HCQ revealed the great potential in the management of cardiovascular risk by controlling glucose homeostasis and lipidic profile. Until now, in this review, we discussed the effect of HCQ alone to counteract cardiovascular complications, mostly in autoimmune patients. Here, we reviewed the multiple pleiotropic actions of HCQ in combination with conventional medication in the most common cardiovascular diseases. The cardioprotective effects of one week of treatment with 50 mg/kg of HCQ i.g. against ischemia-reperfusion injury in type-2 diabetic mice were assessed in combination with the phosphodiesterase-5 inhibitor, tadalafil. The synergistic effect reduced the myocardial infarct size by up to 20% and improved insulin secretion and sensitivity [132]. Moreover, low-dose HCQ (3.4 mg/kg/day) prevented cardiomyocyte apoptosis in the periinfarct myocardium, dampening ischemic cardiomyopathy, and cardiac stroke, as demonstrated by Jalal, et al. [133] in rat models. The role of HCQ in the inhibition of platelet aggregation was evaluated in healthy volunteers in comparison with aspirin or clopidogrel. The addition of 400 mg/day of HCQ to aspirin resulted in a significant increase in aggregation inhibition (31%). This inhibition was passed by reducing fibrinogen and inflammatory status by interfering with the arachidonic acid cascade [134].