Indobufen - An updated review of its use in the management of atherothrombosis

Indobufen inhibits platelet aggregation by reversibly inhibiting the platel et cyclooxygenase enzyme thereby suppressing thromboxane synthesis, Clinica l trials have evaluated the efficacy of oral indobufen in the secondary pre vention of thromboembolic complications in patients with or without atrial fibrillation, in the prevention of graft occlusion after coronary artery by pass graft (CABG) surgery and in the treatment of intermittent claudication . In the secondary prevention of thromboembolic events indobufen 200mg once o r twice daily was significantly more effective than no treatment although n ot as effective as ticlopidine 250mg once or twice daily, during 1-year non blind clinical trials. Compared with placebo, indobufen 100mg twice daily s ignificantly reduced the risk of stroke in a small 28-month trial of patien ts at increased risk of systemic embolism (50% had atrial fibrillation). Fu rthermore, in patients with nonrheumatic atrial fibrillation and a recent c erebrovascular event enrolled in the 1-year Studio Italiano Fibrillazione A triale (SIFA) trial. indobufen 100 or 200mg twice daily was as effective as warfarin (titrated to produce an international normalised ratio of 2.0 to 3.5) in the secondary prevention of thromboembolic events; the incidences o f the composite end-point of major vascular events (10.6 vs 9.0%) and recur rent stroke (5 vs 4%) were similar between treatments. In 2 large 12-month trials, the Studio Indobufene nel Bypass Aortocoronaric o (SINBA) and the UK study, indobufen 200mg twice daily was as effective as aspirin (acetylsalicylic acid) 300 or 325mg plus dipyridamole 75mg 3 times daily in the prevention of early and late occlusion of saphenous grafts in patients after CABG surgery. Indobufen 200mg twice daily for 6 months sign ificantly improved walking capacity compared with placebo, and caused a mor e pronounced improvement in both pain-free and total walking distance than either pentoxifylline 300mg or aspirin 500mg twice daily in separate 6- and 12-month studies of patients with intermittent claudication. Oral indobufen up to 200mg twice daily was generally well tolerated in > 50 00 patients with atherosclerotic disease. Adverse events (predominantly gas trointestinal), reported by 3.9% of patients, rarely required withdrawal fr om treatment. in the SINBA and UK studies, fewer adverse events and less ga strointestinal bleeding were seen with indobufen than with aspirin plus dip yridamole treatment, while in the SIFA trial, noncerebral bleeding events o ccurred significantly less frequently in indobufen than warfarin recipients (0.6 vs 5.1 %) and major bleeding events occurred only in the warfarin gro up. Conclusion: Indobufen is as effective as warfarin in the prophylaxis of thr omhoembolic events in at risk patients with nonrheumatic atrial fibrillatio n, as aspirin plus dipyridamole in the prevention of CABG occlusion and may be more effective than aspirin or pentoxifylline in improving walking capa city in patients with intermittent claudication. The improved tolerability profile of indobufen (favourable gastric tolerance and reduced haemorrhagic complications) compared with aspirin 300 to 325mg 3 times daily or warfari n, in addition to a similar antiplatelet effect, suggests indobufen can be considered a drug with a definite role in the management of atherothromboti c events. In particular, indobufen may be an effective alternative for at r isk patients with nonrheumatic atrial fibrillation in whom anticoagulant th erapy is contraindicated or who are at higher risk of bleeding.