Alirocumab and plaque volume, calf muscle blood flow, and walking performance in peripheral artery disease: A randomized clinical trial.

BACKGROUND: The distal superficial femoral artery (SFA) is most commonly affected in peripheral artery disease (PAD). The effects of the proprotein convertase subtilisin/kexin type 9 (PCSK9) inhibitor alirocumab added to statin therapy on SFA atherosclerosis, downstream flow, and walking performance are unknown. METHODS: Thirty-five patients with PAD on maximally tolerated statin therapy were recruited. Patients were randomized to alirocumab 150 mg subcutaneously (n = 18) or matching placebo (n = 17) therapy every 2 weeks for 1 year. The primary outcome was change in SFA plaque volume by black blood magnetic resonance imaging (MRI). Secondary outcomes were changes in calf muscle perfusion by cuff/occlusion hyperemia arterial spin labeling MRI, 6-minute walk distance (6MWD), low-density lipoprotein (LDL) cholesterol, and other biomarkers. RESULTS: Age (mean ± SD) was 64 ± 8 years, 20 (57%) patients were women, 17 (49%) were Black individuals, LDL was 107 ± 36 mg/dL, and the ankle-brachial index 0.71 ± 0.20. The LDL fell more with alirocumab than placebo (mean [95% CI]) (-49.8 [-66.1 to -33.6] vs -7.7 [-19.7 to 4.3] mg/dL; p < 0.0001). Changes in SFA plaque volume and calf perfusion showed no difference between groups when adjusted for baseline (+0.25 [-0.29 to 0.79] vs -0.04 [-0.47 to 0.38] cm3; p = 0.37 and 0.22 [-8.67 to 9.11] vs 3.81 [-1.45 to 9.08] mL/min/100 g; p = 0.46, respectively), nor did 6MWD. CONCLUSION: In this exploratory study, the addition of alirocumab therapy to statins did not alter SFA plaque volume, calf perfusion or 6MWD despite significant LDL lowering. Larger studies with longer follow up that include plaque characterization may improve understanding of the effects of intensive LDL-lowering therapy in PAD (ClinicalTrials.gov Identifier: NCT02959047).

Cardiovascular Imaging for Ischemic Heart Disease in Women: Time for a Paradigm Shift.

Heart disease is the leading cause of death among men and women. Women have a unique phenotype of ischemic heart disease with less calcified lesions, more nonobstructive plaques, and a higher prevalence of microvascular disease compared with men, which may explain in part why current risk models to detect obstructive coronary artery disease (CAD) may not work as well in women. This paper summarizes the sex differences in the functional and anatomical assessment of CAD in women presenting with stable chest pain and provides an approach for using multimodality imaging for the evaluation of suspected ischemic heart disease in women in accordance to the recently published American Heart Association/American College of Cardiology guidelines for the evaluation and diagnosis of chest pain. A paradigm shift in the approach to imaging ischemic heart disease women is needed including updated risk models, a more profound understanding of CAD in women where nonobstructive disease is more prevalent, and algorithms focused on the evaluation of ischemia with nonobstructive CAD and myocardial infarction with nonobstructive CAD.

Timely Management of Obstructive Prosthetic Valve Thrombosis.

Obstructive bioprosthetic valve thrombosis is associated with hemodynamic compromise, and evidence on management with fibrinolysis is limited. Echocardiography is required to assess thrombus size and its effects on valve gradients, area, and leaflet motion. This case demonstrates use of echocardiography guided slow-infusion low-dose fibrinolytic therapy in a patient with obstructive bioprosthetic valve thrombosis. (Level of Difficulty: Intermediate.).