Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects　― A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial ―

Keech, Anthony; Oyama, Kazuma; Sever, Peter; Tang, Minao; Murphy, Sabina A.; Hirayama, Atsushi; Chen, Lü; Tay, Leslie; Deedwania, Prakash; Siu, Chung‐Wah; Pineda, Armando Lira; Choi, Donghoon; Charng, Min‐Ji; Amerena, John; Ahmad, Wan Azman Wan; Chopra, Vijay; Pedersen, Terje R.; Giugliano, Robert P.; Sabatine, Marc S.

doi:10.1253/circj.cj-20-1051

Cited by 20 publications

(11 citation statements)

References 20 publications

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“…In this study, with 84.5% of participants at very-high cardiovascular risk, tafolecimab demonstrated a favorable risk-benefit profile, with safety profile similar to those identified in previous studies and those of alirocumab and evolocumab [ 8 , 9 , 11 , 15 , 26 ]. Serious adverse events were possibly related to underlying medical conditions of the participants, further reflecting late diagnosis of HeFH in China and high risk for cardiovascular diseases.…”

Section: Discussionsupporting

confidence: 80%

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Chai

He²,

Zhao³

et al. 2023

BMC Med

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Background Heterozygous familial hypercholesterolemia (HeFH) is largely underdiagnosed and undertreated in China where few patients achieved recommended target levels of low density lipoprotein cholesterol (LDL-C). We conducted the first randomized, placebo-controlled clinical trial in Chinese patients with HeFH to assess the efficacy and safety of tafolecimab, a novel fully human proprotein convertase subtilisin/kexin type 9 (PCSK9) monoclonal antibody. Methods Patients diagnosed with HeFH by Simon Broome criteria and on a stable lipid-lowering therapy for at least 4 weeks were randomized 2:2:1:1 to receive subcutaneous tafolecimab 150 mg every 2 weeks (Q2W), tafolecimab 450 mg every 4 weeks (Q4W), placebo Q2W or placebo Q4W in the 12-week double-blind treatment period. After that, participants received open-label tafolecimab 150 mg Q2W or 450 mg Q4W for 12 weeks. The primary endpoint was the percent change from baseline to week 12 in LDL-C levels. Secondary endpoints included proportion of participants achieving ≥50% LDL-C reductions and proportion of participants with LDL-C <1.8 mmol/L at week 12 and 24, the change from baseline to week 12 in non-high density lipoprotein cholesterol (non-HDL-C), apolipoprotein B and lipoprotein(a) levels, as well as the change from baseline to week 24 in lipid levels. Results In total, 149 participants were randomized and 148 received at least one dose of the study treatment. At week 12, tafolecimab treatment induced significant reductions in LDL-C levels (treatment difference versus placebo [on-treatment estimand]: −57.4% [97.5% CI, −69.2 to −45.5] for 150 mg Q2W; −61.9% [−73.4 to −50.4] for 450 mg Q4W; both P <0.0001). At both dose regimens, significantly more participants treated with tafolecimab achieved ≥50% LDL-C reductions or LDL-C <1.8 mmol/L at week 12 as compared with corresponding placebo groups (all P <0.0001). Meanwhile, non-HDL-C, apolipoprotein B and lipoprotein(a) levels were significantly reduced in the tafolecimab groups at week 12. The lipid-lowering effects of tafolecimab were maintained till week 24. During the double-blind treatment period, the most commonly-reported adverse events in the tafolecimab groups included upper respiratory tract infection, increased blood creatine phosphokinase, increased alanine aminotransferase, increased aspartate aminotransferase and hypertension. Conclusions Tafolecimab administered either 150 mg Q2W or 450 mg Q4W yielded significant and persistent reductions in LDL-C levels and showed a favorable safety profile in Chinese patients with HeFH. Trial registration ClinicalTrials.gov, NCT04179669.

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Section: Discussionsupporting

confidence: 80%

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Chai

He²,

Zhao³

et al. 2023

BMC Med

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“… 15 Recently, a sub-analysis of the Fourier trial in patients with ACS reported the safety and efficacy of evolocumab in Asians ( n = 2723) compared with individuals of other racial origins ( n = 24 841). 19 With regard to the patients’ background, myocardial infarction was significantly less prevalent in Asians than in individuals of other races, whereas diabetes mellitus and stroke were more common in Asians. Compared with individuals of other races, BMI and LDL-C levels were significantly lower among Asians, and the use of potent statins was less common in Asians (33.3% Asians vs. 73.3% other races; P < 0.001).…”

Section: Introductionmentioning

confidence: 99%

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events

Tamargo

Kaski

Kimura

et al. 2022

European Heart Journal - Cardiovascular Pharmacotherapy

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Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

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“…Cases of cataracts were reported in the FOURIER and ODYSSEY OUTCOMES trials of evolocumab and alirocumab, respectively. However, more cases of cataracts were reported in the placebo group than in the study group in both trials 31–35 . The meta‐analysis of the cataracts association with statins and PCSK9 inhibitors indicated no significant effect of cholesterol‐lowering with statins or PCSK9 antibodies association with cataracts 13 .…”

Section: Discussionmentioning

confidence: 97%

“…However, more cases of cataracts were reported in the placebo group than in the study group in both trials. [31][32][33][34][35] The meta-analysis of the cataracts association with statins and PCSK9 inhibitors indicated no significant effect of cholesterol-lowering with statins or PCSK9 antibodies association with cataracts. 13 Similarly, our study found no disproportionate signal for cataracts.…”

Section: Discussionmentioning

confidence: 99%

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis

Zhao

Zhu

2022

Brit J Clinical Pharma

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Aims To identify and characterize ocular adverse events (oAEs) that are significantly associated with proprotein convertase subtilisin‐like/kexin type 9 (PCSK9) inhibitors using the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods We conducted a disproportionality analysis of PCSK9 inhibitors in the FAERS (01/2004–12/2021). The association between PCSK9 inhibitors and oAEs was evaluated using the information component (IC) and the reporting odds ratio (ROR), and the difference in oAEs between evolocumab and alirocumab was compared using the ROR. Different sensitivity analyses were conducted to evaluate the robustness of results. Results A total of 103 531 reports involving at least 1 PCSK9 inhibitor were found in the FAERS. PCSK9 inhibitors were associated with higher reporting of increased lacrimation (IC 0.27 [95% confidence interval {CI} 0.02–0.45]; ROR 1.21 [95% CI 1.04–1.40]), seasonal allergy (IC 0.39 [95% CI 0.04–0.64]; ROR 1.32 [95% CI 1.07–1.62]) and eye operation (IC 0.66 [95% CI 0.04–1.10]; ROR 1.60 [95% CI 1.11–2.30]) compared with the full database, and there was no difference between evolocumab and alirocumab. Sensitivity analyses showed that the disproportionate signals of increased lacrimation disappeared after excluding cases with other lipid‐lowering agents in the combined drugs. Except for eye operations, most of these adverse events occurred within 30 days of the first dose, and all 3 oAEs were mostly reported in women and individuals >65 years. Conclusion This pharmacovigilance study identified a possible signal of ocular disorders associated with PCSK9 inhibitors and encourages paying attention to at‐risk populations in PCSK9 inhibitors medication.

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Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects　― A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial ―

Cited by 20 publications

References 20 publications

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis

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Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects ― A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial ―

Cited by 20 publications

References 20 publications

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Efficacy and safety of tafolecimab in Chinese patients with heterozygous familial hypercholesterolemia: a randomized, double-blind, placebo-controlled phase 3 trial (CREDIT-2)

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events

Ocular disorders associated with PCSK9 inhibitors: A pharmacovigilance disproportionality analysis

Contact Info

Product

Resources

About

Efficacy and Safety of Long-Term Evolocumab Use Among Asian Subjects　― A Subgroup Analysis of the Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk (FOURIER) Trial ―