Effect of pentoxifylline on endothelial dysfunction, oxidative stress and inflammatory markers in STEMI patients

Figures & data

Figure 1. Study flow diagram.

Table 1. Comparison of the baseline characteristics for the drug and placebo groups.

Characteristics	Drug group (n = 22)	Placebo group (n = 21)	p-value
Demographics Age (years) Gender, male BMI (kg/m^2)	57.5 (49–60.5) 18 (81.8%) 29.079 ± 5.023	55 (46.5–64.5) 17 (81%) 28.226 ± 3.675	0.77^‡ 1.00^§ 0.53^¶
Smoking status, smoker	10 (45.5%)	11 (52.4%)	0.65^#
Pack-year history	0.00 (0.00–27.00)	6 (0.00–35)	0.65^‡
10-year ASCVD risk	15 (5.975–21.8)	12 (5.55–19.9)	0.87^‡
Previous events, n 0 1 2	18 (81.8%) 4 (18.2%) 0 (0%)	19 (90.5%) 0 (0%) 2 (9.5%)	0.053^§
Multi- vs single-vessel disease Multi-vessel disease Single-vessel disease	9 (40.9%) 13 (59.1%)	3 (14.3%) 18 (85.7%)	0.052^#
Location of MI Anterior MI Non-anterior MI	16 (72.7%) 6 (27.3%)	14 (66.7%) 7 (33.3%)	0.67^#
LVEF%	41.5% (37.5–47.75%)	40% (35–46. 5%)	0.33^‡
Killip class 1 ≥2	20 (90.9%) 2 (9.1%)	20 (95.2%) 1 (4.8%)	1.00^§
PRECISE-DAPT score Very low Low Moderate	13 (59.1%) 6 (27.3%) 3 (13.6%)	8 (38.1%) 7 (33.3%) 6 (28.6%)	0.33^§
Laboratory data Serum creatinine Creatinine clearance ALT AST Total leukocytic count Hemoglobin Platelet count Total cholesterol HDL LDL Triglycerides Random blood glucose INR Total creatine kinase Creatine kinase – MB HbA1c	0.8 (0.8–1.025) 112.545 ± 34.266 38 (23–45) 66 (27.25–183.75) 10.25 (8.15–13.15) 14.223 ± 1.899 245 (217.75–307.25) 194.91 ± 40.734 38.5 (31.5–44.5) 126.5 ± 35.427 141.5 (95.75–194.75) 172.5 (136.5–226.5) 1.055 (1–1.103) 437 (170.5–1555.75) 58.514 (21.75–179.5) 5.8 (4.925–6.671)	1 (0.85–1.1) 97.196 ± 28.518 42 (22–71) 82 (38–181.5) 9.3 (6.6–14.25) 14.152 ± 1.690 268 (229.5–306) 204.048 ± 47.482 39 (33.4–45) 137.705 ± 45.828 115 (99–141.5) 141 (108.5–216.5) 1.1 (1–1.22) 837 (361–1743.34) 72 (42.5–216.5) 5.9 (5.35–8.8)	0.10^‡ 0.10^¶ 0.19^‡ 0.30^‡ 0.42^‡ 0.90^¶ 0.70^‡ 0.50^¶ 0.72^‡ 0.35^¶ 0.18^‡ 0.26^‡ 0.36^‡ 0.17^†† 0.36^†† 0.46^††
Medical history Hypertension Diabetes mellitus Stroke	9 (40.9%) 13 (59.1%) 1 (4.5%)	12 (57.1%) 9 (42.9%) 0 (0%)	0.22^# 0.22^# 0.51^§
Stent type BMS DES	2 (9.1%) 20 (90.9%)	1 (4.8%) 20 (95.2%)	1.00^§
Stents per patient, n 0 1 2	0 (0%) 17 (77.3%) 5 (22.7%)	1 (4.8%) 15 (71.4%) 5 (23.8%)	0.86^§
Medication history before admission Aspirin Plavix Ticagrelor Beta-blockers ACEI CCB Statins Insulin OHG	3 (13.6%) 2 (9.1%) 1 (4.5%) 2 (9.1%) 5 (22.7%) 2 (9.1%) 2 (9.1%) 3 (13.6%) 8 (36.4%)	4 (19%) 4 (19%) 0 (0%) 5 (23.8%) 4 (19%) 0 (0%) 3 (14.3%) 4 (19%) 7 (33.3%)	0.70^§ 0.41^§ 1.00^§ 0.24^§ 1.00^§ 0.49^§ 0.66^§ 0.70^§ 0.84^#
In-hospital and discharge medications Antiplatelets Clopidogrel, n (%) Ticagrelor, n (%) Trimetazidine Ivabradine Aldosterone antagonist	14 (63.6%) 8 (36.4%) 4 (18.2%) 3 (13.6%) 12 (54.5%)	19 (90.5%) 2 (9.5%) 5 (23.8%) 3 (14.3%) 7 (33.3%)	0.037^†^,^# 0.72^§ 1.00^§ 0.16^#

Data are expressed as mean ± SD, number (%), or median (interquartile range).

† A p-value 0.05 denotes significant difference.

‡ Mann–Whitney U test.

§ Fisher's exact test.

¶ Unpaired t-test.

# Pearson Chi-square test.

†† Multiple Imputation then Mann–Whitney U test.

ACEI: Angiotensin-converting enzyme inhibitor; ALT: Alanine transaminase; AST: Aspartate transaminase; ASCVD: Atherosclerotic cardiovascular disease; CCB: Calcium channel blocker; HbA1c: Glycated hemoglobin; HDL: High density lipoprotein; INR: International normalized ratio; IQR: Interquartile range; LDL: Low density lipoprotein; LVEF: Left ventricular ejection fraction; MI: Myocardial infarction; n: Number; OHG: Oral hypoglycemic; PRECISE-DAPT: PREdicting bleeding Complications In patients undergoing stent implantation and subsequent dual antiplatelet therapy; SD: Standard deviation.

Table 2. Comparison of serum concentration of the study biomarkers for both drug and placebo groups.

Parameter	Drug group (n = 22)	Placebo group (n = 21)	p-value
sVCAM-1 (ng/ml) Baseline End point p-value of within group	967.542 (783.083–1104.225) 1203.889 (850.614–1411.699) 0.052^§	922.787 (783.059–1089.488) 1079.547 (908.632–1396.909) 0.18^§	1.00^‡ 1.00^‡
MDA (nmol/ml) Baseline End point p-value of within group	7.709 (6.5–8.808) 7.337 (6.378–9.145) 1.00^§	7.465 (5.477–8.221) 8.419 (6.453–9.477) 0.62^§	0.94^‡ 1.00^‡
IL-1 (ng/l) Baseline End point p-value of within group	35.6 (14.475–39.425) 42.45 (24.725–50.525) 0.064^§	34.2 (29.1–48.75) 34.5 (19.7–40.9) 0.20^§	1.00^‡ 0.26^‡
IL-6 (ng/l) Baseline End point p-value of within group	64.167 (53.583–83.708) 68 (53.333–80.292) 1.00^§	70.5 (56.667–84.167) 79.667 (65.667–87.584) 1.00^§	1.00^‡ 0.68^‡
hs-CRP (mg/ml) Baseline End point p-value of within group	10.057 (9.779–10.331) 9.721 (6.102–10.191) 0.032^†,^§	9.903 (8.481–10.482) 9.509 (7.712–9.856) 1.00^§	1.00^‡ 1.00^‡
TNF-α (mg/ml) Baseline End point p-value of within group	99.125 (55.375–136.063) 102.5 (88.688–139.563) 0.60^§	101.25 (82–136.875) 128.75 (95.75–162.625) 0.056^§	1.00^‡ 0.61^‡

Data are expressed as median (interquartile range).

† A p-value 0.05 denotes significant difference.

‡ Mann–Whitney U test.

§ Wilcoxon signed ranks test.

hs-CRP: High-sensitivity C-reactive protein; IL-1: Interleukin-1; IL-6: Interleukin-6; MDA: Malondialdehyde; sVCAM-1: Soluble vascular cell adhesion molecule-1; TNF-α: Tumor necrosis factor alpha.

Figure 2. Comparison of sVCAM-1 level between group I and group II at baseline and at the end of the study.

Group I (n = 22): patients received 400 mg tablet of PTX thrice daily in addition to their standard treatment for 2 months. Group II (n = 21): patients received placebo tablets in addition to their standard treatment for 2 months. The p-value of end of study level of sVCAM-1 in group I versus group II = 1.00.

n: Number; PTX: Pentoxifylline; sVCAM-1: Soluble vascular cell adhesion molecule-1.

Table 3. Comparison of efficacy and safety between the pentoxifylline and the placebo groups.

Parameter	Drug group (n = 22)	Placebo group (n = 21)	p-value
Total MACEs Anginal pain Myocardial Infarction	6 (27.3%) 6 (27.3%) 0 (0%)	9 (42.9%) 8 (38.1%) 1 (4.8%)	0.35^† 0.45^† 0.49^‡
Side effects Nose bleeding Headache Nausea	0 (0%) 6 (27.3%) 3 (13.6%)	1 (4.8%) 3 (14.3%) 1 (4.8%)	0.49^‡ 0.25^‡ 0.32^‡
Adherence	90.80% ± 6.1	87.81% ± 5.42	0.10^§

Data are expressed as number (%) or mean ± SD.

† Pearson Chi-square test.

‡ Fisher's Exact test.

§ unpaired t-test.

MACE: Major adverse cardiac event; PTX: Pentoxifylline.