Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease
The selection of optimum statin intensity is inconclusive, and the association of plasma exposure of statins and metabolites with major adverse cardiovascular events (MACEs) is unclear. This study sought to compare the effect of low (quartile 1), intermediate (quartiles 2 and 3), and high (quartile...
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Frontiers Media S.A.
2020-05-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/article/10.3389/fphar.2020.00675/full |
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| author | Xiao-hong Zhou Xiao-hong Zhou Xiao-hong Zhou Li-yun Cai Wei-Hua Lai Xue Bai Yi-bin Liu Qian Zhu Guo-dong He Ji-Yan Chen Min Huang Zhi-ling Zhou Shi-long Zhong Shi-long Zhong Shi-long Zhong |
| author_facet | Xiao-hong Zhou Xiao-hong Zhou Xiao-hong Zhou Li-yun Cai Wei-Hua Lai Xue Bai Yi-bin Liu Qian Zhu Guo-dong He Ji-Yan Chen Min Huang Zhi-ling Zhou Shi-long Zhong Shi-long Zhong Shi-long Zhong |
| author_sort | Xiao-hong Zhou |
| collection | DOAJ |
| description | The selection of optimum statin intensity is inconclusive, and the association of plasma exposure of statins and metabolites with major adverse cardiovascular events (MACEs) is unclear. This study sought to compare the effect of low (quartile 1), intermediate (quartiles 2 and 3), and high (quartile 4) plasma exposure of statins and metabolites on MACE, re-ischemia events and death in patients with coronary artery disease (CAD) at 5 years. A total of 1,644 patients in atorvastatin (AT) cohort and 804 patients in rosuvastatin (RST) cohort were included, and their plasma concentration of statins and metabolites was categorized as low-, mid-, or high-group. The association between the plasma levels of statins and metabolites and the incidence of primary endpoint in patients was assessed by Cox proportional hazard models. Intensive AT exposure (Q4 > 5.32 ng/ml) was significantly associated with increased risk of death compared with low (hazard ratio [HR]: 1.522; 95% confidence interval [CI]: 1.035–1.061; P = 0.0022) or moderate exposure (HR: 2.054; 95% CI: 1.348–3.130; P = 0.0008). This association was also found in AT’s five metabolites (all P < 0.01). In patients with RST treatment, moderate RST concentration (0.53–4.29 ng/ml) versus low concentration had a significantly lower risk of MACE and re-ischemia events. (HR: 0.532, 95% CI: 0.347–0.815, P = 0.0061 and HR: 0.505, 95% CI: 0.310–0.823, P = 0.0061, respectively). A higher plasma exposure of AT and metabolites has a significantly higher risk of death, and moderate RST exposure has a significantly lower risk of MACE and re-ischemia events in Chinese patients with CAD. The harms of high plasma exposure should be considered when prescribing statins to patients because it may be a risk factor for having poor prognosis in patients with CAD. |
| first_indexed | 2024-12-22T08:29:31Z |
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| last_indexed | 2024-12-22T08:29:31Z |
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| spelling | doaj.art-22ff414517244b538403a2dfb9bfdfb62022-12-21T18:32:33ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122020-05-011110.3389/fphar.2020.00675490851Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery DiseaseXiao-hong Zhou0Xiao-hong Zhou1Xiao-hong Zhou2Li-yun Cai3Wei-Hua Lai4Xue Bai5Yi-bin Liu6Qian Zhu7Guo-dong He8Ji-Yan Chen9Min Huang10Zhi-ling Zhou11Shi-long Zhong12Shi-long Zhong13Shi-long Zhong14Guangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaLaboratory of Drug Metabolism and Pharmacokinetics, School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, ChinaDepartment of Pharmacy, Zhuhai People’s Hospital (Zhuhai Hospital affiliated with Jinan University), Zhuhai, ChinaGuangdong Provincial Key Laboratory of Coronary Heart Disease Prevention, Guangdong Cardiovascular Institute, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaDepartment of Pharmacy, Guangdong Provincial People's Hospital, Guangdong Academy of Medical Sciences, Guangzhou, ChinaSchool of Pharmaceutical Sciences, Southern Medical University, Guangzhou, ChinaThe selection of optimum statin intensity is inconclusive, and the association of plasma exposure of statins and metabolites with major adverse cardiovascular events (MACEs) is unclear. This study sought to compare the effect of low (quartile 1), intermediate (quartiles 2 and 3), and high (quartile 4) plasma exposure of statins and metabolites on MACE, re-ischemia events and death in patients with coronary artery disease (CAD) at 5 years. A total of 1,644 patients in atorvastatin (AT) cohort and 804 patients in rosuvastatin (RST) cohort were included, and their plasma concentration of statins and metabolites was categorized as low-, mid-, or high-group. The association between the plasma levels of statins and metabolites and the incidence of primary endpoint in patients was assessed by Cox proportional hazard models. Intensive AT exposure (Q4 > 5.32 ng/ml) was significantly associated with increased risk of death compared with low (hazard ratio [HR]: 1.522; 95% confidence interval [CI]: 1.035–1.061; P = 0.0022) or moderate exposure (HR: 2.054; 95% CI: 1.348–3.130; P = 0.0008). This association was also found in AT’s five metabolites (all P < 0.01). In patients with RST treatment, moderate RST concentration (0.53–4.29 ng/ml) versus low concentration had a significantly lower risk of MACE and re-ischemia events. (HR: 0.532, 95% CI: 0.347–0.815, P = 0.0061 and HR: 0.505, 95% CI: 0.310–0.823, P = 0.0061, respectively). A higher plasma exposure of AT and metabolites has a significantly higher risk of death, and moderate RST exposure has a significantly lower risk of MACE and re-ischemia events in Chinese patients with CAD. The harms of high plasma exposure should be considered when prescribing statins to patients because it may be a risk factor for having poor prognosis in patients with CAD.https://www.frontiersin.org/article/10.3389/fphar.2020.00675/fullmajor adverse cardiovascular eventsdeathatorvastatinrosuvastatinmetabolitesplasma exposure |
| spellingShingle | Xiao-hong Zhou Xiao-hong Zhou Xiao-hong Zhou Li-yun Cai Wei-Hua Lai Xue Bai Yi-bin Liu Qian Zhu Guo-dong He Ji-Yan Chen Min Huang Zhi-ling Zhou Shi-long Zhong Shi-long Zhong Shi-long Zhong Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease Frontiers in Pharmacology major adverse cardiovascular events death atorvastatin rosuvastatin metabolites plasma exposure |
| title | Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease |
| title_full | Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease |
| title_fullStr | Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease |
| title_full_unstemmed | Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease |
| title_short | Impact of Plasma Exposure of Statins and Their Metabolites With Major Adverse Cardiovascular Events in Chinese Patients With Coronary Artery Disease |
| title_sort | impact of plasma exposure of statins and their metabolites with major adverse cardiovascular events in chinese patients with coronary artery disease |
| topic | major adverse cardiovascular events death atorvastatin rosuvastatin metabolites plasma exposure |
| url | https://www.frontiersin.org/article/10.3389/fphar.2020.00675/full |
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