Pharmacotherapy of Peripheral Artery Disease Flashcards
Define peripheral artery disease (PAD)
- Clinical disorder consisting of stenosis or occlusion in the aorta or arteries of the limbs
- Mainly caused by Atherosclerosis
patients who are at risk for developing PAD
- Age ≥ 65 years of age
- Age 50–64 years of age, with risk factors for atherosclerosis
- Age < 50 years of age, with diabetes mellitus PLUS 1 additional risk factor for atherosclerosis
- Individuals with known atherosclerotic disease in another vascular bed: coronary arteries, carotid arteries, renal arteries, Abdominal Aortic aneurysm (AAA)
risk factors for atherosclerosis
- History of cigarette smoking – PAD is associated with the duration and amount of cigarettes smoked; this is the single most important risk factor to modify
- Diabetes Mellitus
- Hypertension
- Dyslipidemia
- Family history of PAD
signs & symptoms of lower extremity PAD
- Can be asymptomatic or symptomatic
- Claudication
- Atypical leg pain
- Ischemic rest pain
- Impaired walking function
- Diminished pulses
- Bruits – turbulent sound instead of lub dub
- Pallor upon elevation of extremity (pale)
- Trophic changes
example of trophic changes
- Muscle atrophy
- Shiny, hairless skin
- Nail changes
Claudication
Fatigue, discomfort, cramping, or pain of vascular origin in the muscles of the lower extremities that is consistently induced by exercise and consistently relieved by rest (within 10 minutes)
complications associated with PAD
- Abdominal Aortic aneurysm
- Coronary artery atherosclerosis may cause MI
- Carotid artery atherosclerosis / Cerebral vascular disease -> may cause stroke
- Renal artery atherosclerosis -> may cause Renal artery stenosis
- Acute Limb Ischemia (ALI)
- Critical limb ischemia (CLI)
- Infection
- Amputation
How do you measure the ankle-brachial index (ABI)?
Taking top # of legs BP and dividing it by arm BP (L or R arm – whichever is higher)
How is the ankle-brachial index (ABI) used to diagnose lower extremity PAD?
- If ratio is < 0.9, that is diagnosis for PAD
- That means that the BP is lower in the legs than it is in the arms
What will help improve morbidity / mortality outcomes?
- Decrease Risk of MI, Stroke, and CV Death
- Discontinue Tobacco Use
- Blood pressure control
- High-intensity statin therapy
- Antiplatelet therapy
What will help improve limb-related outcomes?
- Improvement in Symptoms, QoL, and/or Prevent Amputation
- Discontinue Tobacco Use
- Exercise-program
- Cilostazol
- Foot care
- Revascularization
most important lifestyle modification for the treatment of lower extremity PAD
- BLOOD PRESSURE
- CIGARETTE SMOKING
- Diabetes
- Dyslipidemia
exercise
- should be supervised; highly recommended
- can improve functional status and QoL and to reduce leg symptoms
- be careful not to do too much because that can worsen PAD
Antiplatelet therapy
aspirin alone (81mg per day) or clopidogrel alone (75mg per day) is recommended to reduce MI, stroke, and vascular death
Antihypertensive therapy
- should be administered to patients with hypertension AND PAD to reduce the risk of MI, stroke, heart failure, and cardiovascular death
- The use of ACE-inhibitors or ARBs can be effective to reduce the risk of cardiovascular ischemic events in patients with PAD.
- The use of either of these meds are contraindicated in someone who has renal artery stenosis
Cilostazol
effective therapy to improve symptoms and increase walking distance in patients with claudication
ASA
- COX and TxA2 inhibitor
- Prevents platelet from being activated any further
- 81mg ASA enteric coated once daily
Clopidogrel
- blocks ADP from binding to the P2Y12 receptor specifically on the ADP binding site
- alternative to ASA
- 75mg once daily
Vorapaxar (Zontivity)
- PAR- 1 Inhibitor [protease-activated (PAR) -1 receptor potentiates release of other platelet activators]
- inhibits thrombin-induced and thrombin receptor agonist peptide (TRAP)-induced platelet aggregation
- indicated for established PAD
- Used in combination with ASA and/or clopidogrel
- Increases risk of serious bleeding
- 2.08 mg PO once daily
High-intensity Statin Therapy
- Atherosclerotic plaque stabilization
- Atorvastatin 40-80 mg/day or Rosuvastatin 20-40 mg/day
Cilostazol (Pletal®)
- Inhibits phosphodiesterase III [PDE: Dilation and inhibition of platelet aggregation]
- Use when refractory to exercise therapy and smoking cessation
- Use in combination with either ASA or clopidogrel
- 100 mg twice daily
adverse effects of cilostazol
- Headache
- Dizziness
- Nausea
- Diarrhea
- Cardiovascular effects (tachycardia, palpitation, tachyarrhythmia, and/or hypotension)
In which patients should we avoid cilostazol?
- Avoid use in patients who are actively bleeding
- Patients with history of ischemic heart disease may be at increased risk for exacerbation of angina pectoris or myocardial infarction
- contraindicated with patients with heart failure of any severity
precautions for cilostazol
Use with caution in patients with severe renal impairment
Pearls of cilostazol
- Administer cilostazol on an empty stomach 30 minutes before or 2 hours after meals (If taken with high fat meal, can bump AUC by 97%)
- avoid grapefruit juice
drug interactions of cilostazol
- Major substrate of CYP450 isoenzymes
- adjust dose from 100mg BID to 50mg BID if pt is on fluconazole and omeprazole (3A4) or diltiazem, erythromycin, itraconazole, and ketoconazole (2C19)
pharmacotherapy after revascularization
- Dual-antiplatelet therapy (aspirin and clopidogrel) may be reasonable to reduce the risk of limb-related events in patients with symptomatic PAD after lower extremity revascularization
- Usefulness of anticoagulation after revascularization is uncertain
the 6 P’s
- Pain
- Pallor
- Pulselessness
- Poikilothermia (cold)
- Paresthesias
- Paralysis
Acute Limb Ischemia (ALI)
- Acute (<2 weeks), severe hypoperfusion of the limb characterized by the 6 P’s
- Pt should report to hospital
inpatient management of ALI
- UFH using VTE protocol -> Inhibits thrombus propagation and may provide an anti-inflammatory effect that decreases ischemia
- May need revascularization; if revasc. cannot be performed, perform catherter-based thrombolysis
- Medical emergency that requires inpatient pharmacotherapy plus nonpharmacologic interventions to salvage limbs
Critical Limb Ischemia (CLI)
- chronic (≥2 weeks) ischemic rest pain, nonhealing wound/ulcers, or gangrene in 1 or both legs, attributable to objectively proven arterial occlusive disease
- Patients should be referred to the hospital
- May need revascularization
- Medical emergency that may require non-pharmacologic interventions to salvage limbs
What is Peripheral Artery Disease (PAD) caused by?
- ATHEROSCLEROSIS
- Thrombosis
- Vasculitis
- Fibromuscular dysplasia
- Trauma
Ankle-brachial index (ABI) values
- Abnormal: <0.9 abnormal and diagnostic of PAD
- Normal: 1.00-1.40
- > 1.40 is indicative of non-compressible arteries secondary to vascular calcification
- Requires alternative methods of testing
- 0.91-0.99 is considered borderline and may warrant follow-up
- Requires alternative methods of testing
What are the pharmacotherapy options for smoking cessation?
- Nicotine Replacement Therapy (NRT)
- Varenicline (Chantix®)
- Bupropion (Zyban®)
Varenicline (Chantix®)
black box warning for patients with psychiatric issues
Bupropion (Zyban®)
- have to be careful about CV events; can cause drug-induced HTN; can lower seizure threshold
- take in the morning because can cause insomnia
What is revascularization?
- Intervention used to restore blood flow to an ischemic area
- Surgial: Endarterectomy
- Endovascular: “Stenting”
Endarterectomy
pulling out the plaque
