Discussion
The management of LDL-C plays a significant role in the prevention of ASCVD. However, our study showed that less than 10% of patients reached the recommended LDL-C≤1.4mmol/L goal when patients with very high risk and underwent PCI at baseline in China, due to irregular lipid lowering treatment and poor tolerance to high-intensity therapies [13]. After being discharged from hospitals over 6 months, patients received PCSK-9 inhibitor therapy had a significant LDL-c reduction by about 50% patients reached ≤1.4mmol/L goal and reduced 76% risk of cardiovascular events, compared to those with statin w/ow other lipid-lowering therapies. Reduction in cardiovascular events was observed in the overall population, especially in men.
The guidelines of dyslipidemia managements in China recommended that patients with acute coronary syndrome should initial with medium-intensity statins, and adjust the appropriated dosage according to the efficacy and tolerance of individuals. If the cholesterol level fails to meet the goal, other lipid-regulating drugs, including Ezetimibe and PCSK9 inhibitors, should be considered [14-16]. Ezetimibe is an intestinal cholesterol absorption inhibitor by acting on NPC1L1 which is recommended as second line therapy. It can offer additional LDL-C reduction, but the percentage of patients achieving the target level of LDL-C is relatively low [17, 18].
PCSK9 is a negative regulator of the hepatic LDL receptor [19-21]. Our study demonstrated a highly efficient lowering of LDL-c with PCSK-9 inhibitors treatment among the patients with very high risk of ASCVD underwent PCI, which were consistent with previous study. A meta-analysis published in 2010 by Cholesterol Treatment Trialists’ (CTT) Collaboration from 26 clinical trials showed a 22% decrease in MACE for 1 mmol/L (38.7 mg/dl) reduction in LDL-c in patients receiving statins [22]. IMPROVE-IT showed that combination of ezetimibe with simvastatin therapy in high-risk ASCVD patients can reduce LDL level to 1.4 mmol/L (53.2 mg/ dL), compared with reduction to 1.8 mmol/L (69.9 mg/ dL) in patients with simvastatin monotherapy. When added to statin therapy, ezetimibe results in improved cardiovascular outcome, which was 32.7% compared to 34.7% (P=0.016) [14]. The other clinical trial study showed that evolocumab on the background of statin therapy lowered LDL-c levels to a 0.78 mmol/L after 48 weeks treatment and significantly reduced the risk of composite of cardiovascular outcomes [10].
PCSK-9 inhibitor is an innovative therapeutic approach to improve control of elevated LDL-C levels, and recommended as an appropriate clinical use in patients at high risk of cardiovascular risk but still with substantially elevated LDL-C levels by Consensus of ESC and EAS Task. However, time on treatment of PCSK-9 inhibitor in our study was only 1 month, and then all the patients switched to statin therapy. The main reason of short-term time on treatment was poor affordability of evolocumab in China. With acceptable PCSK-9 inhibitor price or be reimbursed, it could benefit more patients especially those with very high risk of ASCVD in Chinese real-world clinical practice. .
This study is a real-world multi-center study based on the national-level patients’ cohort covered more than 30 top hospitals in China. Therefore, our results could be generalized to the whole Chinese patients with high risk of ASCVD underwent PCI. The study results derived from analysis by a propensity score matching, applied to minimize confounding and indication bias. However, it is capable to correct only known confounders and some predictive factors were unbalanced after matching, which could be considered as limitations of retrospective study design. We demonstrated a superior real world effectiveness of PCSK-9 inhibitor despite with short-term usage and 6 months follow-up. Whether the short-term effectiveness could accurately reflect long-term outcomes for patients received PCSK-9 is unknown and need further study with long-term follow-up.
In conclusion, initiated treatment with PCSK-9 inhibitors combined with statins after PCI could significantly reduce LDL levels and risk of cardiovascular events among patients with very high risk of ASCVD.