Effective Vascular Therapeutics for Critical Limb Ischemia

Abstract

Peripheral artery disease (PAD) is one of the most common cardiovascular diseases and is associated with high short-term morbidity and mortality.1,2 It is the primary cause of lower extremity amputation throughout the world and is a powerful marker of advanced systemic atherosclerosis. Chronic critical limb ischemia (CLI) represents the most advanced clinical manifestation of PAD and is defined by the presence of ischemic rest pain, nonhealing wounds, or tissue loss (gangrene). CLI does not represent a single pathophysiologic process (ie, progressive leg arterial atherosclerosis), but is caused by multiple pathogenetic mechanisms, including native artery atherosclerosis, cardioembolic events, inflammatory arteritides (eg, thromboangiitis obliterans), hypercoagulable states, or leg bypass graft failure. Article see p 68 CLI syndromes are currently classified by the clinical stages III and IV of the Fontaine classification, and this equates to the Rutherford categories 4, 5, and 6.1,2 Although there is no consensus regarding the precise level of objective malperfusion that should be required to define CLI, the Second European Consensus Document3 defined CLI by 2 criteria: persistent recurring ischemic rest pain requiring regular adequate analgesia for >2 weeks, with an ankle systolic pressure ≤50 mm Hg, or a toe systolic pressure of ≤30 mm Hg; or ulceration or gangrene of the foot or toes, with an ankle systolic pressure of ≤50 mm Hg, or a toe systolic pressure of ≤30 mm Hg. These definitions remain in widespread use in CLI clinical research. The current incidence and prevalence of CLI, and thus the public health impact of this syndrome, is incompletely defined. Population-based study of this syndrome is hampered by the inability of field surveys to measure incident cases, use of varying CLI definitions, and due to the lack of consistent coding in administrative billing databases. Yet, it has been estimated …