Introduction:Still too few patients (pts)after an acute cardiocerebrovascular(CeVD) event reach LDL-C values recommended by guidelines even in therapy with statins and Ezetimibe(Eze),thus maintaining a high risk of new cardiovascular(CV)episodesPurpose: To evaluate in a long follow-up the effectiveness and the rapidity of Alirocumab(Ali)in the attainment and maintenance of LD-C target values in pts at very high risk in therapy with only Eze because they are intolerant to statinsMethods: Our case studies consist of 72 pts of which 80% are male(58)and 20% female(14),with an average age of 61.9 y,90.2% of pts were hypertensive,34.7% diabetic and 15.2% with peripheral arteriopathy;5.5% had chronic kidney disease (CKD stage III) In the case history the 65.2% had an ACS and the 34.7% had CeVD.84.7% were in therapy only with Eze while 15.3% in association with PUFA N-3. The average value of LDL-C was 169.2 mg/dl. The follow up was 24 months (mths) with clinical checks and value of LDL-C at 3,6,12 and 24. The dosage of Ali varied from 150 to 75 mg in relation to the value of basal LDL-C to achieve a rapid reduction of at least 50%.Triglyceride (Tg) and HDL-C values were also evaluated Results: At 3 mths the reduction of LDL-C was 52.24%, recording in 34,7% of cases a greater reduction of 65%; at 6 mths of 51.18%; at 12 mths of 51.36% and at 24 mths of 52.47%. The 37 pts who had started with 150 mg, had a very high average LDL-C base 183.0 mg/dl, and showed a reduction of C-LDL to 3 mths of 59.04%, to 6 mths of 58.45%, to 12 mths of 65.05%, to 24 mths of 55.76%. The target value of C-LDL recommended by the ESC guidelines was reached for 42.10% at 3 mths; for 52.63% at 6 ; for 63.15% at 12 and for 73.68% at 24. 5.5% of pts with a CKD showed a 73.68% reduction in LDL-C values to 3 mths, 65.22% to 6, 57.49% to 12 and 53.95% to 24. The follow-up to the Tg study showed a reduction of 3.55% to 3 mths, an increase of 8.75% to 6, a reduction of 1.65% to 12 and 7.95% to 24. HDL-C values showed an increase of 4.55% at 3 mths, 3.69% at 6, 10.97% at 12 and 7.82% at 24 Conclusions: Our case studies have confirmed the effectiveness of Ali in reducing LDL-C values in pts at very high CV risk and the rapidity in reaching the target value set by guidelines for the management of CV risk. Our study also confirmed the effectiveness of Ali in increasing the values of HDL-C, in accordance with the guidelines ESC 2019 while it was not possible to confirm the reduction of Tg values.