Keywords
venous thromboembolism - recurrence - sex - men - anticoagulation - treatment
Introduction
Venous thromboembolism (VTE), encompassing both deep vein thrombosis (DVT) and pulmonary
embolism (PE), is the third leading vascular disease after myocardial infarction and
stroke.[1] Patients with incident VTE carry a considerable risk of recurrence with a high risk
of morbidity and mortality.[2]
[3] Within 10 years after a first VTE, more than 20% will experience recurrence, regardless
of the etiology of the first event.[4] Accordingly, anticoagulation constitutes the foundation of VTE treatment and prevention
of recurrence for a majority of patients.
Assessment of VTE recurrence risk after acute VTE is complex. Management with long-term
anticoagulation must be weighed against the long-term risk of major bleeding associated
with anticoagulant therapy. Previous studies have reported that men have an overall
higher VTE recurrence risk compared with women.[5]
[6] In a meta-analysis from 2011, men had a 2.2-fold higher risk of recurrence compared
with women.[6] In a 2019 a meta-analysis on patients with “unprovoked” (no identifiable risk factors
for VTE) VTE, the 10-year cumulative risk for men was 41% (95% confidence interval
28–56%) and 29% (95% confidence interval 20–38%) for women, respectively.[7] According to contemporary European guidelines, patients should be considered candidates
for extended anticoagulant treatment if their estimated risk for long-term recurrence
exceeds 3% per year.[8] However, VTE patients may have heterogeneous risk profiles with various underlying
chronic conditions, risk factors for major bleeding, and recurrence rates.[4]
[9]
[10] We therefore hypothesized that treatment decisions may benefit from a more differentiated
and personalized strategy. Specifically, we estimated crude cumulative recurrence
risks associated with clinical characteristics and comorbidities (recent major surgery,
recent trauma, history of cancer, rheumatic disorder, recent ischemic heart disease,
congestive heart failure, chronic obstructive pulmonary disease, diabetes, chronic
renal disease, varicose veins, alcohol-related diseases, and arterial hypertension)
known or suspected to be associated with an increased risk of developing VTE recurrence.
Patients and Methods
Study Design
This study was a retrospective observational cohort study based on secondary data
collection from Danish nationwide administrative databases, with a study period from
2008 through 2018.
Data Sources
This study was based on linkage of three nationwide Danish registries: (1) The Danish
National Patient Registry which has tracked hospitalizations since 1977, and outpatient
and emergency department visits since 1995[11]; (2) The National Prescription Register, which holds detailed information on purchase
date, Anatomical Therapeutic Chemical (ATC) classification code, package size, and
dosage for every prescription dispensed in Denmark since 1994[11]; and (3) The Danish Person Registry, which contain data on gender, date of birth,
vital and emigration status.[12] All codes used in this study are presented in [Supplementary eTable 2].
Study Population
The source population covered all residents of Denmark from 2008 through 2018. The
study population comprised all men with a first inpatient or outpatient diagnosis
of VTE in the National Patient Register. Both primary and secondary VTE diagnoses
were considered for inclusion. Of note, the primary diagnosis describes the diagnosis
that was the most serious and/or resource-intensive during the hospitalization or
the inpatient encounter, whereas secondary diagnoses are used for conditions that
coexist at the time of admission, or develop subsequently, and that affect the patient
care for the current episode of care. Emergency department diagnoses were excluded
because of a low positive predictive value of 31% in the Danish registries.[13] The date of the incident VTE diagnosis was defined as the index date for baseline
assessments.
To ensure enough clinical record history for risk factors, we excluded patients who
had not been residents in Denmark for at least 5 years prior to VTE diagnosis. Patients
were required to be age 18 years or older at the time of incident VTE. They were considered
for inclusion if they redeemed a prescription for oral anticoagulation within 30 days
after the incident VTE, ensuring a positive predictive value of 90% for the VTE diagnosis.[14] The duration of the anticoagulant treatment period was defined using information
on package size and prescription frequency in the Danish Prescription Registry,[15] including a grace period to allow gaps of maximum 30 days.[16] Since we were interested in estimating recurrence risk without anticoagulation,
patients with a treatment period lasting more than 1 year were excluded. We also excluded
patients with a diagnosis of atrial fibrillation or heart valve replacement at baseline
or after the VTE event in view of the life-long indication for anticoagulation. Finally,
we excluded patients with cancer diagnosis in the year prior to the incident VTE since
these patients constitute a special VTE population in terms of recurrence risk and
need for long-term antithrombotic treatment.[17]
Patient Characteristics
The investigated characteristics and comorbidities were based on risk factors described
by the International Society on Thrombosis and Haemostasis (ISTH) in combination with
relevant guidelines and previous literature.[4]
[8]
[18]
[19] The recurrence risk was investigated according to the following characteristics:
recent major surgery, recent trauma, history of cancer, rheumatic disorder, recent
ischemic heart disease, congestive heart failure, chronic obstructive pulmonary disease,
diabetes, chronic renal disease, varicose veins, alcohol-related diseases, and arterial
hypertension. Patient characteristics were identified either dating 3 months or 10
years prior to the incident VTE dependent on the persistent or transient nature of
the disease. Comorbidity status and patient characteristics were established by coded
hospital records in the registries. Co-medication was based on prescription data within
1 year prior to inclusion. Bleeding during anticoagulant treatment was defined as
patients with a hospital diagnose code of gastrointestinal bleeding or intracranial
bleeding coded during their anticoagulant treatment period.
Additionally, to describe our cohort, we used the “AIM-SHA-RP” risk score (age, incident
PE, major surgery, statin treatment, heart disease, antiplatelet treatment, chronic
renal disease, and Pneumonia/sepsis [[Supplementary eTable 1]].) to categorize patients as having an estimated low (<5%), intermediate (5–10%),
or high (>10%) 2-year recurrence risk after anticoagulation discontinuation.[20]
Outcome
Patients were followed in the registries for 2 years after anticoagulation was discontinued
for the occurrence of recurrent VTE. To ensure the validity of the outcome, hospital
discharge diagnosis of recurrence was required to be the primary in-hospital or ambulatory
diagnosis with a confirmatory imaging examination. According to a validation study,
this approach for identifying recurrent VTE ensured a positive predictive value of
82%.[21]
Statistical Analysis
Patient characteristics at the time of incident VTE were described using proportions
for categorical variables and means with standard deviation (SD) for continuous variables.
Since VTE risk rises steeply after the age of 50 years and because age >50 years previously
has been associated with a high recurrence risk among men, we stratified all analyses
by age 50 years or less.[20]
[22]
[23]
Follow-up began at the date of discontinuation of anticoagulation. We used the Aalen-Johansen
estimator, assuming death as competing risk, to estimate the cumulative risk of recurrence
at 2 years after discontinuation of anticoagulation for patients with and without
major chronic diseases and relevant characteristics, respectively. End of study (January
2019), death, re-initiation of anticoagulation, and emigration were considered as
censoring events.
For comparison with other studies, incidence rates for recurrence were calculated
as the number of events per 100 person-years. The associated risk was not compared
among those with or without the clinical characteristic, thus confounding was not
a concern in our descriptive approach of estimating the risks.
Supplementary and Sensitivity Analyses
Since DVT and PE present as different diseases with variable prognoses,[3] we repeated the main analyses with restriction to patients with DVT versus PE, to
assess whether recurrence risk differed by the type of VTE. If a patient had a diagnosis
of both PE and DVT, preference was given to the PE diagnosis. Additionally, a sensitivity
analysis was done allowing for 18 months initial standard therapy instead of 1 year.
Also, a sensitivity analysis was done repeating the main analysis with age stratified
according to the median and 75 percentile (not including 25 percentile because this
cut was identical to the main analysis). Finally, for clarifying long-term risk of
recurrence, we also reported results with 5-years follow-up.
Analyses were performed using Stata/MP version 15 (StataCorp LP). This study was conducted
in compliance with the General Data Protection Regulation and is part of North Denmark
Region's record of processing activities (j.no. 2017-68). Institutional Review Board
approval is not required for registry-based studies in Denmark.
Results
The study population comprised 13,932 men with incident VTE from 2008 through 2018
([Fig. 1]). Of these, 21% (n = 2,898) were aged <50 years (mean age 40.3 [SD 7.8]) and 79% (n = 11,034) were aged ≥50 years (mean age 67.7 [SD 10.3]). Baseline characteristics
are presented in [Table 1]. Among men aged <50 years, 27% presented with PE, whereas 37% of men aged ≥50 years
had PE. Most men were categorized as having a high (>10%) 2-year recurrence risk (AIM-SHA-RP
score sum higher than −1, [Supplementary eTable 1]) (85.9% of men aged <50 vs. 90.6% of men aged ≥50 years). A similar proportion had
an estimated intermediate (5–10%) risk (6.4% for men aged <50 and 7.4% for men ≥50,
respectively). Estimated low (<5%) recurrence risk was most prevalent in men <50 years
(7.7 vs. 2.2%). During anticoagulant treatment, 0.2% of the men aged <50 and 0.8%
of the men aged ≥50 suffered from major bleeding. Men aged ≥50 had a higher prevalence
of most comorbidities, except for alcohol-related diseases (5.3% among men aged <50
years vs. 4.8% for men aged ≥50).
Fig. 1 Flowchart of the study population.
Table 1
Baseline characteristics of 13,932 men with incident VTE
|
<50 year,
21% (n = 2,898)
|
≥50 year,
79% (n = 11,034)
|
|
Age, mean years (SD)
|
40.3 (7.8)
|
67.7 (10.3)
|
|
Pulmonary embolism % (n)
|
27.3 (792)
|
37.3 (4,121)
|
|
Major diseases
|
|
Previous cancer % (n)
|
0.9 (26)
|
5.8 (644)
|
|
Rheumatic disorder % (n)
|
2.6 (75)
|
6.2 (679)
|
|
Recent[a] ischemic heart disease % (n)
|
0.5 (15)
|
3.7 (407)
|
|
Congestive Heart Failure % (n)
|
1.0 (29)
|
4.4 (486)
|
|
Chronic obstructive pulmonary disease % (n)
|
1.8 (53)
|
8.5 (942)
|
|
Diabetes % (n)
|
2.6 (76)
|
8.1 (891)
|
|
Chronic renal disease % (n)
|
1.1 (33)
|
3.1 (344)
|
|
Varicose veins % (n)
|
2.5 (73)
|
3.6 (400)
|
|
Alcohol related diseases % (n)
|
5.3 (153)
|
4.8 (527)
|
|
Hypertension previous year % (n)
|
4.9 (141)
|
29.2 (3,227)
|
|
Recent[a] trauma % (n)
|
15.4 (446)
|
6.8 (746)
|
|
Recent[a] major surgery % (n)
|
11.7 (338)
|
9.7 (1070)
|
|
AIM-SHA-RP[b] risk score
|
|
AIM-SHA-RP[b], low risk % (n)
|
7.7 (223)
|
2.0 (225)
|
|
AIM-SHA-RP[b], intermediate risk % (n)
|
6.4 (185)
|
7.4 (811)
|
|
AIM-SHA-RP[b], high risk % (n)
|
85.9 (2,490)
|
90.6 (9,998)
|
|
Other characteristics
|
|
Bleeding during treatment % (n)
|
0.2 (6)
|
0.8 (87)
|
|
Recent[a] pneumonia % (n)
|
4.2 (123)
|
7.4 (812)
|
|
Recent[a] sepsis % (n)
|
0.8 (24)
|
0.9 (101)
|
|
Recent[a] central venous catheter
|
1.0 (30)
|
1.0 (105)
|
|
Previous gastrointestinal bleeding % (n)
|
0.6 (16)
|
1.9 (213)
|
|
Statin treatment previous year % (n)
|
4.1 (118)
|
23.4 (2,583)
|
|
Aspirin treatment previous year % (n)
|
2.0 (59)
|
18.6 (2,048)
|
|
Inflammatory bowel disease % (n)
|
2.0 (58)
|
1.4 (153)
|
|
Thrombophilia % (n)
|
0.9 (25)
|
0.3 (34)
|
|
Obesity % (n)
|
4.5 (131)
|
3.9 (429)
|
Abbreviations: n, numbers; SD, standard deviation; VTE, venous thromboembolism.
a Within 90 d.
b AIM-SHA-RP risk score: Men: Age >50 = +1 point, incident PE = +1 point, recent major
surgery = −2 points, statin treatment = −1 point, previous heart disease = +1 point,
antiplatelet treatment = −1 point; Women: age >60 = +2 points, incident PE = +1 point,
recent major surgery: −2 points, chronic renal disease = −1, recent pneumonia or sepsis = −1
point. Score sum: Men/women: low risk (<5% recurrence risk): < − 1/< 0, intermediate
risk (5–10% recurrence risk): −1/0–2, high risk (>10% recurrence risk): > − 1/> 2.
Estimates of cumulative recurrence risk are presented in [Table 2], and recurrence rates are presented in [Supplementary eTable 3]. [Fig. 2] depicts the 2-year cumulative VTE recurrence risk for men aged <50 and men aged
≥50 years with and without the selected patient characteristics, respectively. For
men aged <50 with one of the selected characteristics, recurrence risk varied from
6% (recent major surgery) to 16% (previous cancer) ([Fig. 2]). For men aged <50 years without the selected patient characteristic, the 2-year
recurrence risk was 10% across all subgroups.
Table 2
Cumulative recurrence risk at 2 year after anticoagulant treatment discontinuation
according to selected patient characteristics, stratified by age
|
<50 year,
21% (n = 2,898)
|
≥50 year,
79% (n = 11,034)
|
|
Characteristic % (95% CI)
|
With the disease (95% CI)
|
Without the disease (95% CI)
|
With the disease (95% CI)
|
Without the disease (95% CI)
|
|
Recent[a] trauma
|
6.9 (4.7–9.6)
|
10.3 (9.1–11.6)
|
7.7 (5.9–9.9)
|
10.3 (9.7–10.9)
|
|
Recent[a] major surgery
|
5.5 (3.4–8.4)
|
10.3 (9.1–11.6)
|
6.7 (5.2–8.3)
|
10.5 (9.9–11.1)
|
|
Previous cancer
|
16.2 (5.1–32.9)
|
9.7 (8.6–10.8)
|
9.3 (7.1–11.8)
|
10.2 (9.6–10.8)
|
|
Rheumatic disorder
|
11.5 (5.3–20.2)
|
9.7 (8.6–10.9)
|
10.8 (8.6–13.4)
|
10.1 (9.5–10.7)
|
|
Recent[a] ischemic heart disease
|
13.3 (2.2–34.6)
|
9.7 (8.6–10.9)
|
11.7 (8.7–15.2)
|
10.1 (9.5–10.7)
|
|
Heart failure
|
7.5 (1.3–21.3)
|
9.8 (8.7–10.9)
|
9.1 (6.7–12.0)
|
10.2 (9.6–10.8)
|
|
COPD
|
12.0 (4.8–22.7)
|
9.7 (8.6–10.9)
|
11.5 (9.5–13.7)
|
10.0 (9.4–10.6)
|
|
Diabetes
|
8.8 (3.6–17.0)
|
9.8 (8.7–10.9)
|
9.3 (7.5–11.4)
|
10.2 (9.6–10.8)
|
|
Chronic renal disease
|
6.9 (1.2–19.9)
|
9.8 (8.7–10.9)
|
11.6 (8.4–15.3)
|
10.1 (9.5–10.7)
|
|
Varicose veins
|
9.4 (3.8–18.1)
|
9.8 (8.7–10.9)
|
9.8 (7.0–13.1)
|
10.1 (9.5–10.7)
|
|
Alcohol-related diseases
|
8.9 (5.0–14.2)
|
9.8 (8.7–11.0)
|
9.6 (7.2–12.4)
|
10.1 (9.5–10.8)
|
|
Hypertension within 1 y
|
10.8 (6.2–16.9)
|
9.7 (8.6–10.9)
|
10.0 (8.9–11.1)
|
10.2 (9.5–10.9)
|
Abbreviations: COPD, chronic obstructive pulmonary disease; VTE, venous thromboembolism.
a Within 90 d.
Fig. 2 Cumulative venous thromboembolism recurrence risk for men with and without selected characteristics.
Among men aged ≥50 years with the selected characteristic, recurrence risk ranged
from 7% (recent major surgery) to 12% (for ischemic heart disease, chronic obstructive
pulmonary disease, and chronic renal disease) ([Fig. 2]). For men aged ≥50 without such characteristics, the 2-year recurrence risk was
10% for all groups ([Fig. 2]).
Supplementary and Sensitivity Analyses
Restricting the analyses to patients with DVT and PE yielded virtually unchanged estimates
([Supplementary eTable 4]). Of note, male PE patients aged <50 with recent major surgery and recent trauma
had the lowest 2-year recurrence risk of 4 and 3%, respectively. All remaining groups
had a 2-year recurrence risk of at least 6%. Corresponding risk for DVT patients aged
<50 was 6% for patients with recent major surgery vs. 8% for patients with recent
trauma.
Extending the initial treatment period to 18 months did not change the results (not
shown). Stratifying according to the median age (below/above 63 years) and the 75%
percentile for age (below/above 73 years) revealed a 2-year recurrence risk of 4%
for patients aged ≥73 with alcohol-related diseases, whereas all remaining subgroups
had a recurrence risk of at least 6% ([Supplementary eTable 5]).
When extending follow-up to 5 years, recurrence risk for men aged <50 years ([Supplementary eFig. 1A]) with one of the selected characteristics ranging from 12% (recent trauma) to 18%
(chronic obstructive pulmonary disease). For men aged <50 years without the diseases,
the recurrence risk was 18% ([Supplementary eFig. 1B]). For men aged ≥50 with the selected characteristics, recurrence risk ranged from
12% (recent surgery) to 16% (alcohol related disease) ([Supplementary eFig. 2A]). For men aged ≥50 years without the selected characteristics, the 2-year recurrence
risk was 19% ([Supplementary eFig. 2B]).
Discussion
In this large nationwide cohort of men with incident VTE, we observed an overall 2-year
recurrence risk of at least 6% after anticoagulation was discontinued. In the main
analysis, patients with recent major surgery had the lowest recurrence risk of 6%
for men aged <50 and 7% for men aged ≥50. However, in a sensitivity analysis, men
with PE aged <50 with recent trauma or surgery had a lower 2-year recurrence risk
of 3 and 4%, respectively.
It is well-established that men have a higher risk of recurrent VTE than women. A
previous Danish study using a similar VTE cohort as ours investigated VTE recurrence
risk for both men and women within 2 years after completed anticoagulant treatment
from 2012 through 2017.[20] Among women, 7% had a VTE recurrence risk of <5% 2 years after anticoagulation discontinuation,
73% had a recurrence risk ranging from 5 to 10%, and 20% had a recurrence risk >10%.
For men, 3% had a recurrence risk <5%, 7% had intermediate risk of 5 to 10% and 90%
had a risk >10%. In clinical practice, the treating physician may put extra focus
on the high-risk groups in which the recurrence risk will outweigh the bleeding risk
with more certainty. With 90% of the men in the high-risk category compared with only
20% of the women, these results support the concept of more men receiving extended
anticoagulation without a scheduled end date. In the 2019 systematic review and meta-analysis
on patients with “unprovoked” VTE, the overall 2-year cumulative recurrence risk was
16% (95% confidence interval 13–19%).[7] For men, the 2-year cumulative recurrence risk was 18.3% (95% confidence interval
14.4–22.5%) and for women 13.6% (95% confidence interval 10.1–17.5%), respectively.
In a meta-analysis from 2006, the recurrence risk was 50% higher in men compared with
women after stopping anticoagulant treatment.[5] In 2008, Baglin et al concluded that male sex was the strongest indicator of recurrence
risk (adjusted hazard ratio 2.9 [95% confidence interval [CI] 1.38; 6.01]).[24] Moreuil et al estimated a 7-year recurrence risk of 35% for men and 11% for women.[25] Yet, because there was no difference according to sex in all subgroups, the study
concluded that there were no sex-related differences in recurrence risk.
The clinical decision on whether to continue anticoagulant treatment remains complicated.
When deciding if a patient should receive indefinite anticoagulation, the expected
absolute reduction in major complications and deaths from PE needs to be balanced
against the expected increase in major complications and deaths from bleeding. The
ESC guidelines have defined a VTE recurrence risk threshold to support the clinical
decision of when to safely stop treatment. In the 2019 European Society of Cardiology
PE guidelines, only patients with estimated low recurrence risk (<3% per year) are
recommended for shorter time-limited treatment, whereas all other patients should
be considered for extended treatment without an end date.[8] The ISTH guidelines suggest that it is safe to stop anticoagulation in those whose
recurrence risk 1 year after stopping treatment is <5%.[26] The American Society of Haematology does not recommend a specific time for when
to discontinue treatment but suggests that DVT and/or PE provoked by a persistent
risk factor as well as the majority of patients with unprovoked VTE should receive
indefinite duration antithrombotic therapy.[27]
The 2019 European Society of Cardiology PE guidelines no longer support the terminology
“provoked” and “unprovoked,” as it is “potentially misleading and not helpful for
decision-making regarding the duration of anticoagulation.”[8] Instead, a long-term recurrence risk should be estimated according to transient
or reversible risk factors. Accordingly, in this study, we estimated recurrence risk
according to the major diseases seen in clinic by the treating physician.
European guidelines have initiated a shift in thinking toward extended thromboprophylaxis
for patients with an annual risk of recurrence of 3% or higher. However, a study from
2021 described that less than 3% of patients with incident VTE received extended treatment
after initial standard treatment, suggesting that this recommendation has not been
fully implemented in clinical practice.[28] Also, the counterbalanced risks and consequences of anticoagulant-related major
bleeding are considerable. A 2021 systematic review and meta-analysis including 27
studies presented a 5-year cumulative incidence of major bleeding with vitamin K antagonists
of 6.3% (95% CI 3.6; 10.0) with a case-fatality rate of 8.3% (95% CI 5.1; 12.2).[29] Finding a recurrence risk of 6% must be placed in a clinical context of patient
preferences and bleeding risks. In evidence-based guidelines, it is not recommended
to consider male sex as a risk factor when estimating recurrence risk. While perhaps
male gender alone should not be an absolute indication, it may be included in the
recommendations as a consideration. By analogy, female sex is considered a factor
in the CHA2DS2-VASc score used to support treatment decision for atrial fibrillation patients. Finally,
if the high VTE recurrence risk for men is confirmed by other studies from diverse
populations, future guideline recommendations may place greater emphasis on male sex
as a risk factor for recurrent VTE.
Attempts to refine risk prediction for VTE recurrence have been made.[20]
[30]
[31]
[32]
[33]
[34] However, most of these prediction models were developed only for patients with “unprovoked,”[30]
[31]
[32]
[33] and the models have been sparsely validated,[35]
[36]
[37]
[38] and none are implemented in the guidelines. We used the AIM-SHA-RP risk score in
the current study.[20] This score was originally developed on a cohort of Danish routine care in- and outpatients
with completed anticoagulant treatment for incident VTE,[20] and some of these patients overlap with the current study. In the HER DOO2 study,
the investigators were unable to identify men with a low recurrence risk.[30] In the remaining models, male sex was a predictor of higher risk of recurrence.
To our knowledge, this is the only study trying to refine this overall higher risk
described among men.
Some factors may lead to underestimation of the recurrence risk; not including emergency
ward diagnoses, and fatal VTE's never registered as VTE events. On the other hand,
some VTE ICD-10 codes may not reflect an actual incident event because of inaccurate
coding and misclassification leading to overestimation. However, we tried to minimize
this risk by only including incident VTE patients initiating anticoagulation within
30 days, ensuring a positive predictive value of 90%.[14] Likewise, some recurrent VTE codes may reflect repeated coding of the incident event
and not an actual recurrent VTE. However, by requiring primary recurrent VTE diagnosis
to be in combination with relevant imaging examinations, and by starting follow-up
after anticoagulant treatment cessation, we ensured a positive predictive value of
82% for the recurrent diagnosis.[21] The trauma and surgery codes, on the other hand, have not been validated for VTE
use, potentially introducing some degree of information bias stemming from underlying
misclassification. Also, new diseases/conditions occurring during follow-up were not
considered in the analysis. Unfortunately, the ICD codes neither differentiated in
proximal/distal DVT nor in PE location (central/subsegmental), which is a limitation
of our study. Finally, the Danish population may not be representative of other populations
with greater variability in race and ethnicity, possibly affecting the external validity
of our results.
We followed patients in national registries with prospectively collected data and
virtually complete follow-up in a setting with free access to health services, thus
largely eliminating selection bias.[12] Of note, the nature of our study was descriptive and therefore confounding was not
a concern.
Our study underscores the overall high recurrence risk among men. Male PE patients
aged <50 with recent major surgery and recent trauma had a 2-year recurrence risk
of 4 and 3%, respectively. However, for all other men, even after taking different
risk factors into account, the recurrence risk remained above 6%.
What Is Known on This Topic?
-
Men have a higher risk of recurrent venous thrombosis than do women. However, sex-specific
data on prognostic factors for venous thromboembolism recurrence risk are lacking.
-
In evidence-based guidelines, male sex has not been considered a risk factor when
estimating venous thromboembolism recurrence risk.
What Does This Paper Add?
-
In this nationwide cohort study, we estimated the cumulative recurrence risks associated
with clinical characteristics and comorbidities known or suspected to be associated
with the development of VTE recurrence: recent major surgery, recent trauma, history
of cancer, rheumatic disorder, recent ischemic heart disease, congestive heart failure,
chronic obstructive pulmonary disease, diabetes, chronic renal disease, varicose veins,
alcohol-related diseases, arterial hypertension, and age.
-
Regardless of age category and disease status, men with venous thromboembolism demonstrated
a 2-year recurrence risk after anticoagulation discontinuation of at least 6%.
-
All men were above the European guideline threshold of 3% recurrence risk suggesting
extended treatment. If the recurrence risk for men is confirmed in diverse populations,
future guidelines might put greater emphasize on male sex as a risk factor for recurrent
venous thromboembolism.
