More than four decades ago it was established that an elevated low-density lipoprotein-cholesterol level was a risk for developing coronary artery disease. For the last two decades, statins have been the cornerstone of reducing low-density lipoprotein-cholesterol, but despite significant clinical efficacy in the majority of patients, a large number of patients suffer from side effects and cannot tolerate the required statin dose to reach their recommended low-density lipoprotein-cholesterol goals. Preliminary clinical studies indicate that monoclonal antibodies to PCSK9 appear to be highly efficacious in lowering low-density lipoprotein-cholesterol with a favourable adverse event profile. However, further longer-term clinical studies are required to determine their safety. From the early-proposed concept for high-density lipoprotein-mediated cholesterol efflux for the treatment of coronary artery disease, the concentration of the cholesterol content in high-density lipoprotein particles has been considered a surrogate measurement for the efficacy of the reverse cholesterol transport process. However, unlike the beneficial effects of the statins and monoclonal antibodies to PCSK9 in reducing low-density lipoprotein-cholesterol, no significant advances have been made to increase the levels of high-density lipoprotein-cholesterol. Here it is shown that by a non-pharmacological plasma delipidation means, the atherogenic low-density lipoproteins can be converted to anti-atherogenic particles and that the high-density lipoproteins are converted to particles with extreme high affinity to cause rapid regression of atherosclerosis.