Table 4.

Potential Characteristics of Safety End Points in Trials Assessing PAD Symptoms

	Intermittent Claudication		Critical Limb Ischemia
	Medical Therapies	Revascularization Therapies	Medical Therapies	Revascularization Therapies
Duration	Duration of trial	1. Related to operation/device within 30 d and 2. duration of trial	Duration of trial	1. Related to operation/device within 30 d and 2. duration of trial
All-cause mortality	Considered more unbiased but potentially less specific than cause-specific death
Cardiovascular mortality	Cardiac, cerebrovascular, or vascular death or when unequivocal noncardiovascular death cannot be established; assessment blinded to treatment allocation
Myocardial infarction	Troponin or CK above the upper limit of reference range (99th percentile) and symptoms or ECG changes or loss of viable myocardium or pathological findings at autopsy⁸⁵
TVR or TLR	Defined by symptoms and a decrease in ABI >0.15⁸ or functional walking test; assessment blinded to treatment allocation before imaging, followed by demonstration of physiologically significant restenosis by imaging/pressure gradient
Major bleed	Life-threatening bleed (fatal, into a critical organ, or associated with shock or drop in hemoglobin of >5g/dL) or major bleed (overt bleeding with drop in hemoglobin >3.0 g/dL)¹⁰
Acute kidney injury	Modified RIFLE¹⁰

ABI indicates ankle-brachial index; CK, creatine kinase; PAD, peripheral artery disease; RIFLE, risk, injury, failure, loss, and end-stage kidney disease; TLR, target lesion revascularization; and TVR, target vessel revascularization. Medical therapies include pharmacological or cell-based therapies; revascularization includes open surgical or percutaneous methods.