The differences of the effects on lipid- lowering actions and glucose metabolisms between Rosuvastatin and Atorvastatin in Japanese diabetic patients with hyperlipidemia. - LI pid lowering with highly potent S tatins in hyperlipidemia with T ype 2 diabetes patiEN ts – Hisao Ogawa, Yoshihiko Saito, Hideaki Jinnouchi, Masahiro Sugawara, Seigo Sugiyama, Izuru. Masuda, Kunihiko Matsui, Hisao Mori, Masako Waki, Hirotaka Watada, Minoru Yoshiyama on behalf of the LISTEN Study investigators ESC Congress 2014 August 31, 2014 Barcelona – Spain
24
Embed
The differences of the effects on lipid-lowering actions and glucose metabolisms
The differences of the effects on lipid-lowering actions and glucose metabolisms between Rosuvastatin and Atorvastatin in Japanese diabetic patients with hyperlipidemia. - LI pid lowering with highly potent S tatins in hyperlipidemia with T ype 2 diabetes pati EN ts –. - PowerPoint PPT Presentation
This document is posted to help you gain knowledge. Please leave a comment to let me know what you think about it! Share it to your friends and learn new things together.
Transcript
The differences of the effects on lipid-lowering actionsand glucose metabolisms
between Rosuvastatin and Atorvastatin in Japanese diabetic patients with hyperlipidemia.
- LIpid lowering with highly potent Statins in hyperlipidemia with Type 2 diabetes patiENts –
Hisao Ogawa, Yoshihiko Saito, Hideaki Jinnouchi, Masahiro Sugawara, Seigo Sugiyama, Izuru. Masuda, Kunihiko Matsui, Hisao Mori, Masako Waki, Hirotaka Watada, Minoru Yoshiyama on behalf of the LISTEN Study investigators
ESC Congress 2014August 31, 2014
Barcelona – Spain
Conflict of interest disclosureLISTEN study was funded by the Non-Profit Organization, Hokkaido Kenkoukagaku Institute and the Investigator Sponsored Study Program of AstraZeneca K.K.
Hisao Ogawa, MD, PhD has received research supports or honoraria or both from Astellas Pharma Inc., AstraZeneca K.K., Bayer Yakuhin, Ltd., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb Company, Chugai Pharmaceutical Co., Ltd., Daiichi-Sankyo Company, Limited, Dainippon Sumitomo Pharma Co., Ltd., Kowa Company, Ltd., MSD K.K., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., and Takeda Pharmaceutical Company Limited.
Conflict of interest disclosureYoshihiko Saito, MD, PhD is an adviser at Ono Pharmaceutical Co., Ltd. YS has a clinical commission for an advisor from Ono Pharmaceutical Co., Ltd. YS has received research supports or honoraria or both from Astellas Pharma Inc., AstraZeneca K.K., Daiichi Sankyo Company, Limited, Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, MSD K.K., Novartis Pharma K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Shionogi & Co., Ltd., St. Jude Medical Japan Co., Ltd., and Takeda Pharmaceutical Company Limited. YS has endowed departments by MSD Co., Ltd.
Hiroyuki Watada, MD, PhD has received research supports or honoraria or both from Astellas Pharma Inc., AstraZeneca K.K., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Dainippon Sumitomo Pharma Co., Ltd., Eli Lilly Japan K.K., Johnson & Johnson K.K., Kissei Pharmaceutical Co., Ltd., Kowa Company, Ltd., Kyowa Hakko Kirin Co., Ltd., Mitsubishi Tanabe Pharma Corporation, Mochida Pharmaceutical Co., Ltd., MSD K.K., Novartis Pharma K.K., Novo Nordisk Pharma Ltd., Ono Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., Sanwa Kagaku Kenkyusho Co., Ltd., and Takeda Pharmaceutical Company Limited.
Minoru Yoshiyama, MD, PhD has received research supports or honoraria or both from Astellas Pharma Inc., Boehringer Ingelheim Japan, Inc., Bristol-Myers Squibb Company, Daiichi Sankyo Company, Limited, Dainippon Sumitomo Pharma Co., Ltd., Eisai Co., Ltd., GlaxoSmithKline K.K., Kissei Pharmaceutical Co., Ltd., Kyowa Hakko Kirin Co., Ltd., Mochida Pharmaceutical Co., Ltd., MSD K.K., Otsuka Pharmaceutical Co., Ltd., Pfizer Japan Inc., Sanofi K.K., and Teijn Pharma Limited.
BackgroundThe clinical benefit to prevent cardiovascular events by
using statins in hypercholesterolemic patients with diabetes has been demonstrated in several randomized trials.
Recent data showed that statins were associated with an increased dose-dependent risk of new-onset diabetes.
However, few prospective, randomized, controlled trials have been conducted to investigate the impact of statin on glucose levels in patients with diabetes.
Purpose
The LISTEN study was conducted to examine the effects of statins on both lipids and glucose control in Japanese patients with diabetes.
Endpoints
Primary endpoints
・ Percent Change in non-HDL-C level
・ Change in HbA1c level
Secondary endpoints
・ Changes in other lipids, and glucose metabolism parameters
・ Any intensification in diabetic treatment status
Study design
Atorvastatin 10 mg/day as starting dose (n=500)
0M 3M 12MInformed consent/eligibility
Target population1. Type 2 diabetes2. 6.5% ≤ HbA1c ≤ 7.4%3. Hyper-LDL- cholesterolemia (LDL-C ≥ 120 mg/dL without ASCVD [atherosclerotic cardiovascular disease], ≥ 100 mg/dL with ASCVD)4. ≥ 20 years of age
6M
Rosuvastatin 5 mg/day as starting dose (n=500)
Multicenter, open-label, randomized, parallel-group study
Primary endpoints : Percent Change in non-HDL-C level Change of HbA1c levelNumber of study sites : 132 sites in Japan
Randomized
Participants FlowEnrolled and randomized (n = 1049)
Allocated to Atorvastatin group (n = 524)
Allocated to Rosuvastatin group (n = 525)
Analyzed as Full analysis set (n = 504)
Analyzed as Full analysis set (n = 514)
Administered study treatment (n = 516)
Not administered study treatment (n = 9)Participant’s request (n = 7)Investigator’s decision (n = 1)Other reasons (n = 1)
Excluded from Full analysis set (n = 2)Not performed pre-dose examination (n = 2)Administered prohibit prior medication (n = 0)
Administered study treatment (n = 506)
Not administered study treatment (n = 18)Participant’s request (n = 12)Investigator’s decision (n = 4)Other reasons (n = 2)
Excluded from Full analysis set (n = 2)Not performed pre-dose examination (n = 1)Administered prohibit prior medication (n = 1)
Subtotal of therapy intensification 45 (8.8%) 64 (12.7%) 0.04
Change of therapies on diabetesRosuvastatin Atorvastatin
P value(n = 514) (n = 504)
Change in diabetes therapies 61 (11.9%) 83 (16.5%) 0.04
Drug Changes (other than the intensification)
4 (0.8%) 8 (1.6%)
Decreased dosage 5 (1.0%) 6 (1.2%)
Drug withdrawal 7 (1.4%) 5 (1.0%)
Change timing after the first dose in this study
therapy intensification
0 to 3 months 14 (2.7%) 20 (4.0%)
3 to 6 months 8 (1.6%) 12 (2.4%)
6 to 12 months 23 (4.5%) 32 (6.3%)
other than the above
0 to 3 months 5 (1.0%) 6 (1.2%)
3 to 6 months 5 (1.0%) 5 (1.0%)
6 to 12 months 6 (1.2%) 8 (1.6%)
Hazard ratio: 1.46 (95%CI, 1.00-2.14)P = 0.05
20
15
10
5
0
The cumulative incidence of diabetes treatment intensification
(months)
No. at RiskAtorvastatin Rosuvastatin
504514
471480
451466
182190
Limitations
This was an open-label study, and changing or intensifying the treatment for diabetes was left to the judgment of the investigator, possible bias cannot be excluded.
This was a rather small size study and compared laboratory data mainly as the outcome, in addition to short-term observation period.
We used low doses based on the Japanese regulation compared to those in U.S. and European countries.
ConclusionsRosuvastatin did not reduce non-HDL-C compared with Atorvastatin, but overall did reduce LDL-C significantly.
The intensification of diabetic treatments was significantly less frequent in the Rosuvastatin group than in the Atorvastatin group.
Further prospective studies are required to confirm the differences in the effects on diabetes among statins.
LISTEN Study investigatorsHisao Mori Takao Nagasu Kazuo Maeda Kumio Iroden Kazuaki Uchiyama Toshibumi Hogi Fumiaki Ono