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Invasive Revascularization Or Not in Intermittent Claudication - IRONIC
Description:
The optimal treatment of intermittent claudication (IC) in patients with peripheral arterial disease (PAD) is unclear. The current trial sought to compare an invasive versus conservative strategy in this patient population.
Hypothesis:
An invasive strategy would be associated with superior health-related quality-of-life (QoL) outcomes in patients with IC compared with conservative management alone.
Study Design
- Randomized
- Parallel
Patient Populations:
- Stable (>6 months) IC symptoms
- No important activity-limiting medical condition
- Age 30-80 years
Number of screened applicants: 464
Number of enrollees: 158
Duration of follow-up: 1 year
Mean patient age: 68 years
Percentage female: 48%
Exclusions:
- Mild or very severe IC symptoms
- Weight >120 kg
- Two or more previously failed ipsilateral vascular interventions
- Inability to understand the Swedish language
- Need for open revascularization below the tibioperoneal trunk
Primary Endpoints:
- Health-related QoL between baseline and 12 months, as assessed with the patient-reported instruments SF-36, EQ5D, and VascuQOL
Secondary Endpoints:
- Walking distance on a graded treadmill test
- Self-reported maximum walking distance
- ABI
Drug/Procedures Used:
Following delineation of anatomy by vascular ultrasound, patients with moderate to severe IC were randomized to invasive or conservative strategies. All patients received optimal risk factor modification/medical therapy. This included verbal and written information regarding PAD. Information also included structured training advice instructing the patients to perform submaximal walk exercise sessions for at least 30 minutes at least three times a week. Nordic pole use was encouraged during training sessions. Every patient without contraindications not already on therapy received aspirin 75 mg once daily (or clopidogrel 75 mg, if indicated), statin therapy, and cilostazol (100 mg twice daily). In the invasive arm, surgical or percutaneous interventions were performed depending on anatomy and complexity.
Principal Findings:
A total of 158 patients were randomized at a single center, 79 to an invasive strategy and 79 to conservative management. Baseline characteristics were fairly similar between the two arms. Approximately 19% had diabetes and 29% were smokers, with the majority of patients having symptoms for at least 1 year. The mean baseline ankle-brachial index (ABI) was 0.74. More than half the lesions were in the femoropopliteal arteries. An intervention was performed in 90% (73% endovascular) of patients in the invasive arm and 8% in the conservative arm.
Although both arms demonstrated significant improvements from baseline to 12 months, there was a significantly larger improvement in the invasive arm compared with the conservative arm for the primary endpoint of Short Form-36 (SF-36) physical component score (p < 0.001) and two SF-36 physical subscales (physical functioning and bodily pain). The change in Vascular Quality of Life Questionnaire (VascuQOL) total score and three out of five domain scores (activities, symptoms, and emotional) were significantly larger in the invasive arm as well. Change in treadmill walk distance was also larger in the invasive arm (124 vs. 50 m, p = 0.0003), but not maximal walk distance (59 vs. 30 m, p = 0.17).
During follow-up, 19% underwent re-intervention in the invasive arm, of which 61% were in a new vascular segment, whereas the remainder were primarily to maintain primary patency. ABI measurements were higher in the invasive arm at 12 months (0.85 vs. 0.69, p < 0.001). Acute limb ischemia (ALI) was observed in one patient in the conservative arm. There was one death in the invasive arm, but no amputations in the study. Two patients in the invasive arm and one in the conservative arm suffered procedure-related complications.
Interpretation:
The results of the IRONIC trial indicate that an invasive strategy involving predominantly endovascular interventions is superior to conservative management in patients with IC in improving self-reported health-related QoL outcomes, with a significant improvement in walk distance on a treadmill and ABIs at 1 year. The incidences of ALI and procedural complications were low. The majority of patients in this trial had moderate to severe IC at baseline. An important limitation of the current trial is the lack of blinding, which may be potentially important in a trial assessing QoL outcomes as the primary endpoint.
Literature to date on this topic has been mixed. The National Institutes of Health sponsored trial, CLEVER, compared a supervised exercise program to endovascular interventions and reported greater improvements in peak walking distance with an exercise training program. Patient-related QoL outcomes were, however, superior in the endovascular arm. On the other hand, the ERASE trial suggested that an endovascular approach resulted in greater pain-free walking distance and QoL compared with supervised exercise training. One important distinction of the current trial is that QoL metrics were the primary endpoint, not IC walking distance.
A practical limitation of supervised exercise training programs is availability; since they are not typically reimbursed by third-party payers, most patients with IC are recommended a home walking regimen (as in this trial), which is typically not as effective as a supervised training program.
References:
Nordanstig J, Taft C, Hensäter M, Perlander A, Österberg K, Jivegård L. 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;Aug 5:[Epub ahead of print].
Keywords: Intermittent Claudication, Follow-Up Studies, Ankle Brachial Index, Peripheral Arterial Disease, Ticlopidine, Risk Factors, Pain, Tetrazoles, Quality of Life, National Institutes of Health (U.S.), Surveys and Questionnaires, Insurance, Health, Reimbursement, Diabetes Mellitus, Exercise Test
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