High-dose atorvastatin in peripheral arterial disease (PAD): Effect on endothelial function, intima-media-thickness and local progression of PAD

Abstract

Beneficial effects of aggressive lipid-lowering with high-dose atorvastatin (80 mg/day) have been demonstrated in patients with coronary and cerebrovascular disease. The impact of such a therapy in patients with peripheral arterial disease (PAD) is less known so far. Here we studied the effects of high-dose atorvastatin on brachial artery endothelial function, common carotid intima-media thickness (IMT) and local progression of PAD in these patients. One hundred of 500 patients screened with documented PAD were randomly assigned to receive 80 mg of atorvastatin daily for six months or to continue on conventional medical treatment. Ninety-six percent of patients in the control group were on standard statin treatment. High resolution B-mode ultrasonography was used to study brachial artery flow-mediated dilation (FMD), IMT and ankle-brachial index (ABI) at baseline and at six months. FMD and IMT at baseline and at six months were 4.1 (0.06-8.6) versus 5.0 (0.76 vs. 8.1) %, p = 0.96, and 0.76 (0.66-0.82) versus 0.73 (0.63-0.81) mm, p = 0.41, respectively, in the atorvastatin group, and 2.66 (-1.9-6.9) versus 3.65 (0.0-8.6)%, p = 0.02, and 0.78 (0.71-0.90) versus 0.77 (0.70-0.90) mm, p = 0.48, in the control group. ABI at baseline and at six months was not different in either group. LDL cholesterol was reduced from 2.53 (2.21-3.28) to 1.86 (1.38-2.29) mM (p < 0.0001) in the atorvastatin group, whereas levels remained stable in the control group [2.38 (1.94-3.16) vs. 2.33 (1.82-2.84) mM, p = 0.61]. Major adverse cardiovascular events occurred in 2.1% in the atorvastatin group and 1.9% in the control group (p = 0.61). In conclusion, in this pilot trial aggressive lipid-lowering with 80 mg of atorvastatin daily for six months had no effect on brachial artery FMD in patients with PAD. IMT and ABI were also similar in patients with and without high-dose atorvastatin at six months. Major adverse cardiovasculare vents occurredi n 2.1% in the atorvastatingroup and 1.9% in the control group (p= 0.61). In conclusion, in this pilott riala ggressive lipid-lowering with 80 mg of atorvastatindailyfor six monthshad no effect on brachial artery FMD in patients with PAD. IMT andABI were also similar in patientswith and without high-doseatorvastatin at six months.

Pharmacological Treatment and Current Management of Peripheral Artery Disease

“…122 One study evaluated the efficacy of statins on hemorheologic variables in 100 patients with PAD randomized to either atorvastatin 80 mg daily or low intensity statin. 123 Overall, there was no difference in plasma viscosity, red cell aggregation, whole blood viscosity, hematocrit, leukocytes, or the other parameters measured.…”

Low-Density Lipoprotein Cholesterol Lowering With Evolocumab and Outcomes in Patients With Peripheral Artery Disease

“…9 Moreover, these trials have not specifically looked at the ability of LDL-C lowering to reduce the risk of MALE. 6,[10][11][12][13] Last, because PAD has often been used simply as a risk enhancer, little is known about the effect of LDL-C lowering in patients who have PAD without prior myocardial infarction (MI) or stroke. 8,9,14,15 The FOURIER trial (Further Cardiovascular Outcomes Research With PCSK9 Inhibition in Subjects With Elevated Risk) was a very large cardiovascular outcomes trial of the PCSK9 (proprotein convertase subtilisin/kexin type 9) inhibitor evolocumab that enrolled patients with atherosclerotic disease, in either the coronary, cerebrovascular, or peripheral arterial bed.…”

The effect of superficial femoral artery stenting and some atherosclerosis risk factors on changes in selected global endothelial function tests in patients with chronic lower limb ischemia. A pilot study

“…Spring et al [39] noted the improvement of endothelial dysfunction in patients with peripheral arterial disease treated with atorvastatin. However, these authors did not analyze patients after SFA stenting or the relation between markers of endothelial function and LDL concentration.…”

“…The degree of FMD and PAT values reduction in response to ischemia was proportional to the number of risk factors present in the studied groups of patients and predicted the occurrence of cardiovascular incidents [6,14,15,17,33] including even venous thrombosis [34]. Smoking cessation [33,[35][36][37], hypertension [32,37,38], treatment of hyperlipidemia [39][40][41][42], diabetes control [43], body mass reduction [44], improvement of physical activity [31,45,46] as well as peripheral revascularization involving lower extremities [16,[21][22][23]26] and renal arteries [24,25] were shown to improve the markers of endothelial function not only in the culprit lesion, but also in other vascular beds. In this context it is logical to hypothesize that control of individual risk factors of atherosclerosis may modify the course of changes of global endothelial function after percutaneous revascularization of the lower extremities.…”