**1. Introduction**

Peripheral arterial disease (PAD) is a chronic condition in which stenosis or occlusion of the peripheral arteries [1–3]. The scopes range from the arteries that feed the brain are the carotid artery and the vertebral artery, the upper extremity arteries, the mesenteric arteries, the renal arteries, and the lower extremity arteries [1, 2, 4]. The PAD is primarily caused by the systemic atherosclerosis [5, 6]. There are other causes of PAD, such as thromboangiitis obliterans (TAO) or Buerger's disease, chronic arterial embolism, arterial entrapment, fungal arteritis, Takayasu's disease, inflammatory arterial disease from other causes such as polyarteritis nodosa (PAN) or other uncommon arteriopathies such as drug-induced arteriopathy [7], exercise-related external Iliac arteriopathy, radiation arteritis, fibromuscular dysplasia (FMD), vasculitis secondary to connective tissue diseases), such as rheumatoid arthritis, systemic lupus erythematosus (SLE), etc. [1, 8, 9].

The PAD of the lower extremity or lower extremity arterial disease (LEAD) due to atherosclerosis is a common disease in patients over the age of 60 years [2, 10, 11]. Males having a 1–2 times higher risk of developing PAD than females [1]. There have been 200 million cases of PAD worldwide, with a prevalence in 13–28%. The prevalence rate is expected to be underestimate due to a lack of screening system, which makes it impossible to document the exact number of patients in the group who have no symptoms or have minor symptoms [1–3]. In addition, a half of patients presenting with gangrene and ischemic ulcer of lower limb have no prior document of PAD [3]. According to previous publications data, the presentation of PAD is not typical. 50% of PAD patients are asymptomatic, In addition, among diabetics mellitus (DM) with PAD, have no symptoms of up to 80%. 15% of PAD patients are intermittent claudication. Only 1–3% of PAD patients are chronic limb-threatening ischemia (CLTI) which is a clinical syndrome of the PAD in combination with rest pain, gangrene or lower limb ulceration [3, 12, 13].

The major cause of death in patients with PAD is a cardiovascular disease. A cerebrovascular disease (CVD) and coronary artery disease (CAD) lead to high mortality rates for LEAD patients [14, 15]. The 5-year mortality rate of diagnosed PAD patients is 10–15%. Three-quarters of mortality group are fatal stroke and myocardial infarction (MI). For CLTI patients, the mortality rate is increasing to 25% with 4.5% of fatal stroke and 6.5% acute MI [16]. Thus, the four-point major adverse cardiovascular events (MACE) including acute MI, stroke, cardiovascular mortality, hospitalization for unstable angina or revascularization procedures is an increasingly primary outcome of interest in PAD. Recently, five-point MACE further expands on this with the inclusion of heart failure (HF) [3, 17, 18].

The PAD patients who need to revascularization of lower extremity artery include (1) CLTI which associated with increased mortality, risk of amputation, and impaired quality of life. (2) Disabling claudication patients who have limitation of daily activity and impaired quality of life due to their symptom [3, 13, 17]. All of them are risk of MACE during hospitalization for lower limb procedure such as revascularization, debridement, and amputation. MACE is rapid increasingly during perioperative period due to the stress from the foot infection or active comorbid disease and risk of the anesthesia and operation including revascularization (open vascular bypass, endovascular treatment) as well as amputation. Moreover, the poor performance status which occurred in patients who loss of ambulatory state due to non-functional limb, amputation, limb ulceration, gangrene, rest pain or disabling claudication are increased risk of MACE (**Figure 1**). The Society for Vascular Surgery (SVS) Objective Performance Goals (OPGs) established standardized tools for report benchmark of perioperative outcome including MACE and major adverse limb events (MALE) after revascularization procedures in patients with CLTI. The major adverse limb events (MALE) include major amputation of the revascularized limb and reintervention [19, 20].

Over the past decade, revascularization procedure for treating both simple and complex lower extremity arterial occlusive disease in a minimally invasive fashion

*Cardiovascular Complications Related to Lower Limb Revascularization and Drug-Delivering… DOI: http://dx.doi.org/10.5772/intechopen.107973*

#### **Figure 1.**

*The pathologic process of amputation and MACE during hospitalization in patients with PAD. CAD, coronary artery disease; CLTI, chronic limb-threatening ischemia; CVD, cerebrovascular disease; HF, heart failure; MACE, major cardiovascular events; MI, myocardial infarction; PAD, peripheral arterial disease.*

have increased significantly and induce some to support an "endovascular-first strategy" for most patients with PAD who candidate for revascularization [3, 13]. Most of the endovascular treatment (ET) in CLTI is a minimally invasive intervention which can perform under local anesthesia, which decreased the risk of general anesthesia, especially in multiple co-morbidities patients who cannot tolerate the major operation. In addition, ET can avoid the surgical wound complication and adjacent tissue injury. The length of hospital stay is also decreased in CLTI patients who performed ET when compare with open vascular bypass procedures.

Recently, the novel technology developed the antiproliferative agent -coated and -eluting device which can deliver the drugs to the vessel wall to limit the neointimal growth within de novo vascular system and stent [21–26]. However, some literatures report the MACE, aneurysmal degeneration, vascular fibrinoid necrosis, small vessel inflammation, and budget impact after drug technology device including drug coated balloon (DCB) and drug eluting stent (DES) in patients with ET [27–31]. The longterm MACE after DCB and DES device usage in patients with CLTI is still controversy [30, 32, 33]. This chapter describes the fundamental pathophysiology of MACE related to revascularization in patients with PAD and summarizes the most current data to guide an appropriate strategic treatment with drug-delivering technology under the risk and benefit assessment for ET in CLTI patients.
