Among obese patients with HFpEF and type 2 DM, once weekly subcutaneous semaglutide was superior to placebo in improving body weight and patient-oriented QoL outcomes at 52 weeks. For patients with atherosclerotic cardiovascular disease who hadn't achieved LDL-C levels below 70 mg/dL, the prompt addition of inclisiran resulted in significant reductions in LDL-C levels. Empagliflozin did not lower the risk of a first hospitalization for heart failure (HF) or death from any cause among patients with an increased risk for HF following acute myocardial infarction.

1. ACC 2024
Chronicles

2. Index
Sr. No. Title Page No
1 Carry Clinic Messages from Key Clinical Trials 1
2 STEP-HFpEF DM 3
3 VICTORION-INITIATE 6
4 EMPACT-MI 9
5 PREVENT 12
6 REDUCE-AMI 15
7 ULTIMATE DAPT 18
8 BE ACTIVE 21
9 KARDIA-2 24
10 MINT trial (Pre-specified Subgroup Analysis) 27
11 BRIDGE-TIMI 73a 30
12 SHASTA 2 33
13 AEGIS-II CSL112 36
14 Additional Trials: Quick Takes 39

3. STEP-HFpEF DM Semaglutide Beneficial in HFpEF Patients With Diabetes
VICTORION-
INITIATE
Inclisiran First Strategy Safe & Effective for LDL-C Control in ASCVD
Empagliflozin Fails to Reduce Events After Acute MI
EMPACT-MI
PREVENT Preventive PCI Reduces Cardiac Events in Patients with Vulnerable Plaques
REDUCE-AMI
Long-term beta-blocker treatment may not reduce death or heart attack risk
in MI patients
Ticagrelor Alone Reduces Bleeding Without Increasing Events Post-PCI
ULTIMATE-DAPT
Carry Clinic Messages
1

4. BE ACTIVE
Gamification and financial incentives increase physical activity in patients at
risk for CV events
KARDIA-2 Novel BP-Lowering Drug Reduces SBP With Just One Injection
In acute MI patients with anaemia, a liberal transfusion strategy did not
reduce the risk of recurrent MI or death at 30 days, regardless of MI type.
MINT Trial
BRIDGE-TIMI 73a Initial Olezarsen Results Demonstrate 50% Reduction in Triglycerides
SHASTA 2 Significant Triglyceride Reduction with Plozasiran
CSL112 Associated With Lower Rates of CV Death, MI
AEGIS-II CSL112
Carry Clinic Messages
2

5. STEP-HFpEF
DM
Among obese patients with HFpEF and type 2 DM, once weekly
subcutaneous semaglutide was superior to placebo in improving
body weight and patient-oriented QoL outcomes at 52 weeks
01
3

6. STEP-HFpEF DM: Methods
To compare the safety and efficacy of semaglutide among patients
with obesity-related HFpEF and T2DM
 Patients were randomized in a 1:1 fashion to once weekly
subcutaneous semaglutide (n = 310) or matching placebo (n = 306)
for 52 weeks
 Primary end points: Change from baseline in KCCQ-CSS and
the change in body weight
 Confirmatory secondary end points: change in 6-minute walk
distance; a hierarchical composite end point that included death,
heart failure events, and differences in the change in the KCCQ-CSS
and 6-minute walk distance; and the change in the C-reactive protein
(CRP) level
N Engl J Med 2024;Apr 6:DOI: 10.1056/NEJMoa2313917
4
Objectives
Methods

7. STEP-HFpEF DM: Key results
 Semaglutide was superior to placebo in
improving body weight (~6.4% greater
weight loss) and patient-oriented quality
of life (QoL) outcomes including KCCQ-
CSS and 6MWD
 Change in KCCQ-CSS: 13.7 vs. 6.4 (p <
0.001)
 % change in body weight: -9.8% vs. -3.4%
(p < 0.001)
 Change in 6MWD from baseline to week
52: 12.7 vs. -1.6 m (p = 0.008)
 Time to first HF event: 7 vs. 18 (hazard ratio
0.40, 95% confidence interval 0.15-0.92)
N Engl J Med 2024;Apr 6:DOI: 10.1056/NEJMoa2313917
5

8. VICTORION-
INITIATE
For patients with atherosclerotic cardiovascular disease who hadn't
achieved LDL-C levels below 70 mg/dL, the prompt addition of
inclisiran resulted in significant reductions in LDL-C levels
02
6

9. VICTORION-INITIATE: Methods
To determine the effect of adding inclisiran vs. usual care in achieving
adequate lipid lowering in patients with ASCVD on maximally tolerated
statin therapy or with statin intolerance
J Am Coll Cardiol. Apr 06, 2024. DOI: 10.1016/j.jacc.2024.03.382
7
Objectives
Methods

10. VICTORION-INITIATE: Key results
 “Inclisiran first” strategy led to
significantly greater reductions in LDL-C
(60%) from baseline to Day 330 vs. usual
care (7%) (p<0.001)
 Statin discontinuation rates with “inclisiran
first” (6.0%) were noninferior vs. usual care
(16.7%)
 More “inclisiran first” patients achieved LDL-
C goals vs usual care (<70 mg/dL: 81.8% vs
22.2%; <55 mg/dL: 71.6% vs 8.9%;
p<0.001)
 No new safety concerns
J Am Coll Cardiol. Apr 06, 2024. DOI: 10.1016/j.jacc.2024.03.382
8

11. EMPACT-MI
Empagliflozin did not lower the risk of a first hospitalization for heart failure
(HF) or death from any cause among patients with an increased risk for HF
following acute myocardial infarction.
03
9

12. EMPACT-MI
The trial aimed to assess the impact of adding the sodium-glucose cotransporter-2
(SGLT2) inhibitor empagliflozin to the treatment of acute myocardial infarction
(AMI) on future mortality or heart failure (HF) in high-risk patients."
Objectives
Methods
Primary endpoint: time to first heart
failure hospitalization or all-cause mortality
Am Heart J. 2022 Nov:253:86-98
10

13. EMPACT-MI: Key results
 Empagliflozin did not show a significant
reduction in the risk of time to first
hospitalization for heart failure (HHF) or
all-cause death following acute myocardial
infarction (AMI).
 However, empagliflozin demonstrated a
relative risk reduction of 23% and 33% for
first HHF and total HHF, respectively, which
are components of the primary and key
secondary endpoints.
 The safety profile of empagliflozin observed
in this study was consistent with its known
safety profile
N Engl J Med 2024;Apr 6. DOI: 10.1056/NEJMoa2314051
11

14. PREVENT
Preventative PCI in patients with high-risk vulnerable plaques is more
effective than optimal medical therapy alone at preventing serious cardiac
events.
04
12

15. PREVENT
To assess whether preventive percutaneous coronary intervention of non-flow-
limiting vulnerable plaques improves clinical outcomes compared with optimal
medical therapy alone.
Objectives
Methods
Am Heart J. 2023 Oct:264:83-96.
13

16. PREVENT: Key results
 The primary endpoint of target vessel failure
at 2 years for PCI + OMT vs. OMT alone,
was: 0.4% vs. 3.4% (hazard ratio [HR] 0.11,
95% confidence interval [CI] 0.03-0.36, p =
0.0003).
 Preventive PCI also reduced the composite
patient-oriented outcome of risk of all-cause
death, any MI, or any repeat
revascularization.
 This benefit was sustained throughout the 7-
year follow-up period.
Lancet 2024;Apr 8. DOI:0.1016/S0140-6736(24)00413-6
14

17. REDUCE -
AMI
Long-term use of beta-blockers does not reduce the risk of all cause death
or future myocardial infarction in patients with acute myocardial infarction &
preserved LVEF.
05
15

18. REDUCE-AMI
To evaluate the potential benefit of beta-blockade following acute myocardial
infarction (AMI) in patients with preserved left ventricular ejection fraction (LVEF)
in the modern era of coronary revascularization and medical therapy
Objectives
Methods
• Registry-based, International,
multicenter, Randomized,
Open-label
• Patients with AMI without
reduced LVEF were
randomized in a 1:1 fashion
to receive beta-blockade (n =
2,508) with oral metoprolol
or bisoprolol titrated to a
target dose ≥100 mg daily or
≥5 mg daily, respectively, or
to usual care (n = 2,512).
N Engl J Med 2024;Apr 7. DOI: 10.1056/NEJMoa2401479
16

19. REDUCE-AMI: Key results
 The primary outcome, composite of all-cause death or nonfatal AMI, for beta-blockade vs.
usual care, was: 7.9% vs. 8.3%, hazard ratio (HR) 0.96.
N Engl J Med 2024;Apr 7. DOI: 10.1056/NEJMoa2401479
17

20. ULTIMATE-
DAPT
Switching to ticagrelor alone after one month of dual antiplatelet therapy is
more effective than continuing a 12-month dual antiplatelet therapy with
aspirin and ticagrelor, in reducing clinically significant bleeding without an
increased risk of thrombosis after PCI.
06
18

21. ULTIMATE-DAPT
To assess whether the use of ticagrelor alone, compared with ticagrelor plus aspirin,
could reduce the incidence of clinically relevant bleeding events without an
accompanying increase in major adverse cardiovascular or cerebrovascular events
(MACCE).
Objectives
Methods
• Patients who completed the IVUS-
ACS study and who had no major
ischaemic or bleeding events after 1-
month treatment with dual antiplatelet
therapy were randomly assigned to
receive oral ticagrelor (90 mg twice
daily) plus oral aspirin (100 mg once
daily) or oral ticagrelor (90 mg twice
daily) plus a matching oral placebo,
beginning 1 month and ending at 12
months after percutaneous coronary
intervention (11 months in total).
Lancet 2024;Apr 7. DOI: 10.1016/S0140-6736(24)00473-2
19

22. ULTIMATE-DAPT: Key results
 The primary effectiveness
endpoint, ticagrelor + placebo
vs. ticagrelor + aspirin, was:
2.1% vs. 4.6% (hazard ratio
0.45, 95% confidence interval
0.30-0.66, p < 0.0001).
 BARC 3 or 5: 0.7% vs.
1.7%, p = 0.009
 TIMI major or minor
bleeding: 0.7% vs. 1.6%, p
= 0.01
 The primary safety endpoint, major adverse
cardiovascular or cerebrovascular events
(cardiac death, MI, ischemic stroke, definite
stent thrombosis, clinically driven target vessel
revascularization): 3.6% vs. 3.7%, p < 0.0001
for non-inferiority, p = 0.89 for superiority
The primary effectiveness endpoint-Bleeding
Academic Research Consortium (BARC) 2, 3,
or 5 bleeding
Lancet 2024;Apr 7. DOI: 10.1016/S0140-6736(24)00473-2
20

23. BE ACTIVE
Home-based incentives related to behavioral economics increased
physical activity in patients at risk for CV events over 12 month
intervention period.
07
21

24. BE ACTIVE: Methods
To determine the effect of behaviorally-designed gamification, loss-framed
financial incentives, or the combination on physical activity compared with
attention control over 12-month intervention and 6-month post-intervention
follow-up periods
Circulation. 2024 Apr 7. DOI: 10.1161/CIRCULATIONAHA.124.069531.
22
Objectives
Methods

25. BE ACTIVE: Key results
 Gamification and financial incentive
interventions designed with concepts from
behavioral economic theory substantially
increased physical activity compared with
attention control over 12-month follow-up.
 The combination of gamification and
financial incentives led to the greatest
increase in physical activity over the 12-
month intervention period, which was
sustained over 6-month post-intervention
follow-up
Circulation. 2024 Apr 7. DOI: 10.1161/CIRCULATIONAHA.124.069531.
23

26. KARDIA-2
Treatment with a single subcutaneous dose of zilebesiran 600 mg
was associated with clinically significant reductions in 24-hr mean
ambulatory and office SBP compared with placebo at Month 3
when added to a diuretic, CCB, or maximum-dose ARB
08
24

27. KARDIA-2: Methods
Phase 2, double-blind, placebo-controlled study to evaluate efficacy
and safety of adding novel drug zilebesiran in patients with
inadequately controlled hypertension
Presented by Dr. George L. Bakris at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024
25
Objectives
Methods

28. KARDIA-2: Key results
 Results showed significant additional
reductions in 24-hour ambulatory SBP
with zilebesiran compared with placebo
 For patients assigned to indapamide, the
average incremental reduction was 12 mm
Hg, and it was 9.7 mm Hg for amlodipine
and 4 mm Hg for Olmesartan
 For the secondary endpoint of change in
SBP measured in the clinician's office at
three months, the reductions in the
indapamide, amlodipine and olmesartan
groups were 18.5 mm Hg, 10.2 mm Hg and
7.0 mm Hg, respectively
Presented by Dr. George L. Bakris at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024
26

29. MINT
In patients with acute MI and anemia, a liberal transfusion strategy did not
significantly reduce the risk of recurrent MI or death at 30 days irrespective
of the type of MI & type 1 MI subset demonstrated a signal of increased
harm due to all cause death with a restrictive transfusion strategy.
09
27

30. MINT (Pre-specified SubgroupAnalysis)
To compare the effect of a liberal vs. restrictive blood transfusion strategy on acute
myocardial infarction (MI) in patients with concomitant anemia.
• Patients with a Hb concentration <10 g/dL experiencing MI were randomized to
a liberal (n = 1,755) or restrictive (n = 1,749) blood transfusion strategy during
hospitalization.
• The liberal strategy arm received 1 unit of packed RBC on randomization and
additional transfusions as needed to maintain Hb concentration ≥10 g/dL.
Transfusion in the restrictive arm was permitted for Hb <8 g/dL, strongly
recommended for Hb <7 g/dL, and required for persistent angina refractory to
pharmacotherapy regardless of Hgb.
• A total of 3,504 patients participated in the trial & were followed for 30 days.
• The primary outcome, composite of all-cause death or recurrent nonfatal MI, for
restrictive vs. liberal transfusion strategies at 30 days.
Presented by Dr. Andrew P. DeFilippis at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.
28
Objectives
Methods

31. MINT : Key results
 Prespecified subgroup analysis of secondary
outcomes for restrictive vs. liberal transfusion
strategies:
 All-cause death: p-interaction = 0.26
○ Type 1 MI: 10.5% vs. 7.5%, RR 1.40
○ Type 2 MI: 9.6% vs. 8.8%, RR 1.09
 Recurrent nonfatal MI: p-interaction = 0.43
○ Type 1 MI: 9.3% vs. 7.3%, RR 1.28
○ Type 2 MI: 7.8% vs. 7.3%, RR 1.06
Presented by Dr. Andrew P. DeFilippis at the American College of Cardiology Annual Scientific Session (ACC.24), Atlanta, GA, April 7, 2024.
29

32. BRIGADE
TIMI 73a
Olezarsan showed robust reductions in TGs, ApoB and non HDL cholesterol
in patients with moderate hypertriglyceridemia and elevated CV risk.
10
30

33. BRIGADE TIMI 73a
To assess the efficacy and safety of olezarsen in patients with moderate
hypertriglyceridemia (triglyceride level, 150 to 499 mg/dl) plus elevated
cardiovascular risk and in those with severe hypertriglyceridemia (triglyceride level,
≥500 mg/dl).
• In this phase 2b, randomized, controlled trial, adults either with moderate
hypertriglyceridemia and elevated cardiovascular risk or with severe
hypertriglyceridemia were assigned in a 1:1 ratio to either a 50-mg or 80-mg
cohort.
• Patients were then assigned in a 3:1 ratio to receive monthly sc olezarsen or
matching placebo within each cohort.
• The primary outcome was the percent change in the triglyceride level from
baseline to 6 months, reported as the difference between each olezarsen group
and placebo.
• Key secondary outcomes were changes in levels of APOC3, apolipoprotein B,
non- HDL) cholesterol and LDL cholesterol.
• A total of 154 patients underwent randomization at 24 sites in North America.
31
Objectives
Methods

34. BRIGADE TIMI 73a: Key results
 The 50-mg and 80-mg doses of olezarsen
reduced triglyceride levels by 49.3
percentage points and 53.1 percentage
points, respectively, as compared with
placebo (P< 0.001 for both comparisons).
 As compared with placebo, each dose of
olezarsen also significantly reduced the
levels of APOC3, apolipoprotein B, and
non-HDL cholesterol, with no significant
change in the LDL cholesterol level.
 The risks of adverse events and serious
adverse events were similar in the three
groups.
N Engl J Med. 2024 Apr 7. doi: 10.1056/NEJMoa2402309.
32

35. SHASTA 2
Novel drug Plozasiran showed robust reductions of TGs in patients at risk of
acute pancreatitis.
11
33

36. SHASTA 2
To determine the tolerability, efficacy, and dose of plozasiran, an APOC3-targeted
small interfering–RNA (siRNA) drug, for lowering triglyceride and apolipoprotein
C3 (APOC3, regulator of triglyceride metabolism) levels and evaluate its effects on
other lipid parameters in patients with severe hypertriglyceridemia (sHTG).
• SHASTA-2 was a placebo-controlled, double-blind, dose-ranging, phase 2b
randomized clinical trial enrolling adults with sHTG at 74 centers across the
US, Europe, New Zealand, Australia, and Canada.
• Eligible patients had fasting triglyceride levels in the range of 500 to 4000
mg/dL while receiving stable lipid-lowering treatment.
• Participants received 2 subcutaneous doses of plozasiran (10, 25, or 50 mg) or
matched placebo on day 1 and at week 12 and were followed up through week
48.
• The primary end point evaluated the placebo-subtracted difference in means of
percentage triglyceride change at week 24. 229 patients were included.
Objectives
Methods
JAMA Cardiol. 2024 Apr 7:e240959.
34

37. SHASTA 2: Key results
 Plozasiran induced significant dose-dependent
placebo-adjusted reductions in triglyceride levels
of −57%, driven by placebo-adjusted reductions
in APOC3 of –77% at week 24 with the highest
dose.
 Among plozasiran treated patients, 144 of 159
(90.6%) achieved a triglyceride level of less than
500 mg/dL.
 Plozasiran was associated with dose-dependent
increases in LDL-C level, which was significant in
patients receiving the highest dose.
 However, ApoB levels did not increase, and non
HDL-C levels decreased significantly at all doses,
with a placebo-adjusted change of −20% at the
highest dose.
 There were also significant durable reductions in
remnant cholesterol and ApoB48 as well as
increases in HDL-C level through week 48.
JAMA Cardiol. 2024 Apr 7:e240959.
35

38. AEGIS II
CSL 112
IV infusions of CSL 112, derived from human plasma apoA-1 was linked to
potential decrease in the rates of CV death & MI, although the results
were numerically lower.
12
36

39. AEGIS II CSL 112
To evaluate if the infusions of CSL112 (human apolipoprotein A1 derived from
plasma) can reduce the risk of recurrent cardiovascular events after acute
myocardial infarction.
• This was a international, double-blind, placebo-controlled trial involving patients
with acute myocardial infarction, multivessel coronary artery disease, and
additional cardiovascular risk factors.
• Patients were randomly assigned to receive either four weekly infusions of 6 g
of CSL112 or matching placebo, with the first infusion administered within 5
days after the first medical contact for the acute myocardial infarction.
• The primary end point was a composite of myocardial infarction, stroke, or
death from cardiovascular causes from randomization through 90 days of
follow-up.
• A total of 18,219 patients were included in the trial (9112 in the CSL112 group
and 9107 in the placebo group).
Objectives
Methods
37 N Engl J Med. 2024 Apr 7. DOI: 10.1056/NEJMoa2400969.

40. AEGIS II CSL 112: Key results
 There was no significant difference between the
groups in the risk of a primary end-point event at
90 days of follow-up (439 patients [4.8%] in the
CSL112 group vs. 472 patients [5.2%] in the
placebo group; hazard ratio, 0.93 (P=0.24)
 At the end of 180 days of follow-up (622 patients
[6.9%] vs. 683 patients [7.6%]; hazard ratio,
0.91), or at 365 days of follow-up (885 patients
[9.8%] vs. 944 patients [10.5%]; hazard ratio,
0.93).
N Engl J Med. 2024 Apr 7. DOI: 10.1056/NEJMoa2400969.
38

41. Additional
Trials 13
39

42. Quick Takes
40

43. Quick Takes
41

44. Quick Takes
42
DEDICATE-DZHK6 Trial
TAVR is associated with significantly lower rates of death or stroke at one year without
increased risks, compared to SAVR, in low-risk patients.
ARISE-HFTrial
AT-001, a selective aldose reductase inhibitor, did not significantly impact exercise capacity,
as measured by peak oxygen uptake, in patients with diabetic cardiomyopathy.
IVUS-DCBStudy
Angioplasty for femoropopliteal artery disease guided by IVUS alongside angiography resulted
in significantly higher one-year success rates compared to angiography-guided procedures
alone.
IMPROVE-HCM Study
Ninerafaxstat, a novel cardiac mitotrope targeting energy metabolism, has been proven safe
and effective in treating nonobstructive hypertrophic cardiomyopathy.
10
11
12
13

45. Quick Takes
43
14 15 16 17

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