TERAPIA ANTIAGGREGANTE O ANTICOAGULANTE NEL PAZIENTECON ARTERIOPATIA OBLITERANTE DEGLI ARTI INFERIORI?

Lorenzo Loffredo

I Clinica Medica, “Sapienza” University, Rome, Italy.

Mechanism of action of antithrombotic drugs for the treatment of peripheral artery disease. Currently available antithrombotic drugs for the treatment of peripheral artery disease target platelet activation and/or the coagulation cascade. Antiplatelet targets include the P2Y12 receptor (clopidogrel, ticagrelor, prasugrel), cyclooxygenase-1 (aspirin), and protease activated receptor 1 (vorapaxar). Anticoagulant targets include inhibition of vitamin K epoxide reductase, with a concomitant inhibition of Factors II, VII, IX, and X (warfarin), or more selective inhibition of Factor Xa (edoxaban, rivaroxaban). (vWF, von Willebrand factor; ADP, adenosine diphosphate; PAR 1, protease activated receptor 1; GP, glycoprotein; TP, thromboxaneprostanoid receptor; COX, cyclooxygenase.) Vascular Medicine 2016, Vol. 21(2) 156–169

VASI PERIFERICI DEGLI ARTI INFERIORI

PREVENZIONE PRIMARIA:

Primary Prevention of Cardiovascular

Events in Patients With Asymptomatic PAD

For persons with asymptomatic PAD, we

suggest aspirin 75 to 100 mg daily over no aspirin therapy (Grade 2B) .

CHEST 2012; 141(2)(Suppl):e669S–e690S

RECOMMENDATIONS FOR ANTIPLATELET AGENTS

AHA/ACC GUIDELINES. Circulation 2017

ANTITHROMBOTIC TRIALISTS’ (ATT) COLLABORATION

Lancet 2009; 373: 1849–60

BMJ 2002;324:71–86

ANTITHROMBOTIC TRIALISTS’ (ATT) COLLABORATION:

SUBGROUOP OF PATIENTS WITH PAD

Aspirin for the Prevention of Cardiovascular Events

in Patients With Peripheral Artery Disease

A Meta-analysis of Randomized Trials

JAMA. 2009;301(18):1909-1919

RECOMMENDATIONS FOR ANTIPLATELET AGENTS

AHA/ACC GUIDELINES. Circulation 2017

Vascular Medicine 2016, Vol. 21(2) 156–169

VASI PERIFERICI DEGLI ARTI INFERIORITERAPIA ANTIAGGREGANTE O ANTICOAGULANTE?

EFFICACIA DELLE TIENOPIRIDINE

Thienopyridines AND

Clopidogrel in PAD

Meta-analysis (fixed-effects

model) of Randomized

Controlled Trials of

Thienopyridines vs.

Control for Cardiovascular

Adverse events.

Thromb Haemost 2010; 103: 766–773

Results of clopidogrel versus aspirin for all outcomes in the PAD Subgroup of the CAPRIE study (1996).

Schmit et al. J Am Heart Assoc. 2014;3:e001330

Thienopyridines AND Clopidogrel in PAD

CAPRIE study

EFFECTS OF TICAGRELOR AND CLOPIDOGREL IN PATIENTS

WITH PERIPHERAL ARTERY DISEASE (EUCLID) TRIAL

NEJM 2017

VASI PERIFERICI DEGLI ARTI INFERIORIPREVENZIONE SECONDARIA:

Secondary Prevention of

Cardiovascular

Events in Patients With

Symptomatic PAD

For secondary prevention in patients

with symptomatic PAD, we recommend one of

the two following antithrombotic regimens to

be continued long term over no antithrombotic

treatment: aspirin 75 to 100 mg daily or

clopidogrel 75 mg daily (all Grade 1A) .

CHEST 2012; 141(2)(Suppl):e669S–e690S

ANTITHROMBOTIC TRIALISTS’ (ATT) COLLABORATION

Lancet 2009; 373: 1849–60

Secondary Prevention of

Cardiovascular

Events in Patients With

Symptomatic PAD: ASPIRIN

We suggest not to use dual antiplatelet

therapy with aspirin plus clopidogrel

(Grade 2B)

CHEST 2012; 141(2)(Suppl):e669S–e690S

Ruolo della doppia antiaggregante

RECOMMENDATIONS FOR ANTIPLATELET

AGENTS

AHA/ACC GUIDELINES. Circulation 2017

Dual antiplatelet therapy with aspirin plus clopidogrel vs

Aspirin

CHARISMA trial

European Heart Journal (2009) 30, 192–201

Thienopyridines AND

Clopidogrel in PAD

VASI PERIFERICI DEGLI ARTI INFERIORI

RUOLO DELLA TERAPIA ANTICOAGULANTE

We recommend not to use

an antiplatelet agent with

moderate-intensity warfarin

(Grade 1B) .

CHEST 2012; 141(2)(Suppl):e669S–e690S

AHA/ACC GUIDELINES. Circulation 2017

Oral Anticoagulant and Antiplatelet

Therapy

and Peripheral Arterial Disease

The Warfarin Antiplatelet Vascular

Evaluation Trial Investigators (WAVE)

N Engl J Med 2007;357:217-27.

The effects of oral

anticoagulants in

patients with

peripheral arterial

disease

American Heart Journal 151, 2006, 1–9

There is limited evidence suggesting that restenosis/reocclusion at six months following peripheral endovascular treatment is reducedby use of antiplatelet drugs compared with VKA, but associated information on bleeding and gastrointestinal side effects islacking.

Cochrane Database of Systematic Reviews 2012, Issue 8. Art. No.: CD002071.

Cochrane Database of Systematic Reviews 2014, Issue 5. Art. No.: CD001999.

The benefit of heparin, LMWHs and oral anticoagulants for treatment of intermittent claudication has not been established while anincreased risk of major bleeding events has been observed, especially with oral anticoagulants.

VASI PERIFERICI DEGLI ARTI INFERIORI

RUOLO DELLA TERAPIA ANTICOAGULANTE NEL PAZIENTE CON FIBRILLAZIONE

ATRIALE E PAD

Comparisons of cumulative

incidences between patients

with low and normal ABI. A)

Vascular event; B) Vascular

death; C) Myocardial in-

farction; D) Myocardial

infarction in patients without

previous MI; Survival has been

expressed with logarithmic

transformation; ABI= ankle-

brachial index.

ATRIALFIBRILLATION AND

PADARAPACIS STUDY

Thromb Haemost 2016; 115: 856–863

ATRIALFIBRILLATION

AND PAD

• AF patients with a history of stable vascular disease should be treated with warfarin only (ie, aspirin should not be added because of an excessive risk of bleeding).

Clin. Cardiol. 35, S1, 15–20 (2012)

ATRIAL FIBRILLATION AND PAD

VASI PERIFERICI DEGLI ARTI INFERIORI

RUOLO DEI NUOVI ANTICOAGULANTIORALI

NOAC and PADPrevention of heart attacks, stroke or cardiovascular death in patients

with coronary or peripheral artery disease

COMPASS

Cardiovascular OutcoMes for People

using Anticoagulation StrategieS (2013,

ongoing)

Objective

To evaluate whether treatment with rivaroxaban and ASA or

rivaroxaban alone is better than ASA alone in prevention of major

cardiac events in patients with CAD or PAD

CONCLUSIONI

• La terapia antiaggregante rappresenta la principale terapia antitrombotica nel paziente affetto da PAD

• Nel paziente con fibrillazione atriale, PAD e stabilità vascolare si consiglia la terapia anticoagulante rispetto quella antiaggregante

• L’associazione antiaggreganti/anticoagulanti non dà benefici rispetto alla sola terapia antiaggregante nel paziente con PAD e stabilità vascolare