Phosphodiesterase inhibitors
In addition to the inhibition of the cyclooxygenase-1 enzyme by acetylsalicylic acid and the ADP-P2Y12 receptor by P2Y12 inhibitors, inhibition of the phosphodiesterase enzyme (PDE) by cilostazol and dipyridamole provides another strategy to prevent platelet activation and thrombotic complications. Inhibition of PDE results in increased levels of cAMP, a major intracellular second messenger that modulates various platelet functions. Cilostazol, a specific, reversible and strong inhibitor of PDE3A, is used in patients with peripheral arterial disease to reduce intermittent claudication and after endovascular therapy. Cilostazol has also been reported to reduce restenosis and improve outcomes after lower extremity angioplasty. Cilostazol is widely used to treat stroke patients in Asia. Adverse effects such as headache, diarrhea, dizziness and palpations limit the wider use of cilostazol. Dipyridamole is a specific inhibitor of PDE5. The combination of low dose aspirin plus extended release dipyridamole has been shown to be effective and safe for the secondary prevention of stroke and transient ischemic attack.
