曹承榮: 2022心腎五大試驗結果發表，AHA2023期待再相見（專業版）

美國心腎週

美國心腎很快過去了，兩個大會明年都將在賓州費城舉行（AHA23 11/11-13 ，ASN23 11/02-05），跟各位分享五大重點研究結果：

1. EMPA-KIDNEY: empagliflozin vs pbo in CKD
2. TRANSFORM-HF: torsemide vs furosemide in hosp. HF
3. RESPECT EPA: EPA 1.8g/d + statin vs statin alone in stable CAD
4. ISCHEMIA-EXTENDed: interim mortality analysis of ISCHEMIA & ISCHEMIA-CKD at longer f/u
5. BEST-CLI: EVT vs bypass in patients with critical limb ischemia.

EMPA-KIDNEY

EMPA-KIDNEY (N=6609)
Event-driven (n=1070) RCT of empagliflozin vs placebo in CKD.
Study stopped early in 3/2022 after 1st interim analysis met prespecified stopping criteria based on PEP and CV death or ESKD.

看倌重點：

EMPA-kidney PEP達標，但是CV outcome 沒有。體重減少，血壓減少，血比容增加（2.2，滿多的）倒是符合期待。

兩大問題點：

Null effect on CV death or HHF (in contrast to CREDENCE and DAPA-CKD.

Null effect on CV death and all-cause mortality. This raises the question whether the trial should have been stopped early (it met the prespecified criteria of PEP and ESRD or CV death).

TRANSFORM-HF:

Pragmatic trial of Torsemide vs furosemide in hosp. HF.
Event-driven trial (n=721), 85% power to detect 20% RRR in all-cause mortality (PEP)

RESPECT-EPA

RESPECT-EPA Trial
Open-label active control randomized trial evaluating purified EPA (1.8g/d) + statin vs statin alone in 3900 Japanese patients with stable CAD. PEP: CV death, MI, stroke, hosp. for UA/CR, or CR.

Key question
1. 解答是否EPA才有心臟保護
Will it serve as a tiebreaker given positive results in REDUCE-IT (EPA 4g/d) but not STRENGTH (EPA+DHA 4g/d), OMEMI (EPA+DHI 1.8g/d)? 是的
2.對照組不是用礦物油，對照組：CRP 沒有增加。
No mineral oil placebo used. If results are positive, will it resolve controversy surrounding mineral oil placebo in REDUCE-IT?
3. 觀察組（體內EPA濃度已高者）的預後有差嗎？還沒公佈全文
4. 東方人/日本人 1.8g EPA 就很夠用了？是的，1.8g/day EPA 在日本人的效果跟每天服用4g EPA (REDUCE IT) 的血中EPA 濃度竟然是一樣的（141vs. 144)

好好的用藥治療、四年後開始看到好處，增加胃腸道不適，增加房顫，沒有增加出血，事後分析好處更明顯。

ISCHEMIA-EXTENDed

Prospective observational study with primary outcome of all-cause death, CV death & non-CV death at 10y. Mortality NOT be centrally adjudicated.
Interim analysis results will be presented as a latebreaker.
In ISCHEMIA, HR were 0.87 (0.66-1.15) for CV death (late divergence in favor of INV strategy), 1.05 (0.83-1.32) for ACM, & 1.45 (1.0-2.1) for non-CV death.

原本3.2y f/u，HR: 0.87 (0.66-1.15) CV death, 1.05 (0.83-1.32) ACM, & 1.63 (1.06-2.52) non-CV death.

Extended f/u at 5.7y: Increase in ACM: from 289 to 557, delta 268

HRs：
ACM: 1.00, 0.85-1.18
CV death: 0.78, 0.63-0.96
Non-CV death: 1.44, 1.08-1.91
How to interpret discordant effects on CV vs non-CV death?