Impact of fibrates on circulating cystatin C levels: a systematic review and meta-analysis of clinical trials

Figures & data

Figure 1. Flow chart of the number of studies identified and included into the meta-analysis.

Table 1. Demographic characteristics of the included studies.

Author	Study design	Target population	Treatment duration	n	Study groups	Age, years	Female (n, %)	BMI (kg/m^2)	Total cholesterol (mg/dl)	LDL cholesterol (mg/dl)	HDL cholesterol (mg/dl)	Triglycerides (mg/dl)	Cystatin C (mg/L)
Ansquer et al. [27]	Randomized, double-blind, placebo-controlled, cross-over	Healthy people	6 weeks	24	Overall	ND	7 (30)	24.0*
				24	Placebo				162 ± 31	98 ± 24	44 ± 11	88 ± 74	0.85 ± 0.28
				24	Fenofibrate 160 mg/day				166 ± 28	105 ± 24	46 ± 11	97 ± 108	0.75 ± 0.22
Dierkes et al. [28]	Open-label, controlled	Men with hypertriglyceridemia	6 weeks	10	Fenofibrate 200 mg/day	ND	0 (0)	ND	ND	ND	ND	363 (203–850)^†	0.75 (0.61–0.82)^†
				10	Bezafibrate 400 mg/day	ND	0 (0)	ND	ND	ND	ND	310 (203–726)^†	0.71 (0.53–0.94)^†
Dierkes et al. [29]	Randomized, double-blind, placebo-controlled, cross-over	Men with hyperlipidemia	6 weeks	29	Overall	46 ± 8	0 (0)	28.8 ± 2
				25	Fenofibrate 200 mg/day			0.8	286 (185–417)^†	59 (10–364)^†	35 (21–63)^†	496 (168–1691)^†	0.76 (0.57–0.85)^†
				25	Fenofibrate 200 mg/day + vitamins				324 (193–437)^†	59 (13–220)^†	33 (23–58)^†	558 (141–1594)^†	0.76 (0.52–0.89)^†
Forsblom et al. [30]	Randomized, double-blind, placebo-controlled	Type 2 diabetes	5 years	83	Placebo	61.3 ± 6.7	21 (25)	29.7 (26.8–33.0)^†	189 ± 27	116 ± 23	42 (38–50)^†	150 (115–186)^†	0.85 ± 0.13
				87	Fenofibrate 200 mg/day	62.5 ± 6.3	24 (27)	29.1 (26.3–32.5)^†	201 ± 27	127 ± 23	42 (38–54)^†	132 (97–194)^†	0.92 ± 0.17
Foucher et al. [31]	Randomized, double-blind, active-controlled	Mixed dyslipidemia	12 weeks	109	Fenofibrate 145 mg/day + Simvastatin 20 mg/day	59.6 ± 10.0	38 (35)	32.0 ± 5.2	176.7 ± 23.2	101 ± 18	43 ± 10	226 (117–601)^‡	0.96 ± 0.17
				114	Simvastatin 20 mg/day	60.5 ± 9.3	40 (35)	31.1 ± 4.8	175.2 ± 22.0	100 ± 16	46 ± 12	194 (90–592)^‡	0.95 ± 0.18
				110	Fenofibrate 145 mg/day + Simvastatin 40 mg/day	60.4 ± 8.1	43 (39)	31.4 ± 4.6	179.8 ± 25.5	101 ± 17	46 ± 11	208 (110–1103)^‡	0.92 ± 0.17
				112	Simvastatin 40 mg/day	59.3 ± 9.1	39 (35)	31.3 ± 5.3	181.0 ± 23.2	104 ± 17	46 ± 12	216 (122–576)^‡	0.93 ± 0.14
				111	Fenofibrate 145 mg/day	60.4 ± 9.0	38 (34)	31.6 ± 5.1	184.8 ± 25.9	105 ± 18	46 ± 10	236 (126–843)^‡	0.95 ± 0.16
Ishibashi et al. [32]	Randomized, double-blind, active-controlled	Dyslipidemia	24 weeks		Pemafibrate 0.2 mg/day	53.1 ± 10.8	15 (20)	26.1 ± 3.5	232 ± 30	143 ± 30	42 ± 4	239 ± 53	0.8 ± 0.1
				74	Pemafibrate 0.4 mg/day	53.4 ± 10.3	13 (17)	26.9 ± 4.2	228 ± 30	143 ± 27	42 ± 4	230 ± 62	0.8 ± 0.1
				76	Fenofibrate 106.6 mg/day	52.9 ± 11.6	14 (18)	26.0 ± 3.7	228 ± 27	139 ± 27	42 ± 4	239 ± 70	0.8 ± 0.1
Mychaleckyj et al. [33]	Randomized, placebo-controlled	Type 2 diabetes	12 weeks	321	Fenofibrate 160 mg/day (cases)	67.2 ± 6.2	97 (30)	ND	ND	ND	41.5 ± 10.3	136 ± 74	1.03 ± 0.35
				175	Fenofibrate 160 mg/day (controls)	66.9 ± 6.5	70 (40)	ND	ND	ND	42.6 ± 11.1	160 ± 227	0.95 ± 0.35
				564	Placebo	67.3 ± 7.1	197 (35)	ND	ND	ND	41.5 ± 9.1	163 ± 93	0.95 ± 0.17
Ncube et al. [34]	Open-label	Hyperlipidemia	12 weeks	12	Fenofibrate 267 mg/day	43.5 (33–70)^†	2 (16)	ND	232*	ND	45*	264*	0.79 (0.72–0.92)^†
Westphal et al. [35]	Randomized, active-controlled, cross-over	Men with hypertriglyceridemia	6 weeks	22	Overall	36–66^ǂ	0 (0)	25–37^ǂ
				22	Gemfibrozil 900 mg/day				ND	ND	32 (17–73)^†	682 (221–4694)^†	0.73 (0.57–1.48)^†
				22	Fenofibrate 200 mg/day				ND	ND	34 (15–65)^†	575 (203–5376)^†	0.68 (0.54–1.56)^†

Values are expressed as mean ± standard deviation (SD).

* Mean.

† Median (IQR).

‡ Median (min-max).

ǂ Range.

ND: no data; BMI: body mass index; IQR: interquartile range.

Table 2. Quality of bias assessment of the included studies according to the Cochrane guidelines.

Study	Sequence generation	Allocation concealment	Blinding of participants, personnel and outcome assessors	Incomplete outcome data	Selective outcome reporting	Other sources of bias
Ansquer et al. [27]	U	U	U	L	L	U
Dierkes et al. [28]	H	H	H	L	L	U
Dierkes et al. [29]	U	U	U	L	L	U
Forsblom et al. [30]	U	U	U	L	L	U
Foucher et al. [31]	L	U	L	L	L	U
Ishibashi et al. [32]	L	L	L	L	L	L
Ncube et al. [34]	H	H	H	L	L	U
Westphal et al. [35]	U	H	H	L	L	U
Mychaleckyj et al. [33]	L	U	L	L	L	U

L: low risk of bias; H: high risk of bias; U: unclear risk of bias.

Figure 2. Forest plot detailing weighted mean difference and 95% confidence intervals for the impact of fibrates on plasma cystatin C concentrations in single-arm uncontrolled trials. Lower plot shows the results of leave-one-out sensitivity analysis.

Figure 3. Forest plot detailing weighted mean difference and 95% confidence intervals for the impact of individual fibrates on plasma cystatin C concentrations in single-arm uncontrolled trials. Lower plot shows the results of leave-one-out sensitivity analysis.

Figure 4. Forest plot detailing weighted mean difference and 95% confidence intervals for the impact of fibrates on plasma cystatin C concentrations in randomized controlled trials. Lower plot shows the results of leave-one-out sensitivity analysis.

Figure 5. Funnel plot detailing publication bias in the studies reporting the impact of fibrate fibrates on plasma cystatin C concentrations in single-arm uncontrolled trials. Open circles represent observed published studies; closed circles represent imputed unpublished studies.

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