The Antiischemic Effects and Tolerability of Trimetazidine in Coronary Diabetic Patients. A Substudy from TRIMPOL-1 Hanna Szwed 1 , Zygmunt Sadowski 1 , Robert Pachocki 2 , Ma≥gorzata Domˇ za≥-Boche¥ nska 2 , Krzysztof Szymczak 3 , Zbigniew Szyd≥owski 4 , Andrzej Paradowski 5 , Grzegorz Gajos 6 , Grzegorz Ka≥uˇ za 6 , Irena Kulon 7 , Anna W≤ ator-Brzezi¥ nska 8 , Waldemar Elikowski 9 , and Maria Ku¥ zniak 10 1 National Institute of Cardiology, Warsaw; 2 Servier-Polska, Warsaw; 3 Voivodeship Cardiological Center, £omˇ za; 4 City Hospital, PCK, Bia≥ystok; 5 Department of Ischaemic Heart Disease, Collegium Medicum Jagiellonian University, Cracow; 6 Department of Cardiology, Collegium Medicum Jagiellonian University, Cracow; 7 Voivodeship Specialistic Hospital, G Narutowicza, Cracow; 8 Voivodeship Cardiological Center, Cracow; 9 Strusia Hospital, Pozna¥ n; 10 District Hospital, Olesno, Poland Summary. Diabetes mellitus, a disease with a wide preva- lence, has major cardiovascular effects, being a risk factor for the development of ischemic heart disease and conges- tive heart failure. The aim of this open, multicenter study was to assess the antiischemic ef~cacy and tolerability of trimetazidine, a metabolic agent acting at the myocardial mitochondrial level, in diabetic patients with stable effort angina treated previously with a single conventional an- tianginal drug. Fifty diabetic patients (mean age 58 years) with proven coronary artery disease, stable effort angina for at least 3 months, and positive, comparable results of two initial treadmill exercise tests separated by a 1-week interval were included in the study. They continued their conventional antianginal monotherapy with a long-acting nitrate, beta-blocker, or calcium channel blocker. After sta- bilization, 4-week therapy with trimetazidine, three times daily, 20 mg was initiated in combination with previous treatment. The results showed a signi~cant improvement in exercise tolerance (440.2 vs. 383.2 s; P  0.01), time to 1-mm ST-segment depression (358.3 vs. 301.6 s; P  0.01), time to onset of anginal pain (400.0 vs. 238.3 s; P  0.01), and total work (9.39 vs. 8.67 metabolic equivalents, P  0.01). Maximal ST-segment depression was attenuated com- pared with baseline (1.82 vs. 1.91 mm). Other ~ndings in- cluded a signi~cant decrease in the mean frequency of ang- inal episodes (3.06 vs. 4.79 per week; P  0.01) and in mean nitrate consumption (2.29 vs. 4.2 doses/week). These re- sults suggest that trimetazidine may be effective and is well tolerated as combination therapy for diabetic coronary ar- tery disease patients uncontrolled with a single hemody- namic agent. Cardiovasc Drugs Ther 1999:13 Key Words. trimetazidine, diabetes mellitus, coronary heart disease, ischemia, tolerability Patients with diabetes have a marked propensity for cardiovascular morbidity and mortality. Indeed, the cardiovascular mortality rate is more than doubled among men and more than quadrupled among women with diabetes, even after adjusting for age, hyper- cholesterolemia, hypertension, and smoking, compared with those without diabetes [1]. Long-term epidemio- logical data from the Framingham study have demon- strated that such patients have a two- to threefold higher risk of developing atherosclerosis compared with nondiabetic patients [2]. Coronary stenotic lesions in patients with diabetes were more often found on distal arteries, were more frequently associated with three-vessel disease, and tended to be associated with more diffuse disease [3]. A study of coronary artery stenosis in patients under- going coronary angiography found that moderate stenosis (50–75% luminal narrowing) was signi~cantly more frequent in diabetic than in nondiabetic patients (50.6% vs. 30.3%, P  0.001) [3]. Diabetes was found to be an independent risk factor for moderate stenosis. These results con~rm those of previous studies, which have suggested that the greater amount of moderate stenosis in diabetic patients may be considered a sub- strate for future plaque rupture and may explain the Address for correspondence: Assoc. Prof. H. Szwed, Institute of Cardiology, 02-637 Warsaw, Sparta¥ nska 1, Poland Received 15 September 1998; receipt/review time 38 days; ac- cepted in revised form 14 December 1998 217 Cardiovascular Drugs and Therapy 1999:13:217–222 © Kluwer Academic Publishers. Boston. Printed in U.S.A.