Managing Blood Pressure in the PAD Patient: Selecting Drug and Target

Ehrin J. Armstrong MD MSc Associate Professor of Medicine University of Colorado

Director, Interventional Cardiology Director, Vascular Laboratory Denver VA Medical Center

What Are the Guidelines in Peripheral Artery Disease?

X Copy Here

X

Abbott Vascular, Boston Scientific, Cardiovascular Systems, Medtronic, Philips

Gerhard-Herman et al, 2016 ACC/AHA PAD Guidelines Whelton et al, 2017 Hypertension Clinical Practice Guideline 2017 Multisocietal Guidelines for Hypertension What About Beta Blockers?

• Longstanding concern that beta-adrenergic receptor antagonists could worsen symptoms of claudication. • Unopposed alpha-receptor mediated vasconstriction.

• Initial study of 20 patients with PAD assigned to propanolol, atenolol, labetalol, or captopril demonstrated worsened claudication symptoms with beta blockers, and decreased calf blood flow.

• However, other studies of metoprolol and propanolol did not demonstrate reductions in calf blood flow.

Roberts et al, Lancet 1987;2:650-653; Hiatt et al, Circulation 1985;1226-1231

• 128 patients with claudication and hypertension.

• Randomized to nebivolol 5 mg daily or metoprolol 95 mg daily.

• 48 week treatment period. • Baseline SBP 148 mm Hg in both groups • Similar absolute changes in SBP: -3.9 mm Hg vs. -5.2 mm Hg

Espinola-Klein C et al, Hypertension 2011;58:148-154 Espinola-Klein C et al, Hypertension 2011;58:148-154 Initial and Absolute Claudication Distances

• 177 patients with PAD and HTN

• Randomized to nebivolol 5 mg daily vs. HCTZ 25 mg daily

• Primary endpoint was initial claudication distance at 24 months

Diehm et al, J Hypertens 2011;29:1448-1456 Diehm et al, J Hypertens 2011;29:1448-1456

Reduced 30 Day Mortality With Beta Blockers (Unmatched)

• 1,873 consecutive patients with CLI.

• 394 (21%) treated with beta blockers • Indications were HF or LV dysfunction (31%), CAD (31%), HTN (28%), AF (13%) • Primarily carvedilol (63%)

• All patients underwent endovascular interventions for limb salvage.

• Mean follow-up period of 22 months.

Soga Y et al, J Atheroscler Thromb 2015;22:481-489 Soga Y et al, J Atheroscler Thromb 2015;22:481-489 Similar Amputation Free Survival Evidence for ACEI and ARBs

• ACEI or ARBs are a Class IIa indication for reduction of cardiovascular risk among patients with peripheral artery disease.

• Majority of data derived from the HOPE study (ramipril). • Similar benefit in patients with symptomatic disease and asymptomatic low ABI • Patients were on average normotensive at the time of enrollment.

• Retracted data had suggested a benefit of ACEI on claudication symptoms and walking distance.

Soga Y et al, J Atheroscler Thromb 2015;22:481-489 HOPE Investigators, NEJM 2000; 342:145-153

Decreased Rates of MACE

Event rate 17.8% vs. 13.8%

Ostergren J et al, Eur Heart J 2004;25:17-24 HOPE Investigators, NEJM 2000; 342:145-153 HOPE Investigators, NEJM 2000; 342:145-153 ACEI/ARB in Critical Limb Ischemia Decreased MACE

HR 0.76 (95% CI 0.58-0.99) • 464 patients with critical limb ischemia.

• 269 (58%) prescribed ACEI or ARB • 206 ACEI • 65 ARB

• Baseline differences included higher prevalence of diabetes, hypertension, and established CAD in ACEI/ARB group.

Armstrong et al, Vasc Med 2015;20:237-244 Armstrong et al, Vasc Med 2015;20:237-244

Decreased Mortality Major Adverse Limb Events

HR 0.97 (95% CI 0.69-1.35)

HR 0.71 (95% CI 0.53-0.95)

Armstrong et al, Vasc Med 2015;20:237-244 Armstrong et al, Vasc Med 2015;20:237-244 Conclusions

• In patients with PAD, current guidelines for hypertension management support treatment if SBP ≥130 mm Hg or DBP ≥80 mm Hg.

• Beta-adrenergic blockers do not appear to negatively affect limb perfusion or claudication symptoms.

• ACEI and ARBs reduce the risk of MACE in patients with PAD, irrespective of symptoms or presence of hypertension. Benefits apply to overall PAD population as well as those with critical limb ischemia.