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In a broad range of patients with intermittent claudication, invasive treatment improves quality of life (QoL) at 1 year over conservative care that included exercise recommendations and medication alone, according to a small, randomized trial published online August 5, 2014, ahead of print in Circulation.  

The findings underscore the shortcomings of standard management in most current practice, contends an accompanying editorial. 

In the invasive group, 70 patients (90%) received invasive treatment after a mean time of 20 weeks. During follow-up, 13 patients (19%) underwent 21 reinterventions: 8 in a new vascular segment due to persistent symptoms, 9 to maintain primary patency, and 4 to establish secondary patency. Six patients (8%) in the noninvasive group crossed over to revascularization: 5 due to worsening claudication and 1 due to acute limb ischemia (relieved by thrombolysis followed by angioplasty). During follow-up, 1 reintervention was performed in this group.

Revascularized Patients Improve More

Significant improvements in health-related QoL, assessed by VascuQoL and SF-36 questionnaires, were observed in both the invasive and noninvasive groups. At 12 months there was no difference between invasive patients and an age- and gender-matched sample of the general population with regard to any SF-36 metric, whereas noninvasive patients scored lower than the general population on all but 1 of the SF-36 subscales.

However, improvements in the SF-36 physical component summary (as well as both the physical functioning and bodily pain subscales) and in the VascuQoL total score (as well as 3 out of 5 domain scores) were greater in the invasive group than the noninvasive group (all P < .01). 

Similarly, invasive patients were able to walk farther on a treadmill before experiencing symptoms than were noninvasive patients (+124 m vs +50 m; P = .003), although there was no difference in maximum walking distance between the groups (P = .170). In addition, invasive patients had a higher ankle-brachial index and lower toe pressure than their noninvasive counterparts. 

One patient, in the invasive group, died 6 months after a procedure, for a 1-year mortality rate of 0.6%. No amputations were performed during follow-up. Two invasive patients and 1 noninvasive patient experienced procedure-related complications. Two patients in each group suffered cardiovascular events, all unrelated to any trial procedures. At 1 year, event-free survival was 77% in the invasive group and 88% in the noninvasive group. 

At 6 months, total cholesterol (P = .001) and LDL cholesterol (P = .01) improved over baseline in both invasive and noninvasive patients, but there were no between-group differences. At 3, 6, and 12 months, similar proportions of both groups were taking cilostazol. 

Revascularization Benefit Comes on Top of Standard Treatment  

“The benefits of invasive treatment were demonstrated despite the use of current conservative management, including structured training advice and a vasoactive drug (cilostazol) with established effects on both [health-related QoL] and walking function in claudicants,” the authors say, adding that complications with invasive treatment were “few and benign in character.” 

However, they acknowledge, the fact that the effect of invasive treatment was not assessed specifically in different vascular segments and lesions, using different revascularization techniques, or in patient subsets with different baseline walking capacities limits the findings’ generalizability. 

In an accompanying editorial, Ryan J. Mays, PhD, MPH, of the University of Montana (Missoula, MT), and Judith G. Regensteiner, PhD, of the University of Colorado School of Medicine (Aurora, CO), observe that while several previous studies have shown invasive procedures to improve QoL for PAD patients, the current trial adds to that knowledge base by evaluating outcomes in a broad range of patients with varying morphologies and lesion locations. 

The Rationale for QoL Metrics

According to Drs. Mays and Regensteiner, an innovative aspect of IRONIC is its use of patient-reported QoL as a primary endpoint. The appropriateness of that choice “depends on the goals of the study and the lens through which the results will be viewed,” they comment. While objective measures such as primary patency for revascularization or treadmill walking time for exercise training studies are of interest to clinicians, “a patient may judge the benefit of an intervention by effects on [health-related QoL], which is composed of many dimensions and not just leg symptoms,” they add. However, the editorial authors note, QoL tools have yet to be integrated into standard clinical practice, and the choice and interpretation of the most appropriate aspects of such tools are important for determining the best PAD treatment options. 

In addition, the trial highlights the dearth of effective noninvasive treatments, the editorial authors say. Only 1 drug, the vasodilator cilostazol, is approved for this indication, and it is contraindicated in patients with heart failure. And while supervised walking exercise has been proven effective, it remains underused for a variety of reasons, including:

• Lack of reimbursement
• Patients’ habitual sedentary behavior
• Lack of interest in exercise due to leg pain while walking
• Need to travel to clinics for supervision

Drs. Mays and Regensteiner suggest that “[u]ntil reimbursement is available for supervised walking exercise (as well as resolution to other barriers for program participation), researchers and healthcare providers alike need to continue to perform research on developing exercise programs which can be used in community settings.” Meanwhile, they add, use of health-related QoL metrics in clinical settings “may be one of the next seminal steps in research to treat [intermittent claudication].”

Sources: 
1. Nordanstig J, Taft C, Hensäter M, et al. Improved quality of life after one year with an invasive versus a non-invasive treatment strategy in claudicants: one year results of the IRONIC trial. Circulation. 2014;Epub ahead of print.

2. Mays RJ, Regensteiner JG. Therapy for peripheral artery disease: gaps in treating patients with claudication [editorial]. Circulation. 2014;Epub ahead of print.

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