Long-Term Follow-Up Results following Elective Treatment of Unruptured Intracranial Aneurysms with the Pipeline Embolization Device

Aneurysmal Occlusion

Overall aneurysmal occlusion rates increased from 81.6%, 84.1%, to 93.2% in the 6-month, 1-year, and 2+-year time periods, respectively. Twenty-one of 119 aneurysms were identified as nonoccluded at 6 months; of these, 3 closed by 1-year follow-up, and a further 11, at 2+-year follow-up.

Seven aneurysms were nonoccluded at 2+-year follow-up (Table 1). Four of these patients had stopped clopidogrel at 6 months. Three of 7 patients had an incorporated vessel (discussed below). Two of these 3 patients stopped clopidogrel at 6 months. Of the 4/7 remaining aneurysms, the first (cavernous aneurysm) was initially treated with 1 PED (5 × 20 mm) and had retreatment with a second (4.75 × 16 mm) at 12 months. Final CTA was performed 22 months post-initial PED, after which follow-up was stopped due to the patient being 80 years of age. The second case, patient A (Fig 1), had a basilar blowout aneurysm that was retreated at 20 months (discussed below). The third had a blowout aneurysm of the anterior communicating artery treated with a PED from the left A1 to the right A1/A2 junction without convincing purchase in the distal right A2. The last had a pre-existing stent (Enterprise; Codman & Shurtleff, Raynham, Massachusetts).

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Fig 1.

Frontal-projection DSA images of the basilar artery. Patient A is a 69-year-old man who lived in a remote location and presented with syncope and vertigo caused by mass effect from a 15-mm sidewall blowout basilar trunk aneurysm. A, Pretreatment DSA. B, This was initially treated with 2 PEDs (4 × 14 mm, 4 × 18 mm) and coils (at operator discretion) but continued to fill at 18 months, despite cessation of symptoms and clopidogrel being stopped prematurely at 6 months without issue. A third PED (4 × 20 mm) was inserted at 20 months (C), but the aneurysm continued to fill at 27 months on DSA (not shown). At 33 months (13 months after the last PED insertion), clopidogrel was stopped for an inguinal hernia repair in a distant peripheral hospital, resulting in PED construct thrombosis (perioperative heparin was advised), with symptoms arising 1 day after surgery, progressing to left-sided weakness, obtundation, and MR imaging evidence of multiple posterior circulation infarcts. The patient was intubated and flown to our institution, but emergency neurothrombectomy was unsuccessful (D) and the patient died.

Presence of Incorporated Vessel

Of the 21 nonoccluded aneurysms at 6 months, 10 had an incorporated vessel. This was statistically significant for causing delayed occlusion (P = .009) and nonocclusion at 6 months (10/23 aneurysms with an incorporated vessel, P < .001), and at 1 year (10/23, P < .001), but not at 2+ years (3/23, P = .116). Kaplan-Meier analysis suggested that the presence of an incorporated vessel results in a mean time of closure at 16.7 months (95% CI, 11.4–22.0 months) versus 9.1 months (95% CI, 7.1–11.1 months) in its absence (Fig 2). Seven of the 10 aneurysms had occluded at final follow-up. Two of 10 remained unchanged in size compared with pretreatment; both had only 1 PED and had 26- and 30-month imaging, respectively. The third, patient B (Fig 3), had a second PED at 22 months with 40% reduction in size at 56-month follow-up.

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Fig 2.

Kaplan-Meier curves of aneurysms with an incorporated vessel (solid line) versus no incorporated vessel (dotted line), demonstrating the delayed occlusion of the former group. Shaded circles represent censored observations (representative of nonoccluded aneurysms at the last known time of imaging).

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Fig 3.

A–C, Lateral DSA images of the left ICA. D, Sagittal maximum-intensity-projection reconstruction of CT angiography. Patient B is a 63-year-old man who had an asymptomatic left posterior communicating artery aneurysm, initially treated with a single PED (3.75 × 12 mm). Preinsertion (A) and immediate postinsertion images (B) of a flow diverter demonstrate the large incorporated posterior communicating artery. Twenty-two months after insertion of the initial PED, a second (3.75 × 14 mm) was inserted (not shown). C, Final available catheter angiographic imaging 9 months postinsertion of the second flow diverter. Clopidogrel was stopped 6 months postinsertion of the second PED. D, CT angiography 56 months post-initial flow diversion demonstrates persistence of the aneurysm but with a decrease in its size.

Ten aneurysms had a previous stent, and of these, 6 demonstrated occlusion at 6 months. At 1-year follow-up, none of the remaining 4 had closed. A further 3 were occluded by 2+-years (9/10). The results trended toward significance for nonocclusion at 1 year but not at other intervals (P = .131). No statistically significant influence on occlusion was found for size or morphology (Table 2).

In-Stent Stenosis or Vessel Occlusion

Three cases (2.8%) of in-stent stenosis ≥70% were noted at 6 months. None of the patients were current smokers; all were female. The narrowing lessened with time, and the patients remained asymptomatic. In these cases, aspirin and clopidogrel were maintained. No new stenoses were identified after 6 months.

Two periprocedural PED occlusions were noted. The first patient (a 66-year-old male smoker) was treated for a 78-mm paraclinoid aneurysm with 4 PEDs and had complications from acute stent platelet aggregation requiring abciximab. He presented 12 days postprocedure with seizures and in-stent thrombosis. Two passes with a Solitaire 4 × 15 mm device (Covidien), an 8-mg bolus of intra-arterial abciximab, and a 12-hour intravenous infusion resulted in recanalization. The patient was converted to prasugrel. This center had no P2Y12 testing. No clinical sequelae were noted, and CT at day 9 demonstrated no infarcts. The second case occurred during treatment of a pericallosal aneurysm in a 74-year-old patient, resulting in clinically silent stroke (discussed below).

Two delayed PED occlusions were detected. One, in patient C, was an asymptomatic occlusion in a 3-layer PED construct in a pericallosal fusiform aneurysm (Fig 4). The second, patient A, was in a 69-year-old man (Fig 1) who died after an elective inguinal hernia repair from thrombosis of his 3-layer PED construct in a blowout basilar aneurysm (discussed below).

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Fig 4.

Subtracted frontal views of the left ICA DSA. Patient C is a 62-year-old nonsmoking woman who had a dysplastic 6 × 20 mm pericallosal fusiform aneurysm identified on investigation for headaches and retro-orbital pain. Pretreatment appearance (A) of a dysplastic fusiform A2 segment aneurysm and appearance immediately postdeployment (B) of 3 PEDs (2.5 × 20 mm, 2.5 × 18 mm, and 2.5 × 14 mm). Clopidogrel was stopped after 6 months, and aspirin was continued. C, At DSA 21 months post-PED deployment, the aneurysm demonstrates 90% occlusion with no in-stent stenosis, but spontaneous asymptomatic PED occlusion is found at 35 months (D). It is unknown exactly when the PED construct thrombosed (between 21 and 35 months postimplantation) because the patient was asymptomatic.

Retreatment

Retreatment by using the PED was required in 3/119 aneurysms in the follow-up period. The first patient, previously published,⁴ initially had an elective flow diversion of a 16-mm superior hypophyseal aneurysm with a single PED. Thirty-four days later, on routine CTA, the PED had migrated proximally. Two PEDs were placed that day. The second, patient A (Fig 1), had a blowout basilar trunk aneurysm. This was treated with 2 telescoped PEDs and coils but continued to fill at 18 months, despite cessation of clopidogrel prematurely at 6 months. Retreatment was performed at 20 months with another PED, but the aneurysm was seen as continuing to fill at 27-month DSA.⁷ The third case was a 77-year-old patient presenting with abducens palsy from an 18-mm cavernous aneurysm. Due to nonocclusion at 11 months, a second PED was placed, but the aneurysm remained open, albeit smaller (9 mm), at 22 months. The sixth nerve palsy resolved. This case was classed as a nonocclusion because the patient declined further imaging.

Transient Ischemic Attacks, Strokes, Subarachnoid Hemorrhage, and Deaths

From 0 to 6 months, in addition to the 5 TIAs and 3 strokes (all mRS 1) in the previously reported population,^4,7 2 strokes occurred, for a rate of TIA of 4.2%, minor stroke of 3.4%, and major stroke of 0.8%. The first was in a 57-year-old smoker who underwent elective flow diversion for a recurrent 5-mm right MCA aneurysm, previously coiled for acute rupture in 2009. A single 3 × 14 mm PED was placed uneventfully. The patient's clopidogrel was stopped against instructions for hematuria 11 days postprocedure, and he had an infarct on day 17, with hemiplegia and severe dysphasia (mRS 3). The second was a clinically silent stroke occurring in a 74-year-old patient with a 4-mm pericallosal aneurysm. Two PEDs were placed, and intraprocedural PED occlusion occurred; thus, 4 mg of intra-arterial abciximab was administered. Recanalization occurred within 15 minutes, and the patient remained asymptomatic. Despite this outcome, frontopolar branch and medial lenticulostriate infarcts were noted on routine 1-month CT. The patient remained neurologically intact (mRS 0). Of note, the center also did not use P2Y12 testing.

From 6-month follow-up onward, 1 case of TIA was noted, a 62-year-old smoker who experienced 3 possible TIAs on aspirin between 26 and 53 months post-PED with normal clinical examination and MR imaging findings. No action was taken.

Three deaths occurred during follow-up from all causes, for a mortality rate of 2.5%, with a PED-related mortality of 0.8%. In the first, patient A (Fig 1), the PED thrombosed, and he died at 33 months after initial insertion of 2 PEDs for his blowout basilar aneurysm (13 months after retreatment with a third PED) after stopping clopidogrel for an elective inguinal hernia repair. The second was a 58-year-old man with active non-Hodgkin lymphoma who died of unrelated causes 17 months after receiving a PED. The third was a 66-year-old patient who had undergone treatment of a 78-mm aneurysm with 4 PEDs and was placed on aspirin and prasugrel (clopidogrel resistance). The aneurysm was thrombosed at 6-month DSA, but DAT was continued for heavy smoking, and he died 12 months later from a fall-related posttraumatic right frontal hematoma.