Evidence-based pharmacological prophylaxis recommendations for venous thromboembolism in hospitalized acutely ill medical patients: a systematic review of clinical practice guidelines

Souza, Ana Paula Callejo de; Gabriel, Franciele Cordeiro; Fontes-Mota, Géssica Caroline Henrique; Silva, Mariana de Siqueira; Ribeiro, Eliane

doi:10.1590/1677-5449.202300672

Ana Paula Callejo de Souza

conception and design

analysis and interpretation

data collection

writing the article

statistical analysis

overall responsibility

Universidade de São Paulo - USP, São Paulo, SP, Brasil.

https://orcid.org/0000-0002-0960-3575

Franciele Cordeiro Gabriel

data collection

Universidade de São Paulo - USP, São Paulo, SP, Brasil.

https://orcid.org/0000-0002-4375-3729

Géssica Caroline Henrique Fontes-Mota

data collection

Universidade de São Paulo - USP, São Paulo, SP, Brasil.

https://orcid.org/0000-0003-1986-9155

Mariana de Siqueira Silva

data collection

Universidade de São Paulo - USP, São Paulo, SP, Brasil.

https://orcid.org/0009-0001-6947-3119

Eliane Ribeiro

conception and design

critical revision of the article

final approval of the article

overall responsibility

Universidade de São Paulo - USP, São Paulo, SP, Brasil.

https://orcid.org/0000-0003-0886-368X

Conflicts of interest: No conflicts of interest declared concerning the publication of this article.

Correspondence Ana Paula Callejo de Souza Av. Dr. Cândido Motta Filho, 183/63, Acácia Vila São Francisco CEP: 05351-000 - São Paulo (SP), Brasil Tel.: +55 (11) 9821180-45 E-mail: ana_callejo@usp.br

Author information APCS - Pharmacist, Hospital Universitário, Universidade de São Paulo; MSc candidate, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo. FCG - Pharmacist, PhD, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo. GCHFM - Pharmacist, PhD candidate, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo. MSS - Pharmacy undergraduate, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo. ER - PhD, professor, Faculdade de Ciências Farmacêuticas, Universidade de São Paulo.

Author contributions Conception and design: APCS and ER Analysis and interpretation: APCS Data collection: APCS, FCG, GCHFM, MSS Writing the article: APCS Critical revision of the article: ER Final approval of the article*: ER Statistical analysis: APCS Overall responsibility: APCS, ER *All authors have read and approved of the final version of the article submitted to J Vasc Bras.

PIPOH	INCLUSION CRITERIA
Population	Hospitalized (> 24 hours) adults (> 18 years)
Intervention	Pharmacological prophylaxis for venous thromboembolism
Professional	Multi-professional team at a hospital
Outcome	Prophylaxis of venous thromboembolism in hospitalized patients
Health system	Medium complexity teaching hospital that included urgency/emergency, medium complexity elective procedures, trauma care, and orthopedics¹³13 Conselho Nacional de Secretários de Saúde. Assistência de média e alta complexidade no SUS. Brasília: CONASS; 2007.

DATABASES	SEARCH STRATEGY
MEDLINE (via PubMed)	(“Practice Guidelines as Topic”(MeSH Terms) OR (“Practice Guidelines as Topic”(MeSH Terms) OR (“practice”(All Fields) AND “guidelines”(All Fields) AND “topic”(All Fields) OR “Practice Guidelines as Topic”(All Fields) OR (“clinical”(All Fields) AND “guidelines”(All Fields) AND “topic”(All Fields) OR (“Practice Guidelines as Topic”(MeSH Terms) OR (“practice”(All Fields) AND “guidelines”(All Fields) AND “topic”(All Fields) OR “Practice Guidelines as Topic”(All Fields) OR (“best”(All Fields) AND “practices”(All Fields) OR “best practices”(All Fields) OR (“Practice Guidelines as Topic”(MeSH Terms) OR (“practice”(All Fields) AND “guidelines”(All Fields) AND “topic”(All Fields) OR “Practice Guidelines as Topic”(All Fields) OR (“best”(All Fields) AND “practice”(All Fields) OR “best practice”(All Fields) OR (“Practice Guideline”(Publication Type) OR (“Practice Guideline”(Publication Type) OR “Practice Guidelines as Topic”(MeSH Terms) OR “clinical practice guideline”(All Fields) OR (“ambulatory care facilities”(MeSH Terms) OR (“ambulatory”(All Fields) AND “care”(All Fields) AND “facilities”(All Fields) OR “ambulatory care facilities”(All Fields) OR “clinic”(All Fields) OR “clinic s”(All Fields) OR “clinical”(All Fields) OR “clinically”(All Fields) OR “clinicals”(All Fields) OR “clinics”(All Fields) AND (“Guideline”(Publication Type) OR “guidelines as topic”(MeSH Terms) OR “guidelines”(All Fields) OR “Guideline”(Publication Type) AND (“Venous Thromboembolism”(MeSH Terms) OR (“Venous Thromboembolism”(MeSH Terms) OR (“venous”(All Fields) AND “thromboembolism”(All Fields) OR “Venous Thromboembolism”(All Fields) OR (“thromboembolism”(All Fields) AND “venous”(All Fields) OR “thromboembolism venous”(All Fields)
Embase	('practice guideline'/exp/mj OR 'clinical practice guidelines'/mj OR 'guidelines'/mj OR 'guidelines as topic'/mj OR 'practice guideline'/mj OR 'practice guidelines'/mj OR 'practice guidelines as topic'/mj) AND ('venous thromboembolism'/exp OR 'thromboembolism, venous' OR 'vein thromboembolism' OR 'venous thromboembolism') AND (2011-2021)/py AND (embase)/lim
Cochrane	#1 MeSH descriptor: (Venous Thromboembolism) explode all trees
	#2 (Thromboembolism, Venous)
	#3 #1 OR #2
	#4 MeSH descriptor: (Practice Guidelines as Topic) explode all trees
	#5 Clinical Guidelines as Topic) OR (Best Practices) OR (Best Practice) OR (Practice Guideline) OR (Clinical Guidelines) OR (Guideline)
	#6 #4 OR #5
	#7 #3 AND #6
LILACS	“thromboembolism” OR “venous thromboembolism” (words) AND (“guideline” OR “guideline/protocol” OR “guidelines as topic” OR “guidelines/consensus”) OR “guide of clinical practice” OR “guide of medical practice”) OR “guideline” OR “medical practice guideline” OR “clinical practice guideline” OR “medical practice guideline” OR “guideline/protocol” (words)

Recommendation	Clinical Practice Guideline	Level of Evidence	Strength of the recommendation
After a risk assessment consider pharmacological prophylaxis with:	ACP	Moderate-quality evidence moderately confident in the effect estimate: the true effect is likely close to the estimated effect, but there is a sizable possibility that it is substantially different	Strong
Low Molecular Weight Heparin	ACCP	GRADE 1B	Strong
(ACCP, NHMRC, SIGN^a a LMWHs are preferred to UFH because of their longer half-life, lesser tendency to cause heparin associated thrombocytopenia, and once daily dosing schedule (recommended best practice based on the clinical experience of the guideline development group) , AWMF^b b Preferably with LMWH in high-risk prophylaxis doses. , ASH^c c LMWH (low certainty in the evidence of effects: certainty in these estimated effects was rated as very low owing to risk of bias and imprecision of the estimates) or fondaparinux (very low certainty in the evidence effects: certainty in these estimated effects was very low owing to the risk of bias, the indirect comparison, and imprecision of the estimates) rather than UFH. and NICE^d d LMWH as first-line treatment and if LMWH is contraindicated use fondaparinux. )	ACCP	Randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies	Strong
Unfractionated heparin	NHRMC	Body of evidence can be trusted to guide practice in most situations	B
(ACP, ACCP, NHMRC, SIGN^a; ASH^c),	SIGN	At least one meta-analysis, systematic review, or randomized controlled trials rated as 1++ and directly applicable to the target population; or a body of evidence consisting principally of studies rated as 1+, directly applicable to the target population, and demonstrating overall consistency of result	A
Fondaparinux	AWMF	High quality of evidence (systematic review with or without meta-analysis or randomized controlled trials)	Strong
(ACCP, SIGN^a, AWMF^b, ASH^c, NICE^d)	ASH	Low certainty in the evidence of effects (certainty in these estimated effects was rated as very low owing to risk of bias and imprecision of the estimates)	Conditional (suggest)
	NICE	No specification^e e The quality of evidence was assessed by outcomes using GRADE. After evaluation, the evidence was interpreted for development of recommendations considering the balance between benefits, harm, and cost of each intervention. Recommendations based on weak, conflicting, or absent evidence were developed based on expert opinion. Strong recommendations were described as “offer” and weak recommendations as “consider”.	Strong
For acutely ill hospitalized medical patients at low risk of thrombosis, the recommendation is not to use pharmacologic prophylaxis or mechanical prophylaxis based on the Padua Prediction Score	ACCP	GRADE 1B	Strong
	ACCP	Randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies	Strong
For acutely ill hospitalized medical patients who are bleeding or at high risk for bleeding, the recommendation is not to use anticoagulant thromboprophylaxis based on the Padua Prediction Score	ACCP	GRADE 1B	Strong
	ACCP	Randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies	Strong
Aspirin is not recommended as the sole pharmacological agent for venous thromboembolism prophylaxis in medical patients	SIGN	A body of evidence including studies rated as 2+, directly applicable to the target population and demonstrating overall consistency of results; or extrapolated evidence from studies rated as 2++	C
Medical patients hospitalized for acute illness are recommended Low Molecular Weight Heparin over Direct Oral Anticoagulants for venous thromboembolism prophylaxis	ASH	Moderate certainty in the evidence of effects (certainty in these estimated effects was moderate owing to imprecision of the estimates for the VTE outcomes)	Strong
Drug prophylaxis for patients should generally last 6 to 14 days.	ACCP^f f Until full mobility is restored or until discharge from hospital, whichever comes first.	GRADE 2B	Weak
		Evidence from randomized controlled trials with important limitations (inconsistent results, methodologic flaws, indirect or imprecise) or very strong evidence from observational studies.	Weak
	AWMF	Moderate	Recommended
	AWMF	Randomized controlled trials or cohort studies of limited quality	Recommended
	NICE^g g At least 7 days.	No specification^e	Strong
Recommends inpatient over inpatient plus extended-duration outpatient venous thromboembolism prophylaxis with heparin and direct oral anticoagulants	ASH	Moderate certainty in the evidence of effects certainty in these estimated effects was low owing to imprecision of the estimates and indirect comparisons)	Strong

[1] Conflicts of interest: No conflicts of interest declared concerning the publication of this article.

Brasil

Brasil

Evidence-based pharmacological prophylaxis recommendations for venous thromboembolism in hospitalized acutely ill medical patients: a systematic review of clinical practice guidelines

Recomendações baseadas em evidências científicas de profilaxia farmacológica para tromboembolismo venoso em pacientes hospitalizados com doenças agudas: uma revisão sistemática de diretrizes clínicas

Abstract