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..................................................................................................... Time trend analyses in European, Asian, and North American populations suggest that case fatality rates of acute PE may be decreasing.47,10,11 Increased use of more effective therapies and interventions, and possibly better adherence to guidelines,12,13

has most likely exerted a significant positive effect on the prognosis of PE in recent years. However, there is also a tendency towards overdiagnosis of (subsegmental or even non-existent) PE in the modern era,14 and this might in turn lead to a false drop in case fatality rates by inflating the denominator, i.e. the total number of PE cases. Figure 1 summarizes the existing data on global trends in PE, highlighting increasing incidence rates in parallel with decreasing case fatality rates over an 15 year period. In children, studies have reported an annual incidence of VTE of between 5357 per 100 000 among hospitalized patients,19,20 and between 1.44.9 per 100 000 in the community overall.21,22

3.2 Predisposing factors

There is an extensive collection of predisposing environmental and genetic factors for VTE; a list of predisposing (risk) factors is shown in Table 3. VTE is considered to be a consequence of the interaction between patient-related—usually permanent—risk factors and setting-related—usually temporary—risk factors. Since categorization of temporary and permanent risk factors for VTE is important for assessing the risk of recurrence, and consequently for decisionmaking on chronic anticoagulation, it is discussed in more detail in section 8 of these Guidelines. Major trauma, surgery, lower-limb fractures and joint replacements, and spinal cord injury are strong provoking factors for VTE.23,24 Cancer is a well-recognized predisposing factor for VTE. The risk of VTE varies with different types of cancer;25,26 pancreatic cancer, haematological malignancies, lung cancer, gastric cancer, and brain cancer carry the highest risk.27,28 Moreover, cancer is a strong risk factor for all-cause mortality following an episode of VTE.29

Oestrogen-containing oral contraceptive agents are associated with an elevated VTE risk, and contraceptive use is the most frequent VTE risk factor in women of reproductive age.3032 More specifically, combined oral contraceptives (containing both an oestrogen and a progestogen) are associated with an approximately two- to six-fold increase in VTE risk over baseline.32,33 In general, the absolute VTE risk remains low in the majority of the >100 million combined oral contraceptive users worldwide;34 however, VTE risk factors, including severe inherited thrombophilia (discussed in section 8),35 increase this risk. Third-generation combined oral contraceptives, containing progestogens such as desogestrel or gestodene, are associated with a higher VTE risk than the second-generation combined oral contraceptives, which contain progestogens such as levonorgestrel or norgestrel.36,37 On the other hand, hormone-releasing intrauterine devices and some progesterone-only pills (used at contraceptive doses) are not associated with a significant increase in VTE risk;33,38 consequently, and following counselling and full risk assessment, these options are often proposed to women with a personal or strong family history of VTE. In post-menopausal women who receive hormone replacement therapy, the risk of VTE varies widely depending on the formulation used.39 Infection is a common trigger for VTE.23,40,41 Blood transfusion and erythropoiesis-stimulating agents are also associated with an increased risk of VTE.23,42 In children, PE is usually associated with DVT and is rarely unprovoked. Serious chronic medical conditions and central venous lines are considered likely triggers of PE.43 VTE may be viewed as part of the cardiovascular disease continuum, and common risk factors—such as cigarette smoking, obesity, hypercholesterolaemia, hypertension, and diabetes

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Annual Incidence Rate (number of PE diagnoses / 100.000 inhabitants) Case Finality Rate (number of in-hospital deaths / 100 PE diagnoses; %)

Figure 1 Trends in annual incidence rates (left panel) and case fatality rates (right panel) of pulmonary embolism around the world, based on data retrieved from various references.5,6,11,1417 Reproduced with permission from JACC 2016;67:976-90. PE= pulmonary embolism; US = United States. aPE listed as principal diagnosis. bAny listed code for PE was considered. Downloaded from academic.oup.com/eurheartj/article/41/4/543/5556136 by guest on 07 October 2026