Critical Limb Ischemia: Current Trends and Future Directions

C ritical limb ischemia (CLI), which is at the end of the peripheral artery disease (PAD) spectrum, is associated with excessively high risk for cardiovascular events, including myocardial infarction, and death.[1][2][3] Mortality rates as high as 20% within 6 months from diagnosis and exceeding 50% at 5 years have been reported for CLI, 4-6 whereas 1-year mortality rates in nonrevascularizable, so-called no-option CLI patients range from 10% to 40%.7,8 The high mortality rates exceed those for every other form of occlusive cardiovascular disease, including symptomatic coronary artery disease (CAD), 9,10 and reflect the systemic atherosclerotic burden associated with CLI.Besides poor survival rates, prognosis with respect to limb preservation in CLI patients is poor, 11 particularly in no-option CLI patients, where 6-month major amputation rates have been reported to range from 10% to 40%.[6][7][8] Additionally, CLI is associated with poor quality of life 12 and high treatment costs, 13 especially when amputation is inevitable.13,14 With an estimated yearly incidence of 500 to 1000 new cases per million individuals in Western society, 7 which is ever increasing in concert with the increase in cardiovascular risk factors, 15-17 CLI poses a substantial burden on patients, healthcare providers, and resources.In the current review we will describe how management strategies in CLI have evolved over the past decades and discuss issues that could facilitate more rapid and evidencebased improvements in CLI management and care.Focus will be on factors that may have limited evidence-based management and on actions that could promote progress in this field, especially with respect to clinical research.