Should We Use PPAR Agonists to Reduce Cardiovascular Risk?

Table 3

Selected morbidity and mortality outcomes in large, long-term trials of PPAR- agonists. CHD = coronary heart disease, CVD = cardiovascular disease, MI = myocardial infarction, NR = not reported.

Event rates

PROACTIVE [40]

Nonfatal MI

Stroke

Nonfatal

Total mortality

Hospitalized CHF

Cancer

Mean F/U 2.9 years

MI/stroke/

Type 2 diabetes

any death

Placebo

5.5%

4.1%

13.6%

7.1%

4%

4%

N = 2633

Pioglitazone

4.6%

3.3%

11.6%

6.8%

6%

4%

N = 2605

Hazard ratio (95% CI)

0.83 (0.65–1.06)

0.81 (0.61–1.07)

0.84

0.96 (0.78–1.18)

RR^* 1.5 P = .007

RR^* 1.0

(0.72–0.98)

P = .03

DREAM [50]

All MI

CVD death

Stroke

Nonfatal MI/stroke/ CVD death

Total mortality

CHF

Diabetes

Median F/U 3.0 years

Glucose intolerance

Placebo

0.3%

0.4%

0.2%

0.9%

1.3%

0.1%

25%

N = 2634

Rosiglitazone

0.6%

0.5%

0.3%

1.2%

1.1%

0.5%

10.6%

N = 2365

Hazard ratio (95% CI)

1.66

1.20

1.39

1.39

0.91

7.03

0.38

(0.73–3.80)

(0.52–2.77)

(0.44–4.40)

(0.55–1.49)

(1.60–30.9)

(0.33–0.44)

P = .2

P = .7

P = .6

P = .2

P = .7

P = .01

P < .0001

ADOPT [49]

All MI

Stroke

MI/stroke

CHF

Median F/U 4.0 years

Type 2 diabetes

Metformin (M)

1.5%

1.3%

2.8%

1.3%

N = 1454

38% drop-out rate

Glyburide (G)

1.2%

1.2%

2.4%

0.6%

N = 1441

37% drop-out rate

Rosiglitazone (R)

1.8%

1.1%

2.9%

1.5%

N = 1456

44% drop-out rate

Hazard ratio (95% CI)

R versus M

R versus M

R versus M

R versus M 1.22 (0.66–2.26, P = .52) R versus G 2.20 (1.01–4.79, P = .05)

RR^* 1.2

RR^* 0.85

RR^* 1.03

R versus G

R versus G

R versus G

RR^* 1.5

RR^* 0.92

RR^* 1.21

RECORD [51] interim

All MI

CVD death

Nonfatal MI/stroke/CVD death

Total mortality

CHF

analysis

Mean F/U 3.75 years

Type 2 diabetes

Metformin/sulfonylurea

1.8%

2.1%

5.1%

3.6%

1.0%

N = 2227

10% drop-out rate

Rosiglitazone

2.2%

1.7%

4.9%

3.3%

2.1%

added on to

metformin/sulfonylurea

N = 2220

10% drop-out rate

Hazard ratio (95% CI)

1.23

0.80

0.96

0.93

2.15

(0.81–1.86)

(0.52–1.24)

(0.74–1.24)

(0.67–1.27)

(1.30–3.57)

P = .34

P = .32

P = .74

P = .63

P = .003

^*RR = Crude relative risk; hazard ratio not reported.