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<title>Indonesia Journal of Pharmacy Vol 35 No 3 2024</title>
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<place><placeTerm type="text">Jogjakarta</placeTerm></place>
<publisher>Universitas Gadjah Mada</publisher>
<dateIssued>2024</dateIssued>
<issuance>monographic</issuance>
<edition>Vol 35 No 3 2024</edition>
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<languageTerm type="text">Indonesia</languageTerm>
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<form authority="gmd">Karya Tulis Ilmiah</form>
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<note>Beta-blockers exert cardioprotective effects against heart failure.
However, variability in therapeutic responses is associated with ADRB1
variants. ADRB1 variants contribute to rate control and autonomic
dysfunction. Persistent hyperadrenergic stimulation contributes to the
impairment of the pacemaker (SA node). HCN4 significantly influenced the
regulation of heart rate in the pacemaker. Exploring the effect of beta-blockers
on pacemaker cells is expanding the view of their cardioprotective effects in
heart failure. The objectives of this review were to identify ADRB1 variants
affecting heart rate response in heart failure patients receiving beta-blocker
treatment and to explore the effect of beta-blockers on HCN4/SA node. A
systematic review was performed using three databases (Scopus, PubMed,
and Science Direct). The inclusion criteria were English language and original
manuscripts with relevant topics. The exclusion criteria were duplication and
inaccessibility to the full text. Quality assessment tools were classified based
on the use of research subjects and study designs, including NOS (cohort),
SYRCLE (animal studies), and SciRAP (in vitro studies). Eight of 668
manuscripts were selected. This review found that ADRB1 variants
(A145G(Ser49Gly) and C1165G(Arg389Gly)) can affect heart rate response in

beta-blocker-treated heart failure. The percentage of patients with Ser49Ser-
Gly389X (67%) who achieved the heart rate target was higher than that of the

other haplotypes (48-52%). Among the responders, Arg389Arg required
larger carvedilol equivalent daily doses of beta-blockers to reach the identical
heart rate target than those with Gly389X (&gt;50% (&gt;25mg) versus &le;50% of the
guideline-directed medical therapy (GDMT) target dose (&le;25mg),
respectively). In addition, this review found that beta-blockers demonstrated
beneficial effects in regulating heart rate by inhibiting HCN-gated channels
and improving channel regulation in the SA node. In general, this review
provides important insights into beta-blockers in treating heart failure,

specifically concerning the genetic variability of ADRB1 and the effect of beta-
blockers on SA node/HCN4.

Keywords: Beta-blocker, ADRB1, HCN4, Heart Failure, Heart Rate</note>
<subject authority=""><topic>ADRB1</topic></subject>
<subject authority=""><topic>Beta-blocker</topic></subject>
<subject authority=""><topic>Heart Rate</topic></subject>
<subject authority=""><topic>Heart Failure</topic></subject>
<subject authority=""><topic>HCN4</topic></subject>
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