Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: KEGG:D02027 (Tranilast)
 205 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Restenosis after percutaneous intervention remains a significant clinical problem. Although stent implantation has significantly reduced the rate of restenosis by approximately 25% to 33%, intimal hyperplasia within stents still limits long-term vessel patency. The clinical sequelea of this neointimal proliferation is more pronounced in certain patient subgroups, eg, patients with diatbetes mellitus, diffuse disease, smaller vessels, chronic total occlusions, and lesions located in saphenous vein bypass grafts. Pharmacologic agents studied to date have failed to prevent restenosis. Tranilast, a novel anti-inflammatory agent, interferes with the proliferation and migration of vascular smooth muscle cells (VSMCs) induced by platelet-derived growth factor and transforming growth factor beta-1. Basic and preliminary clinical studies conducted with tranilast in Japan have shown encouraging results in terms of reducing restenosis. The Prevention of Restenosis with Tranilast and its Outcomes study (PRESTO), a double-blind, placebo-controlled study (n = 11,500), will test the efficacy of two doses (300 and 450 mg twice a day) of tranilast administered for 1 and 3 months compared with placebo. The primary objective is to compare the composite clinical event rate (death, myocardial infarction, or the need for ischemia-driven target vessel revascularization) after 9 months in patients treated with tranilast or placebo. Angiographic and intravascular ultrasound studies will be peformed in order to assess the effects of tranilast on angiographic restenosis and the volume of intimal hyperplastic tissue. If successful, tranilast will be the first drug to reduce angiographic and clinical restenosis.
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PMID:Tranilast in the Therapy of Coronary Artery Disease. 1109 62

Diabetic patients undergoing coronary interventions have worse clinical and angiographic outcomes than do patients without diabetes. Metformin, an insulin sensitizer, may decrease the occurrence of these outcomes. Diabetic patients in the Prevention of Restenosis with Tranilast and its Outcomes Trial were identified through their medical records (n = 2,772). In this trial, 1,110 diabetic patients received nonsensitizer therapy (insulin and/or sulfonylureas) and 887 received sensitizer therapy (metformin with or without additional therapy). Logistic regression was used to obtain odds ratios (ORs) (sensitizer vs nonsensitizer therapy) of any clinical event (death, myocardial infarction, or ischemia-driven target vessel revascularization) and adjusted for multiple risk factors. Multivariate analysis showed no effect of lesion characteristics on clinical outcomes. Compared with patients on nonsensitizer therapy, those on sensitizer therapy showed an adjusted OR of 0.72 (95% confidence interval [CI] 0.57 to 0.91, p = 0.005) for any clinical event. The differences between the nonsensitizer therapy group and the sensitizer group were attributable mainly to decreased rates of death (OR 0.39, 95% CI 0.19 to 0.77, p = 0.007) and myocardial infarction (OR 0.31, 95% CI 0.15 to 0.66, p = 0.002). In our retrospective analysis, use of metformin in diabetics undergoing coronary interventions appeared to decrease adverse clinical events, especially death and myocardial infarction, compared with diabetic patients treated with nonsensitizer therapy.
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PMID:Relation of metformin treatment to clinical events in diabetic patients undergoing percutaneous intervention. 1516 12

Patients with previous percutaneous coronary intervention (PCI) are often excluded from clinical trials. As a result, limited data are available on the long-term outcome of such patients undergoing repeat PCI. In this study, we assessed the impact of previous PCI on outcomes in patients undergoing repeat PCI. We compared the baseline features and outcomes of 7,056 patients without previous PCI (group I) with those of 1,281 patients with previous PCI of the original target lesion (group II) and 1,408 patients with previous PCI of a nontarget lesion (group III) undergoing PCI in the Prevention of Restenosis with Tranilast and its Outcomes (PRESTO) trial. Compared with patients in group I, patients in groups II and III were more likely to have diabetes (25% and 24% vs 21%, p <0.02), previous myocardial infarction (51% and 56% vs 29%, p <0.001), and ostial lesions (10% and 7% vs 5%, p <0.001), and less likely to have, as their indication for PCI, myocardial infarction (2% and 7% vs 17%, p <0.001). At 1 month, major adverse cardiac events, including death, myocardial infarction, and repeat revascularization, were low and similar in all 3 groups. Compared with patients in group I, the risk of major adverse cardiac events at 9 months was significantly increased for patients in groups II (34.1% vs 18.6%, relative risk [RR] 2.03, adjusted RR 1.78, 95% confidence interval 1.58 to 2.01) and III (23.9% vs 18.6%, RR 1.30, adjusted RR 1.16, 95% confidence interval 1.02 to 1.33). The increased risk of major adverse cardiac events was entirely due to higher rates of repeat revascularization. In conclusion, despite similar short-term outcomes, patients with previous PCI undergoing PCI of either target or nontarget lesions had lower event-free survival at 9 months of follow-up.
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PMID:Outcome of patients with prior percutaneous revascularization undergoing repeat coronary intervention (from the PRESTO Trial). 1616 50

Tranilast (Tra) reduces intracardiac interstitial fibrosis in the animal models of hypertensive heart failure and diabetic cardiomyopathy by inhibiting cardiac fibroblasts. The present study examined whether Tra has long-term effects on the cardiac remodeling in the remote area of the left ventricle (LV) following myocardial infarction (MI) in the rat. Treatment with Tra (n=40; 150 mg/kg twice daily) or placebo (Plac, n=36) was started at day 28 after induction of a large MI or sham-operation (ShO, n=18) in female Lewis rats. Collagen content was determined using high-performance liquid chromatography. Large MI led to a significant hypertrophy of the two ventricles, a severe dilatation of the LV and a shift of the chamber stiffness variables in the pressure volume curves. The six-month survival rates were Tra, 62.5%; Plac, 75%; and ShO, 100%. No significant difference was identified between Tra and Plac regarding survival rate and collagen content. Treatment with the anti-inflammatory and antifibrotic drug, Tra, started four weeks after the induction of a large MI in the rat, did not attenuate or positively influence remodeling in chronic ischemic heart failure and survival. Further studies are required to explore the effects of Tra on cardiac myocytes post-MI in more detail.
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PMID:Late onset oral treatment with tranilast following large myocardial infarction has no beneficial effects on cardiac remodeling and mortality in rats. 2537 34