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.