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Title: Medical Management of Peripheral Artery Disease 14

1) Cholesterol reduction patients including those with PAD to minimize 25% reduction in vascular death, nonfatal MI, or receiving combination aspirin and warfarin
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According to ACC/AHA guidelines, high-intensity cardiovascular events. Thus, ezetimibe may cerebrovascular accident in subgroups of therapy alone. However, major bleeding events
statin is recommended for patients with prove to be an effective therapy when patients with atherosclerotic vascular disease and intracranial hemorrhage were signiﬁcantly
symptomatic PAD (Target LDL-C of <70) with a co-administered with statin therapy. More (manifested as recent ischaemic stroke, increased. Further analysis reported poor

class I recommendation. 8 speciﬁc studies are required for patients with myocardial infarction, or symptomatic peripheral compliance and a 30% rate of discontinuation of
PAD. arterial disease). 6 warfarin at follow-up. Thus, poor adherence to
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a) Statin therapy could be a possible reason for lack of
In the Heart Protection Study Collaborative c) PCSK9 (proprotein convertase subtil- c) Dual anti-platelet therapy (DAPT) efﬁcacy in study patients. 19

Group in PAD patients, treatment with isin/kexin type 9) inhibitors In the CHARISMA trial (Clopidogrel for High
moderate-intensity statin therapy, simvastatin In the FOURIER trial (Further Cardiovascular Atherothrombotic Risk and Ischemic b) Rivaroxaban
reduced peripheral vascular events by 17%. A Outcomes Research With PCSK9 Inhibition in Stabilization, Management, and Avoidance) The COMPASS trial (Cardiovascular Outcomes
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recent observational study also demonstrated Subjects With Elevated Risk) patients with PAD DAPT was compared to single antiplatelet for People Using Anticoagulation Strategies)
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that high-intensity statin therapy is more showed a 59% reduction in LDL-C with therapy and included patients with PAD. A demonstrated mortality reduction beniﬁt with
effective in preventing limb loss than moderate evolocumab, resulting in a 3.5% absolute risk post-hoc sub-group analysis in PAD patients low-dose rivaroxaban in combination with aspirin
intensity therapy. Besides peripheral vascular reduction in cardiovascular events (MI, death, revealed that DAPT therapy led to non-signiﬁcant for patients with PAD. 20, 21 Major adverse limb
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complications, statin therapy also prevented stroke, hospitalization for unstable angina, and reduction in the primary endpoint (rate of CV events occurred less often in rivaroxaban and

systemic complications and reduced the rate of coronary revascularization) compared with a death, MI, or stroke) - 7.6% in the clopidogrel plus aspirin combination group than aspirin alone. 20, 21
all cardiovascular events : 1.6% absolute risk reduction in patients without aspirin group and 8.9% in the placebo plus There was no signiﬁcant increase in fatal
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PAD. 13,14 Major adverse limb events were also aspirin group (hazard ratio, 0.85; 95% CI, bleeding or symptomatic intracranial bleeding
coronary revascularization (30% reduction)
reduced (acute limb ischemia, major amputation, 0.66–1.08; P = 0.18) between the two treatment groups (P=0.40). 20, 21
major coronary events (21% reduction)
or urgent peripheral revascularization for The Heart Protection Study found a 22% relative
ischemic stroke (26% reduction).
ischemia). 13 3) Anticoagulation risk reduction in the ﬁrst major vascular event
CLI is the consequence of with moderate-intensity statin therapy while the
b) Ezetimibe 2) Antiplatelet therapy atherothromboembolism in the limbs. Clinical COMPASS trial showed a 28% relative risk
Ezetimibe selectively blocks Niemann-Pick evidence highlights that timely anticoagulation in reduction in the primary outcome with the use of
C1-like 1 protein (NPC1L1), that transports a) Aspirin high risk patients may prevent limb-related low-dose rivaroxaban and aspirin. HPS and

cholesterol in the intestines and inhibits lipids Aspirin has been shown to be effective for complications from PAD, as well as other COMPASS were different studies. Mentioned

absorption in the gastrointestinal tract. It is a symptomatic PAD. CLIPS (Critical Leg Ischemia cardiovascular morbidity and mortality. 18 RRR values are for information only, and not for
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promising treatment option to treat Prevention Study) trial provides a direct evidence direct comparison. 20, 21

hypercholesterolemia as it selectively reduces regarding usefulness of low-dose aspirin (81 mg) a) Warfarin
low-density lipoprotein or LDL (“bad” cholesterol) in 366 patients with symptomatic and The WAVE trial (Warfarin Antiplatelet Vascular 4) Blood Pressure management

and triglycerides, without affecting the asymptomatic PAD and showed a 64% relative Evaluation) investigated the use of warfarin in Several prospective and retrospective studies
concentration of “good” cholesterol or high risk reduction in major vascular events [ischemic combination with aspirin for patients with have shown a reduction in mortality with

density lipoproteins (HDL). 11 stroke, MI, and vascular death (P=0.022)]. 15 symptomatic PAD (81.8% of the total trial Angiotensin-converting enzyme (ACE) inhibitors

population), subclavian disease, and carotid and Angiotensin receptor blockers (ARBs) over
The IMPROVE-IT trial (Improved Reduction of b) Clopidogrel disease. The trial found no signiﬁcant difference other antihypertensive agents. 22, 23, 24 Based on

Outcomes: Vytorin Efﬁcacy International Trial) The CAPRIE trial (Clopidogrel Versus Aspirin in in the occurrence of major adverse these ﬁndings, both European Society of

showed that ezetimibe beneﬁts high-risk Patients at Risk for Ischemic Events) showed a cardiovascular events between patients Cardiology and ACC/AHA guidelines have given a

class II recommendation for ACE inhibitors or reduction in major adverse limb events along Am Coll Cardiol 2019;73:e285–e350. 18) Hess CN, Debus ES, Nehler MR, Anand SS, Patel MR,
doi:10.1016/j.jacc.2018.11.003 Szarek M, Capell WH, Hsia J, Beckman JA, Brodmann M, 26) Hageman D, Fokkenrood HJ, Gommans LN, van den
ARBs or ARB for management of PAD. 22 with cardiovascular events. Thus, the novel Diaz R, Habertheuer P, Leeper NJ, Powell RJ, Sillesen H, Houten MM, Teijink JA. Supervised exercise therapy
strategy of rivaroxaban and aspirin holds 9) Heart Protection Study Collaborative Group. Muehlhofer E, Berkowitz SD, Haskell LP, Bauersachs RM, versus home-based exercise therapy versus walking
Randomized trial of the effects of cholesterol-lowering
Bonaca MP. Reduction in Acute Limb Ischemia With
advice for intermittent claudication. Cochrane Database
5) Lifestyle modiﬁcation promise to prevent thrombotic complications with simvastatin on peripheral vascular and other major Rivaroxaban Versus Placebo in Peripheral Artery Disease Syst Rev 2018;4:CD005263. doi:
vascular outcomes in 20,536 people with peripheral After Lower Extremity Revascularization: Insights From 10.1002/14651858.CD005263.pub4
and improve the quality of life of PAD patients. arterial disease and other high-risk conditions. J Vasc VOYAGER PAD. Circulation 2021 Dec
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