REDUCE-AMI: Beta-blockers in MI & LVEF >=50%

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REDUCE-AMI: NEJM 2024 DOI: 10.1056/NEJMoa2401479

Bottom line: In patients with myocardial infarction, LVEF >=50%, and no other indication for beta-blockers (angina, arrhythmia, heart failure), beta-blockers do not meaningfully reduce death or recurrent myocardial infarction. Additional trials that should complete in 2024 will provide additional data, including in patients with LVEF 41-49%.

Patients (n=5020 randomized)

  • Setting: Sweden (95%), Estonia, NZ, 2017-2023

  • Included:

    • Adults 1-7 days from MI

    • Obstructive coronary artery disease (CAD) on coronary angiography (i.e. stenosis >=50%, FFR <=0.8 or iFR <=0.89 in any segment)

    • Echo after MI showing left ventricular ejection fraction (LVEF) >=50% (i.e. preserved)

  • Excluded: Any other indication for beta-blockers; any contraindication to beta-blockers.

  • Baseline:

    • Age 65, 22% female

    • Median 2 days from admission to randomization

    • LVEF & coronary angiography variables not reported

    • STEMI 35%, PCI 95-96%

    • Comorbidities: Prior MI ~7%, diabetes 14%, HTN 46%, smoking ~20%

    • Medications:

      • Beta-blocker prior to admission ~11-12%

      • At discharge: ASA/P2Y12 inhibitor 95-98%, ACEI/ARB 80%, statin, 98-99%

Intervention: Beta-blocker

  • Metoprolol (1st choice; target >=100 mg/d) or bisoprolol (target >=5 mg/d)

  • 96% prescribed beta-blocker on discharge (2/3 metoprolol, 1/3 bisoprolol), ~91% receiving at “month 2” visit, 82% receiving at “1-year” visit

Comparator: No beta-blocker

  • 10% prescribed beta-blocker on discharge

Outcomes @ median 3.5 years

Primary outcome (death from any cause or new MI): Beta-blocker 7.9%, no beta-blocker 8.3% (hazard ratio [HR] 0.96, 95% confidence interval [CI] 0.79-1.16)

  • Death: 3.9% vs 4.1% (HR 0.94, 95% CI 0.71-1.24)

  • MI: 4.5% vs 4.7%

  • Bayesian re-analysis (using https://benjamin-andrew.shinyapps.io/bayesian_trials/): Assuming non-informative prior (ignoring outdated post-MI beta-blocker RCTs from the pre-reperfusion era), posterior probability=19% of an absolute risk reduction of >=1% absolute risk reduction (HR<=0.88) at 3.5 years

Safety

  • Hospitalization for bradycardia, 2-30 AVB, hypotension, syncope, or PPM implantation: 3.4% vs 3.2% (HR 1.08, 95% CI 0.79-1.46)

  • Hospitalization for asthma or COPD: 0.6% in both groups (HR 0.94, 0.46-1.89)

Internal validity

  • Randomization using permuted blocks

  • Allocation via web-based system

  • Performance bias: Moderate crossover (18% from beta-blocker to no beta-blocker by 1 year in intervention group; ~10% to beta-blocker in comparator group) biases the results toward the null

  • Detection bias: No blinding of participants or treating clinicians (open-label), but objective (death from any cause) & semi-objective outcomes (e.g. MI hospitalization) minimize risk of detection bias

  • No loss to follow-up (but missing data for 8 who emigrated, 4 withdrew consent)

  • Intention-to-treat analysis

Generalizability & other considerations

  • Who does these results NOT apply to?

    • These results do NOT apply to patients with another valid cardiovascular indication for beta-blockers, including:

      • Angina (despite PCI/CABG, if indicated)

      • Arrhythmia (ventricular arrhythmia, atrial arrhythmia requiring rate control, congenital long QT syndrome, etc)

      • Ejection fraction <50% [especially those with heart failure]

      • HF with reduced/mildly-reduced/improved LVEF

  • With that said, these results broadly apply to patients not captured within the above, which is most patients with MI seen in contemporary practice

  • This is the first contemporary trial of beta-blockers post-MI (see https://nerdcat.org/studysummaries/beta-blockers-cad for our summary of this previous evidence)

    • Prior to this trial, practice was mainly driven by a 1999 meta-analysis of RCTs conducted 1966-1991; prior to widespread use of now-established treatments for ACS/MI (especially reperfusion with PCI/fibrinolytics, ASA, statins)

  • Several other ongoing trials will shed further light on the role of beta-blockers in patients post-MI with LVEF >40%, including:

    • ABYSS (n=3700, France): Beta-blocker continuation vs discontinuation 6 months post-MI (excluding patients with LVEF <40%, persistent angina/ischemia, HF in last 2 y, arrhythmia)

    • BETAMI (n=2900, Norway) & DANBLOCK (n=2760, Denmark): Beta-blocker vs no beta-blocker post-MI (excluding patients with LVEF <40%, clinical heart failure, LV akinesia in >=3 segments, arrhythmia)

SELECT: Semaglutide in patients with CV disease & overweight/obesity

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SELECT. N Engl J Med 2023; 389:2221-2232

Bottom line: In overweight/obese patients with existing CV disease, semaglutide reduced the risk of death & cardiovascular events and reduced weight, but increased the risk of discontinuation due to GI intolerance. For every 1000 patients treated for 3.3 years, 9 deaths and 10 non-fatal MIs would be avoided, but 84 more patients receiving semaglutide would stop the drug due to GI intolerance.

Patients (n=17,604 randomized)

  • 41 countries, Oct 2018-March 2021

  • Included:

    • Age >=45 years

    • BMI >=27

    • Established cardiovascular disease: Prior MI or stroke (ischemic or hemorrhagic), or symptomatic PAD

  • Key exclusions:

    • Diabetes: Prior diagnosis, A1c >=6.5% at screening, or treatment with GLP1 RA or any other glucose-lowering drug

    • NYHA 4 HF

    • ESRD/dialysis

  • Baseline:

    • Age 62 y, male 72%

    • White 84%, Asian 8%, Black 4%

    • Weight mean 97 kg, BMI mean 33.3 (71.5% BMI >=30)

    • MI 76%, stroke 23%, symptomatic PAD 9%, HF 24%

    • EQ-5D-VAS 77/100

    • ASA 78%, P2Y12i 33-34%, statin 90%, beta-blocker 70%

Intervention: Semaglutide subcutaneous once weekly

  • Starting dose: 0.24 mg q1w

  • Titration: Uptitrated every 4 weeks (to 0.5 -> 1.0 -> 1.7 -> 2.4 mg q1w) as tolerated

  • Target dose: 2.4 mg q1w (reached after 16 weeks)

    • 77% of those still taking the drug at year 2 received the target dose

Comparator: Matching placebo

Outcomes @ median 3.3 years

All % present semaglutide first, then placebo

  • Death: 4.3% vs 5.2%, HR 0.81 (0.71-0.93), i.e. -0.3%/y

  • Primary outcome: Composite of CV death, non-fatal MI, or non-fatal stroke:

    • 6.5% vs 8.0%, HR 0.80 (95% CI 0.72-0.90), -1.5% or ~ -0.5%/y

    • CV death: 2.5% vs 3.0%, HR 0.85 (0.71-1.01)

    • Non-fatal MI: 2.7% vs 3.7%, HR 0.72 (0.61-0.85)

    • Non-fatal stroke: 1.7% vs 1.9%, HR 0.93 (0.74-1.15)

    • Subgroup: Visually fairly consistent results across all subgroups (including sex, age, BMI, with vs without HF), though p-values for interaction by subgroup not provided

  • HF composite (CV death, HF hospitalization or urgent medical visit for HF: 3.4% vs 4.1%, HR 0.82 (0.71-0.96)

  • Renal composite (renal death, dialysis, transplantation, eGFR <15, persistent eGFR reduction >=50%, or persistent uACR >300 mg/g): 1.8% vs 2.2%, HR 0.78 (0.63-0.96)

  • Safety

    • Serious adverse events: 33.4% vs 36.4% (-3%)

    • Treatment discontinuation: 26.7% vs 23.6% (+4.1%)

    • Adverse event leading to discontinuation: 16.6% vs 8.2% (+8.4%)

    • Gallbladder-related disorder: 2.8% vs 2.3% (+0.5%)

    • Acute pancreatitis: 0.2% vs 0.3%

  • Mean difference in %change in weight at 2 years: -8.5% vs placebo

Internal validity

  • Computer-generated random sequence generation

  • Allocation concealment by centralized interactive web-based response system

  • Blinding by matching placebo & titration schedule

  • Intention-to-treat analysis

  • 2.2% lost to follow-up

Generalizability

  • All patients in this trial had some form of prior CVD, mostly atherosclerotic/ischemic disease, and were inherently at “high” risk of recurrent CV event. “Primary prevention” patients, or those with CAD or cerebrovascular disease without prior MI or stroke would inherently be at lower risk & therefore may experience lower absolute benefit.

  • Details on the subgroup of patients with HF are currently sparse, and it is unclear if this benefit extends across the spectrum of LVEF

SODIUM-HF: Sodium restriction in patients with heart failure

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By Hans Haag with editorial support from Ricky Turgeon

SODIUM-HF. Lancet 2022;399:1391-400.

Bottom line: In patients with heart failure (HF), achieved dietary sodium restriction ~1600 mg/day did not reduce the risk of death or cardiovascular hospitalizations/ED visits compared with usual care achieving sodium about 2000 mg/day.

Patients (n=841 randomized, 806 analyzed)

  • Included:

    • Adults with clinical HF

    • NYHA class 2-3

    • Receiving optimal guideline-directed medical therapy

  • Key exclusions:

    • Dietary sodium intake <1500 mg/day

    • Serum sodium <130 mmol/L

    • eGFR <20 mL/min/1.73 m^2 or requiring hemodialysis

    • Within 1 month of cardiovascular hospitalization

  • Baseline

    • Age 67, 33% female, 58% Canadian

    • NYHA 2 (71.4%), NYHA 3 (26.9%), LVEF median 36%, NT-proBNP ~800, HF hospitalization in last 12 months ~33%

    • Comorbidities: HTN 62%, CAD 47%, AF/AFL 39%, diabetes 33%

    • SBP 118, eGFR 61

    • Meds: ACEI/ARB/ARNI 81%, beta-blocker 87%, MRA 57%

      • Diuretic use not reported

    • Baseline median sodium intake ~2200 mg/day (self-report)

Intervention: Dietary sodium intake <1500 mg/d

  • Country-specific meal plans & menus

  • Achieved ~1600 mg/d at 12 months (approximately 400 mg/d lower than comparator group)

Comparator: Usual care

  • General advice to restrict dietary sodium (as provided during routine clinical practice)

  • Achieved ~2000 mg/d at 12 months

Outcomes @ 12 months

  • No difference for any of the clinical outcomes

  • Improvements in some subjective secondary outcomes with the intervention

    • QoL: Mean difference in Kansas City Cardiomyopathy Questionnaire +3.4/100 vs placebo

    • NYHA class 1: 16% vs 11% (odds ratio 1.69 [95% CI 1.16-2.50] for improvement ≥1 NYHA class)

    • 6min walk distance (6MWD): +6.6 meters (95% CI -9 to +22)

Internal validity

  • Low risk of bias for clinical outcomes (death, hospitalizations)

    • Low risk of selection bias: Independent statistician generated randomization list; allocation concealment by automated web-based system. Block randomization according to the study site.

    • Low risk of performance & detection bias: Patients and clinicians unblinded to treatment allocation, but relatively objective outcomes & blinded endpoint adjudication

    • Attrition bias: ITT analysis, LTFU <1%

  • High risk of bias for subjective outcomes (QoL, NYHA, & to lesser extent 6MWD)

    • Low risk of selection bias as above

    • But high risk of performance & detection bias due to subjective nature of these outcomes & extra healthcare visits with in-person dietician visits at months 3 & 9 (possibility to identify & mitigate worsening HF or optimize pharmacotherapy)

  • Trial stopped early due to operational feasibility issues resulting from the COVID-19 pandemic

Other considerations

  • Generalizability: Limited to individuals already fairly restrictive in dietary sodium

    • Patients/comparator:

      • All patients were restricting sodium intake at baseline (~2.2 g/d) compared to the general population (average 4 g/day worldwide). The value of this restriction & ideal targets (e.g. 2-2.5 g/d vs 3-4 g/d) remains unknown.

      • Notably, these results do not apply to patients who are acutely hospitalized with HF, require escalating diuretic doses, or those with advanced chronic kidney disease

    • Intervention: Highly transportable/scalable due to use of meal plans & menus rather than prepared meals

  • Proportion of patients on diuretics used, doses used, & potential changes during the trial have not (yet?) been reported

    • These results could shed light on the secondary outcomes (e.g. could sodium restriction allow for lower diuretic doses -> less urinary frequency -> improve QoL?)

    • Similarly, information on changes to HF pharmacotherapy during the trial could offer further insights into these results

Context

  • Sodium restriction has historically been a cornerstone of HF management for decades due to the role of sodium in contributing to sodium retention and congestive symptoms of HF

    • However, evidence for sodium retention (& specific targets) has been limited to observational studies and small, inconclusive randomized controlled trials.

  • The latest Canadian HF guideline recommendations on dietary sodium intake (2017) acknowledged this uncertainty and recommended personalizing daily targets while still recommending 2000-3000 mg of sodium per day (consistent with the usual care group in SODIUM-HF)

PARAGON-HF: Sacubitril-valsartan in heart failure with ejection fraction >=45%

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By Hans Haag with editorial support from Ricky Turgeon

PARAGON-HF. NEJM 2019;381:1609-20

Bottom line:

  • In patients with heart failure (HF) with left ventricular ejection fraction (LVEF) ≥45%, sacubitril-valsartan did not reduce the composite total HF hospitalizations/cardiovascular (CV) death or death from any cause over ~3 years.

  • Sacubitril-valsartan increased the risk of hypotension (+5%) and angioedema (+0.4%) compared with valsartan.

  • In subgroup analyses (which often lead us astray) sacubitril-valsartan reduced HF hospitalizations in females by ~1.5%/year (but not males) with LVEF in the “lower” range (45-60%).

Patients (n=4822 randomized)

  • Screened 10,359 -> 5746 entered valsartan run-in (~9% discontinued) -> 5205 entered sacubitril-valsartan run-in (7% discontinued) -> 4822 randomized

  • Included:

    • Age 50+

    • NYHA 2-4

    • LVEF ≥45% measured in the last 6 months

    • At least one of the following:

      • HF hospitalization within 9 months prior + NT-proBNP >200 pg/mL (>600 pg/mL if AF)

      • NT-pro-BNP >300 pg/mL (>900 pg/mL if AF)

    • Echo evidence of LA enlargement (e.g. LAV ≥55 mL or LAVi ≥29 mL/m^2) or LVH (septal thickness ≥1.1 cm)

    • Symptomatic HF for at least 30 days prior to screening visit

    • Structural heart disease (LA enlargement or LVH)

  • Key exclusions:

    • Any prior LVEF <40%, history of dilated cardiomyopathy, hemodynamically significant valvular heart disease

    • Uncontrolled/life-threatening dysrhythmia, including AF-RVR

    • History of angioedema

    • Alternate diagnosis to explain HF symptoms (e.g. anemia with Hb <100 g/L, severe COPD)

    • Uncontrolled hypertension

    • SBP <100 mm Hg or symptomatic hypotension

    • eGFR <30 mL/min/1.73m^2 or a reduction of >35% after run-in period

    • K >5.2 mmol/L

  • Baseline:

    • Age 73, 52% female, 82% white, 12% Asian, 2% Black

    • NYHA 2 (77%) & 3 (20%), LVEF median 57%, NT-proBNP ~900 pg/mL, HF hospitalization in last 12 months ~23%

    • Comorbidities: HTN 96%, diabetes 43%, AF/AFlutter 33%

    • Meds: Diuretic 96%, ACEI/ARB 86%, beta-blocker 80%, MRA ~25%

    • SBP 130, eGFR 63

Interventions: Sacubitril-valsartan 97/103 mg BID vs valsartan 160 mg BID

  • Intervention: Sacubitril-valsartan 97/103 mg BID (82% on target dose)

  • Comparator: Valsartan 160 mg BID (85% on target dose)

  • Co-intervention: MRA permitted, all other non-study RAAS inhibitors stopped

Outcomes @ median 35 months (2.9 years)

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Internal validity: Low risk of bias selection, performance, detection & attrition bias

  • Selection bias: Computer-generated random sequence; allocation concealment by interactive web-response system

  • Performance & detection bias: Patients, clinicians & investigators blinded to study allocation via double-dummy placebo

  • Attrition bias: ITT analysis, LTFU <0.1%

Other considerations

  • Generalizability:

    • 16% excluded in single-blind run-in

      • Consisted of (1) Valsartan 40-80 mg BID x 1-2 weeks, then (2) sacubitril-valsartan 49/51 mg BID x2-4 weeks, then randomized

    • PARAGON-HF defined “preserved” ejection fraction as >45%, which differs from the (subsequent) 2021 universal definition and classification of HF’s classification of HF with preserved LVEF as ≥50% and HF with LVEF 41-49% as mildly-reduced

  • Pre-specified subgroup analysis of the primary outcome based on baseline LVEF suggests greater benefit with ARNI in patients with LVEF below the study median (≤ 57%) and in females (but no reduction in death in any subgroup)

  • Are the results clinically important?

    • Yes for: Patients who place higher value on reducing HF hospitalizations and improving quality of life than they do the increase in hypotension, angioedema (and higher cost)

    • Not for:

      • Males

      • Female patients with LVEF ≥60%

      • Female patients who do not care about the benefits noted above, or who are more concerned about costs, pill burden, and the adverse effects noted

    • However, given the more robust evidence and greater certainty for SGLT2 inhibitors and MRAs in this setting (noted below), ARNI should generally be offered after exhausting those other options.

Context

EMPEROR-Preserved: Empagliflozin in heart failure with preserved or mildly-reduced ejection fraction

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References:

Bottom Line: In patients with symptomatic heart failure with preserved (≥50%; HFpEF) or mildly-reduced (41-49%; HFmrEF) ejection fraction, empagliflozin reduced the risk of HF hospitalization vs placebo (-3.2%) and increased the probability of a clinically important improvement in quality of life (+3.8%), but did not reduce deaths or total hospitalizations at 2.2 years. Empagliflozin increased the risk of symptomatic hypotension (+1.4%), genital fungal infections (+1.5), and UTIs (+1.8%).

Patients (n=5988)

  • 11,583 screened -> 5988 randomized

    • Most common reasons for exclusion:

      • 78% NT-proBNP below inclusion criteria threshold

      • 5% LVEF <40%

      • 4% exclusion criteria based on safety

  • Enrolment 2017-April 2020

  • 23 countries

  • Included: Symptomatic chronic HFpEF or HFmrEF with elevated natriuretic peptide

    • Chronic HF (≥3 months)

    • NYHA 2-4

    • LVEF >40% without any prior LVEF ≤40%

    • NT-proBNP

      • >300 pg/mL if in sinus rhythm

      • >900 pg/mL if in atrial fibrillation

    • Either

      • Structural heart disease (LAE &/or LVH) documented on echo

      • HF hospitalization within past 12 months

  • Key exclusions:

    • SBP <100 mm Hg

    • eGFR <20

    • BMI ≥45

    • SGLT2i contraindication (history of ketoacidosis, allergy/hypersensitivity)

    • “Cardiovascular (CV) disease/treatment that increase the unpredictability of or change the patients’ clinical course independent of HF” (e.g. MI/stroke/TIA/CV surgery in past 90 days; infiltrative cardiomyopathy; heart transplant recipient/wait list; severe valvular disease)

    • “Untreated CV condition that might influence the course of HF/study drug tolerability” (e.g. AF with uncontrolled HR, SBP ≥180 mm Hg)

    • “Significant comorbidity that might influence clinical course” (e.g. pulmonary disease requiring O2, PO steroids or requiring hospitalization; acute/chronic liver disease)

  • Baseline characteristics:

    • Age 72, 45% female, 76% White/14% Asian

    • NYHA 2 (81%), 3 (18%)

    • Mean LVEF 54% (~1/3 each in categories 41-49%, 50-59%, ≥60%)

    • Median NT-proBNP ~950-1000 pg/mL

    • HF hospitalization in last 12 months ~23%

    • Comorbidities: HTN 90-91%, AF 51%, eGFR <60 50%, diabetes 49%

    • Meds: Beta-blocker 86%, ACEI/ARB 79%, ARNI ~2%, MRA 37-38%, digitalis 9-10%

    • SBP 132, HR 70

Intervention: Empagliflozin 10 mg qAM

Comparator: Matching placebo

Outcomes at median 26.2 months (2.2 years)

Efficacy outcomes

Effect on quality of life (using Kansas City Cardiomyopathy Questionnaire [KCCQ]; range 0 [worst] to 100 [best]):

  • More likely to have a clinically-important (≥5/100) improvement in quality of life with empagliflozin vs placebo

    • KCCQ-overall summary score at 1 year: Empagliflozin 49.6% vs placebo 45.8% (+3.8%)

    • Similar effect over time (e.g. difference +4.7% at 3 months vs 3.8% at 12 months)

    • Similar difference if considering clinically-important decline (-4.8% at 1 year) or different cutoffs for improvement (+2.3% for ≥10-point improvement & +3.6% for ≥15-point improvement)

    • Similar difference if considering KCCQ subscores (e.g. +4.6% for KCCQ-total symptoms score [HF symptom burden + frequency] at 1 year)

Cumulative incidence curve for the primary composite outcome showing immediate separation of empagliflozin and placebo curves (suggesting early benefit)

Cumulative incidence curve for the primary composite outcome showing immediate separation of empagliflozin and placebo curves (suggesting early benefit)

Safety outcomes

Effect on biometrics & biomarkers (difference vs placebo):

  • Body weight: -1.3 kg

  • SBP -1.2 mm Hg

  • A1c: -0.2%

  • NT-proBNP: -20 pg/mL

Internal validity: Low risk of bias

  • Computer-generated random sequence using permuted blocks

    • Stratified by geographic region, diabetes status, eGFR <60 or ≥60, & LVEF <50% or ≥50%

  • Allocation concealment by central randomization via interactive response technology

  • Blinding of participants and treating clinicians with matching placebo

  • Blinded outcome adjudication

  • Intention-to-treat analysis

  • 3% loss-to-follow-up for primary outcome, 0.6% for death

Other considerations

Are the results clinically important?

  • Maybe; this will very much depend on individual patient/clinician preferences

    • Overall, likely net clinical benefit based on composite of % who died or had a hospitalization due to any cause

      • HF hospitalizations only accounted for 18% of total hospitalization outcomes in this trial, and therefore the 3.2% absolute reduction in the risk of a first HF hospitalization is diluted in total hospitalizations

      • Neutral effect on all-cause death & inconclusive effect on CV deaths

        • CV death accounted for 55% of deaths (sudden death > HF > other), & non-CV deaths accounted for 45% (infection > malignancy > other)

    • QoL improvement with empagliflozin consistent with results of the PRESERVED-HF trial & effects of SGLT2i on QoL in HFrEF trials

      • Brief summary of PRESERVED-HF:

        • P: 324 patients with NYHA 2-4 HF & LVEF >=45% (mixed HFpEF/HFmrEF) + elevated NT-proBNP/BNP + receiving a diuretic + additional enrichment criteria + eGFR >=20 + SBP >=100

        • I: Dapagliflozin 10 mg daily

        • C: Placebo

        • O: KCCQ-23 @ 3 months

          • Mean +4.5/100 in overall-summary score with dapa

          • Clinically-important improvement: Dapa 45.4% vs placebo 34.9% (+10.5%) at 3 months

How do we apply these results to patient care (generalizability)?

  • Although the study defined “preserved” ejection fraction as >40%, the 2021 universal definition and classification of HF further sub-classify HF as HFmrEF if 41-49% (~1/3 of the study population) & HFpEF if ≥50%

    • Subgroup analysis of the primary outcome comparison based on baseline LVEF suggested attenuation of efficacy with increasing LVEF, with uncertain efficacy with LVEF ≥60%

      • Hazard ratio progressively attenuated from LVEF 41-49% (0.71, 95% CI 0.57-0.88), 50-59% (0.80, 95% CI 0.64-0.99), ≥60% (0.87, 0.69-1.10)

      • Risk of the primary outcome increased with lower LVEF, leading to a greater absolute risk reduction in those with lower baseline LVEF (even if we assume constant 21% relative risk reduction regardless of LVEF)

        • LVEF 41-49%: Risk in placebo group 19.5%, absolute risk reduction 4.1%

        • LVEF 50-59%: Risk in placebo group 16.8%, absolute risk reduction 3.5%

        • LVEF ≥60%: Risk in placebo group 14.9%, absolute risk reduction 3.1%

  • Efficacy on primary outcome (in terms of relative effect) similar in females/males, diabetes/no diabetes, AF/no AF, eGFR <60/≥60, & regardless of race/ethnicity

More to come…