Peripheral Artery Disease: Drug Therapy

Therapeutic Targets

Inhibition of the progression of pAVD
Risk reduction of peripheral vascular events.
Reduction of cardiovascular and cerebrovascular events.
- Reduction of LDL cholesterol to levels <70 mg/dl or by at least 50% relative to baseline LDL levels [2017 ESC Guidelines].
Reduction of pain
Improvement of resilience, walking performance and quality of life

Another therapeutic goal is to reduce further vascular interventions (arterial reconstructions) during the clinical course of the disease.

Therapy recommendations depending on Fontaine stage I-IV:

Measure	Fontaine Stadium
Measure	I	II	III	IV
Risk factor management: Nicotine abstinence Diabetes therapy (normoglycemic blood glucose control). Hyperlipidemia/statins (see below therapy goals or “hypercholesterolemia/medicinal therapy”). Hypertension/blood pressure treatment (target blood pressure: <140/90 mmHg);first-line therapy: ACE inhibitors or angiotensin receptor antagonists).	+	+	+	+
Antiplatelet drugs* (acetylsalicylic acid (ASA) or clopidogrel	(+)	+	+	+
PhysicalTherapy (structured gait training).	+	+
DrugTherapy (cilostazol or naftidrofuryl).		+
Structured wound treatment		+		+
Interventional therapy		+*	+	+
Operative therapy		+*	+	+

Legend: + recommendation,* in case of high individual suffering and suitable vascular morphology.

In asymptomatic patients with low ankle-brachial index, there was no reduction in cardiovascular events with acetylsalicylic acid (ASA 100 mg) compared with placebo.
* In the case of lower extremities occlusive disease (LEAD, lower extremities arterial disease), longer-term antiplatelet monotherapy is consistently indicated only in symptomatic patients [2017 ESC Guidelines].
- Clopidogrel may be considered preferentially (IIb recommendation) [2017 ESC Guidelines].
If TASC II criteria are followed, interventional outcomes are comparable to vascular surgery outcomes, at least in the medium term.
See also under “Further therapy” (Fontaine stage I +II: physical therapy/supervised gait training.

Further notes

For secondary prevention of cardiovascular events, CSE inhibitors are indicated in patients with pAVD. Statins reduce morbidity and mortality in pAVD. (Grade of recommendation A, class of evidence 1).
In patients who had asymptomatic peripheral arterial disease with an ankle-brachial index ≤ 0.95 and were free of clinical symptoms of cardiovascular disease, statin therapy resulted in the following outcomes:
- Five fewer major cardiovascular events related to 1,000 person-years occurred than without statin therapy (19.7 events vs 24.7 events per 1,000 person-years)
- All-cause mortality rate: “new users” 24.8 per 1,000 person-years vs. “nonusers” (30.3/1,000 person-years)
Notice: However, in asymptomatic Fontaine stage I, statin therapy is off-label (LDL < 100 mg/dl and optionally < 70 mg/dl).
Patients with critical ischemia and infection should receive systemic antibiotic therapy. (Grade of recommendation A, class of evidence 2).
Iloprost demonstrated higher leg preservation and survival rates with prostanoid therapy
The antiplatelet agent ticagrelor 90 mg twice daily) is equivalently effective as clopidogrel (stage II – IV)

A double-blind study demonstrated that for patients undergoing revascularization (restoration of blood flow to a vessel) of the lower extremities, the risk of peripheral and cardiovascular events can be reduced by adding rivaroxaban to acetylsalicylic acid (ASA): Over 3 years, 508 (17.3%) patients in the rivaroxaban group and 584 (19.9%) patients in the control group, and thus significantly (15%) fewer, met the primary end point. The primary endpoint was defined as follows: acute extremity ischemia (reduced blood flow to the extremities), vascular (vessel-related) major amputations, myocardial infarction (heart attack), ischemic stroke (due to reduced blood flow to the brain), and cardiovascular death (cardiovascular-related death).