A Glimpse Into

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New Drug Approvals

Guideline/Expert Consensus

Landmark Clinical Trials

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New Drug Approval

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New Drug Approval

Mavacamten: For the treatment of adults with

symptomatic New York Heart Association (NYHA) class II-
III obstructive hypertrophic cardiomyopathy (HCM) to
improve functional capacity and symptoms.

Dosage must be individualized based on clinical status

and echocardiographic assessment of patient response.
Dosage forms & strengths: 2.5 mg, 5 mg, 10 mg, and 15
mg capsules.

https://www.fda.gov/drugs/news-events-human-drugs/fda-approves-new-drug-improve-heart-function-adults-rare-heart-condition

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1. Guidelines
2. Expert Consensus

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1. 2022 AHA/ACC/HFSA Guideline for
the Management of Heart Failure

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 Stages of HF

Primary prevention is important for those at risk

for HF (stage A) or pre-HF (stage B).

Stages of HF were revised to emphasize the new

terminologies of “at risk” for HF for stage A and
pre-HF for stage B.

Trajectory of Stage C HF

Patients whose symptoms and signs of HF are resolved are still stage C and should be treated accordingly. If all HF symptoms, signs,
and structural abnormalities resolve, the patient is considered to have HF in remission. HF indicates heart failure; and LV, left
ventricular. *Full resolution of structural and functional cardiac abnormalities is uncommon.

Circulation. 2022 May 3;145(18):e895-e1032. 7

 Classification and Trajectories of HF Based on LVEF

Patients with HFrEF who improve their LVEF to >40% are considered to have HFimpEF and should continue HFrEF treatment.
HF indicates heart failure; HFimpEF, heart failure with improved ejection fraction; HFmrEF, heart failure with mildly reduced
ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; and
LVEF, left ventricular ejection fraction. *There is limited evidence to guide treatment for patients who improve their LVEF from
mildly reduced (41%-49%) to ≥50%. It is unclear whether to treat these patients as HFpEF or HFmrEF.

Circulation. 2022 May 3;145(18):e895-e1032. 8

 Diagnostic Algorithm for HF and EF-Based
Classification

Evidence supporting increased filling

pressures is important for the
diagnosis of HF if the LVEF is >40%.

Evidence for increased filling

pressures can be obtained from
noninvasive (e.g., natriuretic
peptide, diastolic function on
imaging) or invasive testing.

BNP indicates B-type natriuretic peptide; ECG, electrocardiogram; EF, ejection fraction; HF, heart failure; HFmrEF, heart failure with mildly
reduced ejection fraction; HFpEF, heart failure with preserved ejection fraction; HFrEF, heart failure with reduced ejection fraction; LVEF, left
ventricular ejection fraction; LV, left ventricular; and NT-proBNP, N-terminal pro-B type natriuretic peptide.

Circulation. 2022 May 3;145(18):e895-e1032. 9

 Recommendations (Class 1 and 2a) for Patients at Risk
of HF (Stage A) and Those With Pre-HF (Stage B)

Class 1A recommendation for SGLT2i in patients T2DM with

CVD or at high risk of CVD

Class 1A recommendation for RAAS blockers & β-blockers in

patients of pre HF with LVEF≤40%

Management strategies implemented in patients at risk for HF (stage A) should be continued though stage B. ACEi indicates
angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; BP, blood pressure; COR, Class of
Recommendation; CVD, cardiovascular disease; HF, heart failure; ICD, implantable cardioverter-defibrillator; LVEF, left
ventricular ejection fraction; MI, myocardial infarction; and SGLT2i, sodium glucose cotransporter 2 inhibitor.

Circulation. 2022 May 3;145(18):e895-e1032. 10

 Treatment of HFrEF Stages C and D

Guideline-directed medical therapy for heart failure

with reduced ejection fraction now includes 4
medication classes that include sodium-glucose
cotransporter-2 inhibitors.

Step 1 medications may be started simultaneously at initial (low) doses recommended for HFrEF. Alternatively, these medications
may be started sequentially, with sequence guided by clinical or other factors, without need to achieve target dosing before
initiating next medication. Medication doses should be increased to target as tolerated. ACEi indicates angiotensin-converting
enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; COR, Class of
Recommendation; CRT, cardiac resynchronization therapy; GDMT, guideline-directed medical therapy; ICD, implantable
cardioverter-defibrillator; hydral-nitrates, hydralazine and isosorbide dinitrate; HFrEF, heart failure with reduced ejection fraction;
LBBB, left bundle branch block; MCS, mechanical circulatory support; LVEF, left ventricular ejection fraction; MRA,
mineralocorticoid receptor antagonist; NSR, normal sinus rhythm; NYHA, New York Heart Association; and SGLT2i, sodium-
glucose cotransporter 2 inhibitor. *Participation in investigational studies is appropriate for stage C, NYHA class II and III HF.

Circulation. 2022 May 3;145(18):e895-e1032. 11

Additional Medical Therapies for Patients With HFrEF

Newly Added

GDMT indicates guideline-directed medical therapy; HF, heart failure; HFH, heart failure hospitalization; HFrEF, heart failure with reduced
ejection fraction; IV, intravenous; LVEF, left ventricular ejection fraction; LVESD, left ventricular end systolic dimension; MV, mitral valve; MR,
mitral regurgitation; NP, natriuretic peptide; NSR, normal sinus rhythm; NYHA, New York Heart Association; and RAASi, renin-angiotensin-
aldosterone system inhibitors.

Circulation. 2022 May 3;145(18):e895-e1032. 12

Recommendations for Patients With Mildly Reduced LVEF (41%–49%)

SGLT2i have a Class of Recommendation 2a in

HF with mildly reduced ejection fraction.

Weaker recommendations (Class 2b) are made

for ARNi, ACEi, ARB, MRA, and beta blockers in
HFmrEF.

ACEi indicates angiotensin-converting enzyme inhibitor; ARB, angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor;
HFmrEF, heart failure with mildly reduced ejection fraction; HFrEF, heart failure with reduced ejection fraction; LVEF, left ventricular ejection
fraction; MRA, mineralocorticoid receptor antagonist; and SGLT2i, sodium-glucose cotransporter 2 inhibitor.

Circulation. 2022 May 3;145(18):e895-e1032. 13

 Recommendations for Patients With Preserved LVEF (≥50%)

New recommendations for HFpEF are made for SGLT2i (Class of

Recommendation 2a), MRAs (Class of Recommendation 2b),
and ARNi (Class of Recommendation 2b).

Several prior recommendations have been renewed including

treatment of hypertension (Class of Recommendation 1),
treatment of atrial fibrillation (Class of Recommendation 2a),
use of ARBs (Class of Recommendation 2b), and avoidance of
routine use of nitrates or phosphodiesterase-5 inhibitors (Class
of Recommendation 3: No Benefit).

ARB indicates angiotensin receptor blocker; ARNi, angiotensin receptor-neprilysin inhibitor; HF, heart failure; HFpEF, heart failure with
preserved ejection fraction; LVEF, left ventricular ejection fraction; MRA, mineralocorticoid receptor antagonist; and SGLT2i, sodium-glucose
cotransporter-2 inhibitor. *Greater benefit in patients with LVEF closer to 50%.

Circulation. 2022 May 3;145(18):e895-e1032. 14

 Recommendations for Treatment of Patients With HF and
Selected Comorbidities

ACEi indicates angiotensin-converting enzyme inhibitor; AF, atrial fibrillation; ARB, angiotensin receptor blocker; AV, atrioventricular; CHA2DS2-
VASc, congestive heart failure, hypertension, age ≥75 years, diabetes mellitus, stroke or transient ischemic attack [TIA], vascular disease, age 65
to 74 years, sex category; CPAP, continuous positive airway pressure; CRT, cardiac resynchronization therapy; EF, ejection fraction; GDMT,
guideline-directed medical therapy; HF, heart failure; HFrEF, heart failure with reduced ejection fraction; IV, intravenous; LVEF, left ventricular
ejection fraction; NYHA, New York Heart Association; SGLT2i, sodium-glucose cotransporter-2 inhibitor; and VHD, valvular heart disease.
*Patients with chronic HF with permanent-persistent-paroxysmal AF and a CHA2DS2-VASc score of ≥2 (for men) and ≥3 (for women).

Circulation. 2022 May 3;145(18):e895-e1032. 15

 KEY TAKEAWAYS

Guideline-directed medical therapy (GDMT) for heart failure (HF) with reduced ejection fraction
(HFrEF) now includes 4 medication classes that include sodium-glucose cotransporter-2
inhibitors (SGLT2i).

SGLT2i have a Class of Recommendation 2a in HF with mildly reduced ejection fraction

(HFmrEF). Weaker recommendations (Class of Recommendation 2b) are made for ARNi, ACEi,
ARB, MRA, and beta blockers in this population.

New recommendations for HFpEF are made for SGLT2i (Class of Recommendation 2a), MRAs
(Class of Recommendation 2b), and ARNi (Class of Recommendation 2b). Several prior
recommendations have been renewed including treatment of hypertension (Class of
Recommendation 1), treatment of atrial fibrillation (Class of Recommendation 2a), use of ARBs
(Class of Recommendation 2b), and avoidance of routine use of nitrates or phosphodiesterase-
5 inhibitors (Class of Recommendation 3: No Benefit).

Improved LVEF is used to refer to those patients with previous HFrEF who now have an LVEF
>40%. These patients should continue their HFrEF treatment.

Evidence supporting increased filling pressures is important for the diagnosis of HF if the LVEF
is >40%. Evidence for increased filling pressures can be obtained from noninvasive (e.g.,
natriuretic peptide, diastolic function on imaging) or invasive testing (e.g., hemodynamic
measurement).

Primary prevention is important for those at risk for HF (stage A) or pre-HF (stage B). Stages of
HF were revised to emphasize the new terminologies of “at risk” for HF for stage A and pre-HF
for stage B.

Circulation. 2022 May 3;145(18):e895-e1032. 16

2. 2022 ACC Expert Consensus Decision
Pathway on the Role of Nonstatin
Therapies for LDL-Cholesterol Lowering
in the Management of ASCVD Risk

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 Introduction of new non statin therapy with
Bempedoic acid, Inclisiran and Evinacumab.

Introduction of additional higher-risk patient

subgroups that should be considered for
additional LDL-C lowering therapies.

Order of preference in nonstatin therapy 1)

Ezetimibe 2) PCSK9 mab 3) Bempedoic acid 4)
Inclisiran.

Specialized therapies, such as evinacumab or

lomitapide & LDL apheresis to be considered
only in cases of FH on non response to other
non statin therapies.

*PCSK9 mAb includes alirocumab and evolocumab.

ASCVD = atherosclerotic cardiovascular disease;
HDL-C = high-density lipoprotein cholesterol; HoFH
= homozygous familial hypercholesterolemia; LDL-C
= low-density lipoprotein cholesterol; PCSK9 mAb =
proprotein convertase subtilisin/kexin type 9
monoclonal antibodies.

J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418. 18

 Adults With Clinical ASCVD at
Very High Risk on Statin Therapy
for Secondary Prevention
†In very high-risk patients who
require greater lowering of LDL-C at
the time of an ASCVD event,
initiation of combination therapy
with high-intensity or maximally
tolerated statin therapy and
ezetimibe or maximally tolerated
statin therapy with/without
ezetimibe and PCSK9 mAbs may be
considered. §If adults with clinical
ASCVD at very high risk on a statin
therapy for secondary prevention
require >25% additional lowering of
LDL-C, a PCSK9 inhibitor may be
preferred as the initial nonstatin
therapy. #PCSK9 mAb is preferred as
the initial PCSK9 inhibitor of choice in
view of demonstrated safety,
efficacy, and cardiovascular
outcomes benefits in FOURIER and
ODYSSEY Outcomes. Inclisiran may
be considered in patients with
demonstrated poor adherence to
PCSK9 mAbs, adverse effects from
both PSCK9 mAbs, or those who may
be unable to self-inject. There is
currently no evidence for additional
efficacy in LDL-C lowering or
cardiovascular outcomes benefit for
combination therapy with a PSCK9
mAb and inclisiran when added to
maximally tolerated statin therapy
with/without ezetimibe or
bempedoic acid; therefore, if
inclisiran is to be used, it should be
used in place of a PCSK9 mAb.
∗∗Fasting triglycerides ≥150 mg/dL
following a minimum of 4-12 weeks
of lifestyle intervention, a stable dose
of maximally tolerated statin therapy
when indicated, as well as evaluation
and management of secondary
causes of hypertriglyceridemia.

J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418. 19

 Adults With Clinical ASCVD at Very High Risk and
Baseline LDL-C ≥190 mg/dL Not Due to Secondary
Causes and With Clinical Diagnosis or Genetic
Confirmation of Familial Hypercholesterolemia,
on Statin for Secondary Prevention

‡May consider lomitapide or LDL

apheresis in appropriate patients. §If
patients with clinical ASCVD and LDL-
C ≥190 mg/dL require >25%
additional lowering of LDL-C, a PCSK9
mAb may be preferred as the initial
nonstatin agent. ‖Clinicians should
preferentially prescribe drugs that
have been shown in randomized
controlled trials to provide ASCVD
risk-reduction benefits that outweigh
the potential for adverse effects and
drug-drug interactions and consider
patient preferences. ¶No outcome
studies exist for bempedoic acid or
inclisiran. ∗∗Limited data are
available for apheresis. Patients with
clinical ASCVD and persistent
elevation of LDL-C >200 mg/dL
without a clinical or genetic diagnosis
of familial hypercholesterolemia, may
be candidates for LDL apheresis
under the care of a lipid specialist.
††No outcomes studies exist for
evinacumab and lomitapide, and
limited data are available for
apheresis. ‡‡Fasting triglycerides
≥150 mg/dL following a minimum of
4-12 weeks of lifestyle intervention, a
stable dose of maximally tolerated
statin therapy when indicated, as well
as evaluation and management of
secondary causes of
hypertriglyceridemia.

J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418. 20

 Adults With Diabetes and
Without ASCVD and Baseline
LDL-C <190 mg/dL on Statin
Therapy for Primary Prevention
MAJORITY SMALL PROPORTION

∗Diabetes-specific high-risk features include

long duration (≥10 years for type 2 diabetes or
≥20 years for type 1 diabetes, albuminuria ≥30
mcg of albumin/mg creatinine, eGFR <60
mL/min/1.73 m2, retinopathy, neuropathy,
ankle-brachial index <0.9. ‡May consider a bile
acid sequestrant as optional alternative agent
if ezetimibe-intolerant and triglycerides <300
mg/dL. §Fasting triglycerides ≥150 mg/dL
following a minimum of 4-12 weeks of lifestyle
intervention, a stable dose of maximally
tolerated statin therapy when indicated, as
well as evaluation and management of
secondary causes of hypertriglyceridemia.
ASCVD = atherosclerotic cardiovascular
disease; ECDP = Expert Consensus Decision
Pathway; HDL-C = high-density lipoprotein
cholesterol; LDL-C = low-density lipoprotein
cholesterol; RD/RDN = registered
dietician/registered dietician nutritionist; SASE
= statin-associated side effect

Due to the higher frequency of elevated non

HDL-C despite lower levels of LDL-C in patients
with diabetes, non HDL-C thresholds are
important to consider in this high-risk patient
population.

In the absence of ASCVD or baseline LDL-C

≥190 mg/dL, the PCSK9 mAbs, bempedoic
acid, or inclisiran do not currently have an
established, evidence-based role for primary
prevention of ASCVD in patients with diabetes.

J Am Coll Cardiol. 2022 Oct 4;80(14):1366-1418. 21

 KEY TAKEAWAYS
Introduction of new non statin therapy Bempedoic acid, Inclisiran and
Evinacumab. Introduction of additional higher-risk patient subgroups that should
be considered for additional LDL-C lowering therapies.

Importance to non HDL-C thresholds along with LDL-C thresholds. Incorporation

of Subclinical Atherosclerosis Imaging Into Risk Assessment and Treatment for
Adults Without Clinical ASCVD or Diabetes or LDL-C ≥190 mg/dL

Order of preference in nonstatin therapy 1) Ezetimibe 2) PCSK9 mab 3)

Bempedoic acid 4) Inclisiran. Specialized therapies, such as evinacumab or
lomitapide & LDL apheresis to be considered only in cases of FH on non response
to other non statin therapies.

In the absence of ASCVD or baseline LDL-C ≥190 mg/dL, the PCSK9 mAbs,
bempedoic acid, or inclisiran do not currently have an established, evidence-
based role for primary prevention of ASCVD in patients with diabetes.

Do not recommend routine use of nonstatin therapy for primary prevention

patients with ASCVD risk <20%. However nonstatin therapies in recommended
for primary prevention patients with extensive subclinical atherosclerosis
detected on imaging.

For patients with SASEs who meet evidence-based guideline criteria for statin
therapy, avoiding complete discontinuation of statin treatment is strongly
recommended.

Circulation. 2022 May 3;145(18):e895-e1032. 22

Landmark Trials

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 TABEL OF CONTENT

Serial No Content Page no

1 CHAP: Treatment for Mild Chronic Hypertension during 26
Pregnancy
2 POISE 3: Tranexamic Acid in Patients Undergoing 27
Noncardiac Surgery
3 VALOR HCM: Myosin Inhibition in Patients With OHCM 28
Referred for Septal Reduction Therapy
4 SODIUM HF: Reduction of dietary sodium to less than 29
100 mmol in heart failure
5 SCORED: Sotagliflozin in Patients with Diabetes and CKD 30
6 PACMAN AMI: Alirocumab added to High-Intensity Statin 31
in Patients of Acute MI.
7 DELIVER: Dapagliflozin in HFmrEF & HFpEF 32
8 SECURE: Polypill Strategy in Secondary Cardiovascular 33
Prevention
9 TIME: Evening Vs morning dosing of usual 34
antihypertensives - CV outcomes in UK adults
10 REVIVED-BCIS2: Percutaneous Revascularization for 35
Ischemic Left Ventricular Dysfunction
11 ADVOR: Acetazolamide in Acute Decompensated HF with 36
Volume Overload
12 INVICTUS: Rivaroxaban in RHD-Associated AF 37

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 TABEL OF CONTENT

Serial No Content Page no

13 IRONMAN: Intravenous ferric derisomaltose in patients 38
with heart failure and iron deficiency in UK
14 EMPA-KIDNEY: Empagliflozin in Patients with Chronic 39
Kidney Disease
15 OCEAN[a]-DOSE: Small Interfering RNA to Reduce 40
Lipoprotein(a) in Cardiovascular Disease
16 Impact of diabetes on the effects of SGLT2i on kidney 41
outcomes: collaborative meta-analysis of large placebo-
controlled trials
17 PRECISION: Dual endothelin antagonist aprocitentan for 42
resistant hypertension - a multicentre, blinded,
randomised, parallel-group, phase 3 trial
18 BrigHTN: Phase 2 Trial of Baxdrostat for Treatment of 43
Resistant Hypertension
19 Key takeaways 44-47

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 CHAP: Treatment for Mild Chronic Hypertension during
Pregnancy
AIM: To evaluate the benefits and safety of the treatment of mild chronic hypertension (blood
pressure, <160/100 mm Hg) during pregnancy.

METHOD: In this open-label, multicenter, randomized trial, we assigned pregnant women with
mild chronic hypertension and singleton fetuses at a gestational age of less than 23 weeks to
receive antihypertensive medications recommended for use in pregnancy (active-treatment
group) or to receive no such treatment unless severe hypertension (systolic pressure, ≥160 mm
Hg; or diastolic pressure, ≥105 mm Hg) developed (control group). The primary outcome was a
composite of preeclampsia with severe features, medically indicated preterm birth at less than 35
weeks’ gestation, placental abruption, or fetal or neonatal death. A total of 2408 women were
enrolled in the trial.

RESULTS: The incidence of a primary-outcome event was lower in the active-treatment group
than in the control group (30.2% vs. 37.0%), for an adjusted risk ratio of 0.82 (P<0.001). The
incidence of serious maternal complications was 2.1% and 2.8%, respectively (risk ratio, 0.75),
and the incidence of severe neonatal complications was 2.0% and 2.6% (risk ratio, 0.77). The
incidence of any preeclampsia in the two groups was 24.4% and 31.1%, respectively (risk ratio,
0.79), and the incidence of preterm birth was 27.5% and 31.4% (risk ratio, 0.87).

CONCLUTION: In pregnant women with mild chronic hypertension, a strategy of

targeting a blood pressure of less than 140/90 mm Hg was associated with better
pregnancy outcomes than a strategy of reserving treatment only for severe
hypertension, with no increase in the risk of small-for-gestational-age birth weight.
N Engl J Med 2022;386:1781-92. 26
 POISE 3: Tranexamic Acid in Patients Undergoing
Noncardiac Surgery
AIM: To evaluate the efficacy of Tranexamic acid in reducing the perioperative bleeding in
patients undergoing noncardiac surgery.

METHOD: Patients were randomly assigned to receive tranexamic acid (1-g intravenous bolus) or
placebo at the start and end of surgery. The primary efficacy outcome was life-threatening
bleeding, major bleeding, or bleeding into a critical organ (composite bleeding outcome) at 30
days. The primary safety outcome was myocardial injury after noncardiac surgery,
nonhemorrhagic stroke, peripheral arterial thrombosis, or symptomatic proximal venous
thromboembolism (composite cardiovascular outcome) at 30 days. A total of 9535 patients
underwent randomization.

RESULTS: A composite bleeding outcome event occurred in 433 of 4757 patients (9.1%) in the
tranexamic acid group and in 561 of 4778 patients (11.7%) in the placebo group (hazard ratio,
0.76; absolute difference, -2.6 percentage points; two-sided P<0.001 for superiority). A composite
cardiovascular outcome event occurred in 649 of 4581 patients (14.2%) in the tranexamic acid
group and in 639 of 4601 patients (13.9%) in the placebo group (hazard ratio, 1.02; upper
boundary of the one-sided 97.5% CI, 1.14; absolute difference, 0.3 percentage points; one-sided
P = 0.04 for noninferiority).

CONCLUTION: Among patients undergoing noncardiac surgery, the incidence of the

composite bleeding outcome was significantly lower with tranexamic acid than with
placebo. Although the between-group difference in the composite cardiovascular
outcome was small, the noninferiority of tranexamic acid was not established.
N Engl J Med 2022;386:1986-97. 27
 VALOR HCM: Myosin Inhibition in Patients With OHCM
Referred for Septal Reduction Therapy
AIM: To determine whether the oral myosin inhibitor mavacamten enables patients to improve
sufficiently to no longer meet guideline criteria or choose to not undergo septal reduction
therapy.

METHOD: Patients with left ventricular (LV) outflow tract (LVOT) gradient ≥50 mm Hg at
rest/provocation who met guideline criteria for SRT were randomized, double blind, to
mavacamten, 5 mg daily, or placebo, titrated up to 15 mg based on LVOT gradient and LV ejection
fraction. The primary endpoint was the composite of the proportion of patients proceeding with
SRT or who remained guideline-eligible after 16 weeks' treatment. 112 oHCM patients were
enrolled in the study.

RESULTS: After 16 weeks, 43 of 56 placebo patients (76.8%) and 10 of 56 mavacamten patients

(17.9%) met guideline criteria or underwent SRT, difference (58.9%; P < 0.001). Hierarchical
testing of secondary outcomes showed significant differences (P < 0.001) favouring mavacamten,
mean differences in post-exercise peak LVOT gradient -37.2 mm Hg; ≥1 NYHA functional class
improvement 41.1%; improvement in patient-reported outcome 9.4 points; and NT-proBNP and
cardiac troponin I between-groups geometric mean ratio 0.33 and 0.53.

CONCLUTION: In highly symptomatic obstructive HCM patients meeting guideline

criteria for SRT, the addition of mavacamten to maximally tolerated background
medical therapy significantly reduced guideline eligibility for SRT after 16 weeks of
treatment.
J Am Coll Cardiol. 2022 Jul 12;80(2):95-108. 28
 SODIUM HF: Reduction of dietary sodium to less than
100 mmol in heart failure
AIM: Evaluate the effects of a low-sodium diet (<100 mmol), compared to usual care in patients
of HF.

METHOD: This is an international, open-label, randomized, controlled trial that enrolled patients
at 26 sites in six countries. Eligible patients were aged ≥18 years, with chronic HF, and receiving
optimally tolerated GDMT. Patients were randomly assigned (1:1), to either usual care according
to local guidelines or a low sodium diet of less than 100 mmol (ie, <1500 mg/day). The primary
outcome was the composite of cardiovascular-related admission to hospital, cardiovascular-
related emergency department visit, or all-cause death within 12 months in the intention-to-treat
(ITT) population. 806 patients were randomly assigned to a low sodium diet (n=397) or usual care
(n=409).
RESULTS: By 12 months, primary
outcome had occurred in 60 (15%) of
397 patients in the low sodium diet
group and 70 (17%) of 409 in the usual
care group (hazard ratio [HR] 0·89;
p=0·53). All-cause death occurred in
22 (6%) patients in the low sodium
diet group and 17 (4%) in the usual
care group (HR 1·38; p=0·32),
cardiovascular-related hospitalization
occurred in 40 (10%) patients in the
low sodium diet group and 51 (12%)
patients in the usual care group (HR
0·82; p=0·36), and cardiovascular-
related emergency department visits
occurred in 17 (4%) patients in the low
sodium diet group and 15 (4%)
patients in the usual care group (HR
1·21; p=0·60).

CONCLUTION: In ambulatory patients with heart failure, a dietary

intervention to reduce sodium intake did not reduce clinical events.

Lancet. 2022 Apr 9;399(10333):1391-1400. 29

 SCORED: Sotagliflozin in Patients with Diabetes and CKD
AIM: To valuate efficacy and safety of sotagliflozin in preventing cardiovascular events in patients
with diabetes with chronic kidney disease with or without albuminuria.

METHOD: In this multicenter, double-blind trial patients with T2DM (glycated hemoglobin level,
≥7%), chronic kidney disease (eGFR, 25-60 ml per minute per 1.73 m2 of body-surface area), and
risks for cardiovascular disease were randomly assigned in a 1:1 ratio to receive sotagliflozin or
placebo. The primary end point was changed during the trial to the composite of the total
number of deaths from cardiovascular causes, hospitalizations for heart failure, and urgent visits
for heart failure. 10,584 were enrolled, with 5292 assigned to the sotagliflozin group and 5292
assigned to the placebo group, and followed for a median of 16 months.

RESULTS: The rate of primary end-point

events was 5.6 events per 100 patient-
years in the sotagliflozin group and 7.5
events per 100 patient-years in the
placebo group (hazard ratio, 0.74;
P<0.001). The rate of deaths from
cardiovascular causes per 100 patient-
years was 2.2 with sotagliflozin and 2.4
with placebo (hazard ratio, 0.90; P =
0.35). For the original coprimary end
point of the first occurrence of death
from cardiovascular causes, nonfatal
myocardial infarction, or nonfatal
stroke, the hazard ratio was 0.84; for the
original coprimary end point of the first
occurrence of death from cardiovascular
causes or hospitalization for heart
failure, the hazard ratio was 0.77.

CONCLUTION: Sotagliflozin resulted in a lower risk of the composite of deaths

from cardiovascular causes, hospitalizations for HF, and urgent visits for HF
than placebo among patients with T2DM and CKD, with or without
albuminuria.
N Engl J Med 2021;384:129-39 30
PACMAN AMI: Alirocumab added to High-Intensity Statin
in Patients of Acute MI
AIM: To determine the effects of alirocumab on coronary atherosclerosis using serial
multimodality intracoronary imaging in patients with acute myocardial infarction.

METHOD: In this double-blind, placebo-controlled, RCT 300 patients undergoing PCI for acute MI
at 9 academic European hospitals were included. Patients were randomized to receive biweekly
subcutaneous alirocumab (150 mg; n = 148) or placebo (n = 152), initiated less than 24 hours
after urgent PCI of the culprit lesion, for 52 weeks in addition to high-intensity statin therapy
(rosuvastatin, 20 mg). Intravascular ultrasonography (IVUS), near-infrared spectroscopy, and
optical coherence tomography were serially performed in the 2 non-infarct-related coronary
arteries at baseline and after 52 weeks. The primary efficacy end point was the change in IVUS-
derived percent atheroma volume from baseline to week 52.

RESULTS: At 52 weeks, mean change in percent atheroma volume was -2.13% with alirocumab vs
-0.92% with placebo (difference, -1.21%, P < .001). Mean change in maximum lipid core burden
index within 4 mm was -79.42 with alirocumab vs -37.60 with placebo (difference, -41.24, P =
.006). Mean change in minimal fibrous cap thickness was 62.67 μm with alirocumab vs 33.19 μm
with placebo (difference, 29.65 μm; P = .001). Adverse events occurred in 70.7% of patients
treated with alirocumab vs 72.8% of patients receiving placebo.

CONCLUTION: Among patients with acute MI, the addition of subcutaneous

biweekly alirocumab, compared with placebo, to high-intensity statin therapy
resulted in significantly greater coronary plaque regression in non–infarct
related arteries after 52 weeks.
JAMA. 2022 May 10;327(18):1771-1781. 31
 DELIVER: Dapagliflozin in HFmrEF & HFpEF

AIM: To determine the efficacy & safety of dapagliflozin in HF patients with a higher LVEF.

METHOD: We randomly assigned 6263 patients with heart failure and a left ventricular ejection
fraction of more than 40% to receive dapagliflozin (at a dose of 10 mg once daily) or matching
placebo, in addition to usual therapy. The primary outcome was a composite of worsening heart
failure (which was defined as either an unplanned hospitalization for heart failure or an urgent
visit for heart failure) or cardiovascular death, as assessed in a time-to-event analysis.

RESULTS: Over a median of 2.3 years, the primary outcome occurred in 512 of 3131 patients
(16.4%) in the dapagliflozin group and in 610 of 3132 patients (19.5%) in the placebo group
(hazard ratio, 0.82; P<0.001). Worsening heart failure occurred in 368 patients (11.8%) in the
dapagliflozin group and in 455 patients (14.5%) in the placebo group (hazard ratio, 0.79);
cardiovascular death occurred in 231 patients (7.4%) and 261 patients (8.3%), respectively
(hazard ratio, 0.88). Total events and symptom burden were lower in the dapagliflozin group than
in the placebo group.

CONCLUTION: This trial is the evidence to support the use of an SGLT2

inhibitor as essential therapy in patients with HF, regardless of the presence
or absence of T2DM or left ventricular ejection fraction.

N Engl J Med. 2022 Sep 22;387(12):1089-1098. 32

 SECURE: Polypill Strategy in Secondary Cardiovascular
Prevention
AIM: To determine the efficacy & safety of pollypill (aspirin, ACEi and statin) in secondary
prevention of cardiovascular death and complications after myocardial infarction.

METHOD: In this phase 3 RCT, we assigned patients with MI within the previous 6 months to a
polypill-based strategy or usual care. The polypill treatment consisted of aspirin (100 mg),
ramipril (2.5, 5, or 10 mg), and atorvastatin (20 or 40 mg). The primary composite outcome was
cardiovascular death, nonfatal type 1 myocardial infarction, nonfatal ischemic stroke, or urgent
revascularization. The key secondary end point was a composite of cardiovascular death, nonfatal
type 1 myocardial infarction, or nonfatal ischemic stroke. 2499 patients underwent randomization
and were followed for a median of 36 months.

RESULTS: A primary-outcome event occurred in 118 of 1237 patients (9.5%) in the polypill group
and in 156 of 1229 (12.7%) in the usual-care group (hazard ratio, 0.76; P = 0.02). A key secondary-
outcome event occurred in 101 patients (8.2%) in the polypill group and in 144 (11.7%) in the
usual-care group (hazard ratio, 0.70; P = 0.005). Adverse events were similar between groups.

CONCLUTION: Treatment with a polypill containing aspirin, ramipril, and atorvastatin

within 6 months after myocardial infarction resulted in a significantly lower risk of
major adverse cardiovascular events than usual care.

N Engl J Med. 2022 Sep 15;387(11):967-977. 33

 TIME: Evening Vs morning dosing of usual
antihypertensives – CV outcomes in UK adults

AIM: To investigate whether evening dosing of usual antihypertensive medication improves major
cardiovascular outcomes compared with morning dosing in patients with hypertension.

METHOD: In this prospective, pragmatic, decentralized, parallel-group study in UK, eligible

participants were randomly assigned (1:1), without restriction, stratification, or minimization, to
take all of their usual antihypertensive medications in either the morning (0600-1000 h) or in the
evening (2000-0000 h). Participants were followed up for the composite primary endpoint of
vascular death or hospitalization for non-fatal MI or non-fatal stroke. The primary endpoint was
assessed as the time to first occurrence of an event in the intention-to-treat population. 21,104
were randomly assigned to evening (n=10503) or morning (n=10601) dosing groups.

RESULTS: A primary endpoint event

occurred in 362 (3·4%) participants
assigned to evening treatment (0·69
events per 100 patient-years) and
390 (3·7%) assigned to morning
treatment (0·72 events per 100
patient-years; unadjusted hazard
ratio 0·95; p=0·53). No safety
concerns were identified.

CONCLUTION: Evening dosing of usual antihypertensive medication was not

different from morning dosing in terms of major cardiovascular outcomes.
Patients can be advised that they can take their regular antihypertensive
medications at a convenient time that minimizes any undesirable effects.

Lancet. 2022 Oct 22;400(10361):1417-1425. 34

 REVIVED-BCIS2: Percutaneous Revascularization for
Ischemic Left Ventricular Dysfunction
AIM: To investigate whether revascularization by PCI can improve event-free survival and left
ventricular function in patients with severe ischemic left ventricular systolic dysfunction, as
compared with optimal medical therapy.

METHOD: We randomly assigned patients with a LVEF ≤35%, extensive coronary artery disease
amenable to PCI, and demonstrable myocardial viability to a strategy of either PCI plus optimal
medical therapy (PCI group) or optimal medical therapy alone (optimal-medical-therapy group).
The primary composite outcome was death from any cause or hospitalization for HF. Major
secondary outcomes were LVEF at 6 and 12 months and quality-of-life scores. A total of 700
patients underwent randomization, 347 were assigned to the PCI group and 353 to the optimal-
medical-therapy group.

RESULTS: Over a median of 41 months, a

primary-outcome event occurred in 129
patients (37.2%) in the PCI group and in
134 patients (38.0%) in the optimal-
medical-therapy group (hazard ratio,
0.99; P = 0.96). The LVEF was similar in
the two groups at 6 months (mean
difference, -1.6 percentage points) and
at 12 months (mean difference, 0.9
percentage points). Quality-of-life scores
at 6 and 12 months appeared to favor
the PCI group, but the difference had
diminished at 24 months.

CONCLUTION: Among patients with severe ischemic left ventricular systolic

dysfunction who received optimal medical therapy, revascularization by PCI
did not result in a lower incidence of death from any cause or hospitalization
for heart failure.

N Engl J Med. 2022 Oct 13;387(15):1351-1360. 35

ADVOR: Acetazolamide in Acute Decompensated HF with
Volume Overload
AIM: To investigate if acetazolamide can improve the efficiency of loop diuretics, potentially
leading to more and faster decongestion in patients with acute decompensated heart failure with
volume overload.

METHOD: In this multicenter, parallel-group, double-blind, randomized, placebo-controlled trial,

we assigned patients with acute decompensated HF, clinical signs of volume overload and an N-
terminal pro-B-type natriuretic peptide level of >1000 pg/ml or a B-type natriuretic peptide level
of >250 pg/ml to receive either intravenous acetazolamide (500 mg once daily) or placebo added
to standardized iv loop diuretics. Randomization was stratified according to the LVEF (≤40% or
>40%). The primary end point was successful decongestion, defined as the absence of signs of
volume overload, within 3 days after randomization and without an indication for escalation of
decongestive therapy. A total of 519 patients underwent randomization.
RESULTS: Successful decongestion
Successful decongestion occurred in 108 of 256 patients
(42.2%) in the acetazolamide group
and in 79 of 259 (30.5%) in the
placebo group (risk ratio, 1.46;
P<0.001). Death from any cause or
rehospitalization for HF occurred in
76 of 256 patients (29.7%) in the
acetazolamide group and in 72 of
259 patients (27.8%) in the placebo
group (hazard ratio, 1.07).
Acetazolamide treatment was
associated with higher cumulative
urine output and natriuresis. The
incidence of worsening kidney
function, hypokalemia, hypotension,
and adverse events was similar in
the two groups.

CONCLUTION: Addition of acetazolamide to loop diuretic therapy in patients

with acute decompensated heart failure resulted in a greater incidence of
successful decongestion.
N Engl J Med. 2022 Sep 29;387(13):1185-1195. 36
 INVICTUS: Rivaroxaban in RHD-Associated AF

AIM: To evaluate efficacy of actor Xa inhibitors in prevention of cardiovascular events in patients

with rheumatic heart disease-associated atrial fibrillation.

METHOD: We enrolled patients with AF and echocardiographically documented RHD who had any
of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9), a mitral-valve area of
no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were
randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K
antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism,
myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. The
primary safety outcome was major bleeding according to the International Society of Thrombosis
and Hemostasis. Of 4565 enrolled patients, 4531 were included in the final analysis.

RESULTS: In the intention-to-treat

analysis, 560 patients in the
rivaroxaban group and 446 in the
vitamin K antagonist group had a
primary-outcome event. The
restricted mean survival time was
1599 days in the rivaroxaban group
and 1675 days in the vitamin K
antagonist group (difference, -76 days;
P<0.001). A higher incidence of death
occurred in the rivaroxaban group
than in the vitamin K antagonist group
(restricted mean survival time, 1608
days vs. 1680 days; difference, -72
days). No significant between-group
difference in the rate of major
bleeding was noted.

CONCLUTION: Among patients with RHD associated AF, vitamin K antagonist

therapy led to a lower rate of a composite of cardiovascular events or death
than rivaroxaban therapy, without a higher rate of bleeding.
N Engl J Med. 2022 Sep 15;387(11):978-988. 37
 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.
Lancet. 2022 Nov 4:S0140-6736(22)02083-9. 38
 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, N Engl J Med. 2022 Nov 4. doi: 10.1056/NEJMoa2204233. 39
 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 40
 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 41
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. 42
 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 43
 KEY TAKEAWAYS
• In pregnant women with mild chronic hypertension, a strategy of
targeting a blood pressure of less than 140/90 mm Hg was
CHAP associated with better pregnancy outcomes than a strategy of
reserving treatment only for severe hypertension, with no
increase in the risk of small-for-gestational-age birth weight.

• Among patients undergoing noncardiac surgery, the incidence of

the composite bleeding outcome was significantly lower with
POISE 3 tranexamic acid than with placebo. Although the between-group
difference in the composite cardiovascular outcome was small,
the noninferiority of tranexamic acid was not established.

VALOR • In highly symptomatic obstructive HCM patients meeting

guideline criteria for SRT, the addition of mavacamten to
maximally tolerated background medical therapy significantly
HCM reduced guideline eligibility for SRT after 16 weeks of treatment.

SODIUM • In ambulatory patients with heart failure, a dietary intervention

to reduce sodium intake did not reduce clinical events.
HF
• Sotagliflozin resulted in a lower risk of the composite of deaths

SCORED from cardiovascular causes, hospitalizations for HF, and urgent

visits for HF than placebo among patients with T2DM and CKD,
with or without albuminuria.

44
 KEY TAKEAWAYS

PACMAN • Among patients with acute MI, the addition of

subcutaneous biweekly alirocumab, compared with placebo,
to high-intensity statin therapy resulted in significantly
AMI greater coronary plaque regression in non–infarct related
arteries after 52 weeks.

• This trial is the evidence to support the use of an SGLT2

DELIVER inhibitor as essential therapy in patients with HF, regardless

of the presence or absence of T2DM or left ventricular
ejection fraction.

• Treatment with a polypill containing aspirin, ramipril, and

SECURE atorvastatin within 6 months after myocardial infarction

resulted in a significantly lower risk of major adverse
cardiovascular events than usual care.

• Evening dosing of usual antihypertensive medication was

not different from morning dosing in terms of major
TIME cardiovascular outcomes. Patients can be advised that they
can take their regular antihypertensive medications at a
convenient time that minimizes any undesirable effects.

REVIVED • Among patients with severe ischemic left ventricular systolic

dysfunction who received optimal medical therapy,
revascularization by PCI did not result in a lower incidence
BCIS 2 of death from any cause or hospitalization for heart failure.

45
 KEY TAKEAWAYS

• Addition of acetazolamide to loop diuretic therapy in

ADVOR patients with acute decompensated heart failure resulted in
a greater incidence of successful decongestion.

• Among patients with RHD associated AF, vitamin K

INVICTUS antagonist therapy led to a lower rate of a composite of

cardiovascular events or death than rivaroxaban therapy,
without a higher rate of bleeding.

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

intravenous ferric derisomaltose administration was
IRONMAN associated with a lower risk of hospital admissions and
cardiovascular death, further supporting the benefit of iron
repletion in this population.

EMPA • 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
KIDNEY cardiovascular causes than placebo.

OCEAN[a]- • The siRNA olpasiran led to a profound and sustained

reduction in the lipoprotein(a) concentration when
administered every 12 weeks in patients with established
DOSE atherosclerotic cardiovascular disease.

46
 KEY TAKEAWAYS

• SGLT2i safely reduce the risk of kidney disease progression,

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

• In patients with resistant hypertension, aprocitentan was well

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

• Aldosterone synthase inhibition with baxdrostat led to

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

47
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48