Coronary artery ectasia (CAE) is frequently considered an incidental finding during coronary angiography, however, several reports have shown an association with myocardial ischemia and infarction. When acute myocardial infarction (AMI) occurs in cases of CAE, current reperfusion therapies, due to the large arterial size and the massive intracoronary thrombus, when used alone are limited in preventing the development of distal embolization and 'no reflow phenomenon.' In this article, we described the case of a multiple sclerosis (MS) patient with diffuse CAE and ST elevation AMI, treated by coronary dethrombosis multistrategy (mechanical and pharmacologic) during a transradial primary angioplasty. The higher thrombotic burden in MS with CAE was analyzed and possible common pathophysiologic pathways were discovered in the imbalance between proteolytic activities of metalloproteinases and endogenous tissue inhibitor, with subsequent increased proteolysis leading to a risk for coronary plaque rupture. The one-year clinical and angiographic follow-up with coronary computed tomography (CT) angiography, together with long-term antiplatelet therapy, was also evaluated.