co-morbid conditions or the use of concomitant medications. Systematic variation in the response to statins based on these factors could affect the selection of the statin treatment regimen in population subgroups. We investigated whether common comorbidities and co-medications had clinically important effects on statin responses in individual patients.
Methods
This register-based cohort study included 89,006 simvastatin or atorvastatin initiators with measurements of pre-statin and on-statin LDL-C levels, in Denmark, 2008-2018. We defined statin response as the percentage reduction in LDL-C, and used linear regression to estimate percentage reduction differences (PRD) according to 175 chronic comorbidities and 99 co-medications. We evaluated both the statistical significance (P-values corrected for multiple testing) and the clinical importance (PRD of 5 percentage points or more) of the observed associations.
Results
Concomitant use of oral blood-glucose lowering drugs, which included metformin in 96% of treated individuals, was associated with a greater response to statin therapy that was both statistically significant and clinically important, with a PRD of 5.18 (95% confidence interval: 4.79 to 5.57). No other comorbidity or co-medication reached the prespecified thresholds for a significant, clinically important effect on statin response. Overall, comorbidities and co-medications had little effect on statin response, and altogether explained only 1.7% of the total observed population variance.
Conclusion
Most of the studied comorbidities and co-medications did not have a clinically important effect on statin response, suggesting no need to modify treatment regimens. However, use of metformin was associated with a significantly enhanced LDL-C response to statins, suggesting that lower statin doses may be effective in patients taking metformin.
期刊介绍：
The American Heart Journal will consider for publication suitable articles on topics pertaining to the broad discipline of cardiovascular disease. Our goal is to provide the reader primary investigation, scholarly review, and opinion concerning the practice of cardiovascular medicine. We especially encourage submission of 3 types of reports that are not frequently seen in cardiovascular journals: negative clinical studies, reports on study designs, and studies involving the organization of medical care. The Journal does not accept individual case reports or original articles involving bench laboratory or animal research.
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