American Heart Association

Scientific Sessions 2022

AHA 2022
5th-7th November 2022, Chicago

KEY INSIGHTS

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 TABEL OF CONTENT
Serial No Content Page no
1 TRANSFORM-HF: Torsemide vs. Furosemide in Treating 3
Patients With heart failure
2 DCP: Chlorthalidone Compared to Hydrochlorothiazide for 4
the Prevention of Cardiovascular Events in Patients with
Hypertension
3 PROMINENT: Triglyceride Lowering with Pemafibrate to 5
Reduce Cardiovascular Risk
4 IRONMAN: Intravenous ferric derisomaltose in patients 6
with heart failure and iron deficiency in UK
5 EMPA-KIDNEY: Empagliflozin in Patients with Chronic 7
Kidney Disease
6 RESPECT-EPA: Randomized Trial for Evaluating Secondary 8
Prevention Efficacy of Combination Therapy - Statin and
Eicosapentaenoic Acid
7 OCEAN[a]-DOSE: Small Interfering RNA to Reduce 9
Lipoprotein(a) in Cardiovascular Disease
8 Impact of diabetes on the effects of SGLT2i on kidney 10
outcomes: collaborative meta-analysis of large placebo-
controlled trials
9 PRECISION: Dual endothelin antagonist aprocitentan for 11
resistant hypertension - a multicentre, blinded,
randomised, parallel-group, phase 3 trial
10 BrigHTN: Phase 2 Trial of Baxdrostat for Treatment of 12
Resistant Hypertension
11 Key takeaways 13, 14
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 TRANSFORM-HF: Torsemide vs. Furosemide in Treating Patients With HF

AIM: To compare the treatment strategy of torsemide vs. furosemide on long-term clinical
outcomes among patients hospitalized with HF.

METHOD: In this pragmatic, open label study 2,859 patients were randomized at more than 60
U.S. hospitals to either torsemide or furosemide.

RESULTS: After a median of 17.4 months, results showed nearly identical mortality rates in both
the torsemide (26.1%) and the furosemide (26.2%) groups. At 12 months, all-cause death and
hospitalization rates were also similar in the torsemide (47.3%) and furosemide (49%.3) groups.

CONCLUTION: Torsemide had similar effectiveness as furosemide for the clinical

outcomes of mortality and hospitalization in patients hospitalized with HF.

https://www.acc.org/Latest-in-Cardiology/Articles/2022/11/01/22/00/sat-1130am-transform-hf-aha-2022 3
 DCP: Chlorthalidone Compared to Hydrochlorothiazide for the
Prevention of Cardiovascular Events in Patients with Hypertension

AIM: To evaluate the safety and efficacy of hydrochlorothiazide (HCTZ)

compared with chlorthalidone in improving cardiovascular outcomes among
patients with hypertension.

METHOD: Patients over the age of 65 years who were already taking HCTZ
were randomized in an open-label 1:1 fashion to either chlorthalidone (n =
6,756) or continued on HCTZ (n = 6,767). Patients on HCTZ 25 mg were
converted to 12.5 mg chlorthalidone, and 50 mg HCTZ to 25 mg
chlorthalidone. Duration of follow-up was 5 years.

RESULTS: The primary outcome, major adverse cardiovascular events (MACE),

for chlorthalidone vs. HCTZ: hazard ratio (HR) 1.04, 95% confidence interval
(CI) 0.94-1.16 (p = 0.4). For patients with prior stroke: HR 0.73, 95% CI 0.57-
0.94 (p for interaction = 0.035)

Secondary outcomes for chlorthalidone vs. HCTZ: First hospitalization for MI:
HR 1.01, 95% CI 0.80-1.28 (p = 0.91), First hospitalization for stroke: HR 1.0,
95% CI 0.74-1.36 (p = 1.0), First hospitalization for heart failure: HR 1.04, 95%
CI 0.87-1.25 (p = 0.4), Hypokalaemia: 6.0% vs. 4.4% (p < 0.001)

CONCLUTION: There are no differences in cardiovascular

outcomes between chlorthalidone and HCTZ among elderly
veterans with hypertension. Among patients with prior MI, a
benefit was observed.
https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2022/11/04/14/11/dcp
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 PROMINENT: Triglyceride Lowering with Pemafibrate to Reduce
Cardiovascular Risk
AIM: To evaluate the efficacy of Pemafibrate in reducing the CV risk among T2DM patients.

METHOD: In this multinational, double-blind, randomized, controlled trial, we assigned 10,497

patients with T2DM, mild-to-moderate hypertriglyceridemia (triglyceride level, 200 to 499
mg/dl), and HDL-C levels of ≤40 mg/dl to receive pemafibrate (0.2-mg tablets twice daily) or
matching placebo. The primary efficacy end point was a composite of nonfatal MI, ischemic
stroke, coronary revascularization, or death from CV causes. The median follow up was 3.4 years.

RESULTS: As compared with placebo, the effects of pemafibrate on lipid levels at 4 months were
−26.2% for triglycerides, −25.8% for VLDL-C, −25.6% for remnant cholesterol, −27.6% for
apolipoprotein C-III, and 4.8% for apolipoprotein B. A primary end point event occurred in 572
patients in the pemafibrate group and in 560 of those in the placebo group (hazard ratio, 1.03;
95% confidence interval, 0.91 to 1.15), with no apparent effect modification in any prespecified
subgroup. The overall incidence of serious adverse events did not differ significantly between the
groups.

CONCLUTION: Among patients of T2DM with mild-to-moderate

hypertriglyceridemia, and low HDL and LDL cholesterol levels, the incidence
of cardiovascular events was not lower among those who received
pemafibrate than among those who received placebo, although pemafibrate
lowered triglyceride, VLDL-C, remnant cholesterol, and apolipoprotein C-III
levels.

A. Das Pradhan, NEJM NOV 5, 2022, DOI: 10.1056/NEJMoa2210645 5

IRONMAN: Intravenous ferric derisomaltose in patients with heart
failure and iron deficiency in the UK
AIM: To evaluate the long-term effects of intravenous ferric derisomaltose on cardiovascular
events in patients with heart failure.

METHOD: This prospective, randomized, open-label, blinded-endpoint trial was done at 70

hospitals in the UK. Patients aged 18 years or older with HF (LVEF≤45%) and transferrin saturation
l<20% or serum ferritin l <100 µg/L were eligible. Participants were randomly assigned (1:1) using
a web-based system to intravenous ferric derisomaltose or usual care. The primary outcome was
recurrent hospital admissions for HF and CV death. 1137 patients were randomly assigned to
receive intravenous ferric derisomaltose (n=569) or usual care (n=568). Median follow-up was 2.7
years.

RESULTS: 336 primary endpoints (22·4 per

100 patient-years) occurred in the ferric
derisomaltose group and 411 (27·5 per 100
patient-years) occurred in the usual care
group (rate ratio [RR] 0·82 [95% CI 0·66 to
1·02]; p=0·070). No between group
differences in deaths or hospitalizations due
to infections were observed. Fewer patients
in the ferric derisomaltose group had cardiac
serious adverse events (200 [36%]) than in
the usual care group (243 [43%]; difference –
7·00% [95% CI –12·69 to –1·32]; p=0·016).

CONCLUTION: For a broad range of patients with HFrEF and iron deficiency,
intravenous ferric derisomaltose administration was associated with a lower
risk of hospital admissions and cardiovascular death, further supporting the
benefit of iron repletion in this population.
November 5, 2022 https://doi.org/10.1016/ S0140-6736(22)02083-9 6
 EMPA-KIDNEY: Empagliflozin in Patients with Chronic Kidney
Disease
AIM: To assess the effects of treatment with empagliflozin in patients with chronic kidney
disease who are at risk for disease progression.

METHOD: 6609 patients with CKD who had an eGFR of at least 20 but <45 ml/minute/1.73 m2
of body-surface area, or who had an eGFR of at least 45 but <90 ml/minute/1.73 m2 with a
urinary albumin-to-creatinine ratio of at least 200. Patients were randomly assigned to receive
empagliflozin (10 mg once daily) or matching placebo. The primary outcome was a composite of
progression of kidney disease (defined as end-stage kidney disease, a sustained decrease in
eGFR to <10ml/minute/1.73 m2, a sustained decrease in eGFR of ≥40% from baseline, or death
from renal causes) or death from cardiovascular causes.

RESULTS: Progression of kidney disease or death from cardiovascular causes occurred in 432 of
3304 patients (13.1%) in the empagliflozin group and in 558 of 3305 patients (16.9%) in the
placebo group (hazard ratio, 0.72; 95% confidence interval [CI], 0.64 to 0.82; P<0.001). Results
were consistent among patients with or without diabetes and across subgroups. The rate of
hospitalization from any cause was lower in the empagliflozin group than in the placebo group
(hazard ratio, 0.86; 95% CI, 0.78 to 0.95; P=0.003), but there were no significant between-group
differences with respect to the composite out come of hospitalization for heart failure or death
from cardiovascular causes (which occurred in 4.0% in the empagliflozin group and 4.6% in the
placebo group) or death from any cause (in 4.5% and 5.1%, respectively).

CONCLUTION: Among a wide range of patients with CKD who were at risk for disease
progression, empagliflozin therapy led to a lower risk of progression of kidney
disease or death from cardiovascular causes than placebo.
W.G. Herrington, NEJM Nov 4, 2022, DOI: 10.1056/NEJMoa2204233 7
 RESPECT-EPA: Randomized Trial for Evaluating Secondary
Prevention Efficacy of Combination Therapy - Statin and
Eicosapentaenoic Acid

AIM: To evaluate icosapent ethyl, a purified eicosapentaenoic acid (EPA),

compared with control among patients with chronic coronary artery
disease treated with statin therapy.

METHOD: In this parallel, open labelled trial, patients with chronic

coronary artery disease on statin therapy were randomized to icosapent
ethyl 1800 mg daily (n = 1,249) vs. control (n = 1,257). Duration of follow-
up was 5 years.

RESULTS: The primary outcome, cardiovascular death, myocardial

infarction, stroke, unstable angina requiring hospitalization, and
revascularization, occurred in 10.9% of the icosapent ethyl group vs.
14.9% of the control group (p = 0.055).

Secondary outcomes of sudden cardiac death, myocardial infarction,

unstable angina, or coronary revascularization occurred in 8.0% in the
icosapent ethyl group vs. 11.3% in the control group (p = 0.031) &
gastrointestinal disorders occurred in 3.4% in the icosapent ethyl group
vs. 1.2% in the control group (p < 0.001).

CONCLUTION: Among Japanese patients with chronic coronary

artery disease treated with statin therapy, icosapent ethyl may be
associated with a reduction in adverse cardiovascular outcomes.

https://www.acc.org/Latest-in-Cardiology/Clinical-Trials/2022/11/05/03/10/respect-epa
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OCEAN[a]-DOSE: Small Interfering RNA to Reduce Lipoprotein(a) in
Cardiovascular Disease
AIM: To evaluate efficacy of Olpasiran (a small interfering RNA) in reducing lipoprotein(a)
synthesis in the liver.

METHOD: This randomized, double-blind, placebo-controlled, dose-finding trial involved 281

patients with established ASCVD and a lipoprotein(a) concentration of >150 nmol/L. Patients
were randomly assigned to receive one of four doses of olpasiran (10 mg every 12 weeks, 75 mg
every 12 weeks, 225 mg every 12 weeks, or 225 mg every 24 weeks) or matching placebo,
administered subcutaneously. The primary end point was the percent change in the
lipoprotein(a) concentration from baseline to week 36. Safety was also assessed.

RESULTS: At 36 weeks, the lipoprotein(a) concentration had increased by a mean of 3.6% in the
placebo group, whereas olpasiran therapy had significantly and substantially reduced the
lipoprotein(a) concentration in a dose-dependent manner, resulting in placebo adjusted mean
percent changes of −70.5% with the 10-mg dose, −97.4% with the 75-mg dose, −101.1% with the
225-mg dose administered every 12 weeks, and −100.5% with the 225-mg dose administered
every 24 weeks (P<0.001). The overall incidence of adverse events was similar across the trial
groups.

CONCLUTION: The siRNA olpasiran led to a profound and sustained reduction

in the lipoprotein(a) concentration when administered every 12 weeks in
patients with established atherosclerotic cardiovascular disease.
Michelle L. O’Donoghue, NEJM Nov 6, 2022, DOI: 10.1056/NEJMoa2211023 9
 Impact of diabetes on the effects of SGLT2i on kidney outcomes:
collaborative meta-analysis of large placebo-controlled trials
AIM: To evaluate effects of SGLT2i on kidney outcomes separately in patients without diabetes.

METHOD: 13 trials involving 90,409 participants were included. The main efficacy outcomes
were kidney disease progression (standardized to a definition of a sustained ≥50% decrease in
eGFR from randomization, a sustained low eGFR, end-stage kidney disease, or death from
kidney failure), acute kidney injury, and a composite of cardiovascular death or hospitalization
for heart failure. Other outcomes were death from cardiovascular and non-cardiovascular
disease considered separately, and the main safety outcomes were ketoacidosis and lower limb
amputation.

RESULTS: Compared with placebo, allocation to

an SGLT2 inhibitor reduced the risk of kidney
disease progression by 37% (relative risk [RR]
0·63, 95% CI 0·58–0·69) with similar RRs in
patients with and without diabetes. SGLT2
inhibitors reduced the risk of acute kidney injury
by 23% (0·77, 0·70–0·84) and the risk of
cardiovascular death or hospitalization for heart
failure by 23% (0·77, 0·74–0·81), again with
similar effects in those with and without
diabetes. SGLT2 inhibitors also reduced the risk
of cardiovascular death (0·86, 0·81–0·92) but did
not significantly reduce the risk of non-
cardiovascular death (0·94, 0·88–1·02). For these
mortality outcomes, RRs were similar in patients
with and without diabetes.

CONCLUTION: SGLT2i safely reduce the risk of kidney disease progression, acute
kidney injury, cardiovascular death, and hospitalization for HF in patients with
CKD or heart failure, irrespective of diabetes status. The proportional benefits
were similar in patients with and without diabetes and appeared to be evident
across the wide range of kidney function studied.
November 6, 2022 https://doi.org/10.1016/ S0140-6736(22)02074-8 10
 PRECISION: Dual endothelin antagonist aprocitentan for resistant
hypertension - a multicentre, blinded, randomised, parallel-group,
phase 3 trial
AIM: The aim of the study was to assess the blood pressure lowering efficacy of the dual
endothelin antagonist aprocitentan in patients with resistant hypertension.

METHOD: This multicenter, blinded, randomized, parallel-group, phase 3 study was done in 730
patients with SBP ≥140 mm Hg or higher despite taking standardized background therapy
consisting of three antihypertensive drugs, including a diuretic. The primary and key secondary
endpoints were changes in unattended office SBP from baseline to week 4 and from withdrawal
baseline to week 40, respectively. Secondary endpoints included 24-h ambulatory BP changes.

RESULTS: The least square mean (SE) change in office systolic blood pressure at 4 weeks was –15·3
(SE 0·9) mm Hg for aprocitentan 12·5 mg, –15·2 (0·9) mm Hg for aprocitentan 25 mg, and –11·5
(0·9) mm Hg for placebo, for a difference versus placebo of –3·8 (1·3) mm Hg (97·5% CI –6·8 to –
0·8, p=0·0042) and –3·7 (1·3) mm Hg (–6·7 to –0·8; p=0·0046), respectively. The respective
difference for 24 h ambulatory systolic blood pressure was –4·2 mm Hg (95% CI –6·2 to –2·1) and –
5·9 mm Hg (–7·9 to –3·8). After 4 weeks of withdrawal, office systolic blood pressure significantly
increased with placebo versus aprocitentan (5·8 mm Hg, 95% CI 3·7 to 7·9, p<0·0001).

CONCLUTION: In patients with resistant hypertension, aprocitentan was well

tolerated and superior to placebo in lowering blood pressure at week 4 with a
sustained effect at week 40. Aprocitentan represents a novel, effective, and
well tolerated treatment for resistant hypertension.
N Engl J Med. 2022 Nov 7. doi: 10.1056/NEJMoa2213169. 11
 BrigHTN: Phase 2 Trial of Baxdrostat for Treatment of Resistant
Hypertension
AIM: To evaluate the efficacy of baxdrostat for treatment of resistant hypertension.

METHOD: We randomly assigned 248 patients who had treatment-resistant

hypertension, with blood pressure of 130/80 mm Hg or higher, and who were
receiving stable doses of at least three antihypertensive agents, including a diuretic,
to receive baxdrostat (0.5 mg, 1 mg, or 2 mg) once daily for 12 weeks or placebo. The
primary end point was the change in systolic blood pressure from baseline to week
12 in each baxdrostat group as compared with the placebo group.
RESULTS: Dose-dependent
changes in systolic blood
pressure of -20.3 mm Hg, -
17.5 mm Hg, -12.1 mm Hg,
and -9.4 mm Hg were
observed in the 2-mg, 1-mg,
0.5-mg, and placebo groups,
respectively. The difference in
the change in systolic blood
pressure between the 2-mg
group and the placebo group
was -11.0 mm Hg (95%
confidence interval [CI], -16.4
to -5.5; P<0.001), and the
difference in this change
between the 1-mg group and
the placebo group was -8.1
mm Hg (95% CI, -13.5 to -2.8;
P = 0.003).

CONCLUTION: Aldosterone synthase inhibition with baxdrostat led to

substantial reductions in systolic and diastolic blood pressure in
patients with treatment-resistant hypertension.
November 6, 2022 https://doi.org/10.1016/ S0140-6736(22)02074-8 12
 KEY TAKEAWAYS

TRANSFORM- • Torsemide had similar effectiveness as furosemide for the clinical outcomes
of mortality and hospitalization in patients hospitalized with HF.
HF

• There are no differences in cardiovascular outcomes between

DCP chlorthalidone and HCTZ among elderly veterans with HTN.
• Among patients with prior MI, a benefit was observed.

• Among patients with T2DM, mild-to-moderate hypertriglyceridemia, and

low HDL and LDL cholesterol levels, the incidence of CV events was not
PROMINENT lower among those who received pemafibrate than among those who
received placebo, although pemafibrate lowered triglyceride, VLDL
cholesterol, remnant cholesterol, and apolipoprotein C-III levels.

• For a broad range of patients with HFrEF and iron deficiency, intravenous

IRONMAN ferric derisomaltose administration was associated with a lower risk of

hospital admissions and cardiovascular death, further supporting the
benefit of iron repletion in this population.

• Among a wide range of patients with CKD who were at risk for disease
EMPA-KIDNEY progression, empagliflozin therapy led to a lower risk of progression of
kidney disease or death from cardiovascular causes than placebo.

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 KEY TAKEAWAYS

• Among Japanese patients with chronic coronary artery disease treated with
RESPECT-EPA statin therapy, icosapent ethyl may be associated with a reduction in
adverse CV outcomes.

• The siRNA olpasiran led to a profound and sustained reduction in the

OCEAN[a]-DOSE lipoprotein(a) concentration when administered every 12 weeks in patients
with established atherosclerotic cardiovascular disease.

SGLT2i on kidney • SGLT2i safely reduce the risk of kidney disease progression, acute kidney
injury, cardiovascular death, and hospitalization for HF in patients with CKD
outcomes: Meta- or heart failure, irrespective of diabetes status. The proportional benefits
were similar in patients with and without diabetes and appeared to be
analysis evident across the wide range of kidney function studied.

• In patients with resistant hypertension, aprocitentan was well tolerated and

superior to placebo in lowering blood pressure at week 4 with a sustained
PRECISION effect at week 40.
• Aprocitentan represents a novel, effective, and well tolerated treatment for
resistant hypertension.

• Aldosterone synthase inhibition with baxdrostat led to substantial

BrigHTN reductions in systolic and diastolic blood pressure in patients with
treatment-resistant hypertension.

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