Introduction
Atherosclerotic cardiovascular disease (ASCVD) has been demonstrated to
be the leading cause of death and disease burden in China and worldwide,
and lipid lowering drugs are proven to be the cornerstone of treatment
and beneficial to the cardiovascular disease outcomes [1-3].
Numerous studies over the past decades have demonstrated a causal
relationship between LDL-c and progression/ manifestation of CVD.
Elevation of LDL-c is an important risk factor associated with
development of CVD events in acute coronary syndrome (ACS) patients. To
date, all guidelines recommended LDL-c control as the main intervention
target for lipid management [5, 6]. However, adherence and using to
lipid-lowering medications reach desirable LDL cholesterol levels
remains a serious concern in China. The China Chronic Disease and Risk
factor Monitoring Database (CCDRFS) study showed that the LDL compliance
rate was still unsatisfactory [4]. Among individuals with high risk
of ASCVD patients, 74.5% had uncontrolled LDL-C levels
(<2.6mmol/L). For very-high-risk individuals, 93.2% didn’t
achieve their LDL-lowering goals (<1.8mmol/L) and only 14.5%
of them were treated. The AHA/ACC Guidelines and China’s expert
consensus in 2018 recommended that LDL should be controlled below
1.4mmol/L or even lower for patients with very high-risk ASCVD (more
than two severe ASCVD events or one severe ASCVD event combined with
more than two high-risk risk factors).
Although guidelines recommended the early initiation or continuation of
high intensive statin therapy in all ACS patients [5], Chinese
patients have limited benefit from high intensive statin treatment due
to poor tolerance. The DYSIS-China study showed that high-intensity
statins only resulted in an additional 6% reduction in LDL-C [7].
Ezetimibe is recommended as second-line therapy for patients who are
either intolerant to statins or do not achieve their LDL-c goals despite
receiving maximally tolerated statin therapy. Proprotein convertase
subtilisin/kexin type 9 (PCSK9) inhibitors, as a new class of
cholesterol lowering drugs, have been approved for treating
hyperlipidemia in China 2019. The Phase II clinical trial showed that
PCSK-9 inhibitor monotherapy could further reduce LDL-c by 37.3% to
52.5% [8], and reduce by 45-60% combined with statin. ODYSSEY
Outcomes and FOURIER studies have also shown that PCSK-9 inhibitors can
further reduce LDL levels, major cardiovascular events (MACE), and
improve clinical outcomes [9, 10]. Although these large RCTS have
confirmed the clinical efficacy and safety of PCSK-9 inhibitors combined
with statin, using PCSK-9 inhibitors in routine clinical practice of
Chinese setting in very-high risk ASCVD patients is still unknown. In
this study, we aim to compare the real-world effectiveness of PCSK-9
inhibitors combined with statins therapy or statins therapies among
patients with very high risk and underwent percutaneous coronary
intervention (PCI).