Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Table 1

Selected morbidity and mortality outcomes in large, long-term fibrate trials. CHD = coronary heart disease, CVD = cardiovascular disease, MI = myocardial infarction, NR = not reported, ns = reported as “not significant,” RR = Crude relative risk calculated form reported number of events; hazard ratio was not reported.

Event rates
Study treatment	Nonfatal MI	CHD mortality	Nonfatal MI or CHD death	Total stroke	Cancer	Total mortality	Hospitalized CHF
Helsinki Heart [9]
Mean F/U 5.0 years
Primary prevention
Dyslipidemia
High LDL
Placebo	3.5%	0.64%	4.1%	NR	1.3%	2.1%
N = 2030
Gemfibrozil	2.2%	0.53%	2.7%	NR	1.5%	2.2%
N = 2051
Hazard ratio (95% CI)	RR 0.63	RR 0.83	0.66	NR	RR 1.15	RR 1.05
	P < .02	p = NR	P < .02		p = NR	p = NR
VA-HIT [8]
Mean F/U 5.1 years
CHD
HDL < 40 mg/dl
LDL < 140 mg/dl
Placebo	14.5%	9.3%	21.7%	6.0%	10.9%	17.4%	13.3%
N = 1267
Gemfibrozil	11.6%	7.4%	17.3%	4.6%	9.9%	15.7%	10.6%
N = 1264
Hazard ratio (95% CI)	0.77	0.78	0.78	0.75	RR 0.91	0.89	0.78
	(0.62–0.96)	(0.59–1.02)	(0.65–0.93)	(0.53–1.06)		(0.73–1.08)	(0.62–0.98)
	P < .02	P = .07	P = .006	P = .10		P = .23	P = .04
BIP [10]						Noncardiac death
Mean F/U 6.2 years
CHD
Dyslipidemia
Placebo	11.2%	5.7%	15.0%	5.0%	5.9%	4.2%
N = 1542
Bezafibrate N = 1548	9.7%	6.1%	13.6%	4.6%	5.5%	4.3%
Hazard ratio (95% CI)	0.87	RR 1.07	0.91	RR 0.92	RR 0.93	RR 1.02
	P = .18	P = .61	P = .26	𝛼 ns		P = .87
FIELD [11]							Laser therapy	Albuminuria not progressing/ regressing
Mean F/U 5 years
Type 2 diabetes
Dyslipidemia
Low LDL
Placebo	4.2%	1.9%	6%	3.6%	8%	6.6%	5.2%
n = 4900
Fenofibrate	3.2%	2.2%	5%	3.2%	8%	7.3%	3.6%
N = 4895
	0.76	1.19	0.89	0.90		1.11	0.70	RR 1.15 P = .002
Hazard ratio (95% CI)	(0.62–0.94)	(0.90–1.57)	(0.75–1.05)	(0.73–1.12)	RR 1.0	(0.95–1.29)	(0.58–0.85)
	P = .01	P = .22	P = .16	P = .36		P = .18	P = .0003