Comparison of triple therapy (moderate intensity ROSuvastatin plus Ezetimibe plus bempeDoic acid) verus moderate to high intensity statin (ROSuvastatin) in patients with acute coronary syndrome. A first in world randomized ,single centre trial

Atherosclerotic Cardiovascular diseases (ASCVD) remains the major cause for mortality and morbidity globally1.World Health Organization reduce the burden of the same by 25% by 20251. An estimated 62.5 and 12.7 million years of life were lost prematurely in India and the United States, respectively that have been attributed to CVD.2  CVD contribute to 21-29% of total death in low middle countries.3  Currently, the best possible way to decrease atherosclerotic CVD (ASCVD) is to reduce LDL level, and controlling other traditional risk factors associated with ASCVD.4   The four pivotal ways to decrease LDL are

1.      Inhibiting HMG CoA reductase enzyme using statin therapy

2.      Inhibiting Citrate lyase using bEMPEDOIC ACID

3.      Inhibiting the Niemann-pick receptor using Ezetimibe

4.      Reducing the action of

PCSK 9 using antibodies ( alirocumab or everocumab ) or sn-RNA (inclisiran)

 In the EPIC-STEMI study, it was shown that early initiation of PCSK9 inhibitors in addition to statin reduced LDL by 22% compared with sham injection5. Recently published PACMAN-AMI study found that patients who received alirocumab early after PCI (<24 hour)  for  AMI showed signficant reduction in plaque volume measured by IVUS, lipid-core index measured by NIRS, and improvement in fibrous cap thickness measured by OCT as compared with placebo.6   It was observed that nearly 80% of patients did not achieve  guideline-targeted lipid LDL levels within 90 days.7s Lipid testing during index hospitalization was associated in was with higher rates of initiation or escalation of statin therapy. within 90 days of their ACS. They also found that more than  33% would have been eligible for PCSK9 based therapy for achieving their goal.  Hence, the best time to treat them is during their index hospitalization. This will increase adherence, and also ensure proper reduction in LDL.7   Initiation of PCSK9 therapy for all patients with ACS will lead to higher LDL reduction which may translate to better clinical outcomes. In LMIC like India, the cost of PCSK9 therapy makes it beyond the reach of common man. Hence, we propose to study the safety and efficacy of  triple therapy to achieve early LDL reduction using moderate intensity statin plus ezetimibe plus bempedoic acid as compared to high intensity statin whose baseline LDL is more than 100.