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Background Lowering lipid levels after an acute coronary syndrome is critical for preventing recurrent adverse cardiovascular events. Multiple medications are now available, but there is limited evidence comparing how frequently they lead to achievement of guideline-recommended lipid targets.Methods and Results This observational study evaluated the impact of novel lipid lowering therapies (evolocumab, alirocumab, inclisiran, bempedoic acid and icosapent ethyl) in patients at a high risk of and/or with a history of acute coronary syndrome treated with maximum-tolerated doses of high-intensity statin therapy with or without ezetimibe. Our primary assessment was the achievement of LDL-C below 1.4 mmol/L and 2.0 mmol/L as per the ESC and NICE guidelines respectively.The study comprised of 299 patients. Patients treated with alirocumab and evolocumab started from a higher baseline LDL-C than inclisiran, due to the eligibility criteria for the medications. Despite this, inclisiran, evolocumab and alirocumab were all associated with similar proportions of patients achieving LDL targets: 42%, 41% and 38% of patients achieved a guideline-recommended LDL-C target of <1.4 mmol/L and 53%, 56% and 56% achieved LDL-C <2.0 mmol/L respectively. Reduction in LDL-C was greatest with alirocumab and evolocumab, achieving a reduction of 61% (95% confidence interval [CI], 49 to 91, P<0.001) and 60% (95% CI, 48 to 93, P<0.001) respectively. This was followed by inclisiran with a reduction of 51% (95% CI, 39 to 81, P<0.001) and bempedoic acid with a reduction of 36% (95% CI, 22 to 69, P<0.001). None of these were associated with a significant reduction in triglycerides or C-reactive protein. Icosapent ethyl was associated with 17% reduction in triglyceride levels (P=0.023) with no significant reduction in LDL-C.Conclusion Novel lipid-lowering medications were effective in achieving guideline-recommended targets for LDL-C, despite high levels of baseline LDL-C. Alirocumab and evolocumab were associated with the greatest reductions in LDL-C, followed by inclisiran and bempedoic acid.