The SPINACH Study
Dr. Osamu Iida is a member of the Department of Cardiovascular Medicine, Kansai Rosai Hospital in Amagasaki, Japan. He is the lead author on a paper, published in the December issue of Circulation: Cardiovascular Interventions, titled “Three-Year Outcomes of Surgical Versus Endovascular Revascularization for Critical Limb Ischemia” (also known as the SPINACH study).
This multicenter, prospective, observational study enrolled 548 Japanese CLI patients who received either endovascular or surgical revascularization. The results showed no significant difference in the primary outcome (three-year amputation-free survival) between the two strategies. Angioplasty.Org's partner site, TCROSS NEWS, recently interviewed Dr. Iida, a principal investigator of the SPINACH study, regarding background and clinical implications of the study. |
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Osamu Iida, MD |
Q: The present study compared the safety and efficacy between surgical revascularization and endovascular therapy (EVT) treating for the Japanese patients with critical limb ischemia (CLI). Could you explain the background of the present study, and especially how cardiologists and vascular surgeons collaborated on it.
Dr. Iida: When the SPINACH study was proposed in 2011, we (Japanese cardiologists) had started reporting outcomes of EVT to treat CLI patients. Our studies demonstrated that the clinical outcomes including amputation-free survival (AFS) followed by EVT were acceptable. However, vascular surgeons would not accept our findings that were presented in their meetings or conferences. In fact, EVT had no civil rights during the early 2010s. Registries of surgical revascularization for the CLI patients were well established because the Japanese Society for Vascular Surgery manages all surgical revascularization throughout the nation. Therefore, to be accepted, it was necessary to conduct a well-organized study comparing the safety and efficacy between surgical revascularization and EVT for treating CLI patients. I first discussed this with Dr. Nobuyoshi Azuma of the Department of Vascular Surgery at Asahikawa Medical University (he is a co-author of the current study). Even now I still clearly remember that scene in which we discussed the idea at the Japan Endovascular Symposium Meeting in 2011. The main objective of SPINACH was not to find the superiority of one treatment over the other, but instead to seek an appropriate treatment alternative for a certain population, as well as clarify the advantages and disadvantages of both treatment alternatives: we wanted to inform our colleagues about which populations were suitable or not for surgical revascularization. Indeed, since the SPINACH registry, our center currently selects surgical revascularization for a CLI patient with a severe ulcer and/or wound infection.
Q: Have you had any problems recruiting patients in the present study?
Dr. Iida: Since the present study was the first study in which cardiologists and vascular surgeons collaborated, we spent a lot of time designing the study proposal. Once the study design was agreed upon and the protocol established in a short period of time. The design was completed in August 2011, and recruitment started in January 2012. Perhaps Dr. Mitsuyoshi Takahara, a diabetologist at Osaka University Graduate School of Medicine, is the largest contributor of the present study. Dr. Takahara created a data entry form within a short period of time, despite being limited in his knowledge about CLI as well as lacking EVT and surgical revascularization experience. On behalf of the SPINACH investigators, I would like to express my great appreciation to him for his excellent work. After starting the study, we successfully recruited 550 patients in 15 months. We are very proud of all investigators who recruited the patients in such brief period without changing the treatment strategy.
Q: The 3-year mortality rate was 43% in the entire population. Are there any differences between those who died and those who survived?
Dr. Iida: The mortality rate is not different from our previous studies such as OLIVE and J-BEAT (the 1-year mortality rate was approximately 20% and then increased by 10% per year). To reflect the real-world, we minimized exclusion criteria when recruiting patients. So far, we have not yet analyzed the mortality difference in the present study. Further analysis is required to identify potential causes.
Q: There is no significant difference in the primary outcome (amputation-free survival) between surgical revascularization and EVT, but surgical revascularization showed better major amputation and revascularization rate. What are your opinions regarding this issue?
Dr. Iida: The outcomes of the present study are acceptable in the Japanese real-world clinical practice. The difference is mainly attributed to the revascularization rate in the target lesion. In fact, a higher revascularization rate associated with EVT as compared to surgical revascularization is known from previous reports. The key issue is whether revascularization following EVT affects the primary clinical outcome. In this regard, our previous retrospective study (https://www.ncbi.nlm.nih.gov/pubmed/27369976), involving isolated infra-inguinal lesions, demonstrated that revascularization following EVT showed a significant risk factor for major amputation. In the present study, we would also like to evaluate how revascularization following EVT affects subsequent clinical outcomes.
Q: Please define patients appropriate for surgical revascularization or patients suitable for endovascular revascularization.
Dr. Iida: SPINACH identified a subgroup of the patients who experienced better outcomes following surgical revascularization or EVT. We first screened possible factors that indicated interaction, and then interaction effects yielding a <1.5-fold or <0.67-fold difference were underlined in relation to revascularization and AFS. As the result, the screening analysis identified (1) WIfI classification W-3, (2) fI-2/3, (3) history of ipsilateral minor amputation, (4) history of revascularization after CLI onset, and (5) bilateral CLI as the factors more favorable for surgical reconstruction. On the other hand, (6) history of nonadherence to cardiovascular risk management, (7) lower hemoglobin levels (<10 g/dL), (8) diabetes mellitus, (9) renal failure (including regular dialysis), and (10) contralateral major amputation were shown to be less favorable for surgical reconstruction.
We then provisionally developed a favorability score for surgical reconstruction, with one point added for each of the former 5 factors and 1 point subtracted for each of the latter 5. The higher score benefited more from surgical reconstruction, whereas the lower score benefited more from EVT. Thus, we can easily select a more favorable revascularization strategy based upon the evaluation of clinical factors in each patient. This is one of the most important findings from the SPINACH study.
Q: Domestic high-volume centers as well as the Japanese major centers participated the present study. Aren’t these outcomes heavily dependent upon an individual operator?
Dr. Iida: Yes, the Japanese high-volume centers participated in SPINACH. Hence, outcomes possibly are dependent on the operator. The clinical outcome in the Japanese CLI practice is not always uniform because each center or each region has strengths and weaknesses in both revascularization strategies. We hope the present study will be a landmark of Japanese CLI practice. The investigators in SPINACH wish those who perform CLI to utilize the findings from the present study.
Q: Compared to the EVT group, the surgical group was more likely to achieve initial technical success. Does the outcome change if initial technical success regarding EVT improves?
Dr. Iida: Yes, you are right. The initial outcome is expected to affect long-term prognosis. Subsequent revascularization rate is significantly higher in EVT as compared to surgical revascularization, though the availability of new devices, including atherectomy devices, drug-coated balloons, and drug-eluting stents is expected to overcome the difference. However, previous studies demonstrated that physical status (low BMI, non-ambulatory status, under-nutrition, low ejection fraction rate), limb condition (severe ulcer, wound infection), and run-off below the ankle are known as prognostic factors. Unfortunately, the introduction of new devices is not the solution for the improvement of CLI hard endpoints because they do not modify these contributors. Therefore, multifaceted approaches including treatment prior to onset of the symptoms of CLI, intensive intervention immediately after diagnosis, and after-care following treatment, are all required to improve long-term prognosis as well as limb salvage.
Q: Based upon the present study, what is the most important finding to communicate to the audience?
Dr. Iida: Based upon the study outcome, I would like to highlight "the presence of a population appropriate for either EVT or surgical revascularization strategy" rather than "no significant difference in 3-year AFS between EVT and surgical revascularization." Physicians involved in CLI treatment should have common sense and discard the prejudice regarding EVT and surgical revascularization, and select the best treatment alternative to each patient. For example, surgical revascularization should be selected for a patient with a severe case (W-3, fI-2/3) whereas EVT is preferred for a patient with a history of major amputation and dialysis. Atherectomy devices and drug-eluting devices will become major players in new era in this field. We will hope to conduct SPINACH II study comparing EVT and surgical revascularization using new devices in near future.
This interview was conducted in December 2017
by TCROSS NEWS, Tokyo, Japan |
