Heart Institute of Japan apan-PR PRoper level of lipid lOwering - - PowerPoint PPT Presentation

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Heart Institute of Japan apan-PR PRoper level of lipid lOwering - - PowerPoint PPT Presentation

Oct 25, 2022 42 likes •127 views

Heart Institute of Japan apan-PR PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute co coRonary syndrome LDL cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidemia:

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SLIDE 1

LDL cholesterol targeting with pitavastatin + ezetimibe for patients with acute coronary syndrome and dyslipidemia: the HIJ-PROPER, a randomized trial

Nobuhisa Hagiwara, Erisa Kawada-Watanabe, Ryo Koyanagi, Hiroyuki Arashi, Jun-ichi Yamaguchi, Koichi Nakao, Tetsuya Tobaru, Hiroyuki Tanaka, Kunihiko Matsui, Hiroshi Ogawa The HIJ-PROPER Investigators

Heart Institute of Japan apan-PR PRoper level of lipid lOwering with Pitavastatin and Ezetimibe in acute co coRonary syndrome

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SLIDE 2

Conflict of Interests

The HIJ-PROPER study group received research support to perform clinical trials through the

he Jap apan an Res esea earch h Prom

  • mot
  • tion
  • n Soc
  • ciet

ety for

  • r Car

ardi diov

  • vas

ascul ular ar Disea eases es.

Sponsored by Mochida Pharmaceutical Co., Ltd., Pfizer Japan Inc., AstraZeneca K.K., Daiichi Sankyo Company, Limited, Novartis Pharma K.K., Bristol-Myers K.K., Kowa Pharmaceutical Co.Ltd., MSD K.K., Nippon Boehringer Ingelheim Co., Ltd., Bayer Yakuhin, Ltd., Sanofi K.K., Takeda Pharmaceutical Company Limited, Boston Scientific Corporation, and Abbott Vascular Japan Co., Ltd.

  • N. Hagiwara: honoraria from Nippon Boehringer Ingelheim Co., Ltd., and Bristol-Myers

K.K., and grants from Daiichi Sankyo Company, Limited, Astellas Pharma Inc., Takeda Pharmaceutical Company Limited, Mitsubishi Tanabe Pharma Corporation, Shionogi & Co., Ltd., Eisai Co., Ltd., and Otsuka Pharmaceutical Co., Ltd.

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SLIDE 3

Hypothesis HI

HIJ-PR PROP OPER ER is

 a prospective,

spective, randomized, domized, open-label, label, blinded nded endpoint dpoint multi ticent center er tr trial

 to

to dete termine rmine whether ther st standard ndard st statin tin dose se + + ezetimibe, etimibe, ta targeting geting LDL-C C of f < 7 < 70 mg/dL dL would ld reduce duce cardiovascular diovascular events nts more th than st statin tin monothera

  • therapy,

py, ta targeting geting LDL-C C of f 90 to to 100 0 mg/dL dL

 in pati

tients ents with th acute te coronary

  • nary syndrome

rome (ACS) ) and d dys yslipi lipidemia emia

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SLIDE 4

ACS S with dysli lipide pidemia ia n = 1 1734

Min inimum imum 3 years ars follow low-up up (me mean: an: 3.9 years) ars)

Primar imary y Endpoint point: : All-cau cause se death th, , Non-fatal fatal myocardial

  • cardial infa

farc rction, tion, Non Non-fatal fatal stroke,

  • ke, Unstable

table angina, ina, Ischemia hemia-driven driven revas ascula cularization rization

Pitava tava n = 8 857 (loss loss of f fo follow low-up n = 8 8) Follow llow-up rate te 99.1 .1% Pitava tava/EZ /EZ n n = 8 864 64 (loss loss of f fo follow low-up n = 5 5) Follow llow-up rate te 99.4 .4%

1:1 Randomi

  • mizat

zation

  • n

Pitava tavasta statin tin + Ezetimibe timibe LDL DL-C < 7 70 mg/dL /dL n = 8 869 Pitava tavasta statin tin monot nothera rapy py 90 ≤ LDL-C < 100 0 mg/dL /dL n = 865 865

Study Design

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SLIDE 5

1yr mean Pitava, mg/dL Pitava/EZ, mg/dL Δ in mg/dL 87.2 67.5

  • 19.7*

LDL-C TC TG HDL-C 165.3 142.7

  • 22.6*

144.2 125.2

  • 19.0*

Pitava mean dose (mg/day) 2.02 2.36 50.3 50.9 +0.6 Pitava va Pitava va/EZ /EZ

† Mean time avg

Time e since ce rando domiza mization ion (mont

  • nths)

hs) Mean an LDL-C C (mg/ g/dL dL)

140 120 100 80 60 3 6 12 24 36

135.6 .6 84. 84.6† (Δ-37.6 .6%) %) 134.8 .8 65.1† (Δ-51.7 .7%) %)

LDL-C and Lipid Changes

*P<0.001

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SLIDE 6

857 618 566 507 280 134 864 622 584 536 302 140

Number at risk

Primary Endpoint (composite)

Event nt rate

720 1080 1440 1800 0.0 0.1 0.2 0.3 0.4

Time since randomi mizatio zation (days)

Pitava va: : 36.9% % (128. 28.12 12 / 1 1000 0 pt-yr) yr)

HR HR = 0.89, 9, 95% CI CI (0.76-1.04) 1.04) Log Log-ran rank k test P = 0.152

360

Pitava va/EZ: /EZ: 32.8% % (111.58 11.58 / 1000 0 pt-yr) yr) Pitava va Pitava va/EZ /EZ

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SLIDE 7

< 2.2 μg/mL (median)

360 720 1080 1440 1800 0.1 0.2 0.3 0.4

Time e since randomiza mizati tion

  • n (days)

Event ent rate

HR = 1.11 (0.88-1.3 1.39) 9) P = 0.388

0.0

38.2% % (157 / 411) 35.7% % (142 / 398) Pitava ava Pitava ava/EZ /EZ

≥ 2.2 μg/mL (median)

360 720 1080 1440 1800

Time e since randomiza mizati tion

  • n (days)

Event ent rate

HR = 0.71 (0.56-0.9 0.91) 1) P = 0.006

0.1 0.2 0.3 0.4 0.0

37.5% % (156 / 416) 27.8% % (111 / 399) Pitava ava Pitava ava/EZ /EZ

Subgroup Analysis: Sitosterol Primary Endpoint (composite)

Sitoster sterol (choleste holesterol

  • l absorpt
  • rption
  • n mark

rker) er) P-va value lue for intera raction ction = 0 0.010 10

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SLIDE 8

Conclusions

 Int

ntensi ensive ve LD LDL-C C low

  • wer

ering ng wi with h stat atin n (standard andard do dose) e) + ez ezetimibe imibe did not signifi ficantly cantly reduce ce CV CV ev events ts mo more e than statin n alone in pa patients nts wi with ACS CS an and dysl slip ipidemia idemia.

 Statin

in + ez ezetimibe mibe did reduce ce CV CV ev events ts mo more than stati tin n alone in pa patients ts wi with hi higher r baseli line ne levels s of sitosterol

  • sterol,

, a c a cho holes esterol terol ab absorpt

  • rption

ion ma marker. er.

 Th

This intesti tinal nal cholesterol esterol absorptio rption n ma marker er ma may

  • ffer

er a p potentia tial l therapeuti peutic c target et for the treatment ment of dysl slip ipidemia idemia in patients ts wi with ACS CS.