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【論文摘要】Session 1: Treat-to-target Strategy", as Compared to "Fire-and Forget" Strategy, Is the Preferred Approach Regarding LDL-Lowering Therapy (Antagonist)
摘要
Since the introduction of ACC/AHA 2013 new cholesterol guideline, the debate between these two strategies, 〞Treat-to-target〞 versus 〞Fire-and-forget〞, remains unsettled. Before the feasibility of PCSK9 inhibitor in clinical practice, it was considered very hard to bring down LDL-C to goal in very high-risk ASCVD patients for secondary prevention. In ACC/AHA 2013 new cholesterol guideline, high-intensity statins that could cut down 50% LDL-C, e.g. atorvastatin 40-80mg, or rosuvastatin 20-40mg, were emphasized for high-risk clinical ASCVD patients. The updated ASCVD guideline 2019 pointed out those 〞very high〞 risk patients and emphasizes the use of non-statin agents, including ezetimibe and/ or PCSK9 inhibitors. Once the patients were categorized to be the 4 statin-benefit groups, moderate to high-intensity statin should be immediately given without question about the LDL-goal. The rationale behind that has been validated by the publication from our Center of Lipid Bioscience in Kaohsiung Medical University Hospital that these 4-statin benefit patients groups are characterized by higher toxic and atherogenic electronegative LDL subfraction, and before PCSK9i era, it was almost impossible to eradicate all of them merely by statin alone on the planet. The other rationale for supporting 〞Fire-and-forget〞 strategy is that no statin RCTs were designed to evaluate the major adverse cardiovascular events (MACE) based upon the preset LDL-goal. Actually, the Expert Panel did not find evidence to support titrating cholesterol-lowering drug therapy to achieve optimal LDL-C or non-HDL-C levels because the clinical trials were essentially fixed-dose trials. After the results of recent RCT trials, including Improve-it in 2014, Fourier & Odyssey Outcomes trials in 2017 & 2018, as well as 4 g pure EPA fish oils from Reduce-IT trial last November on AHA2018 in Chicago, now physicians, can use non-statin therapy on top of statin to achieve even lower LDL-C or non-HDL-C goal and obtain more MACE rate reduction. The combination of ezetimibe and high-intensity statin might achieve 70% LDL-C reduction, and PCSK9i currently is indicated for the following 3 specific groups: (1) clinical ASVCD with statin resistance (2) statin intolerance (3) familial hypercholesterolemia, heterozygous & homozygous. The adherence of lipid-lowering agent use is of paramount importance for patients' success in reducing further MACEs. rate For the physician, it should be kept in mind that avoiding so-called 〞physician inertia〞, and it is critically important to prescribe adequate intensity & dose of statin +/- non-statin agent at the initial visit. Based upon the rule of 〞6〞, it might be relatively difficult to achieved goal only by doubling the statin dose if the gap of actual LDL-C to the goal is too large. 〞Treat-to-target〞 strategy is merely to monitor the response of lipid-lowering therapy and inform medication adherence for patients, given the fact that the initial lipid-lowering Rx can be well- chosen based upon the initial lipid profile and risk stratification by the updated cholesterol guideline. 〞Fire-and-forget〞 emphasized the importance of adequately powerful lipid-lowering agents at a maximally tolerated dose (MTD) should be used in the first place, and don't bother to frequently check the LDL-C and adjust statin dose from time to time. For example, we use aspirin and P2Y12 for patients with acute coronary syndrome and PCI patients, but there is no need to check the platelet aggregation. For eligible patients with AF, we used NOAC based upon the clinical evidence and no need to check the prothrombin time or direct thrombin time. For PCSK9i use, the requirement of LDL-C remaining more than 135 mg/dL after MTD statin + ezetimibe use is partially due to national health reimbursement issue, but also reflect the phenomenon that most of those especially high-risk patients with high LDL-C are resistance to current oral lipid-lowering treatments as with regard to secondary prevention. It stands true for 〞Fire-and-forget〞 strategy, however, that once you fire PCSK9 inhibitor, just forget it because all you have to do is keep it indefinitely. In conclusion, 〞Fire-and-forget〞 strategy is much more feasible and realistic for patients and physicians then 〞Treat-to-target〞 one in real-world daily practice.