Impact of Advanced Age on Procedural and Acute Angiographic Outcomes in Patients Treated for Peripheral Artery Disease With Orbital Atherectomy: A CONFIRM Registries Subanalysis

Abstract: Purpose. Data on the outcomes of elderly patients with peripheral arterial disease (PAD) who undergo orbital atherectomy are limited. This analysis compares the procedural and acute angiographic outcomes of PAD patients treated with orbital atherectomy stratified by age (≥75 years of age [elderly] vs <75 years of age [younger]). Methods. The CONFIRM registry series with non-missing age was analyzed and included 2995 real-world PAD patients (4557 lesions) with 1753 younger patients (2637 lesions) and 1242 elderly patients (1920 lesions) treated with orbital atherectomy. The composite rate of adverse events including dissection, perforation, slow flow, vessel closure, spasm, embolism, and thrombus formation was compared between groups. Results. Elderly patients had a higher proportion of females (47.5% vs 35.3%; P<.001), more patients with critical limb ischemia (49.9% vs 39.3%; P<.001), longer lesion length (75.0 ± 74.1 mm vs 69.9 ± 68.9 mm; P=.01), and more lesions treated below the knee (38.9% vs 34.4%; P=.01). Younger and elderly patients had similar rates of composite adverse events (22.0% vs 21.3%; P=.81), dissection (11.4% vs 10.5%; P=.72), vessel closure (1.7% vs 1.1%; P=.13), spasm (6.3% vs 6.4%; P=.96), and embolism (2.5% vs 1.6%; P=.31). Elderly patients had a lower rate of thrombus formation (0.9% vs 1.6%; P=.03), but a higher perforation rate (1.2% vs 0.4%; P=.01). Conclusions. Orbital atherectomy resulted in similar composite rates of adverse events despite the elderly having unfavorable baseline Rutherford classification and lesion characteristics. The higher rate of perforation may be explained by longer and more below-the-knee lesions. 

J INVASIVE CARDIOL 2015;27(8):381-386

Key words: orbital atherectomy, peripheral arterial disease, vascular calcification, elderly

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Peripheral artery disease (PAD) is a common circulatory problem resulting in narrowed arteries and reduced blood flow to the limbs.¹ PAD affects approximately 27 million individuals in the United States and Europe, and advanced PAD accounts for over 150,000 lower-extremity amputations in the United States annually, making it a significant health burden.^2,3 There are currently 40.3 million Americans >65 years old, and the fastest growing age group is those >85 years in age.⁴ The incidence of PAD is on the rise due to an aging population. The prevalence of PAD increases exponentially with age, and affects between 12%-20% of all Americans over the age of 60.^5,6 The presence of PAD in the elderly population is also associated with increased risk of developing severe cardiovascular disease and increased mortality.⁷ While advanced age is associated with significant co-morbidities leading to higher prevalence of PAD, numerous negative intrinsic changes in the cardiovascular system of the elderly also exist. Even in otherwise healthy individuals, advanced age is associated with thickening of arterial walls, increased collagen and calcium deposits, and decreased vessel compliance, which results in higher blood pressure and decreased cardiovascular performance.⁸ 

PAD is marked by atherosclerotic lesions, and at its worst, calcific plaques, which restrict blood flow to the lower extremities. Calcific PAD makes peripheral vascular interventions such as balloon angioplasty and stenting less successful, often resulting in high rates of restenosis. ^9,10 Treatment techniques to address calcific plaques include the use of atherectomy for plaque modification prior to angioplasty.^11-14 The Orbital Atherectomy System (OAS), developed by Cardiovascular Systems, Inc, is a minimally invasive atherectomy system developed for improving luminal diameter in patients with PAD by treating a broad range of plaque types in the lower limbs.^14-19

The elderly represent a large, rapidly growing population with significant co-morbidities and risk factors for PAD. Studies have shown that preoperative quality of life in elderly patients following cardiovascular intervention is significantly worse than in younger patients.²⁰ Despite these factors, data on the outcomes of elderly patients with PAD who undergo orbital atherectomy are limited. The current analysis compared the procedural and acute angiographic outcomes of PAD patients treated with orbital atherectomy stratified by age (≥75 years vs <75 years). 

Methods

Design. The CONFIRM I, II, and III registries are large, multicenter, non-randomized, all-comer registries of patients with PAD who were treated in the United States with the OAS.²¹ There were no inclusion or exclusion criteria for enrollment in order to mimic “real-world” practice, and all patients with non-missing age were included in this analysis. Data collected included demographics; ankle-brachial index (ABI); Rutherford classification; lesion characteristics including lesion length, plaque morphology, and extent of stenosis before and after treatment; procedural data; device usage parameters; adjunctive therapy; and acute procedural outcomes. Plaque morphology was reported by the principal interventionist using the following criteria: severe calcium (>75%); moderate calcium (50%-75%); mild calcium (25-50%); minimal calcium (<25%); fibrotic; or soft plaque. Plaque reduction was determined angiographically by the principal interventionist with no core-lab adjudication. The three combined registries included 2995 patients with non-missing age, totaling 4557 lesions, and these patients were divided into two groups based on age at the time of procedure: age <75 years (younger group; 1753 patients with 2637 lesions) and age ≥75 years (elderly group; 1242 patients with 1920 lesions). This analysis compared stenosis rates pre-OAS and post-OAS treatment, final residual stenosis after OAS treatment, adjunctive therapy, and the procedural complication rate in younger vs elderly patients in the CONFIRM series. 

Device description. All patients were treated with the OAS. Three device iterations were evaluated. CONFIRM I evaluated the Diamondback360° exclusively; CONFIRM II evaluated the Predator360° exclusively; and CONFIRM III evaluated the Diamondback360°, Predator360°, and Stealth360° devices, all of which have been previously described.^12,15,17-19 The current subanalysis pooled the results from the three CONFIRM registries, and did not differentiate between device iterations. Crown sizes ranged from 1.25-2.25 mm, allowing for treatment of vessels throughout the lower extremities, from above the knee to the foot. 

Statistical analysis. Data regarding patient characteristics are reported as frequency counts and percentages. Percentages were computed using available data only, with unknown values excluded from analyses. Means and standard deviations are reported for quantitative measurements, whereas minimum and maximum values are reported to indicate data ranges. Relationships between various patient or lesion characteristics and patient outcomes were analyzed by cross-tab analysis. Rarely observed data categories were combined (eg, pretreatment stenosis percentages of <70% were collapsed into a single category of stenosis ≤70%) as necessary to allow sufficient counts in cross-tab cells for valid Chi-square analysis. Chi-squared (χ²) values are reported. P-values <.05 were considered statistically significant. Statistical analyses were done using SAS version 9.3. A multivariate analysis was performed evaluating age as a predictor of the primary endpoint of composite angiographic complications. Baseline factors including age, gender, history of smoking, diabetes, coronary artery disease, renal disease, hypertension, hyperlipidemia, presence of critical limb ischemia, lesion length, and lesion location were investigated as possible predictors of composite angiographic outcomes.

Results

Baseline clinical characteristics. Compared with the younger group, the elderly patient group had a higher prevalence of females (47.5% vs 35.3%; P<.001), but had fewer current or previous smokers (68.1% vs 81.4%; P<.001) and fewer patients with diabetes (54.5% vs 63.3%; P<.001) (Table 1). The elderly group had more patients with pain at rest (Rutherford class 4, 19.7% vs 15.7%; P=.01) and moderate to severe ischemic ulceration (Rutherford class 5-6, 30.2% vs 23.6%; P<.001). Elderly patients had longer lesions (75.0 ± 74.1 mm vs 69.9 ± 69.8 mm; P=.01) and a trend toward a higher percentage of severe calcium (45.9% vs 43.4%; P=.07) (Table 2).

Procedural characteristics. No significant difference in preprocedural stenosis was observed between the two groups (Table 3). Elderly patients had a higher number of vessels treated (1.4 ± 0.7 vs 1.4 ± 0.6; P=.01). The maximum balloon inflation pressure was lower in the elderly group (5.5 ± 2.8 atm vs 5.8 ± 2.9 atm; P=.04). Elderly patients had more below-the-knee lesions (38.9% vs 34.4%; P=.01) and a trend toward more popliteal lesions treated (17.9% vs 15.7%; P=.06). Younger patients had more above-the-knee lesions treated than the elderly (49.8% vs 43.2%; P<.001) (Table 4). A more detailed account of treatment locations is presented in Table 4. Adjunctive balloon and stent rates were similar in both groups (Table 5). 

Clinical outcomes. Elderly and younger patients had similar rates of composite angiographic complications including dissection (flow-limiting and non-flow limiting), perforation, slow-flow, vessel closure, spasm, embolism, and thrombus formation (21.3% vs 22.0%; P=.81) (Table 6). Elderly patients had a lower incidence of thrombus formation (0.9% vs 1.6%; P=.03), but a higher rate of perforation (1.2% vs 0.4%; P=.01) and a trend toward a higher rate of slow-flow (5.3% vs 4.0%; P=.08). The multivariate analysis evaluating independent predictors of composite angiographic complications produced a non-significant P=.40 for age (odds ratio, 0.934; two-sided confidence interval [CI], 0.798-1.094), suggesting that age is not a predictor of composite angiographic complications. 

Discussion

The results of our study suggest that orbital atherectomy provided similar clinical outcomes with regard to dissection, slow-flow, vessel closure, spasm, and embolization in both elderly and younger patients despite the elderly having unfavorable baseline Rutherford classification and lesion characteristics. The higher rate of perforation may be explained by a higher percentage of below-the-knee lesions, which typically represent a greater challenge in treatment.    

The prevalence of PAD increases exponentially with age²³ and was 7.0% (95% CI, 5.6%-8.4%) for those aged 60-69, 12.5% (95% CI, 10.4%-14.6%) for those aged 70-79, and 23.2% (95% CI, 19.8%-26.7%) for those aged 80 and older in the United States.²⁴ These rates may even be conservative when estimating the incidence of PAD in the elderly; elderly patients with common co-morbidities that limit movement such as arthritis, congestive heart failure, and pulmonary disease may not identify symptoms associated with PAD.²⁵ Vascular calcification is common in severe PAD and is associated with additional procedural complications including dissections and perforations.⁹ Vascular calcification also increases with age; in a study designed to assess calcification in 650 patients, vascular calcification was identified in two-thirds of patients <50 years and 100% of patients >70 years.²⁶ Despite the prevalence of PAD in the general population and the known co-morbidity of increased age, the prevalence of PAD in the elderly may be underestimated because this population is typically excluded from clinical trials.²⁷ 

Modification of calcified plaque prior to other interventional therapies may decrease periprocedural complications, including dissection⁹ and embolism,²⁸ and thus improve procedural success rates in otherwise high-risk patients. This observation has led to the development and utilization of several devices designed to modify or remove this heavy calcium burden, including orbital atherectomy.²¹ The orbital atherectomy device utilizes an eccentrically mounted crown to modify calcific plaque to reduce the rates of dissection while leaving compliant tissue relatively unscathed. The CONFIRM registry series demonstrated the ability of the OAS to successfully treat patients with calcified peripheral lesions. Over three-quarters of the lesions treated in the CONFIRM registries had either severely (44.4%) or moderately (38.5%) calcified peripheral lesions. While lesions in elderly patients trended toward higher rates of severe calcium (45.9% vs 43.4%; P=.07), lesions in younger patients had a higher rate of moderate calcium (39.8% vs 36.7%; P=.03). In the largest available database of patients with PAD who underwent orbital atherectomy, we found that the use of OAS provided similar procedural and acute angiographic outcomes in patients, regardless of age. 

Study limitations. This is a non-randomized, single-arm registry of all patients undergoing treatment of PAD with the use of the OAS. As such, observational bias may be present because there was no blinding. There were no data regarding distal protection collected. There was no core-lab adjudication of the angiographic data, and the grading system to determine calcification was subjective. The duration of follow-up was short. Patients with claudication and critical limb ischemia were included in the analysis; there were significant differences in baseline and lesion characteristics, which may complicate our findings.

Conclusion

In an analysis of the CONFIRM I, II, and III registries, the largest available data set for the treatment of PAD with an atherectomy device, the overall procedural success with orbital atherectomy was equally favorable in elderly and younger patients. These results, however, suggest that additional studies should be completed to further understand the increased risks for patients of advanced age versus their younger counterparts during endovascular procedures.

Acknowledgments. The authors thank Brad J. Martinsen, PhD, and Nick Hargus, PhD, of Cardiovascular Systems, Inc, for editing and critical review of this manuscript.

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From the ¹Depts of Medicine and Cardiology, UCLA Medical Center, Los Angeles, California; ²Departments of Vascular and Interventional Radiology, Mount Sinai Medical Center, Miami Beach, Florida; and ³Departments of Cardiovascular and Peripheral Vascular Research, Rex Healthcare, Raleigh, North Carolina.

Funding: Cardiovascular Systems, Inc, sponsored the CONFIRM Registries and financially supported the statistical analysis for this age subanalysis.

Disclosure: The authors have completed and returned the ICMJE Form for Disclosure of Potential Conflicts of Interest. Dr Lee, Dr Beasley, and Dr Adams report consulting agreements with Cardiovascular Systems, Inc.

Manuscript submitted December 8, 2014, provisional acceptance given December 17, 2014, final version accepted January 28, 2015.

Address for correspondence: Michael S. Lee, MD, Associate Professor of Medicine, 100 Medical Plaza Suite 630, Los Angeles, CA 90095. Email: mslee@mednet.ucla.edu