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25% reduction in vascular death, nonfatal MI, or
1) Cholesterol reduction
patients including those with PAD to minimize
therapy alone. However, major bleeding events
cerebrovascular accident in subgroups of
cardiovascular events. Thus, ezetimibe may
19
12
According to ACC/AHA guidelines, high-intensity
patients with atherosclerotic vascular disease
and intracranial hemorrhage were signiﬁcantly
prove to be an effective therapy when
statin is recommended for patients with
increased. Further analysis reported poor
(manifested as recent ischaemic stroke,
co-administered with statin therapy. More
symptomatic PAD (Target LDL-C of <70) with a
compliance and a 30% rate of discontinuation of
myocardial infarction, or symptomatic peripheral
speciﬁc studies are required for patients with
class I recommendation.
8
arterial disease).
warfarin at follow-up. Thus, poor adherence to
PAD.
19
a) Statin
therapy could be a possible reason for lack of
c) Dual anti-platelet therapy (DAPT)
In the Heart Protection Study Collaborative c) PCSK9 (proprotein convertase subtil-
efﬁcacy in study patients.
19
isin/kexin type 9) inhibitors
In the CHARISMA trial (Clopidogrel for High
Group in PAD patients, treatment with
b) Rivaroxaban
In the FOURIER trial (Further Cardiovascular
and
Ischemic
Atherothrombotic
moderate-intensity statin therapy, simvastatin
Outcomes Research With PCSK9 Inhibition in
The COMPASS trial (Cardiovascular Outcomes
Stabilization, Management, and Avoidance)
reduced peripheral vascular events by 17%. A
9
Subjects With Elevated Risk) patients with PAD
DAPT was compared to single antiplatelet
for People Using Anticoagulation Strategies)
recent observational study also demonstrated
showed a 59% reduction in LDL-C with
demonstrated mortality reduction beniﬁt with
therapy and included patients with PAD. A
17
that high-intensity statin therapy is more
evolocumab, resulting in a 3.5% absolute risk
post-hoc sub-group analysis in PAD patients
low-dose rivaroxaban in combination with aspirin
effective in preventing limb loss than moderate
reduction in cardiovascular events (MI, death,
Major adverse limb
revealed that DAPT therapy led to non-signiﬁcant
for patients with PAD.
intensity therapy. Besides peripheral vascular
20, 21
10
stroke, hospitalization for unstable angina, and
reduction in the primary endpoint (rate of CV
events occurred less often in rivaroxaban and
complications, statin therapy also prevented
coronary revascularization) compared with a
death, MI, or stroke) - 7.6% in the clopidogrel plus
aspirin combination group than aspirin alone.
20, 21
systemic complications and reduced the rate of
1.6% absolute risk reduction in patients without
There was no signiﬁcant increase in fatal
aspirin group and 8.9% in the placebo plus
all cardiovascular events :
9
Major adverse limb events were also
PAD.
13,14
bleeding or symptomatic intracranial bleeding
aspirin group (hazard ratio, 0.85; 95% CI,
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).
3) Anticoagulation
ischemia).
13
risk reduction in the ﬁrst major vascular event
CLI
is
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
11
cardiovascular morbidity and mortality.
18
RRR values are for information only, and not for
promising
treatment
option
treat
to
Prevention Study) trial provides a direct evidence
direct comparison.
20, 21
hypercholesterolemia as it selectively reduces
a) Warfarin
regarding usefulness of low-dose aspirin (81 mg)
low-density lipoprotein or LDL (“bad” cholesterol)
in 366 patients with symptomatic and
The WAVE trial (Warfarin Antiplatelet Vascular
4) Blood Pressure management
and
without
the
affecting
triglycerides,
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).
stroke, MI, and vascular death (P=0.022)].
symptomatic PAD (81.8% of the total trial
11
15
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
Based on
other antihypertensive agents.
22, 23, 24
The CAPRIE trial (Clopidogrel Versus Aspirin in
Outcomes: Vytorin Efﬁcacy International Trial)
major
the
of
occurrence
in
adverse
these ﬁndings, both European Society of
Patients at Risk for Ischemic Events) showed a
showed that ezetimibe beneﬁts high-risk
events
between
cardiovascular
Cardiology and ACC/AHA guidelines have given a
17
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