Heart valve disease module 7: anti-thrombotic therapy for valvular heart disease

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Both native valve disease and prosthetic valves may increase the risk of embolic stroke and systemic embolism. This section will address which patients require antithrombotic treatment and what regimes to use.

Antithrombotic options

Figure 1
Figure 1. Warfarin can reduce but not eliminate the risk of thromboembolism

There are two main therapies used to anticoagulate patients with heart valve replacement. This is either with a heparinoid or a vitamin K antagonist. The use of non-vitamin K oral anticoagulants (NOACs) in valvular heart disease and in those with heart valve replacements has become increasingly popular but data on their long term safety and efficacy are awaited. This is covered in a separate section.

Vitamin K antagonists

Anticoagulation with vitamin K antagonists (VKA), such as warfarin, can reduce but not eliminate the risk of thromboembolism (see figure 1). They carry a substantial bleeding risk. The balance between risk and benefit must be carefully considered in every patient, particularly when valvular surgery is planned. The risk of bleeding on warfarin increases with age. Mechanical heart valves are more durable than prosthetic heart valves and life long anticoagulation is required due to the thrombogenicity of the valve. In addition, the incidence of thromboembolism is highly dependant on other factors, such as valve design and patient related risk factors.1 The risk of valvular thromboembolism is estimated at 0.2−1.5% per year and the risk of major bleeding to be around 1–2.5% per year.


Intravenous unfractionated heparin (UFH) is suitable for short-term anticoagulation such as at the initiation of anticoagulation or when it has to be interrupted for invasive procedures. It is not suitable for long-term anticoagulation since inpatient monitoring of APTT ratio is required. Prolonged use of subcutaneous UFH is associated with osteoporosis and therefore not recommended as long-term therapy.

Low molecular weight heparins (LMWH) are not licensed at the current time for valvular heart disease but are extensively used short term as an alternative to UFH and offer effective and stable anticoagulation. This is, however, an off-label use and there is a lack of randomised control trials comparing its safety and efficacy against warfarin. In addition, there are ongoing concerns regarding its pharmacokinetics in patients of extreme body habitus (body mass index <15 and >25) and also the lack of specific antidote. The current European Society of Cardiology (ESC)/European Association for Cardiothoracic Surgery (EACTS) guidelines recommend anti-Xa monitoring if LMWH heparin is used.

Antiplatelet agents

Antiplatelet drugs are not an adequate substitute for anticoagulation with VKA where this is specifically indicated, but may be useful for reducing risk in patients with incidental valve disease who have other vascular risk factors, in the absence of a clear indication for anticoagulation. Aspirin may also be considered as an adjunct to VKA in some patients who have embolic events despite good anticoagulant control.

Native valve disease

Rheumatic mitral valve disease

This carries a substantial thrombotic risk. Patients may present with a systemic embolism as the first manifestation of the disease. Anticoagulation with VKA to a target INR of 2.5 is indicated in the presence of:

  • Previous systemic embolism
  • Atrial fibrillation (AF), persistent or paroxsysmal
  • Left atrial thrombus.

Anticoagulation should also be considered when there is significant left atrial enlargement in the absence of the above features. The presence of left atrial thrombus that does not resolve with anticoagulation is a contraindication for percutaneous mitral valvotomy.

Other valve disease

Mitral valve prolapse and mitral ring calcification are not in themselves indications for anticoagulation. Aortic, tricuspid or pulmonary valve disease do not carry such a high risk of thromboembolism as rheumatic mitral valve disease, and anticoagulation with a VKA is not indicated unless there are other complications such as AF.