Fenofibrate Delays the Need for Dialysis and Reduces Cardiovascular Risk Among Patients With Advanced CKD
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Design
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Retrospective, observational cohort study
N= 52,890
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Objective
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To compare outcomes among advanced chronic kidney disease (CKD) patients treated with fenofibrate, statins, a combination of both, or none of the above
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Study Groups
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Nonuser (n= 27,996)
Fenofibrate (n= 1,774)
Statins (n= 22,338)
Fenofibrate + statin (F+S) combination (n= 782)
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Inclusion Criteria
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Aged ≥20 years with advanced CKD (erythropoiesis-stimulating agent first prescribed after outpatient CKD diagnosis between the index date), diagnosed hyperlipidemia
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Exclusion Criteria
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Never diagnosed with hyperlipidemia, received kidney transplantation, received any dialysis before the index date, or taken another type of fibrate or gemfibrozil within three months before the index date
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Methods
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Patient data was collected from Taiwan’s National Health Insurance Research Database and randomized into four cohorts based on whether they received no fenofibrate or statin therapy, fenofibrate monotherapy, statin monotherapy, or a combination of fenofibrate and a statin.
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Duration
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Index date: January 1, 2001 to December 31, 2013
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Outcome Measures
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All-cause mortality, cardiovascular death, major adverse cardiac and cerebrovascular events (MACCEs), and incidence of permanent dialysis
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Baseline Characteristics
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Nonuser (n= 27,996)
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Fenofibrate (n= 1,774)
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Statins (n= 22,338)
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F+S combination (n= 782)
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Age, years
20-64
65-74
≥ 75
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66.8 ± 12.6
11,541 (41.2%)
8,322 (29.7%)
8,133 (29.1%)
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63.7 ± 12.5
921 (51.9%)
488 (27.5%)
365 (20.6%)
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63.4 ± 12.4
11,985 (53.7%)
6,145 (27.5%)
4,208 (18.8%)
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60.9 ± 11.1
499 (63.8%)
205 (26.2%)
78 (10.0%)
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Female
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49.6% |
49.9% |
51.7% |
49.7% |
CKD duration, years
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5.5 ± 3.8 |
5.5 ± 3.7 |
5.3 ± 3.9 |
5.7 ± 3.7 |
Outpatient visits in previous year
At nephrology
In general
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13.0 ± 10.0
42.0 ± 24.0
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13.0 ± 11.0
45.0 ± 23.0
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14.0 ± 10.0
43.0 ± 22.0
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13.0 ± 11.0
47.0 ± 24.0
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Comorbid conditions
HTN
Diabetes mellitus
Atrial fibrillation
Liver cirrhosis
PAD
Dementia
SLE
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24,854 (88.8%)
19,219 (68.7%)
928 (3.3%)
900 (3.2%)
1,170 (4.2%)
1,060 (3.8%)
228 (0.81%)
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1,596 (90.0%)
1,438 (81.1%)
44 (2.5%)
29 (1.6%)
74 (4.2%)
44 (2.5%)
12 (0.68%)
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20,039 (89.7%)
17,556 (78.6%)
482 (2.2%)
395 (1.8%)
958 (4.3%)
495 (2.2%)
192 (0.86%)
|
714 (91.3%)
683 (87.3%)
14 (1.8%)
9 (1.2%)
32 (4.1%)
11 (1.4%)
0
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History of event
Heart failure
Stroke
Myocardial infarction
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6,518 (23.3%)
6,357 (22.7%)
1,998 (7.1%)
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352 (19.8%)
374 (21.1%)
115 (6.5%)
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4,784 (21.4%)
4,630 (20.7%)
1,997 (8.9%)
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168 (21.5%)
185 (23.7%)
78 (10.0%)
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Medications
ACEi/ARB
Other anti-HTN
Aspirin/clopidogrel
NSAIDs
Steroid
Proton pump inhibitor
Insulin
Sulfonylurea
DPP-4 inhibitors
Acarbose
Loops diuretics
Ketosterila
Pentoxyfillin
Sodium bicarbonate
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12,852 (45.9%)
21,671 (77.4%)
7,220 (25.8%)
2,507 (9.0%)
1,404 (5.0%)
2,089 (7.5%)
5,730 (20.5%)
5,828 (20.8%)
1,390 (5.0%)
2,062 (7.4%)
14,218 (50.8%)
326 (1.2%)
4,632 (16.6%)
1,899 (6.8%)
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1,025 (57.8%)
1,511 (85.2%)
642 (36.2%)
188 (10.6%)
71 (4.0%)
143 (8.1%)
699 (39.4%)
435 (24.5%)
142 (8.0%)
205 (11.6%)
959 (54.1%)
17 (0.96%)
360 (20.3%)
105 (5.9%)
|
12,996 (58.2%)
19,357 (86.7%)
8,496 (38.0%)
1,603 (7.2%)
1,228 (5.5%)
1,485 (6.7%)
7,187 (32.2%)
6,180 (27.7%)
2,077 (9.3%)
2,534 (11.3%)
13,793 (61.8%)
354 (1.6%)
4,974 (22.3%)
1,630 (7.3%)
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524 (67.0%)
697 (89.1%)
345 (44.1%)
78 (10.0%)
28 (3.6%)
48 (6.1%)
369 (47.2%)
241 (30.8%)
115 (14.7%)
128 (16.4%)
489 (62.5%)
14 (1.8%)
201 (25.7%)
54 (6.9%)
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Follow-up, years
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3.2 ± 2.8 |
3.3 ± 2.6 |
3.3 ± 2.7 |
3.2 ± 2.5 |
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Results
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Endpoint
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HR or SHR (95% CI) (column vs row)
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Incidencea (95% CI) |
Fenofibrate (n= 1,774)
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Statins (n= 22,338)
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F+S combination (n= 782)
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All-cause mortality
Nonuser
Fenofibrate
Statin
Combination
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15.4 (15.2 to 15.6)
13.5 (13.3 to 13.7)
13.9 (13.7 to 14.1)
13.2 (13.0 to 13.5)
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0.88 (0.81 to 0.96)c
--
--
--
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0.91 (0.88 to 0.93)c
1.03 (0.94 to 1.12)
--
--
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0.88 (0.76 to 1.01)
0.99 (0.84 to 1.17)
0.97 (0.84 to 1.12)
--
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Cardiovascular death
Nonuser
Fenofibrate
Statin
Combination
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7.9 (7.8 to 8.1)
6.7 (6.5 to 6.8)
7.4 (7.3 to 7.6)
8.0 (7.8 to 8.1)
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0.84 (0.75 to 0.94)c
--
--
--
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0.94 (0.90 to 0.97)c
1.12 (0.995 to 1.25)
--
--
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1.01 (0.82 to 1.24)
1.20 (0.95 to 1.51)
1.08 (0.88 to 1.32)
--
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MACCEsb
Nonuser
Fenofibrate
Statin
Combination
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11.6 (11.4 to 11.8)
11.3 (11.1 to 11.5)
11.2 (11.0 to 11.3)
11.8 (11.6 to 12.0)
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0.97 (0.88 to 1.07)
--
--
--
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0.96 (0.93 to 0.995)c
0.99 (0.90 to 1.09)
--
--
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1.02 (0.86 to 1.21)
1.05 (0.86 to 1.27)
1.06 (0.89 to 1.26)
--
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Permanent dialysis
Nonuser
Fenofibrate
Statin
Combination
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131.6 (130.4 to 132.8)
87.4 (86.5 to 88.3)
126.5 (125.3 to 127.6)
92.9 (91.8 to 94.1)
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0.78 (0.77 to 0.80)c
--
--
--
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1.00 (0.99 to 1.01)
1.27 (1.26 to 1.29)c
--
--
|
0.90 (0.89 to 0.91)c
1.15 (1.13 to 1.17)c
0.90 (0.89 to 0.92)c
--
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Adverse Events
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See Results
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Study Author Conclusions
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For patients with advanced CKD, continuing fenofibrate may provide a protective effect on CV outcomes equal to that of statins, and it may further delay the need for permanent dialysis. The combination of fenofibrate and high-intensity statins may have additional benefits.
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InpharmD Researcher Critique
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Due to the study design, adverse events other than major adverse cardiac and cerebrovascular events were not addressed, which limits the safety data collected from this trial with respect to patients with advanced CKD. Data derived from a Taiwanese database may not be applicable to a domestic patient population.
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