Dr. Osamu Iida is with the Cardiovascular Center at Kansai Rosai Hospital in Amagasaki, Hyogo, Japan. He is lead author on a paper, published in the June 12 issue of JACC: Cardiovascular Interventions, titled "Prognostic Impact of Revascularization in Poor-Risk Patients With Critical Limb Ischemia: The PRIORITY Registry (Poor-Risk Patients With and Without Revascularization Therapy for Critical Limb Ischemia)."
Frailty is not uncommon in critical limb ischemia (CLI), especially when accompanied by various comorbidities. In previous studies, revascularization demonstrated favorable outcomes treating patients with CLI. However, patients included in these studies tended to be less frail. The PRIORITY registry was conducted between January 2014 and April 2015 in 37 participating centers in Japan. Angioplasty.Org's partner site, TCROSS NEWS, recently interviewed Dr. Iida, a principal investigator of the PRIORITY registry, regarding background and clinical implications of the study.
Q: What is background of the study?
Dr. Iida: The PRIORITY registry tested the hypothesis whether revascularization improves poor-risk CLI patients who require assistance in their daily lives because of their disability and/or impairment of cognitive function. Although poor-risk CLI patients are often present in clinical practice, they have often been excluded in clinical trials and investigator-initiated trials, resulting in a lack of evidence in this population. Should we treat a poor-risk CLI patient by revascularization or should we manage him/her conservatively?
Q: The registry focused on poor-risk CLI patients. Does revascularization still remain a favorable treatment strategy for non-poor-risk CLI patients as shown in previous studies?
Dr. Iida: RCTs comparing revascularization strategy and non-revascularization strategy are lacking even for those who are not classified in poor-risk CLI patients. However, prognosis following revascularization has shown superiority as far as comparing data from natural prognosis, and thereby it is recommended by various guidelines.
Q: In the PRIORITY registry, percutaneous intervention was performed in 92.7%, whereas 5.3% of the population underwent surgical intervention. Are there any differences in proportions of revascularization strategies among the hospitals included in the registry?
Dr. Iida: Of course, preference or expertise of revascularization strategy is different in each hospital included in the present study. Therefore, I was not surprised by the proportion revealed in the study. In the present study, we included vascular interventionalists and surgeons who were familiar with both treatment strategies. Under these conditions, we assumed that investigators selected the optimal revascularization strategy to each patient. As a result, only 5.3% of poor-risk CLI patients received surgical revascularization strategy in the present study.
Q: Is survival rate influenced by success or failure of revascularization or by treated lesion or wound location?
Dr. Iida: In the present study, we did not evaluate the relationship between success and failure of revascularization, as well as treated lesions and wound locations. However, as a common opinion, critical limb ischemia is known as a “life-threatening limb”. In other words, limb salvage links directly to life of the patient, thereby success of revascularization is crucial. Therefore, it is concluded that success or failure is assumed to influence prognosis of this patient population.
In addition, initial success rate in the revascularization strategy was 93% in propensity score matching analysis. In the stratified analysis, benefits of revascularization are significant in patients in Fontaine IV. Although wound details were not evaluated in the present study, we assumed that percutaneous revascularization is not preferred revascularization strategy for severe ulcers developed in (1) heel and (2) planta pedis requiring adequate blood flow and enough time to wound healing. As a matter of fact, we believe that severe ulcers potentially affect prognosis in poor-risk CLI patients.
Q: In the present study, the 1-year survival rate showed no significant difference between the revascularization group and the non-revascularization group. However, the 1-year amputation-free survival rate and rest pain following the revascularization strategy demonstrated significant benefits in the revascularization strategy. So what is the meaning of revascularization in poor-risk CLI patients.
Dr. Iida: First of all, we reconsider for whom and why should we perform revascularization. As the trend of the past, revascularization is expected to perform not only to limb salvage, but also to improve ADL as well as prognosis. Unfortunately, revascularization in the present study failed to recover the level of ADL prior to the onset of CLI and prognosis was equivalent to non-revascularization strategy in the poor-risk CLI patients. However, the revascularization group showed a significant improvement in amputation-free survival and rest pain. In addition, QOL was significantly improved in the revascularization group who survived at 1-year following the index procedure.
Taken together these results, revascularization does not affect the extension of the life in poor-risk CLI patients, but is expected to improve the quality of life expectancy. But, one should note that complication often occurs during perioperative period. Therefore, inform and consent, explaining risks and benefits of revascularization, are mandated. We are looking forward to further studies, focusing on medical economics in an objective manner.
Q: Stratification analysis explored a subgroup in favor of revascularization including old age, heart failure, or/and wound-free CLI.
Dr. Iida: The effect of revascularization strategy does not favor the outcome pre-specified as a “survival prognosis” in those who have the risk factors. In other words, revascularization is preferred in poor-risk CLI patients without old age, heart failure, and/or wound-free CLI, despite establishing “survival” as the outcome.
However, the indication of revascularization should not be determined according to these risk factors because they were only driven by the secondary analysis (revascularization showed a favorable outcome on AFS even in the total population). Although the secondary analysis can be used as a reference, we should consider treatment strategy based upon the condition of each patient.
Q: At the 3-month follow-up, survival rate was 83.1% in the revascularization group and 76.5% in the non-revascularization group, and there was a significant intergroup difference (p=0.007 by the stratified log-rank test). However, at the 1-year follow-up, the rate was 55.9% versus 51.0%, with no significant difference (p=0.120 by the stratified log-rank test). Please explain the difference between the 3-month and 1-year period.
Dr. Iida: I am positive about this outcome. The result indicates that revascularization demonstrated significant benefits in survival over the first 3 months, even in poor-risk CLI patients.
However, no significant difference between the groups was observed in the 1-year follow-up. It means that (1) revascularization does not affect long-term survival. Long-term survival or prognosis is influenced by total management; thereby the effect of revascularization is not superior to that of the optimal conservative therapy. And (2) it means a certain group of patients in the non-revascularization group can be effectively managed by conservative treatment.
Q: In the Discussion section of the paper, you mentioned the importance of ADL and cognitive function in long-term outcome. Has there been any further progress on research in this field?
Dr. Iida: Unfortunately, no progress has been made so far regarding a rehabilitation program. As we become more involved in the treatment of CLI in daily clinical practice, we are keenly aware of different clinical feature in each case.
For example, patients differ in preoperative ADL status and degree of wound infection. Furthermore, distribution and pattern of culprit lesions widely extend from iliac artery to superficial femoral artery and then in some case to below the knee. Under these circumstances, it is not possible to unify discussion regarding prognosis. CLI is not simply identified as single disease. Therefore, we must continuously study issues associated with CLI treatment including ADL, cognitive function, rehabilitation, and medical cost.