Page 16 - Vasoclick emagazine_Issue1_revised

1) Cholesterol reduction
cerebrovascular accident in subgroups of
therapy alone. However, major bleeding events
cardiovascular events. Thus, ezetimibe may
12
According to ACC/AHA guidelines, high-intensity
19
and intracranial hemorrhage were significantly
patients with atherosclerotic vascular disease
prove to be an effective therapy when
statin is recommended for patients with
(manifested as recent ischaemic stroke,
increased. Further analysis reported poor
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
6
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
Ischemic
and
Atherothrombotic
Risk
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
therapy and included patients with PAD. A
demonstrated mortality reduction benifit with
17
that high-intensity statin therapy is more
evolocumab, resulting in a 3.5% absolute risk
low-dose rivaroxaban in combination with aspirin
post-hoc sub-group analysis in PAD patients
effective in preventing limb loss than moderate
reduction in cardiovascular events (MI, death,
for patients with PAD.
Major adverse limb
revealed that DAPT therapy led to non-significant
intensity therapy. Besides peripheral vascular
20, 21
10
stroke, hospitalization for unstable angina, and
events occurred less often in rivaroxaban and
reduction in the primary endpoint (rate of CV
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
aspirin group and 8.9% in the placebo plus
There was no significant increase in fatal
all cardiovascular events :
9
PAD.
Major adverse limb events were also
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,
between the two treatment groups (P=0.40).
0.66–1.08; P = 0.18)
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
is
the
of
CLI
consequence
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.
RRR values are for information only, and not for
18
promising
option
to
treatment
Prevention Study) trial provides a direct evidence
direct comparison.
20, 21
a) Warfarin
hypercholesterolemia as it selectively reduces
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
the
affecting
without
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
15
11
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)
occurrence
of
the
major
adverse
in
these findings, both European Society of
Patients at Risk for Ischemic Events) showed a
showed that ezetimibe benefits high-risk
between
patients
cardiovascular
events
Cardiology and ACC/AHA guidelines have given a
Title: Medical Management of Peripheral Artery Disease treat patients including those with PAD to minimize 25% reduction in vascular death, nonfatal MI, or receiving combination aspirin and warfarin
16
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
a) Smoking cessation Surg 2007;45:645–654; discussion 653–654. doi: 7;144(23):1831-1841. doi:
10.1016/j.jvs.2006.12.054 10.1161/CIRCULATIONAHA.121.055146.
Patients with PAD report smoking-related References
complications and increased mortality. Patients 10) Arya S, Khakharia A, Binney ZO, DeMartino RR, 19) Anand S, Yusuf S, Xie C, Pogue J, Eikelboom J, Budaj
1) Jones WS, Patel MR, Dai D, Vemulapalli S, Subherwal S, Brewster LP, Goodney PP, Wilson PWF. Association of A, Sussex B, Liu L, Guzman R, Cina C; Warfarin Antiplatelet
with PAD who underwent angiography, Stafford J, Peterson ED. High mortality risks after major statin dose with amputation and survival in patients with Vascular Evaluation Trial Investigators. Oral anticoagulant
lower extremity amputation in Medicare patients with peripheral artery disease. Circulation and antiplatelet therapy and peripheral arterial disease. N
continuous smoking led to increased mortality peripheral artery disease. Am Heart J 2013;165:809–815, 2018;137:1435–1446.doi:10.1161/CIRCULATIONAHA.117 Engl J Med 2007;357:217–227. doi:
(31% versus 14%; P<0.05) and higher amputation 815.e1. doi: 10.1016/j.ahj.2012.12.002 .032361 10.1056/NEJMoa065959
rate (40% versus 19%; P<0.05). Though clear 2) Ohman EM, Bhatt DL, Steg PG, Goto S, Hirsch AT, Liau 11) Phan BA, Dayspring TD, Toth PP. Ezetimibe therapy: 20) Eikelboom JW, Connolly SJ, Bosch J, Dagenais GR,
25
CS, Mas JL, Richard AJ, R ther J, Wilson PW; REACH mechanism of action and clinical update. Vasc Health Hart RG, Shestakovska O, Diaz R, Alings M, Lonn EM,
evidence is lacking for any direct association Registry Investigators. The Reduction of Risk Manag 2012;8:415-27. doi: 10.2147/VHRM.S33664. Anand SS, et al; COMPASS Investigators. Rivaroxaban
between pharmacotherapy to manage smoking Atherothrombosis for Continued Health (REACH) registry: with or without aspirin in stable cardiovascular disease. N
an international, prospective, observational investigation 12) Bohula EA, Morrow DA, Giugliano RP, Blazing MA, He P, Engl J Med 2017;377:1319–1330.
and PAD-related mortality, these interventions in subjects at risk for atherothrombotic events-study Park JG, Murphy SA, White JA, Kesaniemi YA, Pedersen doi:10.1056/NEJMoa1709118
design. Am Heart J 2006;151:786.e1–786.10. doi: TR, et al. Atherothrombotic risk stratification and
are included under class IA recommendations 10.1016/j.ahj.2005.11.004 ezetimibe for secondary prevention. J Am Coll Cardiol 21) Connolly SJ, Eikelboom JW, Bosch J, Dagenais G, Dyal
for PAD patients for their overall health benefits. 22 2017;69:911–921. doi: 10.1016/j.jacc.2016.11.070 L, Lanas F, Metsarinne K, O’Donnell M, Dans AL, Ha JW, et
3) Fowkes FGR, Murray GD, Butcher I, Heald CL, Lee RJ, al; COMPASS Investigators. Rivaroxaban with or without
Chambless LE, Folsom AR, Hirsch AT, Dramaix M, 13) Bonaca MP, Nault P, Giugliano RP, Keech AC, Pineda aspirin in patients with stable coronary artery disease: an
b) Physical exercise deBacker G, et al; Ankle Brachial Index Collaboration. AL, Kanevsky E, Kuder J, Murphy SA, Jukema JW, Lewis international, randomised, double-blind,
BS, et al. Low-density lipoprotein cholesterol lowering with
Ankle brachial index combined with framingham risk
placebo-controlled trial. Lancet 2018;391:205–218. doi:
Supervised exercise therapy programs aim to score to predict cardiovascular events and mortality: a evolocumab and outcomes in patients with peripheral 10.1016/S0140-6736(17)32458-3
meta analysis. JAMA 2008;300:197–208. doi: artery disease: insights from the FOURIER trial (Further
improve claudication symptoms related to PAD 10.1001/jama.300.2.197 Cardiovascular Outcomes Research With PCSK9 22) Gerhard-Herman MD, Gornik HL, Barrett C, Barshes
Inhibition in Subjects With Elevated Risk). Circulation NR, Corriere MA, Drachman DE, Fleisher LA, Fowkes FG,
and are highly effective. However, such 4) Murabito JM, Evans JC, Larson MG, Nieto K, Levy D, 2018;137:338–350. doi: Hamburg NM, Kinlay S, et al. 2016 AHA/ACC guideline on
26
interventions lack direct evidence on PAD related Wilson PW; Framingham Study. The ankle-brachial index 10.1161/CIRCULATIONAHA.117.032235 the management of patients with lower extremity
in the elderly and risk of stroke, coronary disease, and peripheral artery disease: executive summary: a report of
mortality and amputation rates. death: the Framingham Study. Arch Intern Med 14) Sabatine MS, Giugliano RP, Keech AC, Honarpour N, the American College of Cardiology/American Heart
2003;163:1939–1942. doi: 10.1001/archinte.163.16.1939 Wiviott SD, Murphy SA, Kuder JF, Wang H, Liu T, Association task force on clinical practice guidelines.
Wasserman SM, et al; FOURIER Steering Committee and Circulation 2017;135:e686–e725. doi:
Conclusion 5) Marrett E, DiBonaventura Md, Zhang Q. Burden of Investigators. Evolocumab and clinical outcomes in 10.1161/CIR.0000000000000470
peripheral arterial disease in Europe and the United patients with cardiovascular disease. N Engl J Med
Recent advancements in therapeutic strategies States: a patient survey. Health Qual Life Outcomes 2017;376:1713–1722. doi:10.1056/NEJMoa1615664 23) Armstrong EJ, Chen DC, Singh GD, Amsterdam EA,
and improved application of available 2013;11:175. doi: 10.1186/1477-7525-11-175 Laird JR. Angiotensin-converting enzyme inhibitor or
15) Catalano M, Born G, Peto R; Critical Leg Ischaemia angiotensin receptor blocker use is associated with
pharmacotherapies for PAD management have 6) Berger JS, Ladapo JA. Underuse of prevention and Prevention Study (CLIPS) Group. Prevention of serious reduced major adverse cardiovascular events among
lifestyle counseling in patients with peripheral artery vascular events by aspirin amongst patients with patients with critical limb ischemia. Vasc Med
demonstrated promising results and satisfactory disease. J Am Coll Cardiol 2017;69:2293–2300. doi: peripheral arterial disease: randomized, double-blind trial. 2015;20:237–244. doi:10.1177/1358863X15574321
clinical outcome. Antithrombotic therapy is the 10.1016/j.jacc.2017.02.064 J Intern Med 2007;261:276–284. doi:
10.1111/j.1365-2796.2006.01763.x 24) Feringa HH, van Waning VH, Bax JJ, Elhendy A,
mainstay of treatment of PAD. Dual antiplatelet 7) Bevan GH, Solaru KTW. Evidence-based medical Boersma E, Schouten O, Galal W, Vidakovic RV, Tangelder
management of peripheral artery disease Arterioscler 16) CAPRIE Steering Committee. A randomised, blinded, MJ, Poldermans D. Cardioprotective medication is
therapy (clopidogrel and aspirin) showed Thromb Vasc Biol 2020;40:541–553. DOI: trial of Clopidogrel Versus Aspirin in Patients at Risk of associated with improved survival in patients with
reduction in MI, stroke, and other major adverse 10.1161/ATVBAHA.119.312142 Ischaemic Events (CAPRIE). CAPRIE steering committee. peripheral arterial disease. J Am Coll Cardiol
Lancet 1996;348:1329–1339. 2006;47:1182–1187. doi:10.1016/j.jacc.2005.09.074
cardiac events, while in patients with PAD, limb 8) Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, doi:10.1016/s0140-6736(96)09457-3
Blumenthal RS, Braun LT, de Ferranti S, Faiella-Tommasino 25) Armstrong EJ, Wu J, Singh GD, Dawson DL, Pevec WC,
outcomes were not studied or reported. The J, Forman DE, et al. 2018 AHA/ACC/AACVPR/AAPA/ABC/ 17) Cacoub PP, Bhatt DL, Steg PG, Topol EJ, Creager MA; Amsterdam EA, Laird JR. Smoking cessation is
addition of oral anticoagulant rivaroxaban at ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on CHARISMA Investigators. Patients with peripheral arterial associated with decreased mortality and improved
the management of blood cholesterol: a report of the disease in the CHARISMA trial. Eur Heart J amputation-free survival among patients with
vascular dose (2.5 mg bid) to aspirin resulted in American College of Cardiology/American Heart 2009;30:192–201. doi: 10.1093/eurheartj/ehn534 symptomatic peripheral artery disease. J Vasc Surg
Association task force on clinical practice guidelines. J 2014;60:1565–1571. doi: 10.1016/j.jvs.2014.08.064