Journal Reading

Pendahuluan
 LVH a/ prediktor mortalitas dan prevalensi tinggi pada
pasien dg penyakit jantung iskemik
 LVH a/ salah satu faktor prognosis pada PJK
 Observasi Tek.Darah efektif pada evaluasi LVH
 Selain TD, insulin resistance (IR) dan obesitas sentral juga
berpengaruh pada LVH
 Metformin  mekanisme kerjanya pada AMPK-dependent &
independent yg berimplikasi pd hipertrofi jantung
 Metode
 Study Design : MET-REMODEL (single centre, doubleblind,
placebo-controlled trial)
 Evaluasi terapi Metformin 1000 mg 2x1 selama 12 bulan
pada LVH non-diabet dg PJK, LVH dan IR dan/atau pre-
diabet.
 Study participants : 68 patients between April 2015-
September 2016 from Tayside, Scotland.
 Rekruitmen Partisipan
Kriteria Inklusi Kriteria Eksklusi
 Usia 18-85 thn dg PJK  DM tipe 1 atau 2
tanpa diabet  Gagal Jantung atau fraksi
 Riwayat resistensi insulin ejeksi ventrikel kiri <45%
(FIRI > 2.7) (FIRI = GDP dg echocardiography
x Insulin Puasa/ 25)  Kontraindikasi utk MRI
dan/atau pre-diabet  Rwyt keganasan
(HbA1c > 39 mmol/mol
& < 48 mmol/mol)  Penyakit ginjal; eDFR <45
 Normotensi TD < 140/85  Wanita hamil&menyusui
mmHg  Peserta uji klinis lain
 METODE
 Follow Up dg MRI, FMD, Investigasi Laboratorium (GDP,
HbA1c, Insulin puasa, Biomarker ; IL-6, ST2, NTproBNP,
TBARs), Vital Signs (TD, Nadi, Weight), Efek samping.
 Endpoints
- Hasil primer : Cardiac MRI utk menilai regresi LVMI
- Hasil sekunder : Perubahan LV fraksi ejeksi, mass & volume,
Obesitas sentral dinilai dg MRI, parameter glikemi, fungsi
endotel, biomarker darah
 Analisis Statistik
 Perbandingan antar grup intervensi dan plasebo
menggunakan independent samples t-tests
 Tambahannya: analisis sensitif dg ANCOVA (analysis of
covariance) utk evaluasi efek terapi thd perubahan pada
LVMI, LVM, usia, jenis kelamin, bb, TD, inhibitor enzim
angiotensin-converting, angiotensin II receptor blockers, &
beta-blocker as covariates
 P-value <0.05 : Signifikan
 RESULTS
Recruitment and follow-up
 Screening 187 pasien, 68
masuk kriteria inklusi (34 per
grup)
 5 pasien tereksklusi, 7 pasien
tdk melanjutkan terapi
 63 pasien mengikuti
penelitian, inklusi analisis
hanya 56 pasien (27 grup
metformin & 29 grup
plasebo)
Patient characteristics
 Grup Metformin memiliki
karakter lebih tinggi pada
index IR puasa, absolute
LV mass, weighed more,
frequent positive exercise
tolerance testing & use of
CCB (tidak signifikan scra
statistik)
 HASIL
Primary outcome Secondary outcomes
Metformin  reduced LVMI Treatment with metformin
significantly reduced
 LVM
 SCAT
 The concentration of TBARs;
a by-product of lipid
peroxidation and a marker of
oxidative stress
 Body weight and SBP in the
mITT and per-protocol
analysis arm of the study
Tolerability and safety of metformin
Metformin Group Placebo Group
 19 AEs and 6 SAEs (N=31)  15 AEs and 4 SAEs (n=32)
 Due to severe diarrhoea or  T2DM (1)
abdominal discomfort (4)  No reported CV SAEs
 Dose was reduced to 1 g (myocardial infarction,
daily : 1610mg per day arrhythmias, stroke, and
 One participant had a heart failure)
stroke
 DISCUSS
 This is the first RCT investigating the effect of metformin on
LVH in non-diabetic CAD patients identified to have IR
and/or pre-diabetes
 Consistent with experimental animal studies showing that
metformin can regress LVH.
DISCUSS
 Limitations
 Jumlah sampel sedikit (68)
 Analisis statistik tidak meliputi hasil sekunder penelitian lain
 Terbatas pada pasien PJK
 Hanya 1 biomarker stres oksidatif
 Pasien disglikemi dg IR atau pre-diabet atau keduanya