The Latest Studies Make Progress in Life Expectancy and Quality-of-Life Issues for CLI Patients

Recent clinical studies and trial data analyses show a continued focus on finding safe and effective treatment options for critical limb ischemia (CLI), with ongoing efforts to diagnose the disease in its early stages and slow its advance in later ones.

In addition, new research evidences increased attention to better classification and treatment of infrapopliteal lesions, utilizing data from follow-up studies, and improving life expectancy and quality-of-life issues for patients with CLI, a disease that often has a noticeable impact on both a patient’s outlook and their outward appearance.

Infrapopliteal Lesions: Expanded Classification and Effective Treatments

In 2015, the TASC Steering Committee introduced an important supplement to the 2007 TASC II guidelines. It provides “an updated literature review of endovascular techniques and practice patterns, as well as a complete lower-limb TASC lesion classification, which includes the infrapopliteal segment.” By offering complete lesion classification, the supplement enhances diagnostic accuracy for patients with CLI.¹

However, while the new TASC supplement did not include any “formal treatment recommendations,” another 2015 study of infrapopliteal treatment options did offer its performance results, which focused on the use of drug-eluting balloons vs plain balloon angioplasty for CLI patients.

That same study compared the safety and efficacy of a “novel paclitaxel-coated, drug-eluting balloon (DEB) versus an uncoated percutaneous transluminal angioplasty (PTA) balloon catheter for the treatment of stenotic, restenotic, or occluded infrapopliteal arteries in patients experiencing claudication or CLI,” with results from its 72 patients showing the DEB option was safe and effective, with outcomes comparable to existing PTA treatments.²

Patient Studies: Trials, Testing, Risks, and Results

As any physician knows, the key to advancing treatment of a disease or condition is patient trials, with long-term trials providing the best data for patient prognosis. A recent 2015 study focused on OLIVE registry patients who received infrainguinal endovascular therapy (EVT) for CLI, and their results after 3 years. The percentage of these patients who completed the 3 years was 95%, with 55.2% being amputation free, 84% free from major adverse limb event (MALE), and 49.6% wound free after 3 years. The study concluded the results were “reasonable, despite the high reintervention and moderate ulcer recurrence rate.”³

Another 2015 study focused on the accuracy of ankle-brachial index (ABI) and toe-brachial index (TBI) in evaluating CLI. In a study lasting almost 2 years, 89 patients underwent NIV testing for “indications of rest pain, as well as minor and major ischemic tissue loss.” Results showed that nearly “one-third of patients with ischemic tissue loss had a normal or mildly reduced ABI.” The researchers also concluded that clinical severity assessment and the use of TBI “are likely to enhance the diagnostic evaluation of CLI over ABI alone, especially among individuals with tissue loss.”⁴

In a study published in 2014, results reported were from the IDEAS trial that compared paclitaxel-coated balloon (PCB) with drug-eluting stent (DES) in long infrapopliteal lesions for the treatment of CLI. This trial lasted just over a year and included 50 patients who underwent PCB angioplasty or primary DES placement. The authors concluded that, “compared with PCB, DESs are associated with significantly better immediate residual post-procedure stenosis, and reduced vessel restenosis at 6 months.” However, they also asserted that larger trials are needed to verify these results even further.⁵

Also focusing on DES therapy, a significant study evaluated 611 patients from 5 trials. The patients – diagnosed with atherosclerotic disease of infrapopliteal arteries – were randomly assigned to DES vs a control of plain balloon angioplasty/bare-metal stent (BMS) implantation. At a follow-up of 1 year, results showed the “DES therapy demonstrated reduced restenosis and greater clinical efficacy compared with plain balloon angioplasty or BMS therapy, and reduced the risk of reintervention and amputation without any impact on mortality and Rutherford class.”⁶

Life Expectancy: Findings and Factors Affecting Patient Outcomes

When faced with a disease as serious as CLI, physicians are forced to consider all the factors that can potentially have an impact on a patient’s medical prognosis and mortality. A recent study that focused on life expectancy in CLI patients included 995 patients who underwent EVT. The study authors used a “risk score based on predictors of all-cause mortality within 2 years.”⁷

The results of the study included patient data from a follow-up period of <730 days, and concluded that 7 independent prognostic factors were responsible for the 2-year life expectancy (2YLE) of CLI patients. According to the authors, the factors included “age, body mass index, non-ambulatory status, hemodialysis, cerebrovascular disease, left ventricular ejection factor, and tissue loss.” The study reported that a “2YLE score of less than or equal to 8 points indicated a greater than 50% probability of 2-year survival, and seemed to be helpful in identifying CLI with a poor prognosis.”

Further to this study, additional medical authors agree the study’s findings have “helped improve the process of patient selection for revascularization.” The same authors suggest that additional factors should be included in the patient’s prognostic assessment, such as “the impact of the procedure on sustained functional recovery, independence, and quality of life.”⁸

Quality of Life: Improving Outcomes and Outlooks

When looking to heal a patient, physicians and surgeons also must consider how each treatment option and surgical procedure will affect the patient’s quality of life. A 2016 study focused on results from the ACHILLES trial, which compared a sirolimus-eluting stent (SES) with PTA for the treatment of infrapopliteal arterial occlusive lesions. The study included 200 patients, and results showed that complete wound closure was higher in the DES group – 72.9% vs 55.6% with PTA. In addition, the DES was also the winner in health-related, quality-of-life scores, as well as with a trend of more quality-adjusted life years up to 1 year after randomization. The study ultimately concluded that “infrapopliteal SES implantation accelerates wound healing, and may improve quality of life compared to PTA.”⁹ However, a 2016 editorial comment on the study of the ACHILLES trial took issue with the findings of the trial analysis and report. The main point of the follow-up comment asserted that “although ACHILLES demonstrated benefits in restenosis and patency with SES in infrapopliteal arteries, it remains unclear whether those results translate into meaningful clinical benefits for the patients.” As such, the comment suggests further research is necessary to ensure CLI patients receive a treatment that best contributes to their quality of life.¹⁰

Among physicians and surgeons who treat CLI patients, clinical trials continue to be key for researchers, with many closely guarding their optimism for a better tomorrow because of an inadequate today. These same authors and medical professionals look forward to new and emerging treatment options that address the causes of disease better than current standards of care – which can only serve to benefit both patients and physicians alike.

References

1. Jaff MR, White CJ, Hiatt WR, et al. An update on methods for revascularization and expansion of the TASC lesion classification to include below-the-knee arteries: a supplement to the Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II). J Endovasc Ther. 2015;22:663-677.
2. Zeller T, Beschorner U, Pilger E, et al. Paclitaxel-coated balloon in infrapopliteal arteries: 12-month results from the BIOLUX P-II Randomized Trial (BIOTRONIK’S first in man study of the Passeo-18 LUX drug-releasing PTA balloon catheter vs. the uncoated Passeo-18 PTA balloon catheter in subjects requiring revascularization of infrapopliteal arteries). JACC Cardiovasc Interv. 2015;8:1614-1622.
3. Iida O, Nakamura M, Yamauchi Y, et al. 3-year outcomes of the OLIVE registry, a prospective multicenter study of patients with critical limb ischemia: a prospective, multi-center, three-year follow-up study on endovascular treatment for infra-inguinal vessels in patients with critical limb ischemia. JACC Cardiovasc Interv. 2015;8:1493-1502.
4. Bunte MC, Jacob J, Nudelman B, et al. Validation of the relationship between ankle-brachial and toe-brachial indices and infragenicular arterial patency in critical limb ischemia. Vasc Med. 2015;20:23-29.
5. Siablis D, Kitrou PM, Spiliopoulos S, et al. Paclitaxel-coated balloon angioplasty versus drug-eluting stenting for the treatment of infrapopliteal long-segment arterial occlusive disease: the IDEAS randomized controlled trial. JACC Cardiovasc Interv. 2014;7:1048-1056.
6. Fusaro M, Cassese S, Ndrepepa G, et al. Drug-eluting stents for revascularization of infrapopliteal arteries: updated meta-analysis of randomized trials. JACC Cardiovasc Interv. 2013;6:1284-1293.
7. Soga Y, Iida O, Takahaera M, et al. Two-year life expectancy in patients with critical limb ischemia. JACC Cardiovasc Interv. 2014;7:1444-1449.
8. Beckman JA, Creager MA. Critical limb ischemia and intermediate-term survival. JACC Cardiovasc Interv. 2014;7:1450-1452.
9. Katsanos K, Spiliopoulos S, Diamantopoulos A, et al. Wound healing outcomes and health-related quality-of-life changes in the ACHILLES Trial: 1-year results from a prospective randomized controlled trial of infrapopliteal balloon angioplasty versus sirolimus-eluting stenting in patients with ischemic peripheral arterial disease. JACC Cardiovasc Interv. 2016;9:259-267.
10. Hawkins BM. ACHILLES and the Achilles heel of peripheral vascular intervention. JACC Cardiovasc Interv. 2016;9:268-270.