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Frontiers of Medicine

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ISSN 2095-0225(Online)

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Front. Med.    2019, Vol. 13 Issue (6) : 713-722    https://doi.org/10.1007/s11684-018-0661-9
RESEARCH ARTICLE
Long-term effects of various types of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on changes in glomerular filtration rate in Korea
Seo Yeon Baik1, Hyunah Kim2, So Jung Yang1, Tong Min Kim1, Seung-Hwan Lee3, Jae Hyoung Cho3, Hyunyong Lee4, Hyeon Woo Yim5, Kun-Ho Yoon1,3, Hun-Sung Kim1,3()
1. Department of Medical Informatics, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
2. College of Pharmacy, Sookmyung Women’s University, Seoul 04310, Republic of Korea
3. Division of Endocrinology and Metabolism, Department of Internal Medicine, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
4. Clinical Research Coordinating Center, Catholic Medical Center, The Catholic University of Korea, Seoul 06591, Republic of Korea
5. Department of Preventive Medicine, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea
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Abstract

Few long-term follow-up studies have compared the changes in renal function according to the type of statin used in Korea. We compared the long-term effects of statin intensity and type on the changes in the glomerular filtration rate (GFR). We extracted data of patients who took statin for the first time. We analyzed whether or not different statins affect the changes in GFR at 3 months after baseline and 4 years after. We included 3678 patients and analyzed the changes in GFR. The GFR decreased by 3.2%±0.4% on average 4 years after the first statin prescription, indicating statistically significant deterioration (from 83.5±0.4 mL/min/1.73 m2 to 79.9±0.4 mL/min/1.73 m2, P<0.001). When comparing the GFR among different statins, significant differences were observed between atorvastatin and fluvastatin (−5.3%±0.7% vs. 1.2%±2.2%, P<0.05) and between atorvastatin and simvastatin (−5.3%±0.7% vs. −0.7%±0.8%, P<0.05). In pitavastatin (odds ratio [OR]=0.64, 95% confidence interval [CI]=0.46–0.87, P<0.005) and simvastatin (OR=0.69, 95% CI=0.53–0.91, P<0.008), the GFR rate that decreased by<60 mL/min/1.73 m2 was significantly lower than that of atorvastatin. Regarding long-term statin intake, GFR changed with the type of statin. This work is the first in Korea to compare each statin in terms of changes in the GFR after the statin prescription.
Keywords statin      glomerular filtration rate      HMG-CoA reductase inhibitor      chronic kidney disease     
Corresponding Author(s): Hun-Sung Kim   
Just Accepted Date: 09 October 2018   Online First Date: 03 December 2018    Issue Date: 16 December 2019
 Cite this article:   
Seo Yeon Baik,Hyunah Kim,So Jung Yang, et al. Long-term effects of various types of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors on changes in glomerular filtration rate in Korea[J]. Front. Med., 2019, 13(6): 713-722.
 URL:  
https://academic.hep.com.cn/fmd/EN/10.1007/s11684-018-0661-9
https://academic.hep.com.cn/fmd/EN/Y2019/V13/I6/713
Fig.1  Study flow diagram. GFR, glomerular filtration rate. MDRD, modification of diet in renal disease.
Atorvastatin Fluvastatin Pitavastatin Pravastatin Rosuvastatin Simvastatin Simvastatin
+ Ezetimibe
10 mg 20 mg 40 mg 40 mg 80 mg 2 mg 10 mg 20 mg 40 mg 10 mg 20 mg 20 mg 40 mg 10 mg 20 mg
n 767 166 33 42 78 500 85 127 129 741 56 680 33 145 96
Sex (male), n (%) 376 (49.0) 85 (51.2) 19 (57.6) 25 (59.5) 32 (41.0) 212 (42.4) 34 (40.0) 44 (34.7) 57 (44.2) 350 (47.2) 26 (46.4) 288 (42.4) 20 (60.6) 65 (44.8) 37 (38.5)
Age, year 66±11 65±12 70±12 59±12 67±8 66±11 68±10 64±10 65±10 65±12 62±12 67±12 68±8 65±10 62±12
Age (>65 years), n (%) 441 (57.5) 88 (53.0) 22 (66.7) 17 (40.5) 48 (61.5) 253 (50.6) 48 (56.5) 56 (44.1) 68 (52.7) 375 (50.6) 22 (39.3) 404 (59.4) 22 (66.7) 72 (49.7) 36 (37.5)
Diabetes mellitus, n (%) 361 (47.1) 65 (39.2) 15 (45.5) 7 (16.7) 34 (43.6) 209 (41.8) 28 (32.9) 42 (33.1) 37 (28.7) 353 (47.6) 24 (42.9) 300 (44.1) 15 (45.5) 68 (46.9) 35 (36.5)
Fasting blood glucose, mg/dL 135±65 137±60 155±90 120±35 118±32 126±44 122±41 121±39 125±42 137±72 150±98 124±39 124±28 135±50 137±81
HbAlc, % 7.2±1.6 7.1±1.6 7.2±1.5 6.6±0.9 6.8±0.9 6.9±1.4 6.78±1.2 7.1±1.7 6.7±1.2 7.4±1.8 7.7±2.4 6.9±1.2 6.7±0.8 7.1±1.4 7.0±2.0
BUN, mg/dL 16±5 17±7 17.1±4.0 16±6 17±4 16±5 16±6 15±5 16±5 16±5 16±7 16±5 15±5 16±6 16±5
Creatinine, mg/dL 0.9±0.3 0.9±0.3 0.9±0.2 1.0±0.3 0.9±0.3 0.9±0.2 0.9±0.3 0.8±0.2 0.9±0.3 0.9±0.2 0.9±0.3 0.9±0.2 0.9±0.2 0.9±0.3 0.8±0.2
MDRD-GFR, mL/min/1.73m2 83.4±22.2 82.2±21.8 81.3±20.6 83.6±19.7 77.0±18.0 85.1±21.4 79.1±18.9 86.0±19.5 85.2±19.8 82.4±20.0 85.3±27.6 83.6±26.4 81.7±14.2 85.5±22.8 88.6±19.6
MDRD-GFR category
≥90 mL/min/1.73 m2, n (%) 263 (34.3) 58 (34.9) 9 (27.3) 12 (28.6) 17 (21.8) 183 (36.6) 22 (25.9) 50 (39.4) 55 (42.6) 237 (32.0) 16 (28.6) 208 (30.6) 6 (18.2) 57 (39.3) 52 (54.2)
60–89 mL/min/1.73m2,
n (%)		 409 (53.3) 82 (49.4) 21 (63.6) 26 (61.9) 48 (61.5) 274 (54.8) 50 (58.8) 66 (52.0) 65 (50.4) 410 (55.3) 34 (60.7) 389 (57.2) 24 (72.7) 70 (48.3) 37 (38.5)
<60 mL/min/1.73 m2, n (%) 95 (12.4) 26 (15.7) 3 (9.1) 4 (9.5) 13 (16.7) 43 (8.6) 13 (15.3) 11 (8.7) 9 (7.0) 94 (12.7) 6 (10.7) 83 (12.2) 3 (9.1) 18 (12.4) 7 (7.3)
Total cholesterol, mg/dL 183±43 198±54 208±82 223±45 178±36 203±47 197±37 215±43 215±47 196±56 228±71 180±43 177±57 195±45 234±51
Triglyceride, mg/dL 154±82 172±116 267±454 192±144 136±71 160±87 167±87 160±78 144±72 169±125 184±97 152±100 181±75 163±98 178±122
HDL-C, mg/dL 50±13 48±11 43±12 44±10 52±13 51±13 50±13 50±16 52±12 52±14 49±13 53±14 51±13 52±15 51±12
LDL-C, mg/dL 110±35 126±47 121±45 140±42 103±32 128±39 127±31 143±34 131±45 125±45 157±62 104±37 108±48 117±36 145±46
AST, IU/L 26±17 25±13 24±11 40±30 23±7 27±14 24±9 26±19 27±15 25±13 28±17 25±11 24±10 27±16 28±21
ALT, IU/L 28±24 29±22 25±15 59±57 25±12 31±27 25±13 28±20 30±25 28±19 30±16 28±21 26±13 29±19 33±26
ALP, IU/L 67±47 64±20 59±18 77±50 60±18 65±26 68±23 63±22 71±22 67±45 65±20 66±24 70±22 64±20 63±20
Sodium, mEq/L 141±3 140±3 140±3 141±2 141±2 141±2 141±3 141±2 141±3 141±3 141±3 141±3 141±2 140±2 141±3
Potassium, mEq/L 4.4±0.4 4.3±0.4 4.2±0.4 4.3±0.5 4.4±0.3 4.3±0.4 4.3±0.4 4.3±0.4 4.3±0.4 4.3±0.4 4.4±0.5 4.4±0.4 4.3±0.4 4.4±0.4 4.3±0.4
CPK, IU/L 111±140 98±71 113±65 101±74 107±65 108±124 99±79 127±180 127±160 104±72 143±167 105±127 100±44 116±98 95±65
Tab.1  Baseline characteristics of patients prescribed a statin for the first time
n Baseline 3 months later % (SE) Pvalue 4 years later % (SE) P value
High intensity statin 89 83.8±2.7 86.3±4.3 2.6±2.2 0.204 78.6±3.3 −6.5±2.5* 0.441
Moderate to high intensity statin 940 82.3±0.7 85.1±0.9 3.9±0.4** 79.5±0.7 −2.6±0.7**
Moderate to low intensity statin 2154 83.7±0.5 85.6±0.6 3.1±0.3** 79.9±0.5 −3.2±0.5**
Low intensity statin 254 83.3±1.2 86.6±1.8 2.1±0.8* 80.0±1.4 −3.13±1.3*
Tab.2  Comparison of changes in the MDRD-GFR rate at 3 months and 4 years after a statin was prescribed
n Baseline 3 months later % (SE) P value 4 years later % (SE) P value
Atorvastatin 966 83.2±0.7 84.1±0.7 2.2±0.4** <0.001 77.7±0.8 −5.3±0.7** <0.001
Fluvastatin 120 79.3±1.7 82.3±1.9 4.0±1.2** 79.5±2.0 1.2±2.2
Pitavastatin 500 85.1±1.0 87.4±1.0 3.5±0.6** 82.0±1.0 −2.9±0.8**
Pravastatin 341 84.0±1.1 84.3±1.1 0.9±0.7 79.1±1.2 −4.7±1.2**
Rosuvastatin 797 82.6±0.7 86.0±0.8 4.3±0.5** 79.8±0.8 −2.8±0.8**
Simvastatin 713 83.5±1.0 85.5±0.9 0.2±0.5** 81.2±0.8 −0.7±0.8
Simvastatin+ Ezetimibe 241 86.7±1.4 88.2±1.4 2.6±0.9* 81.6±1.5 −4.6±1.4**
Total 3678 83.5±0.4 85.4±0.4 3.2±0.2 <0.001 79.9±0.4 −3.2±0.4 <0.001
Tab.3  Comparison of changes in the MDRD-GFR rate at four years after a statin was prescribed
Univariable Multivariable*
OR (95% CI) P value OR (95% CI) P value
Age 1.08 (1.07−1.09) <0.001 1.08 (1.07−1.09) <0.001
Sex (male) 1.06 (0.89−1.26) 0.536 1.29 (1.07−1.55) 0.008
Statin 0.018 0.045
Atorvastatin Reference Reference
Fluvastatin 0.85 (0.52−1.40) 0.520 1.01 (0.61−1.70) 0.959
Pitavastatin 0.61 (0.45−0.83) 0.001 0.64 (0.46−0.87) 0.005
Pravastatin 0.70 (0.50−0.99) 0.041 0.79 (0.56−1.13) 0.195
Rosuvastatin 0.81 (0.63−1.03) 0.089 0.89 (0.69−1.14) 0.353
Simvastatin 0.74 (0.57−0.95) 0.021 0.69 (0.53−0.91) 0.008
Simvastatin+Ezetimibe 0.61 (0.41−0.92) 0.018 0.75 (0.49−1.14) 0.173
Tab.4  Association between a specific statin and change in the MDRD-GFR
MDRD-GFR MDRD-GFR reduction P value
N Baseline Visit 2 (4 years) % (SE)
High intensity statin
Atorvastatin (40 mg) 33 81.3±3.6 72.1±3.7 −11.4±3.1** 0.094
Rosuvastatin (20 mg) 56 85.3±3.7 82.4±4.7 −3.5±3.4
Moderate to high intensity statin
Atorvastatin (20 mg) 166 82.2±1.7 77.8±1.8 −3.5±2.0 0.234
Rosuvastatin (10 mg) 741 82.4±0.7 79.7±0.8 −2.7±0.8**
Simvastatin (40 mg) 33 81.7±2.5 83.9±3.2 3.5±3.2
Moderate to low intensity statin
Atorvastatin (10 mg) 767 83.4±0.8 77.9±0.9 −5.5±0.8** <.001
Fluvastatin (80 mg) 78 77.0±2.0 76.2±2.3 0.4±3.1
Pitavastatin (2 mg) 500 85.1±1.0 82.0±1.0 −2.9±0.8**
Pravastatin (40 mg) 129 85.2±1.8 79.4±1.8 −5.2±1.9**
Simvastatin (20 mg) 680 83.6±1.0 81.0±0.8 −0.9±0.8
Low intensity statin
Fluvastatin (40 mg) 42 83.6±3.0 85.6±3.6 2.8±2.7 0.117
Pravastatin (20 mg) 127 86.1±1.7 82.2±2.1 −4.0±1.9*
Pravastatin (10 mg) 85 79.1±2.1 73.9±2.2 −4.8±2.2*
Others
Simvastatin (20mg) + Ezetimibe (20 mg) 96 88.6±2.0 85.1±2.1 −2.2±2.3 0.135
Simvastatin (20mg) +Ezetimibe (10 mg) 145 85.5±1.9 79.3±1.9 −6.3±1.7**
Tab.5  Comparison of changes in the MDRD-GFR rate at 4 years after a statin was prescribed among the subgroups
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