著者
Atsushi Hirayama Shizuya Yamashita Andrea Ruzza Hyoe Inomata Marcoli Cyrille Chen Lu Andrew W. Hamer Masayuki Yoshida Arihiro Kiyosue Tamio Teramoto
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.83, no.5, pp.971-977, 2019-04-25 (Released:2019-04-25)
参考文献数
11
被引用文献数
1

Background: Treatment with evolocumab reduces mean low-density lipoprotein cholesterol (LDL-C) up to 75% and cardiovascular events by 16% in the first year and 25% thereafter. Methods and Results: Japanese patients with hypercholesterolemia enrolled in the parent YUKAWA-1-2 studies could enroll, once eligible, in the OSLER studies (n=556). OSLER re-randomized patients 2:1 to evolocumab plus standard of care (SOC; evolocumab+SOC) or SOC alone for 1 year; after year 1, patients could enter the all-evolocumab+SOC open-label extension of OSLER. Patients received evolocumab+SOC from the 2nd year through up to 5 years. Long-term efficacy and safety, including antidrug antibodies, were evaluated. Of 556 patients, 532 continued to the all-evolocumab+SOC extension: mean (standard deviation [SD]) age 61 (10) years, 39% female. A total of 91% of 532 patients completed the studies. Mean (SD) LDL-C change from parent-study baseline with evolocumab from a mean (SD) baseline of 142.3 (21.3) and 105.0 (31.1) mg/dL in OSLER-1 and OSLER-2, respectively, was maintained through the end of the study: −58.0% (19.1%) at year 5 in OSLER-1, −62.7% (25.6%) at year 3 in OSLER-2. The overall safety profile of the evolocumab+SOC periods was similar to that of the year-1 controlled period. Antidrug antibodies were detected transiently in 3 patients. No neutralizing antibodies were detected. Conclusions: Japanese patients who continued evolocumab+SOC for up to 5 years experienced sustained high LDL-C level reduction. Long-term evolocumab+SOC exposure showed no new safety signals.
著者
Saurabh P. Nagar Pratik P. Rane Kathleen M. Fox Juliana Meyers Keith Davis Anne Beaubrun Hyoe Inomata Yi Qian Kouji Kajinami
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
pp.CJ-17-0811, (Released:2017-12-23)
参考文献数
29
被引用文献数
1 22

Background:This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months’ pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months’ post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort.Conclusions:High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.
著者
Koutaro Yokote Junya Ako Kazuo Kitagawa Hyoe Inomata Toshihiko Sugioka Keiko Asao Yasuhiko Shinmura Junichiro Shimauchi Tamio Teramoto
出版者
The Japanese Circulation Society
雑誌
Circulation Reports (ISSN:24340790)
巻号頁・発行日
vol.1, no.5, pp.219-227, 2019-05-10 (Released:2019-05-10)
参考文献数
15
被引用文献数
4

Background:Evolocumab is the first monoclonal antibody against proprotein convertase subtilisin/kexin type 9 (PCSK9) approved in Japan for the treatment of patients with familial hypercholesterolemia (FH) and hypercholesterolemia (HC). This study assessed the 12-week effectiveness and safety of low-density lipoprotein cholesterol (LDL-C)-lowering therapy by PCSK9 inhibition in patients with FH (homozygous [HoFH] or heterozygous [HeFH]) and HC by analyzing evolocumab data collected in the real-world setting in Japan.Methods and Results:Overall, 427 patients (mean±SD age, 61.6±13.8 years; female, 38.4%; 28 HoFH, 320 HeFH, 79 HC), enrolled from 299 clinical sites, were included in the safety analysis set. The major cardiovascular risk factors were coronary artery disease (77.3%), diabetes mellitus/impaired glucose tolerance (38.6%), and hypertension (65.1%). Median follow-up duration was 85.0 days. After 12 weeks of evolocumab treatment, the mean±SD percent change from baseline in LDL-C was −45.5%±27.0% (n=23) in HoFH (P<0.001 vs. baseline; t-test), −54.2%±29.0% (n=280) in HeFH (P<0.001), and −64.6%±22.4% (n=72) in HC (P<0.001) patients. The incidence of adverse drug reactions was 5.4% (23/427).Conclusions:Results suggest that patients receiving evolocumab treatment in the real-world setting were predominantly those with FH and HC in the secondary prevention group. LDL-C-lowering effectiveness with evolocumab was observed in FH (both HoFH and HeFH) and HC patients.
著者
Saurabh P. Nagar Pratik P. Rane Kathleen M. Fox Juliana Meyers Keith Davis Anne Beaubrun Hyoe Inomata Yi Qian Kouji Kajinami
出版者
The Japanese Circulation Society
雑誌
Circulation Journal (ISSN:13469843)
巻号頁・発行日
vol.82, no.4, pp.1008-1016, 2018-03-23 (Released:2018-03-23)
参考文献数
29
被引用文献数
22

Background:This study examined treatment patterns, possible statin intolerance, and incidence of cardiovascular events (CVEs) in 2 cohorts of patients with high cardiovascular risk (i.e., patients with atherosclerotic cardiovascular disease [ASCVD] and patients with diabetes mellitus).Methods and Results:A retrospective cohort study examined adults initiating either a statin or ezetimibe from 1 January 2006 to 31 May 2014 in the Japan Medical Data Center database. The first observed statin or ezetimibe prescription defined the index date. Patients had ≥12 months of pre- and post-index date plan enrollment. Two high-risk cohorts, the ASCVD cohort and diabetes cohort, were created based on diagnoses observed during the 12 months’ pre-index date. Treatment patterns, possible statin intolerance, and incidence of CVEs were reported. In the ASCVD cohort (n=5,302), 32.9% discontinued therapy, 7.7% switched to a non-index statin or non-statin lipid-lowering therapy, and 11.2% augmented index therapy in the 12 months’ post-index date; only 0.3% were using high-intensity statins and 10% had possible statin intolerance. Also, 8.1% had any new CVE during the follow-up period. Treatment patterns and incidence of CVEs among the diabetes cohort were similar to those of the ASCVD cohort.Conclusions:High cardiovascular risk Japanese patients had frequent treatment modifications, although use of high-intensity statin doses was rare. These patterns may indicate that alternative therapies for lipid lowering are needed.