Table 1.

Characteristics of the included studies (n = 9)

Author	Year	Study Design	Follow up	Intervention (mg)	Control	Cumulative dose	Patient population	Outcomes	Sample size Randomized [E/C]	Male% [E/C]	Mean age [E/C]	Country	Outcome assessment
Ali [32]	2016	DB-RCT	4 months	500 × 2	Placebo	1000	STEMI patients	LVEF (4 months), LVM, LVMI, and diastolic function (E, e′, E/e, and LAVI)	118/119	80.5/74.8	57.9/58.2	Netherlands	2D Echocardiography (Vivid 7)
Gupta [33]	2020	OL-RCT	12 months	1000 × 2	SOC	2000	Documented CAD (angiographically documented or a previous history of myocardial infarction/angina), verified HF functional class III, FIRI ≥ 2.5 by receiving basic therapy for CAD and CHF (HFrEF, HFmrEF and HFpEF)	LVEF, Incidence of MI, hospitalization for HF decompensating, all-cause death, and conversion from Prediabetic to diabetes. secondary outcomes: QoL, (MLHFQ), neurohormonal, lipid profile, renal function, Insulin, aldosterone, and Nt-proBNP, 6 MWT	39/37	72.9/43.6	62/62	India	Transthoracic echocardiography (iE33 xMATRIX | Philips)
Ladeiras-Lopes [15]	2021	OL-RCT	3, 6, and 12 months	1000 × 2	SOC	2000	Non-diabetic adults aged 40–65 years with non-diabetic MetS and diastolic dysfunction	e′ velocity, LVEF, LVMI (g/m2), Pro-BNP, QoL (SF-36), CPX (Peak Vo2), FIRI, CRP	27/27	46/64	51.2/52.4	Portugal	2D Echocardiography
Larsen [16]	2020	DB-RCT	3 months	1000 × 2	SOC	2000	Insulin-resistant chronic HF patients without diabetes	LVMI (g/m2), LVEF, QoL (MLHFQ), HBA1c, HOMA-IR, Pro-BNP, E/e ratio, GLS, Myocardial efficiency (WMI, MEE), CPX (resting and max Vo2), 6 MWT	19/17	89/71	68/61	Denmark	2D Echocardiography (Vivid E9 and E95, GE Healthcare, Horten, Norway)
Mohan [14]	2019	DB-RCT	12 months	1000 × 2	Placebo	2000	CAD with IR and/or pre-diabetes	LVMI (g/m1.7), LVEF, Wt, TBA derivatives, Pro-BNP, A1C, HOMA-IR, systolic BP	31/32	84/75	64.5/64.5	UK	Cardiac MRI (CMR)
Sardu [34]	2021	DB-RCT	12 months	850 × 2	Placebo	1700	Obese patients with pre-diabetes. All 83 patients underwent abdominoplastic surgery and, after treatment, received a hypocaloric diet	inflammatory/oxidative stress, miRs’ expression, and cardiovascular function (LVMI and LVEF)	28/27	28.6/33.3	42.5/41.8	Italy	2D Echocardiography
Stakos [35]	2005	DB-RCT	12, and 24 months	500 mg × 1	Placebo	500	Non-diabetic patients with IR	Insulin sensitivity, glucose tolerance, lipid profile, LVMI (g/m2), aortic distensibility, aortic PWV	59/97	24/26	40.5/41	Greece	2D Echocardiography M-Mode Echocardiography
Velázquez [18]	2016	OL-RCT	Six months	850 × 1	SOC	850	35–60 years, diastolic dysfunction, abdominal obesity, and MS diagnosed according to the ATP III criteria. At least three of the five diagnostic criteria of MS	Echocardiographic parameters, Lipid profile, BP, and CRP	20/20	46/46	44.5/44	Mexico	2D Echocardiography (Phillips model IE33)
Wong [17]	2012	DB-RCT	4 months	1000 × 2	Placebo	2000	Non-diabetic IR HF patients (FIRI ≥ 2.7)	CPX (Peak Vo2 was the primary outcome), FIRI, VE/VCO2 slope, BNP, LVEF, 6-min walk test, MLHFQ	39/23	89.7/95.6	64/68	UK	2D Echocardiography

E experimental group, C control group, BP blood pressure, CAD coronary artery disease, MS metabolic syndrome, CRP C reactive protein, CPX cardiopulmonary exercise testing, FIRI fasting insulin resistance index, HFrEF heart failure with reduced ejection fraction, HFmrEF heart failure with mid-range ejection fraction, HFpEF heart failure with preserved ejection fraction, IR insulin resistance, PWV pulse wave velocity, QoL quality of life, OL-RCT open-label randomized clinical trial; DB-RCT: Double-blinded randomized clinical trial, LAVI left atrial ventricular index, LVEF left ventricular ejection fraction, LVMI left ventricular mass index, SOC standard of care, TBA thiobarbituric acid derivatives