Cardiology

Importance: Superficial vein thrombosis (SuVT) is characterized by thrombus in the superficial veins, typically in the lower or upper extremities, and has an estimated annual incidence of 64 to 131 per 100 000 person-years. Approximately 10% of patients with SuVT progress to deep vein thrombosis (DVT) or pulmonary embolism (PE).

Observations: Endothelial injury (caused by infection or intravenous devices), venous stasis (such as from chronic venous insufficiency or prolonged immobility), and hypercoagulability (due to cancer or pregnancy) are pathophysiologic factors associated with SuVT. Clinical risk factors for lower extremity SuVT are similar to those of DVT and PE and include pregnancy, varicose veins, and active cancer. The incidence of SuVT is greater in females than males (78-167 compared with 49-116 per 100 000 person-years). In contrast with lower extremity SuVT, upper extremity SuVT is primarily caused by indwelling intravenous catheters. Patients typically present with a tender, red, palpable cord under the skin in the upper or lower extremity. D-dimer testing has a sensitivity of approximately 48% to 74.3% and, therefore, is not reliable for excluding SuVT. Approximately 25% of patients with lower extremity SuVT present with concomitant DVT, likely because risk factors for SuVT and DVT are similar and because SuVT can extend into deep veins. In people without classic symptoms and signs of SuVT, ultrasonography can establish the presence and extent of the thrombus. Management may include elastic compression stockings and nonsteroidal anti-inflammatory drugs. For patients with SuVTs that are at least 5 cm long or those with persistent or worsening symptoms despite several days of conservative therapy, treatment includes anticoagulation with fondaparinux 2.5 mg. Alternative anticoagulation treatment includes rivaroxaban 10 mg once daily and low-molecular-weight heparins (eg, enoxaparin 40 mg once daily), which may reduce subsequent venous thromboembolic events. SuVT located within 3 cm of a deep vein should be treated with therapeutic doses of anticoagulation such as direct oral anticoagulants.

Conclusions and relevance: SuVT typically presents as a tender, painful, palpable cord under the skin. Management may include elastic compression stockings, nonsteroidal anti-inflammatory drugs, and systemic anticoagulation with fondaparinux 2.5 mg or rivaroxaban 10 mg. SuVTs within 3 cm of a deep vein should be treated with therapeutic dose anticoagulation.

Author/s:

Gregory Piazza, Darsiya Krishnathasan, Nada Hamade

Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation: The ALONE-AF Randomized Clinical Trial

Megan George — Tue, 02 Sep 2025 13:46:16 +0000

Date Added:

September 2, 2025

Journal/Publication:

JAMA

Publication Date:

August 31, 2025

URL:

Long-Term Anticoagulation Discontinuation After Catheter Ablation for Atrial Fibrillation: The ALONE-AF Randomized Clinical Trial

Type:

Clinical Research Results

Format:

Article

DOI (1):

10.1001/jama.2025.14679

Keywords

clinical pharmacy and pharmacology

PMID (1):

40886309

MeSH

ischemic attack, transient

Discontinuation of anticoagulants after catheter ablation for atrial fibrillation appears to be am appropriate option. James W. Mold, MD, MPH

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Importance: Data from randomized clinical trials on a long-term anticoagulation strategy for patients after catheter-based ablation for atrial fibrillation (AF) are lacking.

Objective: To evaluate whether discontinuing oral anticoagulant therapy provides superior clinical outcomes compared with continuing oral anticoagulant therapy in patients without documented atrial arrhythmia recurrence after catheter ablation for AF.

Design, setting, and participants: A randomized clinical trial including 840 adult patients (aged 19-80 years) who were enrolled and randomized from July 28, 2020, to March 9, 2023, at 18 hospitals in South Korea. Enrolled patients had at least 1 non-sex-related stroke risk factor (determined using the CHA2DS2-VASc score [range, 0-9]) and no documented recurrence of atrial arrhythmia for at least 1 year after catheter ablation for AF. The CHA2DS2-VASc score is used as an assessment of stroke risk among patients with AF (calculated using point values for congestive heart failure, hypertension, ≥75 years of age, diabetes, stroke or transient ischemic attack, vascular disease, between 65 and 74 years of age, and sex category). The date of final follow-up was June 4, 2025.

Interventions: The patients were randomly assigned in a 1:1 ratio to discontinue oral anticoagulant therapy (n = 417) or continue oral anticoagulant therapy (with direct oral anticoagulants; n = 423).

Main outcomes and measures: The primary outcome was the first occurrence of a composite of stroke, systemic embolism, and major bleeding at 2 years. Individual components of the primary outcome (such as ischemic stroke and major bleeding) were assessed as secondary outcomes.

Results: Of the 840 adults randomized, the mean age was 64 (SD, 8) years, 24.9% were women, the mean CHA2DS2-VASc score was 2.1 (SD, 1.0), and 67.6% had paroxysmal AF. At 2 years, the primary outcome occurred in 1 patient (0.3%) in the discontinue oral anticoagulant therapy group vs 8 patients (2.2%) in the continue oral anticoagulant therapy group (absolute difference, -1.9 percentage points [95% CI, -3.5 to -0.3]; P = .02). The 2-year cumulative incidence of ischemic stroke was 0.3% in the discontinue oral anticoagulant therapy group vs 0.8% in the continue oral anticoagulant therapy group (absolute difference, -0.5 percentage points [95% CI, -1.6 to 0.6]). Major bleeding occurred in 0 patients in the discontinue oral anticoagulant therapy group vs 5 patients (1.4%) in the continue oral anticoagulant therapy group (absolute difference, -1.4 percentage points [95% CI, -2.6 to -0.2]).

Conclusions and relevance: Among patients without documented atrial arrhythmia recurrence after catheter ablation for AF, discontinuing oral anticoagulant therapy resulted in a lower risk for the composite outcome of stroke, systemic embolism, and major bleeding vs continuing direct oral anticoagulant therapy.

Trial registration: ClinicalTrials.gov Identifier: NCT04432220.

Author/s:

Daehoon Kim, MD, Jaemin Shim, MD, Eue-Keun Choi, MD

Management of Peripheral Artery Disease

Megan George — Sun, 06 Jul 2025 18:44:56 +0000

Date Added:

July 6, 2025

Journal/Publication:

JAMA Clinical Guidelines Synopsis

Publication Date:

July 2, 2025

URL:

https://jamanetwork.com/journals/jama/fullarticle/2835911?guestAccessKey=4bf0464…

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi:10.1001/jama.2025.8408

Keywords

guidelines

surgery

vascular surgery

peripheral arterial disease

Cardiology

PMID (1):

40601325

MeSH

Peripheral Vascular Diseases

atherosclerosis

Ischemia

Guidance regarding management of patients with peripheral artery disease. James W. Mold, MD, MPH

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This JAMA Clinical Guidelines Synopsis summarizes the American College of Cardiology and American Heart Association’s 2024 guidelines on management of lower extremity peripheral artery disease.

Author/s:

Aman Kansal, MD, Andrew M. Davis, MD, MPH, Jennifer A. Rymer, MD, MBA

Management of Peripheral Artery Disease

Megan George — Sun, 06 Jul 2025 18:44:50 +0000

Date Added:

July 6, 2025

Journal/Publication:

JAMA Clinical Guidelines Synopsis

Publication Date:

July 2, 2025

URL:

https://jamanetwork.com/journals/jama/fullarticle/2835911?guestAccessKey=4bf0464…

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

doi:10.1001/jama.2025.8408

Keywords

guidelines

surgery

vascular surgery

peripheral arterial disease

Cardiology

PMID (1):

40601325

MeSH

Peripheral Vascular Diseases

atherosclerosis

Ischemia

Guidance regarding management of patients with peripheral artery disease. James W. Mold, MD, MPH

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This JAMA Clinical Guidelines Synopsis summarizes the American College of Cardiology and American Heart Association’s 2024 guidelines on management of lower extremity peripheral artery disease.

Author/s:

Aman Kansal, MD, Andrew M. Davis, MD, MPH, Jennifer A. Rymer, MD, MBA

What Is Atrial Fibrillation?

Erin Blanchette — Wed, 30 Apr 2025 21:32:57 +0000

Date Added:

April 30, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

April 24, 2025

URL:

What Is Atrial Fibrillation?

Type:

Patient Education Materials

Format:

Article

DOI (1):

10.1001/jama.2025.2888

Keywords

atrial fibrillation

Cardiology

Patient Information

jama Patient Information

Rhythm Disorders

PMID (1):

40272794

MeSH

myocardial infarction

hypertension

stroke

sleep apnea syndromes

Information for patients about atrial fibrillation. James W. Mold, MD, MPH

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Atrial fibrillation is an abnormal heart rhythm that can cause stroke, heart failure, heart attack, chronic kidney disease, dementia, and death.

Atrial fibrillation is classified as paroxysmal (intermittent episodes lasting 7 days or less), persistent (lasting more than 7 days), long-standing persistent (lasting more than 1 year), or permanent.1

In the US, atrial fibrillation affects about 10.55 million people and is more common among men than women. Other risk factors include older age, smoking, high blood pressure, diabetes, heart disease, high alcohol consumption, sleep apnea, an overactive thyroid gland, and possibly genetic factors.

Author/s:

Rebecca Voelker

Lipoprotein(a)

Erin Blanchette — Wed, 30 Apr 2025 21:25:24 +0000

Date Added:

April 30, 2025

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

April 24, 2025

URL:

Lipoprotein(a)

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2025.2373

Keywords

Cardiovascular Risk Factors

diet

PMID (1):

40272827

MeSH

Lipoproteins

LDL

Lipoprotein(a)

cardiovascular diseases

diet

A summary of what we know currently about lipoprotein (a) and its association with ASCVD, James W. Mold, MD, MPH

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Lipoprotein(a) is a low-density lipoprotein-like particle that carries oxidized phospholipids and has proinflammatory and proatherogenic properties. In prospective studies, higher levels of lipoprotein(a) are associated with significantly higher risk of atherosclerotic cardiovascular disease (ASCVD) and all-cause mortality.1 In a meta-analysis of 29 069 patients, the incidence of ASCVD events per 1000 person-years was 80.0 (95% CI, 75.3-84.9) among people with lipoprotein(a) greater than or equal to 50 mg/dL and 55.3 (95% CI, 53.4-57.3) for people with lipoprotein(a) less than 15 mg/dL (adjusted hazard ratio, 1.35 [95% CI, 1.11-1.66]).2 A similar association of elevated lipoprotein(a) with ASCVD was observed among 460 506 participants from the UK Biobank study.3 Medications such as pelacarsen, olpasiran, and lepodisiran reduce lipoprotein(a) production in the liver and lower plasma lipoprotein(a) by up to 99%, and are currently undergoing testing in randomized clinical trials to determine whether they reduce rates of ASCVD in people with elevated lipoprotein(a).4

Author/s:

Samia Mora, Florian Kronenberg

Management of Atrial Fibrillation

Erin Blanchette — Mon, 18 Nov 2024 14:34:46 +0000

Date Added:

November 18, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

November 14, 2024

URL:

Management of Atrial Fibrillation

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.19565

Keywords

atrial fibrillation

coronary artery disease

PMID (1):

39541112

MeSH

atrial fibrillation

Atrial Fibrillation* / diagnosis

Platelet Aggregation Inhibitors

Mitral Valve Stenosis

Atrial Appendage

coronary artery disease

heart failure

stroke

2023 guidelines from the ACC/AHA/ACCP/HRS on treatment of patients with atrial fibrillation. James W. Mold, MD, MPH

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Atrial fibrillation has a lifetime prevalence of 15% to 40% and predisposes patients to stroke and cardiac dysfunction. This JAMA Clinical Guidelines Synopsis focuses on recommendations for long-term management of AF, including new paradigms for rhythm control and stroke risk reduction.

Author/s:

Francis J Alenghat, Jason T Alexander, Gaurav A Upadhyay

Calcific Aortic Stenosis: A Review

Erin Blanchette — Mon, 18 Nov 2024 14:17:56 +0000

Date Added:

November 18, 2024

Journal/Publication:

JAMA

Publisher:

American Medical Association

Publication Date:

November 11, 2024

URL:

Calcific Aortic Stenosis: A Review

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2024.16477

Keywords

Valvular Heart Disease

Cardiology

aortic valve surgery

Calcific Aortic Stenosis

aortic stenosis

PMID (1):

39527048

MeSH

Aortic Valve, Calcification of

Aortic Valve

Transcatheter Aortic Valve Replacement

antihypertensive agents

Aortic Valve Stenosis

Cardiology

A review of what is currently known about calcific aortic stenosis. James W. Mold, MD, MPH

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Importance: Calcific aortic stenosis (AS) restricts the aortic valve opening during systole due to calcification and fibrosis of either a congenital bicuspid or a normal trileaflet aortic valve. In the US, AS affects 1% to 2% of adults older than 65 years and approximately 12% of adults older than 75 years. Worldwide, AS leads to more than 100 000 deaths annually.

Observations: Calcific AS is characterized by aortic valve leaflet lipid infiltration and inflammation with subsequent fibrosis and calcification. Symptoms due to severe AS, such as exercise intolerance, exertional dyspnea, and syncope, are associated with a 1-year mortality rate of up to 50% without aortic valve replacement. Echocardiography can detect AS and measure the severity of aortic valve dysfunction. Although progression rates vary, once aortic velocity is higher than 2 m/s, progression to severe AS occurs typically within 10 years. Severe AS is defined by an aortic velocity 4 m/s or higher, a mean gradient 40 mm Hg or higher, or a valve area less than or equal to 1.0 cm2. Management of mild to moderate AS and asymptomatic severe AS consists of patient education about the typical progression of disease; clinical and echocardiographic surveillance at intervals of 3 to 5 years for mild AS, 1 to 2 years for moderate AS, and 6 to 12 months for severe AS; and treatment of hypertension, hyperlipidemia, and cigarette smoking as indicated. When a patient with severe AS develops symptoms, surgical aortic valve replacement (SAVR) or transcatheter aortic valve implantation (TAVI) is recommended, which restores an average life expectancy; in patients aged older than 70 years with a low surgical risk, 10-year all-cause mortality was 62.7% with TAVI and 64.0% with SAVR. TAVI is associated with decreased length of hospitalization, more rapid return to normal activities, and less pain compared with SAVR. However, evidence supporting TAVI for patients aged younger than 65 years and long-term outcomes of TAVI are less well defined than for SAVR. For patients with symptomatic severe AS, the 2020 American College of Cardiology/American Heart Association guideline recommends SAVR for individuals aged 65 years and younger, SAVR or TAVI for those aged 66 to 79 years, and TAVI for individuals aged 80 years and older or those with an estimated surgical mortality of 8% or higher.

Conclusions: Calcific AS is a common chronic progressive condition among older adults and is diagnosed via echocardiography. Symptomatic patients with severe AS have a mortality rate of up to 50% after 1 year, but treatment with SAVR or TAVI reduces mortality to that of age-matched control patients. The type and timing of valve replacement should be built on evidence-based guidelines, shared decision-making, and involvement of a multidisciplinary heart valve team.

Author/s:

Catherine M Otto, David E Newby, Graham S Hillis

Shorter Dual Antiplatelet Therapy for Older Adults After Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis

Erin Blanchette — Sun, 31 Mar 2024 22:11:00 +0000

Date Added:

March 31, 2024

Journal/Publication:

JAMA Network Open

Publisher:

American Medical Association

Publication Date:

March 4, 2024

Issue:

Volume:

URL:

Shorter Dual Antiplatelet Therapy for Older Adults After Percutaneous Coronary Intervention: A Systematic Review and Network Meta-Analysis

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jamanetworkopen.2024.4000

Keywords

Cardiology

elderly patients

heart health

dual antiplatelet therapy

PMID (1):

38546647

MeSH

aged

Heart

Data Accuracy

Network Meta-Analysis

Percutaneous Coronary Intervention

Platelet Aggregation Inhibitors* / therapeutic use

It is likely that, in older adults, one to three months of dual antiplatelet therapy following PCI is as effective and safer than six to twelve months of therapy. James W. Mold, MD, MPH

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Importance: The optimal duration of dual antiplatelet therapy (DAPT) for older adults after percutaneous coronary intervention (PCI) is uncertain because they are simultaneously at higher risk for both ischemic and bleeding events.

Objective: To investigate the association of abbreviated DAPT with adverse clinical events among older adults after PCI.

Data sources: The Cochrane Library, Google Scholar, Embase, MEDLINE, PubMed, Scopus, and Web of Science were searched from inception to August 9, 2023.

Study selection: Randomized clinical trials comparing any 2 of 1, 3, 6, and 12 months of DAPT were included if they reported results for adults aged 65 years or older or 75 years or older.

Data extraction and synthesis: The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) reporting guideline was used to abstract data and assess data quality. Risk ratios for each duration of DAPT were calculated with alternation of the reference group.

Main outcomes and measures: The primary outcome of interest was net adverse clinical events (NACE). Secondary outcomes were major adverse cardiovascular events (MACE) and bleeding.

Results: In 14 randomized clinical trials comprising 19 102 older adults, no differences were observed in the risks of NACE or MACE for 1, 3, 6, and 12 months of DAPT. However, 3 months of DAPT was associated with a lower risk of bleeding compared with 6 months of DAPT (relative risk [RR], 0.50 [95% CI, 0.29-0.84]) and 12 months of DAPT (RR, 0.57 [95% CI, 0.45-0.71]) among older adults. One month of DAPT was also associated with a lower risk of bleeding compared with 6 months of DAPT (RR, 0.68 [95% CI, 0.54-0.86]).

Conclusions and relevance: In this systematic review and meta-analysis of different durations of DAPT for older adults after PCI, an abbreviated DAPT duration was associated with a lower risk of bleeding without any concomitant increase in the risk of MACE or NACE despite the concern for higher-risk coronary anatomy and comorbidities among older adults. This study, which represents the first network meta-analysis of this shortened treatment for older adults, suggests that clinicians may consider abbreviating DAPT for older adults.

Author/s:

Dae Yong Park, Jiun-Ruey Hu, Yasser Jamil, Michelle D Kelsey, W Schuyler Jones, Jennifer Frampton, Ajar Kochar, Wilbert S Aronow, Abdulla A Damluji, Michael G Nanna

Management of Heart Failure

Aubrey Delammermore — Sat, 24 Sep 2022 05:00:00 +0000

Date Added:

September 24, 2022

Journal/Publication:

JAMA Clinical Guidelines Synopsis

Publisher:

American Medical Association

Publication Date:

September 15, 2022

Pages:

E1-E2

URL:

Management of Heart Failure

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.1001/jama.2022.16667

Keywords

Stroke Volume

American Heart Association

Cardiology

heart failure

Sodium

PMID (1):

36107415

MeSH

Mineralocorticoid Receptor Antagonists

Angiotensin Receptor Antagonists

Sodium-Glucose Transporter 2 Inhibitors

Angiotensin-Converting Enzyme Inhibitors

Angioedema

Updated guidelines for management of congestive heart failure rom the American College of Cardiology and the American Heart Association. James W. Mold, MD, MPH

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GUIDELINE TITLE 2022 American College of Cardiology
(ACC)/American Heart Association AHA)/Heart Failure
Society of America (HFSA) Guidelines for the Management
of Heart Failure
RELEASE DATE April 1, 2022
PRIOR VERSIONS 2017 ACC/AHA/HFSA Focused Update
of the 2013 ACCF/AHA Guideline for the Management of
Heart Failure and 2013 ACCF/AHA Guideline for the
Management of Heart Failure
DEVELOPER AND FUNDING SOURCE ACC/AHA Joint
Committee on Clinical Practice Guidelines
TARGET POPULATION Adult patients with a diagnosis of
or at risk for heart failure (HF)
MAJOR RECOMMENDATIONS
• Classifications for HF are separated into 4 categories based
on ejection fraction (EF) and disease history: HF with
reduced EF (EF 40%), HF with mildly reduced EF
(EF 41%-49%), HF with preserved EF (EF 50%), and HF
with improved EF (EF previously 40% with improvement
to >40%).
• In patients with chronic HF with reduced EF, angiotensin
receptor–neprilysin inhibitors (ARNIs) are preferred over
angiotensin-converting enzyme inhibitors (ACEIs) and
angiotensin II receptor blockers (ARBs). If ARNI use is not
feasible, ACEIs are preferred over ARBs, unless there is
significant cough or angioedema (class 1, level of
evidence [LOE] A).
• Sodium-glucose cotransporter 2 (SGLT2) inhibitors should
be included across all HF categories (symptomatic HF with
reduced EF [class 1, LOE A]; HF with mildly reduced EF and
HF with preserved EF [class 2a, LOE B-R]).
• Patients with HF with improved EF should continue to
receive medical therapy originally indicated for HF with
reduced EF (class 1, LOE B-R).
• Evidence-based treatment of HF with preserved EF
includes blood pressure control (class 1, LOE C-LD),
SGLT2 inhibitors (class 2a, LOE B-R), mineralocorticoid
antagonists, ARBs, and ARNIs (class 2b, LOE B-R).

Author/s:

Belkin, M. N., Cifu, A. S., Pinney, S.

Milestones in Heart Failure: How Far We Have Come and How Far We Have Left to Go

Saige Blanchard — Mon, 03 Jan 2022 06:00:00 +0000

Date Added:

January 3, 2022

Journal/Publication:

Cureus Journal of Medical Science

Publication Date:

December 12, 2021

URL:

Milestones in Heart Failure: How Far We Have Come and How Far We Have Left to Go

Type:

Meta-analyses, Reviews, and Guidelines

Format:

Article

DOI (1):

10.7759/cureus.20359

Keywords

MeSH

Angiotensin Receptor Antagonists

heart failure

Disease Progression

A nice summary of what we currently know about the pharmacologic treatment of congestive heart failure. James W. Mold, MD, MPH

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Heart failure is a clinically complex syndrome that results due to the failure of the ventricles to function as pump and oxygenate end organs. The repercussions of inadequate perfusion are seen in the form of sympathetic overactivation and third spacing, leading to clinical signs of increased blood pressure, dyspnea, fatigue, palpitations, etc. This article provided a brief overview of the clinical syndrome of heart failure; its epidemiology, risk factors, symptoms, and staging; and the mechanisms involved in disease progression. This article also described several landmark trials in heart failure that tested the efficacy of first-line drugs such as beta-blockers, angiotensin receptor blockers, angiotensin-converting enzyme inhibitors, and the latest drugs in the field of heart failure: angiotensin receptor neprilysin inhibitors. Most studies described in this article were guideline-setting trials that revolutionized the practice of medicine and cardiology.

Author/s:

H., Kela, I., Kakarlala, C., Hassan, M., Belavadi, R., Gudigopuram, S. V. R., Raguthu, C., Modi, S., Sange, I.

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

Brian Desmarais — Sat, 24 Aug 2019 19:20:10 +0000

Date Added:

August 24, 2019

Journal/Publication:

The Lancet

Publication Date:

August 22, 2019

URL:

Identifying optimal doses of heart failure medications in men compared with women: a prospective, observational, cohort study

Type:

Clinical Research Results

Format:

Article

DOI (1):

https://doi.org/10.1016/S0140-6736(19)31792-1

Keywords

Cardiology

Vascular medicine

MeSH

ventricular dysfunction, left

Peptidyl-Dipeptidase A

Angiotensin-Converting Enzyme Inhibitors

Angiotensin Receptor Antagonists

It appears, from this analysis of a large clinical trial, that women with CHF need only half the doses of ACEs, ARBs, and beta blockers that men do to achieve the same benefits. James W. Mold, MD, MPH

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Summary

Background

Guideline-recommended doses of angiotensin-converting-enzyme (ACE) inhibitors or angiotensin-receptor blockers (ARBs), and β blockers are similar for men and women with heart failure with reduced ejection fraction (HFrEF), even though there are known sex differences in pharmacokinetics of these drugs. We hypothesised that there might be sex differences in the optimal dose of ACE inhibitors or ARBs and β blockers in patients with HFrEF.

Methods

We did a post-hoc analysis of BIOSTAT-CHF, a prospective study in 11 European countries of patients with heart failure in whom initiation and up-titration of ACE inhibitors or ARBs and β blockers was encouraged by protocol. We included only patients with left ventricular ejection fraction less than 40%, and excluded those who died within the first 3 months. Primary outcome was a composite of time to all-cause mortality or hospitalisation for heart failure. Findings were validated in ASIAN-HF, an independent cohort of 3539 men and 961 women with HFrEF.

Findings

Among 1308 men and 402 women with HFrEF from BIOSTAT-CHF, women were older (74 [12] years vs 70 [12] years, p<0·0001) and had lower bodyweights (72 [16] kg vs 85 [18] kg, p<0·0001) and heights (162 [7] cm vs 174 [8] cm, p<0·0001) than did men, although body-mass index did not differ significantly. A similar number of men and women reached guideline-recommended target doses of ACE inhibitors or ARBs (99 [25%] vs 304 [23%], p=0·61) and β blockers (57 [14%] vs 168 [13%], p=0·54). In men, the lowest hazards of death or hospitalisation for heart failure occurred at 100% of the recommended dose of ACE inhibitors or ARBs and β blockers, but women showed approximately 30% lower risk at only 50% of the recommended doses, with no further decrease in risk at higher dose levels. These sex differences were still present after adjusting for clinical covariates, including age and body surface area. In the ASIAN-HF registry, similar patterns were observed for both ACE inhibitors or ARBs and β blockers, with women having approximately 30% lower risk at 50% of the recommended doses, with no further benefit at higher dose levels.

Interpretation

This study suggests that women with HFrEF might need lower doses of ACE inhibitors or ARBs and β blockers than men, and brings into question what the true optimal medical therapy is for women versus men.

Funding

European Commission.

Author/s:

Santema, B.T., Ouwerkerk, W., Tromp, J., Sama, I.E., Ravera, A., Regitz-Zagrosek, V.