Pentoxifylline for vascular health: a brief review of the literature

Pentoxifylline is a methylxanthine derivative that has been used for several decades in the symptomatic management of intermittent claudication. For reasons that remain fairly obscure, this drug benefits blood rheology in a number of complementary ways: decreasing blood and plasma viscosity, lowering plasma fibrinogen while promoting fibrinolysis, and improving blood filterability by enhancing erythrocyte distensibility and lessening neutrophil activation. Anti-inflammatory effects on neutrophils and macrophage/monocytes—some of them attributable to pentoxifylline metabolites—appear to play a mediating role in this regard. Although clinical trials with pentoxifylline have often been too small in size to reach statistically significant findings regarding impacts on hard end points, a review of the existing literature suggests that pentoxifylline may have potential for slowing the progression of atherosclerosis, stabilising plaque, reducing risk for vascular events, improving the outcome of vascular events, dampening the systemic inflammatory response following cardiopulmonary bypass, providing symptomatic benefit in angina and intermittent claudication, enhancing cerebral blood flow in patients with cerebrovascular disease while slowing progression of vascular dementia, improving prognosis in congestive heart failure, and aiding diabetes control. This safe and usually well-tolerated drug works in ways quite distinct from other drugs more commonly used for cardiovascular protection, and hence may confer complementary benefit when used in conjunction with them. Major clinical trials of adequate statistical power are now needed to confirm the scope of benefits that pentoxifylline can confer; studies evaluating hard end points in acute coronary syndrome, stroke/transient ischaemic attack and systolic heart failure might be particularly valuable.