Impact of Trimetazidine on Incidence of Myocardial Injury and Contrast-Induced Nephropathy in Diabetic Patients With Renal Dysfunction Undergoing Elective Percutaneous Coronary Intervention Mohamed Shehata, MD* Trimetazidine is an anti-ischemic agent with antioxidant activity. This study evaluated the effect of periprocedural administration of trimetazidine on the incidence of percutaneous coronary intervention (PCI)einduced myocardial injury and contrast-induced nephropathy (CIN) in diabetic patients with mild-to-moderate renal dysfunction. One hundred patients with a mean glomerular filtration rate of 48 – 16 (ml/min/1.73 m2) were prospectively enrolled, then randomly assigned to receive (50 patients; trimetazidine group) or not receive (50 patients; control group) periprocedural trimetazidine (70 mg/day) for 72 hours. The serum creatinine level was measured pre-PCI, 72 hours, and 10 days thereafter. An increase in the serum creatinine level by >0.5 mg/dl or 0.25% of the baseline value is considered as CIN. Cardiac troponin I levels were measured before and 6, 12, and 24 hours after PCI. Mean age of the study cohort was 59 – 6 years (men 68%). The serum creatinine level in the control group increased significantly 3 days after PCI and decreased on the tenth day. However, it showed no significant change in the trimetazidine group. Incidence of CIN was 12% in the trimetazidine group and 28% in the control group (p 0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05

Categorical variables are presented as number (percentage). Continuous variables are presented as mean  SD. Trimetazidine þ ¼ trimetazidine group; trimetazidine 0 ¼ control group. * The Pearson chi-square test was used to compare categorical variables, and the Student t test was used to compare continuous variables.

Table 2 Preliminary angiographic characteristics in the two study groups Trimetazidine þ Trimetazidine 0 *p (no. ¼ 50) (no. ¼ 50) Value

Variable Vascular access Femoral artery Radial artery

40 (80%) 10 (20%)

38 (76%) 12 (24%)

>0.05 >0.05

Worst lesion type†

A B C

28 (56%) 15 (30%) 7 (14%)

26 (52%) 17 (34%) 7 (14%)

>0.05 >0.05 >0.05

Number of vessels

1 2 >2

23 (46%) 18 (36%) 9 (18%)

24 (48%) 16 (32%) 10 (20%)

>0.05 >0.05 >0.05

All variables are presented as number (percentage). Trimetazidine þ ¼ trimetazidine group; trimetazidine 0 ¼ control group. * The Pearson chi-square test was used to compare categorical variables. † According to American Heart Association/American College of Cardiology classification.

enrolled in this study. All patients underwent PCI on elective basis. The present study comprises 50 patients randomly assigned to the trimetazidine group receiving the drug according to the previously described dosing regimen and 50 others randomly assigned to the control group. Pretreatment with trimetazidine was well tolerated with no serious adverse events during the in-hospital follow-up. The mean age of the whole study cohort was 59  6 years, 68 (68%) being male patients. The 2 study groups were matched regarding age, gender, risk factors of coronary artery disease, and baseline transthoracic echocardiographic data. No statistically significant difference was found between the 2 groups concerning baseline mean glycated hemoglobin levels, serum creatinine, eGFR, body mass index, and frequency of preprocedural intake of oral anti-ischemic medications and metformin oral

hypoglycemic drug. Table 1 lists baseline characteristics of the 2 study groups. Most of the patients in both study groups were accessed through the femoral artery. Patients in both groups received a comparable mean volume of contrast agent with no recorded stent loss or improper stent placement. There was no statistically significant difference between both groups regarding preliminary angiographic findings and procedural characteristics. Final TIMI III flow was more frequently achieved in the trimetazidine group, with a trend toward lesser incidence of procedural complications, yet these finding were not statistically significant. PCI-related data are summarized in Tables 2 and 3. The number of patients showing an increase in postprocedural cTnI above the upper limit of the control range was not significantly different between the 2 groups. However, the postprocedural mean cTnI level was significantly higher in the control group (6 hours: 8  0.3 vs 16  0.2 pg/ml, p 0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05 >0.05

Categorical variables are presented as number (percentage). Continuous variables are presented as mean  SD. Trimetazidine þ ¼ trimetazidine group; trimetazidine 0 ¼ control group. * Pearson chi-square and Fisher’s exact tests were used to compare categorical variables. The Student t test was used to compare continuous variables. 30 24.3

cTnI (pg/ml)

25 20 15.7

14

15 10

12.5 8.2

Group A (Trimetazidine) Group B (Control)

7.4

5

s. creaƟnine (mg/dL)

3

2.7

2.5 2

1.9

2

2.2

2.2 1.94

1.5

Group A (Trimetazidine)

1

Group B (Control)

0.5 0 baseline 3 d (post- 10 d (post(pre-PCI) PCI) PCI)

0 6h

12 h

24 h

Time (post-PCI)

Time

Figure 1. Graphic presentation showing changes in mean cTnI levels in both study groups.

Figure 2. Graphic presentation showing changes in mean serum creatinine levels in both study groups.

recorded acute ischemic insults during the same period. CIN developed in 8 patients (3 patients in the trimetazidine group and 5 patients in the control group) already taking metformin, necessitating drug stoppage. One patient in the trimetazidine group and 3 patients in the control group developed controllable acute pulmonary edema, in the first 48 hours after PCI. They were managed successfully using IV furosemide.

Incidence of CIN is highly dependent on the renal function before contrast media administration and additional risk factors, of which diabetes mellitus is the most important one.9 Incidence varies from 0.05 >0.05

>0.05 >0.05

>0.05 >0.05

T0

Estimated glomerular filtration rate (mL/minute/1.73 m2) Serum creatinine (mg/dL)

50  15 2  0.4

42  10 2.7  0.8

47  14 2  0.3

0.05