New antiplatelet agents and prosthetic heart valves.

Sir, Despite advances in prosthetic valve design, patients who undergo valve replacement are at risk of arterial thromboembolism and valve thrombosis. We present four cases where new antiplatelet agents have been used. A 61-year-old man with aortic valve endocarditis underwent early mechanical valve replacement. He developed mitral regurgitation and an aorticright-atrial fistula requiring surgical closure and mitral valve replacement. He had a persistent sternal wound infection with a sinus. After four operations, his sternum was finally reconstructed. He then presented with epistaxis secondary to high INR and an ischaemic right leg. He was diagnosed with Candida endocarditis, an aortic pseudoaneurysm and a large intrathoracic haematoma. He underwent an aortic root repair and femoral embolectomy. In view of post-operative haemorrhage, haematoma and persistent pseudoaneurysm, he was not anticoagulated. He was maintained on aspirin 150 mg once daily and clopidogrel 75 mg once daily for 2 months. Warfarin was restarted subsequently and he is well 17 months later. Aged 3 months, a boy underwent surgery for a VSD and truncus arteriosus with a composite homograft conduit in 1982. In 1996, he developed increasing tricuspid regurgitation and underwent a St Jude valve replacement. His target INR was 3.5–4.5. In 1997 he had erratic anticoagulation control; his warfarin was stopped for 4 days and he was admitted with prosthetic valve thrombosis and an INR of 2.0. He was treated with tissue plasminogen activator and unfractionated heparin, and made a good recovery. His target INR was increased to 4.0–4.5 and aspirin 150 mg daily added. He suffered a further prosthetic valve thrombosis in 2001, with an INR of 2.4, and was treated with tissue plasminogen activator. He was unable to tolerate dipyridamole and so was maintained on clopidogrel 75 mg daily, aspirin 150 mg daily and a target INR of 4.0–4.5. He is well 8 months later. A 55-year-old lady who had a mitral valve replacement 4 months previously, presented with 3 weeks of breathlessness. Transthoracic echocardiography demonstrated a dilated left atrium, no paraprosthetic mitral regurgitation, but a prolonged pressure half-time compared to that post-operation. Transoesophageal echocardiography showed an echogenic mass attached to the mitral valve replacement. Blood cultures were negative. A diagnosis of prosthetic valve thrombosis was made, and surgery was offered but declined. With an INR of 2.6, she received 50 mg of tissue plasminogen activator followed by a standard loading dose of 0.25 mg/kg of abciximab and 12 h infusion at 125 mg/kg/min. Repeat echocardiography at 24 h showed a 50% increase in the mitral valve area and marked symptomatic improvement. Aspirin 75 mg daily was added, and the target INR set at 3–4. Three weeks later, breathlessness returned and transoesophageal echocardiography showed a recurrent large mobile thrombus. Urgent valve replacement was undertaken, and histology revealed pannus formation with adherent organized thrombus. A 78-year-old man presented with confusion and a subdural haematoma. Ten years earlier, he had had a Starr-Edwards mitral valve prosthesis inserted. His target INR was 2.5–3.5. Following neurosurgical opinion, conservative therapy was recommended; anticoagulation was discontinued and reversed with intravenous vitamin K. He was managed with clopidogrel 75 mg and aspirin 75 mg daily without warfarin for 3 weeks. His symptoms resolved, and repeat CT scanning demonstrated haematoma resolution. Warfarin was restarted, he was discharged and was well at 3 months. Anticoagulation reduces the risk of thromboembolic events, but introduces the risk of severe or fatal bleeding, and may be contra-indicated in some patients. Antiplatelet agents are not as effective as warfarin, but do reduce thromboembolic risk when used with warfarin. The use of the new antiplatelet agents clopidogrel and abciximab in patients with prosthetic valves has not been described previously. These cases demonstrate their potential, but further studies are required to find their position in routine management. J. Timperley N.R.A. Clarke A.P. Banning Cardiology Department Oxford Radcliffe Hospital NHS Trust John Radcliffe Hospital Oxford email: [email protected] (Dr Timperley)