Real world effectiveness of PCSK-9 inhibitors combined with statins versus statins among patients with very high risk of atherosclerotic cardiovascular disease in China (RWE-PCSK study)

Abstract

Background The efficacy and safety of PCSK-9 inhibitors were confirmed by several clinical trials, but its effectiveness in routine clinical practice in China is unknown. Objective To describe the real world effectiveness of initiated with PCSK-9 inhibitors combined with statins compared with statins among patients with very high risk of ASCVD and underwent percutaneous coronary intervention (PCI). Methods This is a prospective study, enrolled patients from 32 hospitals between January to June 2019. The lipid control rate and incidence of cardiovascular events over 6 months were compared between two groups. A propensity score-matched analysis was used to balance two groups on confounding factors. Survival analysis using Kaplan-Meier methods was applied for cardiovascular events. Results In a total of 3063 patients, 89.91% had received moderate or high-intensity statin therapy before PCI, but only 9.47% had LDL levels below 1.4mmol/L at baseline. In the PSM selected patients, LDL level was reduced by 42.57% in PCSK-9 inhibitor group and 30.81% (P<0.001) in statins group after 6 months. The proportion of LDL[?]1.0mmol/L increased from 5.29% to 29.26% in PCSK-9 inhibitor group and 0.23% to 6.11% in statins group, and the proportion of LDL[?]1.4mmol/L increased from 10.36% to 47.69% and 2.99% to 18.43% (P<0.001 for both). PCSK-9 inhibitor significantly reduced the incidence of cardiovascular events versus statins treatment (2.07% vs 8.29%, HR, 0.24, 95% CI, 0.12-0.51). Conclusion In the real world, PCSK-9 inhibitors combined with statins could significantly reduce LDL levels and risk of cardiovascular events among patients with very high risk of ASCVD.

Safety, adherence and efficacy of PCSK9 inhibitors: a retrospective real-world study

“…These findings are consistent with those observed in outcome trials, real-world studies and metaanalyses. 6,7,9,10,[16][17][18][19][20]23,24 ADRs reported by study patients were mostly nonspecific (e.g., gastrointestinal side effects, dizziness, etc.). The relationship to PCSK9 inhibitor use is temporal and causation cannot be inferred.…”

“…Similar to other countries, high medication costs were associated with poor adherence of PCSK9 inhibitors and had great impact on medication persistence. 14,15,18 While the price to patient for standard doses of both alirocumab and evolocumab are similar, more patients had poor adherence to alirocumab compared to evolocumab. This is likely due to the higher proportion of patients being initiated on off-label longer dosing intervals of evolocumab that resulted in cost savings, whereas 93.1% of patients initiated on alirocumab were prescribed the standard 2-weekly dosing regimen.…”

“…Of note, only 13.2% and 9.9% of subjects in the ODYSSEY OUTCOMES and FOURIER trials, respectively, were Asian, and realworld studies of PCSK9 inhibitor use have largely focused on Western cohorts. [8][9][10][11][12][13][14][15] While a few real-world studies have been conducted on Asian cohorts, [16][17][18][19][20][21] Singapore's unique multi-racial population and genetic differences may impact drug tolerability and efficacy; and social and culture factors, drug adherence and access. In this study, we aimed to study the safety and tolerability of PCSK9 inhibitors among Singaporean patients and determine factors, including method of drug payment, affecting their adherence in the real world.…”

Effect of the Early Application of Evolocumab on Blood Lipid Profile and Cardiovascular Prognosis in Patients with Extremely High-Risk Acute Coronary Syndrome

“…PCSK9 inhibitors, such as proprotein convertase subtilisin inhibitors, have become a new treatment strategy for lowering LDL-C levels. ODYSSEY and FOURIER tri-als showed that PCSK-9 inhibitors can further reduce LDL-C levels on the basis of statin therapy, reduce MACEs, and improve clinical prognosis, 9,10) especially in those with elevated LDL-C levels. 11) No matter what lipidlowering drugs are used in elderly patients, every 1-mmol/ L decrease in LDL-C level can reduce adverse cardiac events by 26%.…”

Antithrombotic therapy and bleeding risk in the era of aggressive lipid-lowering: current evidence, clinical implications, and future perspectives

“…A recent observational study in China compared the efficacy and safety of evolocumab on top of statin therapy for 434 ACS patients against 434 propensity score-matched cohorts treated with statins alone. [26] Current guidelines are an LDL-C target <55 mg/ dL for this population. During a 6-month follow-up period, evolocumab treatment was associated with a numerically higher incidence of major adverse cardiovascular events (5/434 vs. 2/434; hazard ratio [HR]: 2.52, 95% confidence interval [CI]: 0.49-12.97) despite 47.7% of the evolocumab group and 18.4% in statin-alone group achieving an LDL-C goal of 55 mg/dL.…”