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CLINICAL STUDY

Troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non–insulin dependent diabetes mellitus

A serial intravascular ultrasound study

^a Division of Cardiology, Kobe General Hospital, Minatojima Nakamachi 4-6, Chuo-Ku, Kobe, Japan
^b Division of Cardiology, Department of Internal Medicine, Kawasaki Medical University, Kurashiki, Japan

Manuscript received October 25, 1999; revised manuscript received April 24, 2000, accepted June 21, 2000.

Reprint requests and correspondence: Dr. Tsutomu Takagi, Division of Cardiology, Kobe General Hospital, Minatojima Nakamachi 4-6, Chuo-Ku, Kobe, Japan
tx-tkg{at}ka2.so-net.ne.jp

OBJECTIVES

The aim of the present study was to determine whether troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with non–insulin dependent diabetes mellitus (NIDDM).

BACKGROUND

Increased in-stent restenosis in patients with diabetes mellitus is due to accelerated neointimal tissue proliferation after coronary stent implantation. Troglitazone inhibits intimal hyperplasia in experimental animal models.

METHODS

We studied 62 stented lesions in 52 patients with plasma glucose levels (PG) 11.1 mmol/liter at 2 h after 75 g oral glucose load. The study patients were randomized into two groups: the troglitazone group of 25 patients with 29 stents, who were treated with 400 mg of troglitazone, and the control group of 27 patients with 33 stents. All patients underwent oral glucose tolerance tests before and after their six-month treatment period. The sum of PG (PG) and the sum of insulin levels (IRI) were measured. Serial (postintervention and at six-month follow-up) intravascular ultrasound studies were performed. Cross-sectional images within stents were taken at every 1 mm, using an automatic pullback. Stent areas (SA), lumen areas (LA), and intimal areas (IA = SA – LA) were measured and averaged over a number of selected image slices. The intimal index was calculated as intimal index = averaged IA/averaged SA x 100%.

RESULTS

There were no differences between the two groups before treatment in PG (31.35 ± 3.07 mmol/liter vs. 32.89 ± 4.87 mmol/liter, respectively, p = 0.2998) and IRI (219.6 ± 106.2 mU/liter vs. 209.2 ± 91.6 mU/liter, respectively, p = 0.8934). However, reductions in PG at the six-month follow-up in the troglitazone group were significantly greater than those in the control group (–21.4 ± 8.8% vs. –4.5 ± 7.4%, respectively, p < 0.0001). Likewise, decreases in IRI were greater in the troglitazone-treated group (–31.4 ± 17.9% vs. –1.9 ± 15.1%, respectively, p < 0.0001). Although, there were no differences between the two groups in SA at postintervention (7.4 ± 2.2 mm² vs. 7.3 ± 1.7 mm², respectively, p = 0.9482) and at follow-up (7.3 ± 2.3 mm² vs. 7.3 ± 1.8 mm², respectively, p = 0.2307), the LA at follow-up in the troglitazone group was significantly greater than that in the control group (5.3 ± 1.7 mm² vs. 3.7 ± 1.7 mm², respectively, p = 0.0002). The IA at follow-up in the troglitazone group was significantly smaller than that in the control group (2.0 ± 0.9 mm² vs. 3.5 ± 1.8 mm², respectively, p < 0.0001). This was also true for intimal index (27.1 ± 11.5% vs. 49.0 ± 14.4%, respectively, p < 0.0001).

CONCLUSIONS

Serial intravascular ultrasound assessment shows that administration of troglitazone reduces neointimal tissue proliferation after coronary stent implantation in patients with NIDDM.

Abbreviations and Acronyms   DM = diabetes mellitus   HDL = high-density lipoprotein   IA = intimal areas   IGT = impaired glucose tolerance   IRI = immunoreactive insulin level   IVUS = intravascular ultrasound   LA = cross-sectional lumen areas   LDL = low-density lipoprotein   MLD = minimal lumen diameter   NIDDM = non-insulin dependent diabetes mellitus   OGTT = oral glucose tolerance test   PDGF = platelet-derived growth factor   PG = plasma glucose level   SA = cross-sectional stent areas   VSMC = vascular smooth muscle cell

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