Medical Therapy or Stenting for Aortoiliac PAD?
Abstract & Commentary
By Andrew J. Boyle, MBBS, PhD, Assistant Professor of Medicine, Interventional Cardiology, University of California, San Francisco
Source: Murphy TP, et al. Supervised exercise versus primary stenting for claudication resulting from aortoiliac peripheral srtery disease. Six-month outcomes from the Claudication: Exercise Versus Endoluminal Revascularization (CLEVER) study. Circulation 2012;125:130-139.
Peripheral arterial disease (PAD) can cause symptomatic claudication and it can reduce quality of life. Medical therapy for atherosclerotic vascular disease is indicated for patients with PAD, and guidelines also advocate regular exercise, as this can improve claudication symptoms. Endovascular treatment, predominantly stenting, has emerged as a common adjunctive treatment modality for patients with PAD. However, the optimal initial treatment strategy for patients with aortoiliac PAD is not known: Should patients be treated with medical therapy alone, a supervised exercise regimen, or should they undergo endovascular stenting as the initial management strategy? Murphy and colleagues designed a randomized, controlled clinical trial to address this question.
At 22 sites, they enrolled 111 patients with moderate-to-severe symptomatic claudication and objective evidence of significant obstructive PAD at the aortoiliac level. All patients were scheduled to receive optimal medical therapy (OMT) according to the ACC/AHA guidelines. They were then randomized into three groups: OMT alone, OMT plus supervised exercise program (SE), or OMT plus stenting (ST). Patients underwent initial exercise testing with standard protocol and were then followed for 6 months for symptoms, exercise capacity, and quality of life (QOL). Patients with critical limb ischemia were excluded and all patients received cilostazol as tolerated. The primary endpoint was change in walking time.
Baseline clinical and demographic characteristics were not different between groups, although there was a trend toward more women in the SE group. Patients were well managed with mean LDL 105 mg/dL and HDL 48 mg/dL. There was no statistically significant difference in the use of aspirin, thienopyridines, and statins.
Over the 6-month study period, walking time remained unchanged in the OMT group (+1.2 ± 2.6 minutes), and increased in both the SE group (5.8 ± 4.6 minutes, P < 0.001 vs OMT) and the ST group (3.7 ± 4.9 minutes, P = 0.02 vs OMT). The improvement in walking time was significantly greater in the SE group than the ST group (2.1 minutes, P = 0.04). There was no change in the ankle brachial index (ABI) in the OMT and SE groups, but ABI significantly improved in the ST group (+0.29, P < 0.001). In the measures of QOL, both SE and ST groups showed greater improvement than the OMT group, with the ST showing a significantly greater improvement in QOL. There were four serious adverse events in the ST group, related to the procedure, and none in the other groups. The authors conclude that SE results in superior treadmill walking performance than ST for patients with aortoiliac PAD. The contrast between better walking performance for SE and better patient-reported QOL for ST warrants further study.
Exercise training increases collateral artery formation in lower extremity PAD and improves symptoms. Endovascular treatment in the thigh and below the knee is complicated by high rates of restenosis. While controversy exists about the optimal revascularization strategy for lower extremity PAD, aortoiliac disease is widely believed to be optimal for stenting because restenosis rates are lower here. Thus, this trial enrolled the population that one would expect the best possible outcome for ST (significant symptoms and aortoiliac disease). The significant improvement in objective walking parameters in the SE groups may be due to improved collateral vessel formation, or may be due to improved general cardiovascular health, not just due to limb-specific circulatory improvements. There also may be an element of treadmill learning associated with SE programs. This was the primary endpoint of the study and showed that SE was superior to OMT and OMT + stenting as an initial strategy. However, that is not the whole story. ST was the only treatment that improved the functional blood flow to the leg measured by ABI, and this was associated with improved QOL, suggesting that ST may also be a reasonable strategy in some patients. OMT alone appears to be associated with the worst outcomes. It should be noted, however, that this study was conducted over 6 months, a relatively short follow-up period. Longer-term outcomes and cost-effectiveness analyses are awaited from this cohort. Also, the number of patients included in this study was small and recruitment was stopped at half the prespecified number of patients. Importantly, we do not know if the effects of SE and ST are additive or if use of one of these therapies realizes the maximal improvement possible. There was initially a combined treatment group who underwent both SE and ST, but enrollment into this group was abandoned early due to slow enrollment.
This study extends previous studies of PAD in the lower limbs that show SE is beneficial to now include aortoiliac disease. It strengthens the evidence base upon which we recommend to patients that they increase their exercise levels. It may be slightly premature to recommend starting "vascular rehab" programs for our patients with PAD, because the long-term outcomes and cost-effectiveness analyses are yet to be presented. However, we should continue to emphasize the importance of exercise to our patients.