Bayer Pharma AG

Essence of this Article

Between 20% and 50% of patients who develop deep vein thrombosis (DVT) go on to develop post-thrombotic syndrome (PTS), a condition that is associated with substantial morbidity. Patients with PTS are generally managed using compression therapy and leg elevation, although surgical intervention may be appropriate in some cases. Approximately 1 in 25 patients will develop chronic thromboembolic pulmonary hypertension (CTEPH) within 2 years of a first acute PE. If left untreated, CTEPH is fatal however there is a potential cure by pulmonary endarterectomy (PEA) surgery. Approximately two thirds of patients are either not eligible for PEA, or suffer from persistent or recurrent CTEPH following surgery. For these patients medical therapy is recommended. Riociguat is the only approved medical treatment with proven efficacy in patients with inoperable CTEPH or persistent/recurrent CTEPH after PEA. Other treatment options include balloon pulmonary angioplasty although still an experimental procedure, and lung transplantation for patients with persistent severe symptomatic PH.

Treatment of the complications of venous thromboembolism

Post-thrombotic syndrome

Between 20% and 50% of patients who develop DVT go on to develop PTS, a condition that is associated with substantial morbidity.64 The exact cause of PTS is not well understood, but it may involve damage to venous valves, ultimately leading to increased venous pressure.171

The main symptom is chronic pain. Signs of PTS include:

  • Swelling
  • Discolouration of the affected leg
  • Skin ulceration (severe cases)

In addition to pain, patients with PTS may experience a sensation of heaviness, as well as cramps, itching and tingling.171

In general, patients with PTS are managed using compression therapy and leg elevation.171 In particular, elastic compression stockings can reduce leg swelling, heaviness and aching. There is some evidence that venoactive or phlebotonic remedies such as aescin or rutoside may reduce the symptoms of PTS, but this remains unproven.171 There is no evidence that diuretics are helpful in the management of PTS.171 Surgical intervention may be appropriate in cases where patients have chronic obstruction of the veins, sometimes in combination with endophlebectomy, bypass surgery or valvular repair.172

Chronic thromboembolic pulmonary hypertension

Chronic thromboembolic pulmonary hypertension (CTEPH) is a form of pulmonary hypertension (PH) caused by partial obstruction of pulmonary artery branches, primarily resulting from an unresolved pulmonary embolism (PE).614, 615 Approximately 1 in 25 patients may go on to develop CTEPH within 2 years, following a first acute PE.616

CTEPH is the only type of PH that is potentially curative, through the surgical procedure known as pulmonary endarterectomy (PEA),617 thus early and correct diagnosis is crucial.617 All CTEPH patients should be assessed for operability,614 and approximately 60% of patients are considered eligible,618 based on surgical risk. Without intervention, 3-year mortality rates are as high as 90% in patients with elevated pulmonary artery pressure >50 mmHg.617, 619

The symptoms of CTEPH are non-specific and are similar to those seen in patients with an acute PE (e.g. shortness of breath, chest pain).617, 620, 621 The 2014 European Society of Cardiology (ESC) acute PE guidelines recommend that patients with a history of PE who have persistent or exercise-induced dyspnea after at least 3 months of effective anticoagulation are screened to exclude CTEPH.622

Diagnosis of CTEPH occurs in a stepwise process, starting with an echocardiogram, to determine the probability of PH.614 A ventilation/perfusion (V/Q) scan is then performed as a normal V/Q scan rules out the presence of CTEPH.614 Diagnostic confirmation and PEA operability assessment is based on pulmonary angiography and right heart catheterization, to assess CTEPH severity and the site and accessibility of the obstruction.614, 617 PEA is a complex and highly technical procedure that should only be performed in an expert center by an experienced multidisciplinary team,614, 617, 623 including a radiologist and a surgeon.

Approximately one third of patients are not eligible for PEA surgery,618 and a further third suffer from persistent or recurrent CTEPH following PEA.624 In these patients, medical therapy is recommended.614 Riociguat is the only approved medical treatment with proven efficacy in patients with inoperable CTEPH or persistent/recurrent CTEPH after PEA.625, 626 Anticoagulant therapy may reduce the risk of recurrent thromboembolism, and lifelong anticoagulation is recommended for all CTEPH patients, including those who have undergone PEA.614

Interventional balloon pulmonary angioplasty (BPA) may also be considered in patients who are technically non-operable or carry an unfavorable risk:benefit ratio for PEA. BPA is still an experimental procedure and should only be performed in experienced and high-volume CTEPH centers.614

In patients with persistent, severe symptomatic PH after all other options have been explored, lung transplantation should be considered.614


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