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Abstract
Background Bioactive polyglycolic/polylactic acid (PGLA)-coated Matrix detachable coils were reported to incite intra-aneurysmal inflammation and fibrosis. Multiple large case series with Matrix-1 coils have shown no advantage with respect to aneurysm recurrence. Second-generation Matrix-2 coils were designed with improved platinum support and reduced copolymer friction. We assessed the safety and efficacy of Matrix-2 coil embolization.
Methods 84 aneurysms were embolized primarily with Matrix-2 coils. Anatomic results were evaluated using a modified Raymond scale with progressive occlusion or recanalization/recurrence strictly defined as any interval change in intra-aneurysmal opacification.
Results Mid-term (8.9±3.4 months) and long-term (23.0±7.4 months) follow-up was available for 65 aneurysms. At mid-term, 55 (85%) aneurysms remained stable (or progressed to occlusion) versus 10 (15%) recurrent aneurysms, 7 (11%) requiring retreatment. At long term, 49 (75%) aneurysms remained stable versus 16 (25%) recurrent aneurysms, 12 (18%) requiring retreatment. Statistically significant factors affecting recanalization included ruptured aneurysms 9/20 (45%), large aneurysms 5/8 (71%), post-procedure residual aneurysms 6/12 (50%) and differential coil packing density of recurrent (21%) versus stable (28%) aneurysms. Patient morbidity (5%) was limited to thromboembolic complications (n=4) or aneurysm rerupture (n=1). Patient mortality (5%) was secondary to subarachnoid hemorrhage complications (n=4) with no procedure-related deaths (0%).
Conclusion Coil embolization with Matrix-2 coils is safe and effective, preventing recanalization in small aneurysms at mid-term. Although these aneurysm recurrence rates initially appeared lower than previous reports with Matrix-1 or platinum coils, significant late recanalization was observed on long-term follow-up. We postulate that any derived benefit from Matrix-2 coils is directly dependent on post-procedure outcomes and coil packing density.
- Aneurysm
- brain
- coil
- coil embolization
- intervention
- intracranial aneurysm
- Matrix
- PGLA
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Introduction
Endovascular treatment of intracranial aneurysms has emerged as a viable alternative to surgical clipping in both ruptured and unruptured aneurysms since the advent of platinum Guglielmi detachable coils (GDCs) in the 1990s. The International Subarachnoid Aneurysm Trial (ISAT) demonstrated improved clinical outcomes (relative risk reduction of 22.6% at 1 year) in ruptured aneurysms treated with coil embolization versus microsurgical clipping.1 Although no randomized trial for unruptured intracranial aneurysms has been completed, recent evidence from the International Study on Unruptured Intracranial Aneurysms (ISUIA) suggests a role for endovascular treatment in patients aged >50 years, aneurysms >12 mm and posterior circulation aneurysms, due to poor surgical outcomes in these subgroups.2
Despite these advantages, the long-term durability of endovascular treatment with bare platinum coils remains problematic, with aneurysm recurrence secondary to coil compaction and recanalization ranging from 15% to 40% in large single-center series.3–7 Aneurysm recurrence is most frequent in wide-necked or large/giant aneurysms that are partially thrombosed or incompletely coiled.6 7 Since the risk of aneurysm rupture from recanalized aneurysms is not well defined, close angiographic follow-up is mandated and retreatment is not uncommon, revealing important drawbacks of endovascular treatment.
To prevent aneurysm recurrence, several strategies have been directed toward increasing packing density or accelerating thrombus organization with connective tissue deposition. Both clinical and animal experimental studies have utilized complex platinum coils,8 radioactive coils9 and coated coils with proteins (collagen),10 fibroblasts,11 12 cytokines/growth factors (fibroblast growth factor, vascular endothelial growth factor),12 13 hydrophilic polymers (hydrogel)14 or bioabsorbable polyglycolic/polylactic acid (PGLA) copolymers.15 16
Available since late 2005, PGLA-coated second-generation Matrix-2 detachable coils (Boston Scientific, Natick, Massachusetts, USA) were designed with improved platinum coil support and reduced friction of the bioactive copolymer to address the relatively high recanalization rates of first-generation Matrix-1 coils. We evaluated a large series of ruptured and unruptured aneurysms treated at our institution with Matrix-2 coils to assess their safety and technical/clinical efficacy at mid-term and long-term follow-up.
Methods
Patient and aneurysm populations
The study was reviewed and approved by our Institutional Review Board. Utilizing our institution's prospective neurointerventional database, we studied a near-consecutive population of ruptured and unruptured intracranial aneurysms treated via coil embolization with Matrix-2 detachable coils from March 2006 to October 2007. Inclusion criteria were set for saccular aneurysms ≤25 mm in size and insertion of Matrix-2 coils comprising >50% of the total coil length. Fusiform/dissecting or giant aneurysms (n=4) and aneurysms co-embolized with other bioactive coils (n=3) were excluded.
We studied patient demographics, aneurysm characteristics, coil embolization procedures, complications, aneurysm packing density, immediate, mid-term and long-term anatomic and clinical outcomes. Patient demographics included age, sex and race. Aneurysms were classified by specific location (anterior vs posterior circulation), presentation (ruptured or unruptured), aneurysm size (small ≤10 mm or large >10–25 mm) and neck size (narrow ≤4 mm or wide >4 mm) as described by Murayama et al.7
Procedures
Informed consent for all procedures was provided by patients or their guardians. All patients with unruptured aneurysms were pretreated with aspirin 81 mg and clopidogrel 75 mg (Plavix, Bristol-Myers Squibb, New York, New York, USA) for 5 days prior to the procedure. Interventions were performed under general anesthesia in a biplane angiographic suite (Axiom Artis; Siemens AG, Munich, Germany). Heparin anticoagulation was provided to achieve an activated clotting time of >250–300 s for all unruptured cases. Modest heparin anticoagulation was initiated in ruptured aneurysms during deployment of the first coil (activated clotting time 200–250 s).
Selective catheterization of aneurysms was accomplished using a microcatheter–microwire complex through a proximal 6F guide catheter or sheath. Coil embolization was performed with Matrix-2 or a combination of Matrix-2 and GDC coils (Boston Scientific). Calculation of total coil length and percentage of Matrix-2 versus GDC coils confirmed that all aneurysms met the inclusion criteria for embolization with >50% Matrix-2 coils. To assure sampling of a continuous population, stent- or balloon-assisted procedures were included in our analysis.
Heparin anticoagulation was allowed to dissipate post procedure without reversal. Clopidogrel 75 mg was continued for 2–4 weeks in unruptured aneurysm patients and for at least 12 weeks for procedures requiring stent placement. Aspirin 81 mg was continued in all patients post procedure indefinitely.
Thromboembolic complications were treated with intra-arterial glycoprotein IIb/IIIa platelet inhibitor abciximab (Reopro; Eli Lilly, Indianapolis, Indiana, USA) or tissue plasminogen activator t-PA (Activase; Genentech, South San Francisco, California, USA).
Aneurysm volumes and packing density
Biplane and 3D rotational digital subtraction angiography was available for all aneurysms prior to coil embolization. Aneurysm dimensions were obtained in multiple perpendicular planes from both planar and 3D reconstructed (Leonardo 3D Workstation; Siemens) angiographic projections. Coil volume calculations assumed a cylindrical morphology and the outer coil diameters were provided by the manufacturer, including the PGLA copolymer coating for Matrix-2 coils. Aneurysm elliptical volumes and packing densities (coil volume/aneurysm volume) were calculated as reported by Tamatani et al.17
Angiographic and clinical follow-up
Anatomic results on immediate post-procedure, mid-term and long-term follow-up angiography were graded independently using a modified three-point Raymond classification scale: 1, complete occlusion—no remaining opacification within the aneurysm or neck; 2, neck remnant—residual opacification limited to the aneurysm base or neck interface of the coil loops and parent vessel; 3, residual aneurysm—intra-aneurysmal opacification extending beyond the aneurysm neck into the fundus or coil loop interstices. After comparing post-procedure and follow-up angiograms for each aneurysm, progressive occlusion or recanalization/recurrence was strictly defined as any interval change in aneurysm opacification, regardless of change in the modified Raymond scale. In contrast, aneurysms unchanged on comparison angiograms were classified as stable aneurysms.
Angiographic evaluations were performed primarily with digital subtraction angiography, ranging from 2 to 12 months at mid-term and 13 to 42 months at long-term follow-up. Angiographic projections and magnification were chosen to match prior coiling views and delineate the aneurysm neck. Follow-up MR (n=5) or CT (n=1) angiography was necessary in a few patients for various reasons.
Clinical outcomes were similarly assessed immediately post procedure and during each follow-up interval. Pertinent medical history, procedural complications, follow-up neurological examination/deficits and deaths were recorded in our prospective database as well as the patients' medical records.
Statistical analysis
Mean and standard deviations were calculated for patient age (years), aneurysm neck size (mm), follow-up time (months) and aneurysm packing density (percentage). Categorical data with respect to aneurysm recurrence were analyzed using Fisher's exact test. Differences in aneurysm packing density between anatomic subgroups were analyzed using an unpaired Student t test. A p value of ≤0.05 was assumed for statistical significance. Multivariate logistic regression analysis was performed on statistically significant factors affecting aneurysm recanalization on univariate analysis (aneurysm size, rupture, post-procedure outcomes and packing density) to assess for independent predictors.
Results
Patient demographics and aneurysm characteristics
An initial population of 80 patients with 84 intracranial aneurysms satisfied inclusion criteria. Subsequently, 13 patients were lost to follow-up, 2 refused follow-up and 4 patients died. Finally, 61 patients with 65 aneurysms returned for mid-term (mean 8.9±3.4 months) and long-term (mean 23±7.4 months) assessment.
Patient demographics and aneurysm characteristics were preserved in comparing initial and follow-up populations, summarized in tables 1 and 2. Both populations were skewed toward Caucasian female patients (mean age 57–58 years, range 14–91 years).
Patient demographics
Aneurysm characteristics
In the initial group, 53/84 (63%) unruptured aneurysms were an incidental finding. Seven (8%) of the unruptured aneurysms were symptomatic, presenting with headache or diplopia. Ruptured aneurysms comprised the remaining 31/84 (37%) cases presenting with subarachnoid hemorrhage, Hunt–Hess grades I–III in 25 (30%) cases and grades IV–V in 6 (7%) cases. The ratio of unruptured to ruptured aneurysms was sustained in the follow-up population of 65 aneurysms.
In the follow-up group, aneurysm locations maintained anterior circulation dominance in 44/65 (68%) cases. The majority involved the paraclinoid/supraclinoid internal carotid artery in 23 (35%) cases followed by the anterior cerebral artery and anterior communicating artery in 11 (17%) cases. We noted a relatively small population of posterior communicating artery aneurysms with 4 (6%) cases due to a proclivity for surgical clipping at our institution. There was considerable representation from the posterior circulation in 21 (32%) cases, specifically 12 (18%) basilar tip aneurysms.
The vast majority of aneurysms classified by size were 57/65 (88%) small aneurysms (≤10 mm) and 48/65 (74%) narrow neck (≤4 mm) aneurysms. Further subgroup analysis yielded 44 (68%) small aneurysms with narrow necks (SANN), 13 (20%) small aneurysms with wide necks (SAWN), and 8 (12%) large aneurysms (>10 mm).
Procedures
All coil embolization procedures were performed with >50% Matrix-2 coils (table 3). Both initial and follow-up populations demonstrated an equivalent percentage of aneurysms treated with 100% Matrix-2 coils (64% vs 63%), utilization of adjunctive techniques including balloon remodeling and stent placement (28% vs 27%) and mean aneurysm packing density (26±15%). On follow-up, the majority of aneurysms in 51/65 cases (78%) had been embolized with >90% Matrix-2 coils.
Coil embolization procedures
Anatomic outcomes
Immediate post-procedure angiographic results are reported for the initial and follow-up populations in table 4, as well as the mid-term and long-term follow-up angiographic results. Following coil embolization, aneurysms were classified as 33/65 (51%) complete occlusions, 20 (31%) neck remnants and 12 (18%) residual aneurysms. At mid-term follow-up, 55/65 (85%) aneurysms remained stable or progressed to occlusion; 10 (15%) aneurysms recurred or recanalized with 7 (11%) requiring retreatment. All large aneurysm recurrences in 5/8 (62%) cases were encountered early on mid-term follow-up. In contrast, 5/57 (9%) small aneurysms recanalized at mid-term, with 3/57 (5%) requiring retreatment.
Immediate post-procedure, mid-term and long-term follow-up angiographic results
At long-term follow-up, 49/65 (75%) aneurysms remained stable or progressed to occlusion, but interval recanalization resulted in a total of 16/65 (25%) recurrent aneurysms with 12 (18%) requiring retreatment. In subgroup analysis of post-procedure outcomes, 11/65 (17%) aneurysms exhibited progressive occlusion: 9 neck remnants and 2 residual aneurysms improving toward complete occlusion or neck remnant. Conversely, 10/53 (19%) aneurysms that were completely occluded or with neck remnants demonstrated recanalization: 7 complete occlusions and 3 neck remnants regressing toward recurrence. In comparison, 6/12 (50%) residual aneurysms recanalized with only 4/12 initial residual aneurysms remaining unchanged on final assessement.
Specific aneurysm subgroups were studied to determine factors affecting recanalization/recurrence on long-term follow-up (table 5). Higher recanalization rates in large aneurysms 5/8 (62%) versus small aneurysms 11/57 (19%) were found to be statistically significant with a p value of <0.02 using Fisher's exact test. The respective retreatment rates of large 4/8 (50%) versus small 8/57 (14%) aneurysms corroborated these findings. Elevated recurrence rates in ruptured aneurysms 9/20 (45%) and residual aneurysms 6/12 (50%) on immediate post-treatment angiogram were statistically significant with a p value of <0.03. Although there were trends for wide neck (>4 mm) aneurysms 6/17 (31%) and small aneurysm with wide neck 4/13 (31%) toward increased recanalization, these were not statistically significant. No significant difference in recanalization was noted with respect to aneurysm location (anterior vs posterior circulation) or utilization of adjunctive devices (balloons/stents). Specific subgroup analysis of adjunctive devices showed no advantage with equivalent recurrence in 1/4 (25%) balloon- and 3/13 (23%) stent-assisted embolization of aneurysms. On long-term follow-up, a cohort of stable and progressively occluded aneurysms demonstrated significantly greater mean aneurysm packing density (28±15%) in comparison with recanalized/recurrent aneurysms (21±10%) with a p value of <0.03 using an unpaired Student t test. However, multivariate analysis with logistic regression could not demonstrate independence of these predictors of aneurysm recanalization, though trends toward significance were noted for post-procedure outcomes (p<0.2), large aneurysm size (p<0.12) and ruptured aneurysms (p<0.051), probably related to insufficient power.
Factors affecting recanalization/recurrence on long-term follow-up
Complications and clinical outcomes
Procedural thromboembolic complications 4/84 (4.7%) were related to the coil mass or stent placement and three procedures required emergency thrombolysis. Subsequently, three patients suffered permanent neurological complications resulting in patient morbidity of 3/80 (3.8%). During coil embolization procedures, two instances of a stretched coil were either successfully manipulated into the aneurysm or secured with stent placement without an adverse outcome. There were no intraprocedural vessel dissections, vessel/aneurysm ruptures, serious groin hematomas or retroperitoneal hemorrhages.
There were no procedure-related deaths (0% procedural mortality). However, four patients died from subarachnoid hemorrhage complications with an overall patient mortality of 4/80 (5%). Clinically symptomatic vasospasm in seven patients and hydrocephalus in two patients were noted in the subarachnoid hemorrhage population.
On follow-up, a single partially thrombosed posterior communicating artery aneurysm reruptured in 1/65 (1.5%) patients following coil compaction at 2 months post-treatment leading to overall patient morbidity of 4/80 (5%). Other than transient post-embolization headaches, there were no incidents of chemical meningitis or delayed hydrocephalus. The majority of patients improved neurologically or remained stable at baseline throughout mid-term and long-term clinical follow-up.
Discussion
Although Matrix-1 coils were approved by the US Food and Drug Administration in 2002, embolization of intracranial aneurysms with first-generation Matrix-1 coils has been clinically disappointing. Multiple single-center studies reported no significant difference or even increased rates of aneurysm recanalization (15%–54%) when compared with historical rates of recurrence with bare platinum coils.3–7 18–26 In direct comparison of consecutive patient populations, two retrospective studies failed to demonstrate any advantage of Matrix-1 coils over bare platinum coils with high recanalization rates (36% and 41%).23 26
The criteria to define recanalization or recurrence have varied significantly in the literature with the following definitions: >10% increase in aneurysm opacification (20%)18; change in Raymond classification (24%–26%);19–21 any interval increase in aneurysm opacification (36%–54%)22–24; and inclusive of stable residual aneurysms as final recurrences (41%).25 Pierot et al21 commented that their recanalization rate (26%) would compare equally with the apparently higher rate in the study by Niimi et al23 (54% to 28%), if assessed as a change in Raymond classification. Hence, more uniform recanalization rates are observed if analyzed for major recanalization or retreatment ranging from 9% to 23% across all studies.
A few studies reported extraordinarily high major recanalization or retreatment rates (21%–23%).23–25 When post-procedure outcomes are examined in these studies, an inability to achieve complete occlusion during coil embolization, comprising <17%–28% of the post-procedure results, contributed significantly to recurrence. The factors affecting ‘undercoiling’ of intracranial aneurysms particularly with Matrix-1 coils have been debated in the literature. Individual studies were susceptible to skewed populations of large aneurysms or ruptured aneurysms, known to have higher recanalization rates.7 9 However, several authors claimed that the inherent Matrix-1 coil design was flawed due to the outer PGLA copolymer friction and/or absorption or degradation of the copolymer (10–12 weeks) prior to the formation of an organized thrombus, both resulting in poor volumetric aneurysm occlusion.18 23 24 26
First-generation Matrix-1 coils were manufactured with an outer 55% biopolymer (90% polyglycolic/10% poly-l-lactic acid copolymer coating) and 45% platinum core composition. If the central hollow core wire volume were to be excluded from the calculation, the PGLA copolymer constituted up to ∼70% of the coil volume. The platinum core wire was reduced in diameter to accommodate the peripheral PGLA copolymer, diminishing its biomechanical strength and increasing coil friction during microcatheter advancement and aneurysm embolization. In an experimental elastase-induced rabbit aneurysm model, relatively increased recanalization rates were observed with Matrix-1 coils when compared with bare platinum coils (33% vs 22%), and directly correlated with reduced volumetric packing.27
We hypothesize that the increased incidence of post-procedure neck remnants or residual aneurysms (Raymond class 2 or 3), in the preliminary Matrix-1 coil embolization studies,23–25 is primarily due to ineffective packing density and less attributable to coil radiolucency, improved angiographic equipment or continued heparinization as previously suggested. Although Fiorella et al24 reported achieving high packing densities (mean 30.8%) with Matrix-1 coils, there was no translation to their initial post-procedure or mid-term durability results. In contrast, a larger prospective multicenter registry of 165 patients by Pierot et al21 demonstrated statistically significant higher recurrence rates with packing densities of <25%. Additionally, the lowest published recanalization data with Matrix-1 coils, albeit in a small cohort of patients, cited a 29% mean packing density.26
The importance of coil packing density (>24%) in preventing aneurysm recurrence is well studied with significant discrepancies of mean embolized coil volumes in stable versus recanalized aneurysms.17 28 Technological advancements in complex bare platinum coil design have enabled homogeneous aneurysm filling and elevated volume percentage occlusion (>35%), correlating with reduced rates of aneurysm recanalization.8 However, perceived packing density may be illusive with Matrix coils in particular. First, the reduced platinum core and friction from the outer PGLA copolymer may decrease biomechanical strength and inhibit ideal volumetric packing during coil embolization. Second, PGLA bioabsorption or degradation over several months, especially in non-responsive aneurysms without development of an organized thrombus, may have deleterious delayed effects on coil volume and packing density. Third, persistent aneurysm inflow from incomplete aneurysm occlusions (neck remnants or residual aneurysms), can preclude intra-aneurysmal scar formation by ‘washing out’ the PGLA copolymer as it degrades and/or predispose to coil compaction in an aneurysm with baseline low platinum volume. Interestingly, residual aneurysms have shown markedly increased recanalization rates (>50%–60%) suggesting that PGLA content may be far less important than the initial packing density and immediate post-procedure outcomes.23–25 In fact, the bioactive inflammatory response expected from PGLA may be dependent on a stable maturing thrombus in a completely occluded aneurysm.
Second-generation Matrix-2 coils were designed with reduced PGLA copolymer content and relatively greater platinum support, resulting in an outer 32% biopolymer and 68% platinum core composition. Since several groups specifically described difficulty in advancing PGLA-coated coils through the microcatheter or into an aneurysm with pre-existing Matrix-1 coils,18 23 26 the Matrix-2 PGLA copolymer was enhanced with EASE biopolymer technology to reduce coil friction by 35%. Moreover, the manufacturer developed complex three-dimensional (3D) coil configurations (Matrix-2 3D and Matrix-2-360 coils) to promote uniform coil distribution for increased aneurysm packing density and reduced compartmentalization.
The first single-center study reporting results with Matrix-2 coil embolization (79 aneurysms) compared immediate and mid-term outcomes with the largest accumulated experience with Matrix-1 coil embolization (155 aneurysms) at the University of California-Los Angeles (UCLA). Ishii et al29 concluded that the enhanced mechanical performance of Matrix-2 coils was responsible for improved anatomic outcomes and a decreased rate of aneurysm recurrence in comparison with Matrix-1 coils. Interestingly, the group recharacterized their definition of recanalization from >10% increase in aneurysm opacification to a stricter interpretation as ‘any increase in contrast filling, with or without coil mass remodeling’ in contrast to their earlier series on Matrix-1 coils,18 further exhibiting the benefit of Matrix-2 coils. In 79 aneurysms primarily embolized with Matrix-2 coils, the rate of immediate complete occlusion increased to 43.0%, and the rate of neck remnant and residual aneurysm decreased to 36.7% and 20.3%, respectively. On mid-term assessment of 118 Matrix-1 and 53 Matrix-2 aneurysms, they noted significant improvement in the Matrix-2 cohort with respect to progressive thrombosis (35.8% vs 28.8%) and decreased rates of recanalization (9.4% vs 16.9%). However, they did not differentiate between major recanalizations or retreatment in either subset, reporting a cumulative (Matrix-1 and Matrix-2) recanalization rate of 16.1% and retreatment rate of 15.6%, suggesting that most represented major recanalizations. In addition, there was a remarkably low level of recurrence with large aneurysms (15.4%), attributed to utilization of 3D and GDC 0.018 coils; though it will be noteworthy to follow this population.
D'Agostino et al30 recently published a series of 100 aneurysms treated with Matrix-2-360 coils with an exceptionally elevated percentage (80%) of complete occlusions (Raymond class 1) on immediate post-procedure results. However, mid-term outcomes were available for only 38 aneurysms (mean follow-up of 11.9 months) and the data were less promising than the UCLA study. Using a change in Raymond class to characterize recanalization, usually an underestimation of recurrence, they observed a recanalization rate of 36.8% and major recanalization/retreatment rate of 15.8%, not significantly different from the above-described Matrix-1 data.
Our study represents the largest series on Matrix-2 coil embolization (84 aneurysms) and the only study to examine both mid-term (8.9 months) and long-term (23.0 months) outcomes of 65 aneurysms. Despite strict criteria for recanalization as any interval increase in aneurysm opacification, we observed improved mid-term outcomes (15% recanalization, 11% retreatment rates) with respect to previous reports with GDC and Matrix-1 coils, specifically in small aneurysms (9% recanalization, 5% retreatment rates).3–7 18–26 The data parallel the findings of Ishii et al,29 and similarly, we appreciated a greater ability to obtain complete occlusion 41/84 (49%) on immediate post-procedure outcomes, possibly related to the improved mechanical performance of Matrix-2 coils.
More importantly, our results provide insights into the durability of PGLA-coated Matrix-2 coils. Despite favorable mid-term outcomes, our long-term assessment (25% recanalization, 18% retreatment rates) is concerning. Since all large aneurysm recurrences were noted early on mid-term follow-up, delayed long-term failure primarily involved small aneurysms (19% recanalization, 14% retreatment rates) that are typically resilient to recurrence. Initial aneurysm packing density and post-procedure outcomes were statistically significant factors affecting recanalization. Although we obtained modest mean volume percentage occlusion (26%), Matrix-2 coils could not match the potential packing density of complex bare platinum coils, suggestive of residual friction that may benefit from further PGLA surface optimization or modification.8 29 Moreover, Matrix-2 coil packing density may not be sustainable if an organized thrombus is not formed prior to PGLA degradation. Persisting aneurysm inflow and coil compaction may lead to earlier mid-term recurrence, as seen in large aneurysms and nearly 50% of our post-procedure residual aneurysms, and eventually long-term recurrence of even small aneurysms. As with Matrix-1 coils, initial packing density resulting in complete aneurysm occlusion appears to be a prerequisite to derive any long-term benefit from the PGLA copolymer and promoting intra-aneurysmal fibrosis.
We identified several strengths of our study including a prospective database to assess clinical and anatomic outcomes in a consecutive patient population. The majority of aneurysms in the initial and follow-up groups were embolized with >90% Matrix-2 coils. Active recruitment of our mid-term follow-up population (65 aneurysms) required persistence and enabled long-term assessment in 77% of the initial population, accounting for the elapsed time since the completion of our enrollment in October 2007. Furthermore, the initial and follow-up populations exhibited uniform patient and aneurysm demographics.
Limitations of our retrospective study resemble other single-center series with a relatively small aneurysm population, inevitable patient loss (14%) between the initial and follow-up cohorts and no concomitant control population treated with either bare platinum or Matrix-1 coils for direct comparison. We await results of the randomized, multicenter Matrix and Platinum Science (MAPS)31 trial for greater statistical power. Another limitation is the imprecise methodology in calculating coil packing density due to the assumed ellipsoid morphology of intracranial aneurysms and aneurysm diameter measurements. We attempted to limit artifactual errors commonly associated with 3D rotational angiographic reconstructions by correlating our measurements with orthogonal planar angiographic measurements analogous to other groups.8 21 24 26
Inadequacies intrinsic to the design of Matrix coils must be considered. An outer PGLA copolymer may limit initial volumetric packing and when absorbed or degraded can result in delayed reduction of aneurysm packing density. Newer bioactive Cerecyte coils (Micrus, Inc., San Jose, California, USA) possess an outer platinum core and inner bioactive polyglycolic acid strand, facilitating coil embolization by reduced friction and maintaining coil volume with a stable platinum frame regardless of polyglycolic acid degradation. It will be interesting to compare the results of both the MAPS trial and the Cerecyte Coil Trial.31 32
Conclusion
Although our data support the efficacy of Matrix-2 coils with improved immediate and mid-term outcomes, these results may not be sustained on long-term follow-up as significant late recanalization was observed. We caution against the optimism of mid-term outcomes in evaluating the efficacy of PGLA-coated Matrix-2 coils, including the anticipated MAPS trial data. The long-term efficacy of PGLA-coated bioactive coils and the inherent design of Matrix-2 coils remain in question.
Key messages
Multiple large case series with Matrix-1 coils have shown no advantage with respect to intracranial aneurysm recurrence. Second-generation Matrix-2 coils were designed with improved platinum support and reduced copolymer friction. We report the largest single-center experience with Matrix-2 coil embolization to date. Although Matrix-2 coils appear safe and effective, preventing recanalization in small aneurysms at mid-term, significant late recanalization was noted on long-term follow-up. We caution against the optimism of mid-term outcomes in evaluating the efficacy of PGLA-coated Matrix-2 coils, including the anticipated MAPS trial data. The long-term efficacy of PGLA-coated bioactive coils and the inherent design of Matrix-2 coils remain in question.
Acknowledgments
James Myles Ph.D, Michigan Institute for Clinical Health Research, University of Michigan Health System, Ann Arbor, Michigan, USA Ben Adarkwa Dwamena, MD, Assistant Professor, Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA
References
Footnotes
Competing interests None to declare.
Ethics approval This study was conducted with the approval of the Institutional Review Board, University of Michigan, Ann Arbor, Michigan, USA.
Provenance and peer review Not commissioned; externally peer reviewed.