We compared the long-term effects on estimated glomerular filtration rate (eGFR) among five calcium channel blockers (CCBs), i.e. amlodipine, nifedipine, azelnidipine, benidipine, and cilnidipine, and investigated the association of treatment duration with eGFR and serum creatinine level in diabetic patients with hypertension. |
We found no significant association between treatment duration and both eGFR and serum creatinine level, and no significant difference in the change in eGFR and serum creatinine level, among the five CCBs. |
These five CCBs might be safely used in diabetic patients with hypertension. |
1 Introduction
2 Methods
2.1 Data Source
2.2 Study Population
2.3 Exposure and Measurements
2.4 Data Elements
2.5 Statistical Analysis
Variables | Amlodipine (n = 693) | Nifedipine (n = 189) | Azelnidipine (n = 91) | Benidipine (n = 183) | Cilnidipine (n = 61) |
p value |
---|---|---|---|---|---|---|
Patient data | ||||||
Age, years (mean ± SE) | 66.3 ± 0.4 | 66.4 ± 0.8 | 63.8 ± 1.2 | 64.7 ± 0.9 | 62.5 ± 1.5 | 0.0202* |
Female sex | 321 (46.3) | 74 (39.1) | 40 (44.0) | 68 (37.2) | 19 (31.2) | 0.0351* |
Duration of DM, years (mean ± SE) | 2.2 ± 0.1 | 1.9 ± 0.3 | 3.2 ± 0.4 | 2.5 ± 0.3 | 2.7 ± 0.4 | 0.0540 |
Medical history | ||||||
Urinary protein | 103 (14.9) | 34 (18) | 6 (6.6) | 18 (9.8) | 12 (19.7) | 0.0249* |
Cerebrovascular disease | 166 (24) | 38 (20.1) | 24 (26.4) | 60 (32.8) | 19 (31.1) | 0.0410* |
Ischemic heart disease | 252 (36.4) | 58 (30.7) | 38 (41.8) | 133 (72.7) | 24 (39.3) | <0.0001* |
Other heart disease | 344 (49.6) | 86 (45.5) | 64 (70.3) | 136 (74.3) | 19 (31.1) | <0.0001* |
Rheumatoid arthritis | 89 (12.8) | 25 (13.2) | 11 (12.1) | 20 (10.9) | 3 (4.9) | 0.4396 |
Liver disease | 319 (46) | 78 (41.3) | 41 (45.1) | 74 (40.4) | 28 (45.9) | 0.6034 |
Kidney disease | 143 (20.6) | 37 (19.6) | 27 (29.7) | 49 (26.8) | 20 (32.8) | 0.0324* |
Hyperlipidemia | 333 (48.1) | 77 (40.7) | 57 (62.6) | 112 (61.2) | 38 (62.3) | <0.0001* |
Medication | ||||||
Insulin | 36 (5.2) | 9 (4.8) | 9 (9.9) | 8 (4.4) | 4 (6.6) | 0.3645 |
Oral hypoglycemic drugs | 77 (11.1) | 19 (10.1) | 15 (16.5) | 25 (13.7) | 13 (21.3) | 0.0844 |
Antithrombotic drugs | 168 (24.2) | 39 (20.6) | 23 (25.3) | 68 (37.2) | 11 (18) | 0.0013* |
Liver disease therapeutics | 50 (7.2) | 13 (6.9) | 5 (5.5) | 2 (1.1) | 3 (4.9) | 0.0395* |
Corticosteroids | 106 (15.3) | 32 (16.9) | 8 (8.8) | 15 (8.2) | 8 (13.1) | 0.0482* |
NSAIDs | 188 (27.1) | 63 (33.3) | 14 (15.4) | 40 (21.9) | 10 (16.4) | 0.0035* |
Statins | 85 (12.3) | 13 (6.9) | 15 (16.5) | 36 (19.7) | 4 (6.6) | 0.0017* |
Number of examinations | ||||||
Treatment duration | ||||||
Baseline | 693 | 189 | 91 | 183 | 61 | |
0–3 months | 2837 | 978 | 187 | 533 | 136 | |
3–6 months | 1073 | 264 | 87 | 248 | 81 | |
6–9 months | 702 | 161 | 54 | 132 | 42 | |
9–12 months | 579 | 120 | 40 | 143 | 39 |
3 Results
Drug | Period | eGFR (mL/min/1.73 m2) | Serum creatinine (mg/dL) | ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Unadjusted | Adjusteda
| Unadjusted | Adjusteda
| ||||||||||
LSM | 95% CI |
p value | LSM | 95% CI |
p value | LSM | 95% CI |
p value | LSM | 95% CI |
p value | ||
Amlodipine | 0.0794 | 0.1397 | 0.1109 | 0.1659 | |||||||||
Baseline | 75.5 | 74.1–77.0 | 75.1 | 73.7–76.5 | 0.74 | 0.72–0.76 | 0.73 | 0.71–0.76 | |||||
0–3 months | 76.1 | 74.7–77.5 | 75.8 | 74.4–77.1 | 0.74 | 0.72–0.76 | 0.73 | 0.71–0.75 | |||||
3–6 months | 75.4 | 73.9–76.9 | 75.1 | 73.6–76.5 | 0.77 | 0.74–0.79 | 0.76 | 0.73–0.78 | |||||
6–9 months | 74.7 | 73.1–76.3 | 74.4 | 72.9–76.0 | 0.76 | 0.73–0.79 | 0.75 | 0.72–0.77 | |||||
9–12 months | 74.8 | 73.2–76.5 | 74.6 | 73.0–76.2 | 0.76 | 0.73–0.79 | 0.75 | 0.72–0.78 | |||||
Nifedipine | 0.6286 | 0.6652 | 0.9098 | 0.8725 | |||||||||
Baseline | 73.6 | 70.7–76.5 | 72.7 | 69.9–75.5 | 0.78 | 0.75–0.81 | 0.76 | 0.73–0.79 | |||||
0–3 months | 74.6 | 71.9–77.3 | 73.8 | 71.2–76.4 | 0.77 | 0.74–0.80 | 0.75 | 0.72–0.78 | |||||
3–6 months | 73.9 | 70.9–76.9 | 73.2 | 70.2–76.1 | 0.77 | 0.74–0.80 | 0.75 | 0.72–0.78 | |||||
6–9 months | 72.8 | 69.6–76.1 | 72.3 | 69.1–75.4 | 0.78 | 0.74–0.81 | 0.76 | 0.72–0.79 | |||||
9–12 months | 73.8 | 70.3–77.2 | 73.3 | 69.9–76.8 | 0.77 | 0.73–0.81 | 0.75 | 0.72–0.79 | |||||
Azelnidipine | 0.0719 | 0.0806 | 0.1763 | 0.1945 | |||||||||
Baseline | 77.7 | 73.9–81.5 | 77.3 | 73.9–80.8 | 0.73 | 0.69–0.76 | 0.72 | 0.68–0.75 | |||||
0–3 months | 77.1 | 73.4–80.9 | 76.8 | 73.3–80.2 | 0.74 | 0.70–0.77 | 0.73 | 0.69–0.76 | |||||
3–6 months | 74.5 | 70.6–78.5 | 74.1 | 70.5–77.8 | 0.75 | 0.71–0.79 | 0.74 | 0.71–0.78 | |||||
6–9 months | 75.7 | 71.6–79.8 | 75.3 | 71.4–79.2 | 0.75 | 0.71–0.79 | 0.74 | 0.70–0.78 | |||||
9–12 months | 74.7 | 70.4–79.0 | 74.2 | 70.1–78.4 | 0.75 | 0.71–0.79 | 0.74 | 0.70–0.78 | |||||
Benidipine | 0.748 | 0.7781 | 0.9491 | 0.9474 | |||||||||
Baseline | 73.7 | 71.0–76.4 | 73.1 | 70.4–75.8 | 0.79 | 0.76–0.82 | 0.76 | 0.73–0.79 | |||||
0–3 months | 73.5 | 70.9–76.2 | 73.0 | 70.4–75.6 | 0.79 | 0.76–0.82 | 0.76 | 0.73–0.79 | |||||
3–6 months | 72.6 | 69.9–75.3 | 72.0 | 69.3–74.8 | 0.79 | 0.76–0.83 | 0.77 | 0.74–0.80 | |||||
6–9 months | 73.2 | 70.2–76.1 | 72.6 | 69.7–75.6 | 0.79 | 0.75–0.82 | 0.76 | 0.73–0.79 | |||||
9–12 months | 73.0 | 70.0–75.9 | 72.5 | 69.5–75.5 | 0.79 | 0.76–0.83 | 0.77 | 0.73–0.8 | |||||
Cilnidipine | 0.1092 | 0.2343 | 0.1406 | 0.2501 | |||||||||
Baseline | 74.4 | 69.0–79.9 | 76.5 | 71.2–81.9 | 0.82 | 0.74–0.91 | 0.75 | 0.67–0.83 | |||||
0–3 months | 72.8 | 67.4–78.1 | 75.0 | 69.6–80.3 | 0.84 | 0.75–0.92 | 0.77 | 0.69–0.85 | |||||
3–6 months | 72.7 | 67.2–78.2 | 75.0 | 69.5–80.5 | 0.88 | 0.79–0.97 | 0.81 | 0.72–0.89 | |||||
6–9 months | 70.2 | 64.4–76.0 | 72.7 | 66.9–78.5 | 0.87 | 0.78–0.97 | 0.80 | 0.71–0.89 | |||||
9–12 months | 70.1 | 64.2–76.0 | 72.6 | 66.7–78.6 | 0.89 | 0.79–0.98 | 0.81 | 0.72–0.91 |
Laboratory parameters | Period | Drug | Unadjusted | Adjusteda
| ||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
LSM | 95% CI | Vs. nif | Vs. Azel | Vs. Beni | Vs. Cil | LSM | 95% CI | Vs. Nif | Vs. Azel | Vs. Beni | Vs. Cil | |||
ΔeGFR | 0–3 months | Amlodipine | 0.47 | −0.42 to 1.37 | 0.9945 | 0.9260 | 0.9880 | 0.5088 | 0.02 | −2.01 to 2.13 | 0.9925 | 0.9605 | 0.9887 | 0.5833 |
Nifedipine | 0.85 | −0.77 to 2.47 | – | 0.8684 | 0.9528 | 0.4514 | 0.43 | −2.12 to 2.97 | – | 0.9099 | 0.9508 | 0.5076 | ||
Azelnidipine | −0.74 | −3.51 to 2.03 | – | – | 0.9934 | 0.9609 | −1.01 | −4.45 to 2.43 | – | – | 0.9983 | 0.9597 | ||
Benidipine | −0.03 | −1.82 to 1.76 | – | – | – | 0.7716 | −0.50 | −3.16 to 2.15 | – | – | – | 0.8321 | ||
Cilnidipine | −2.20 | −5.40 to 0.99 | – | – | – | – | −2.51 | −6.31 to 1.29 | – | – | – | – | ||
3–6 months | Amlodipine | −0.39 | −1.46 to 0.67 | 1.0000 | 0.2707 | 0.9729 | 0.7572 | −0.26 | −2.8 to 2.27 | 1.0000 | 0.2584 | 0.9969 | 0.6909 | |
Nifedipine | −0.42 | −2.59 to 1.75 | – | 0.4177 | 0.9913 | 0.8332 | −0.24 | −3.41 to 2.92 | – | 0.3870 | 0.9986 | 0.7704 | ||
Azelnidipine | −3.84 | −7.06 to −0.61 | – | – | 0.6135 | 0.9879 | −3.82 | −7.90 to 0.25 | – | – | 0.5107 | 0.9929 | ||
Benidipine | −1.10 | −3.08 to 0.89 | – | – | 0.9461 | −0.68 | −3.80 to 2.43 | – | – | – | 0.8668 | |||
Cilnidipine | −2.63 | −6.17 to 0.91 | – | – | −2.76 | −7.05 to 1.53 | – | – | – | – | ||||
6–9 months | Amlodipine | −1.29 | −2.54 to −0.04 | 0.9981 | 1.0000 | 1.0000 | 0.9201 | −2.00 | −5.00 to 1.00 | 0.9998 | 0.9975 | 0.9999 | 0.8698 | |
Nifedipine | −1.74 | −4.40 to 0.91 | – | 1.0000 | 0.9987 | 0.9803 | −2.25 | −6.09 to 1.58 | – | 0.9998 | 1.0000 | 0.9410 | ||
Azelnidipine | −1.53 | −5.19 to 2.14 | – | – | 0.9999 | 0.9781 | −2.65 | −7.27 to 1.96 | – | – | 0.9996 | 0.9828 | ||
Benidipine | −1.23 | −3.76 to 1.30 | – | – | – | 0.9383 | −2.19 | −5.98 to 1.61 | – | – | – | 0.9341 | ||
Cilnidipine | −3.19 | −7.50 to 1.11 | – | – | – | – | −4.24 | −9.39 to 0.91 | – | – | – | – | ||
9–12 months | Amlodipine | −1.33 | −2.70 to 0.05 | 0.9996 | 0.9949 | 0.9967 | 0.9912 | −1.55 | −4.85 to 1.75 | 0.9994 | 0.9972 | 0.9997 | 0.9748 | |
Nifedipine | −0.97 | −4.04 to 2.10 | – | 0.9900 | 0.9926 | 0.9852 | −1.15 | −5.61 to 3.30 | – | 0.9924 | 0.9977 | 0.9640 | ||
Azelnidipine | −2.27 | −6.77 to 2.22 | – | – | 0.9999 | 1.0000 | −2.38 | −7.98 to 3.21 | – | – | 0.9997 | 0.9995 | ||
Benidipine | −1.87 | −4.58 to 0.83 | – | – | – | 0.9995 | −1.86 | −6.04 to 2.32 | – | – | – | 0.9928 | ||
Cilnidipine | −2.50 | −7.36 to 2.37 | – | – | – | – | −3.13 | −8.92 to 2.66 | – | – | – | – | ||
ΔCre | 0–3 months | Amlodipine | 0.0004 | −0.009 to 0.010 | 0.8345 | 0.9687 | 0.9990 | 0.5120 | 0.0186 | −0.004 to 0.041 | 0.7864 | 0.9791 | 0.9999 | 0.6306 |
Nifedipine | −0.0103 | −0.028 to 0.007 | – | 0.7659 | 0.9773 | 0.2676 | 0.0070 | −0.020 to 0.034 | – | 0.7758 | 0.9506 | 0.3336 | ||
Azelnidipine | 0.0108 | −0.020 to 0.041 | – | – | 0.9522 | 0.9326 | 0.0280 | −0.009 to 0.066 | – | – | 0.9774 | 0.9566 | ||
Benidipine | −0.0025 | −0.022 to 0.017 | – | – | – | 0.5170 | 0.0171 | −0.012 to 0.046 | – | – | – | 0.6729 | ||
Cilnidipine | 0.0296 | −0.005 to 0.065 | – | – | – | – | 0.0448 | 0.003 to 0.086 | – | – | – | – | ||
3–6 months | Amlodipine | 0.0295 | −0.004 to 0.063 | 0.9665 | 1.0000 | 0.9703 | 0.9878 | 0.0937 | 0.015 to 0.173 | 0.9059 | 1.0000 | 0.9880 | 0.9949 | |
Nifedipine | 0.0042 | −0.064 to 0.073 | – | 0.9930 | 1.0000 | 0.9245 | 0.0599 | −0.039 to 0.158 | – | 0.9813 | 0.9979 | 0.9133 | ||
Azelnidipine | 0.0310 | −0.071 to 0.133 | – | – | 0.9946 | 0.9963 | 0.0947 | −0.032 to 0.222 | – | – | 0.9978 | 0.9984 | ||
Benidipine | 0.0067 | −0.056 to 0.069 | – | – | – | 0.9304 | 0.0751 | −0.022 to 0.172 | – | – | – | 0.9694 | ||
Cilnidipine | 0.0590 | −0.053 to 0.171 | – | – | – | – | 0.1172 | −0.016 to 0.251 | – | – | – | – | ||
6–9 months | Amlodipine | 0.0135 | 0.003 to 0.024 | 0.9978 | 0.9999 | 0.9057 | 0.5828 | 0.0215 | −0.004 to 0.047 | 0.9997 | 1.0000 | 0.9258 | 0.6045 | |
Nifedipine | 0.0175 | −0.005 to 0.040 | – | 0.9979 | 0.8867 | 0.7975 | 0.0240 | −0.008 to 0.056 | – | 1.0000 | 0.9346 | 0.7709 | ||
Azelnidipine | 0.0114 | −0.019 to 0.042 | – | – | 0.9918 | 0.7205 | 0.0217 | −0.017 to 0.060 | – | – | 0.9831 | 0.7893 | ||
Benidipine | 0.0030 | −0.018 to 0.024 | – | – | – | 0.3662 | 0.0112 | −0.021 to 0.043 | – | – | – | 0.4072 | ||
Cilnidipine | 0.0416 | 0.006 to 0.078 | – | – | – | – | 0.0495 | 0.006 to 0.093 | – | – | – | – | ||
9–12 months | Amlodipine | 0.0184 | 0.006 to 0.031 | 0.9967 | 1.0000 | 0.9792 | 0.5987 | 0.0153 | −0.014 to 0.045 | 0.9969 | 1.0000 | 0.9647 | 0.5948 | |
Nifedipine | 0.0130 | −0.015 to 0.041 | – | 0.9999 | 0.9999 | 0.5792 | 0.0098 | −0.030 to 0.050 | – | 1.0000 | 0.9994 | 0.5753 | ||
Azelnidipine | 0.0166 | −0.024, 0.057 | – | – | 0.9991 | 0.7725 | 0.0127 | −0.038 to 0.063 | – | – | 0.9983 | 0.7588 | ||
Benidipine | 0.0105 | −0.014 to 0.035 | – | – | – | 0.4825 | 0.0053 | −0.032 to 0.043 | – | – | – | 0.4555 | ||
Cilnidipine | 0.0518 | 0.008 to 0.096 | – | – | – | – | 0.0496 | −0.003 to 0.102 | – | – | – | – |