Applied Evidence

Primary prevention of VTE spans a spectrum

Author and Disclosure Information

High mortality from VTE makes primary prevention appealing. Guidelines and assessment tools offer a variety of patient-specific strategies and agents.


› Consider the mild reduction in the risk of venous thromboembolism (VTE) provided by statins when contemplating their use for cardiovascular disease prevention. B

› Avoid testing for thrombophilia to determine the risk of VTE, except in pregnant patients who meet criteria for antiphospholipid syndrome or have a family history of VTE. B

› Recommend an intrauterine device or progestin-only pill for contraception if the patient’s risk of VTE is high. B

› Stratify hospitalized medical and nonorthopedic surgical patients by risk score to determine the need for VTE prophylaxis. B

Strength of recommendation (SOR)

A Good-quality patient-oriented evidence
B Inconsistent or limited-quality patient-oriented evidence
C Consensus, usual practice, opinion, disease-oriented evidence, case series



Venous thromboembolism (VTE) is a common and dangerous disease, affecting 0.1%-0.2% of the population annually—a rate that might be underreported.1 VTE is a collective term for venous blood clots, including (1) deep vein thrombosis (DVT) of peripheral veins and (2) pulmonary embolism, which occurs after a clot travels through the heart and becomes lodged in the pulmonary vasculature. Two-thirds of VTE cases present clinically as DVT2; most mortality from VTE disease is caused by the 20% of cases of pulmonary embolism that present as sudden death.1

VTE is comparable to myocardial infarction (MI) in incidence and severity. In 2008, 208 of every 100,000 people had an MI, with a 30-day mortality of 16/100,0003; VTE disease has an annual incidence of 161 of every 100,000 people and a 28-day mortality of 18/100,000.4 Although the incidence and severity of MI are steadily decreasing, the rate of VTE appears constant.3,5 The high mortality of VTE suggests that primary prevention, which we discuss in this article, is valuable (see “Key points: Primary prevention of venous thromboembolism”).

Key points: Primary prevention of venous thromboembolism

  • Primary prevention of venous thromboembolism (VTE), a disease with mortality similar to myocardial infarction, should be an important consideration in at-risk patients.
  • Although statins reduce the risk of VTE, their use is justified only if they are also required for prevention of cardiovascular disease.
  • The risk of travel-related VTE can be reduced by wearing compression stockings.
  • The choice of particular methods of contraception and of hormone replacement therapy can reduce VTE risk.
  • Because of the risk of bleeding, using anticoagulants for primary prevention of VTE is justified only in certain circumstances.
  • Pregnancy is the only condition in which there is a guideline indication for thrombophilia testing, because test results in this setting can change recommendations for preventing VTE.
  • Using a risk-stratification model is key to determining risk in both medically and surgically hospitalized patients. Trauma and major orthopedic surgery always place the patient at high risk of VTE.

Risk factors

Virchow’s triad of venous stasis, vascular injury, and hypercoagulability describes predisposing factors for VTE.6 Although venous valves promote blood flow, they produce isolated low-flow areas adjacent to valves that become concentrated and locally hypoxic, increasing the risk of clotting.7 The great majority of DVTs (≥ 96%) occur in the lower extremity,8 starting in the calf; there, 75% of cases resolve spontaneously before they extend into the deep veins of the proximal leg.7 One-half of DVTs that do move into the proximal leg eventually embolize.7

Major risk factors for VTE comprise inherited conditions, medical history, medical therapeutics, and behaviors (TABLE 1).9-11 Unlike the preventive management of coronary artery disease (CAD), there is no simple, generalized prevention algorithm to address VTE risk factors.

Venous thromboembolism risk factors

Risk factors for VTE and CAD overlap. Risk factors for atherosclerosis—­obesity, diabetes, smoking, hypertension, ­hyperlipidemia—also increase the risk of VTE (TABLE 1).9-11 The association between risk factors for VTE and atherosclerosis is demonstrated by a doubling of the risk of MI and stroke in the year following VTE.11 Lifestyle changes are expected to reduce the risk of VTE, as they do for acute CAD, but studies are lacking to confirm this connection. There is no prospective evidence showing that weight loss or control of diabetes or hypertension reduces the risk of VTE.12 Smoking cessation does appear to reduce risk: Former smokers have the same VTE risk as never-smokers.13

Thrombophilia testing: Not generally useful

Inherited and acquired thrombophilic conditions define a group of disorders in which the risk of VTE is increased. Although thrombophilia testing was once considered for primary and secondary prevention of VTE, such testing is rarely used now because proof of benefit is lacking: A large case–control study showed that thrombophilia testing did not predict recurrence after a first VTE.14 Guidelines of the American College of Chest Physicians (ACCP) do not address thrombophilia, and the American Society of Hematology recommends against thrombophilia testing after a provoked VTE.15,16

Primary prophylaxis of patients with a family history of VTE and inherited thrombophilia is controversial. Patients with both a family history of VTE and demonstrated thrombophilia do have double the average incidence of VTE, but this increased risk does not offset the significant bleeding risk associated with anticoagulation.17 Recommendations for thrombophilia testing are limited to certain situations in pregnancy, discussed in a bit.16,18,19

Continue to: Primary prevention of VTE in the clinic


Next Article: