Introduction

Venous thromboembolism (VTE) is a common and potentially preventable and treatable condition that includes deep vein thrombosis (DVT) and pulmonary embolism (PE). It is the third most common cardiovascular disease after myocardial infarction (MI) and ischemic stroke (IS), with an estimated annual incidence of approximately 150 per 100 000 individuals in the general population.¹ VTE covers a wide range of severity, from isolated distal DVT, which is usually treated for several weeks only, to iliofemoral thrombosis and high‑risk PE that may require invasive treatment approaches.^2,3 The burden of VTE is particularly significant because of its recurrent nature, potential for sudden death, and long‑term complications, such as post‑thrombotic syndrome (PTS) and chronic thromboembolic pulmonary hypertension (CTEPH).⁴ Despite these clear epidemiological data, the impact of VTE on cardiovascular and total mortality is often greatly underestimated. For example, the Global Burden of Disease Study does not list VTE or PE as a cause of death.⁵ Likewise, public awareness regarding the potential danger of VTE is considerably lower than that of MI or IS.⁶ In this article, we summarize the current state of knowledge and recent data on the epidemiology of VTE, including age- and sex‑specific differences, with a particular focus on mortality. We also discuss the clinical consequences and implications of these epidemiological data.

Incidence rates including age- and sex‑related aspects

VTE can manifest as isolated DVT, DVT with concomitant PE, or PE without diagnosed DVT. Table 1 lists the incidence for DVT, PE, and VTE in studies almost exclusively from high‑income countries, spanning from 1980 until 2025.^7-47 In Europe and North America, VTE is a common disease with annual incidence rates of 150 (95% CI, 131–169), 90 (95% CI, 72–109), and 67 (95% CI, 54–80) per 100 000 population for VTE, DVT, and PE, respectively. It is well known that the incidence of VTE increases with age, with rates starting from less than 5 per 100 000 in children, and reaching over 500 per 100 000 in individuals aged 80 years and older (Figure 1).^11,18,36 It has been reported that VTE may be more frequent in women, probably due to the effects of estrogens on the coagulation cascade.^17,41 However, this was not consistently found in all studies (Table 1).²² When the incidence rates are standardized for age, no clear difference between men and women can be found (Figure 1).³³ Importantly, the risk of recurrent VTE after the first episode of VTE without an identified major trigger is more than 3 times higher in men than in women.⁴⁸

Global burden

Most of the data on the incidence of VTE come from high‑income countries, and the burden in low- and middle‑income countries is likely underreported due to limited diagnostic capabilities. Notably, considerably lower incidence rates of VTE have consistently been reported from East Asia in comparison with the European and North American countries (Table 1).

Recently, however, incidence rates appear to increase also in Asia.⁴³ In large studies from the United States, the incidence of VTE was higher in African Americans than white people, and the lowest in individuals of Asian or Pacific Islander descent.^14,49,50

Risk factors for venous thromboembolism

The occurrence of VTE is influenced by a variety of risk factors, both acquired and inherited. The acquired risk factors include surgery, trauma, cancer, hospitalization, immobilization, pregnancy, and the use of hormonal therapy. Inherited traits of thrombophilia, such as factor V Leiden or the G20210A prothrombin gene mutation, also contribute to the frequency of VTE (Table 2).⁵¹ The risk factors for VTE can be classified according to their duration into permanent and temporary, and according to their mode of action into provoking and not provoking.⁵² In practical terms, their predictive value for VTE is of interest. Table 2 lists common risk factors according to their odds ratio.^4,53 Recently, is has been acknowledged that the risk factors for VTE may partly overlap with risk factors for arterial thrombosis.⁵⁴ A considerable number of cases are observed during or shortly after hospitalization, making VTE a partially preventable disorder.

Temporal trends and emerging risk factors for venous thromboembolism

While the incidence of DVT has remained relatively stable over the past 2 decades, the incidence of PE has increased. This trend is largely attributed to the broader availability and use of computed tomography pulmonary angiography, enabling the detection of subsegmental PE, which often has unclear clinical significance (Table 1).^32,55 This phenomenon may also be linked to suboptimal adherence to evidence‑based diagnostic pathways outlined in current guidelines.^56,57

Clinical implications

To reduce the burden and especially the mortality from VTE, adequate diagnosis and early initiation of anticoagulant treatment are crucial. However, in many countries, the diagnosis of acute PE remains suboptimal due to restricted availability of continuous imaging services, insufficient access to multidisciplinary consultations, inadequate protocols for transferring patients to higher‑tier referral centers, and limited physician awareness of established risk stratification principles. These deficiencies may compromise the comprehensiveness of diagnostic evaluation, thereby contributing to both under- and overdiagnosis. Improving access to diagnostic tools, standardizing referral pathways (eg, via PE response teams), and strengthening medical education are necessary steps to address these deficiencies.⁸⁸ Effective risk stratification tools, such as the Pulmonary Embolism Severity Index, help clinicians in identifying patients at a higher risk of mortality and complications.^4,89 Appropriate anticoagulant therapy is the cornerstone of VTE treatment, and has significantly improved survival. However, the risk of bleeding remains an important limitation, particularly in elderly patients and in the presence of comorbidities.

Given its preventable nature, hospital‑associated VTE is a major target for health interventions. Thromboprophylaxis in high‑risk patients—including those undergoing surgery or experiencing prolonged immobilization—has been shown to significantly reduce VTE incidence. Despite guidelines, implementation remains inconsistent, and there is an urgent need for improved adherence and constant re‑evaluation of prophylactic strategies.⁹⁰

Survivors of VTE events often face substantial morbidity. PTS occurs in up to 50% of patients with proximal DVT, leading to chronic leg pain, swelling, and ulceration.⁹¹ CTEPH, a rare but severe complication, is expected to develop in approximately 2.4% of patients with acute PE, and it contributes to long‑term functional decline and increased mortality.⁹² Both PTS and CETPH have distinct risk factors in patients with VTE that are summarized in Table 5.^92-94 A recent meta‑analysis reported similar rates of PTS across different anticoagulation regimens (vitamin K antagonists [VKAs], direct oral anticoagulants [DOACs], low‑molecular‑weight heparin) with a possible lower rate of severe PTS in patients treated with a DOAC than a VKA.⁹⁵

The epidemiological data summarized in this article have direct clinical implications. Important risk factors, such as the age of an individual patient should be integrated in the diagnostic workup. The higher risk for recurrent VTE in men has profoundly influenced clinical prediction scores for discontinuing anticoagulation.^96,97

Conclusions

VTE is a leading cause of cardiovascular mortality, ranking—at least in Europe and North America—at the third place for cardiovascular diseases and at the fifth place for death from all causes (Figure 2). Greater emphasis on risk assessment, adherence to prophylaxis guidelines, early diagnosis, and effective long‑term management are essential to reduce the burden of the disease. Improved surveillance and public health initiatives, such as the World Thrombosis Day, which has been organized every year since 2014, are needed to address these issues and to improve awareness of VTE.^81,98 Nevertheless, mortality from PE is greatly underestimated, and has not been included in the Global Burden of Disease Study.⁵ VTE should urgently be recognized as a distinct entity, similarly to other main vascular diseases, and not summarized under “other cardiovascular diseases”, since risk factors and treatment modalities differ significantly from those applying to arterial diseases.