UCAS (prospective) 

- 2001-2004 in Japan 

- N=5720 patients, 6697 aneurysms (3050 : treatment before rupture @ median of 48 days, 3647: not treated before rupture) 

- Rupture rate of 0.95% per aneurysm-year ; rupture rates associated with 35% mortality, 29% mRS 3-5 

Rupture rates according to location and size:  

Whereas ISUIA found increased rates in all posterior circulation aneurysms, UCAS found higher rupture rates with Acomm and Pcomm (but not more with say, BTAs..... however the total number of VA/BTA aneurysms was small (see below chart)

Graphical representations of rupture rates by location and size: 

Multivariate analyses of predictors of rupture: 

*smoking status (former or current) not associated with rupture rate! 

*previous SAH not predictive of rupture - however only 3% of the cohort had ever had a SAH 

Criticisms: 

- Japanese population: which has the same incidence of aneurysm, but a higher risk of SAH compared to the rest of the world. Unclear if this data can be applied to US or european populations.
- Same selection bias as ISUIA - non-randomized data; the aneurysms believed to be high risk were all treated.

ISUIA (prospective) 
- 1991-1998
- N=4060 patients (1692 no surgery, 1917 surgery, 451 endovascular)
- Overall rupture rate -- 3% over 4.1 years of follow up; 65% mortality with ruptures

Rupture rates by location, size and presence of previous SAH*

 *All aneurysms examined in this study were unruptured, however some people in the study had a history of SAH from another source/another aneurysm. Those were designated as "group 2" --- vs "group 1", which denotes those who had no history of SAH.

Graphical representation of rupture rates by size and history of SAH: 

Multivariate model of predictors of aneurysmal rupture: 

Size: 

<7 mm (ref) 

7–12 mm, [RR] 3·3 [95% CI 1·3–8·2], p=0·01  

> 12 mm, [RR]17·0 [8·0–36·1], p<0·0001

Location:**

ICA (ref)

Basilar tip - [RR] 2·3 [1·1–4·8], p=0·025

Cavernous - [RR]  0·15 [0·04–0·64], p=0·01

Pcomm - [RR] 2·1 [1·1–4·2], p=0·02

Age: [RR] 1·007, [0·98–1·03], p=0·56 

- Morphological characteristics such as multiple lobes, presence of a daughter sac, and a family history of subarachnoid haemorrhage were not predictive of SAH 

**other locations not statistically significantly associated with rupture


Table comparing the observation vs intervention cohorts. 

Criticisms of the study: 
- Data from 1991-1998 -- before the era of widespread use of aspirin and statins, which decrease the rate of aneurysmal rupture. Also really before the era of endovascular techniques, which have significantly altered practice patterns such that the data from the people who were observed during this study is unlikely to apply to people we would observe today.
- Not randomized -- (most) everyone who was believed to be a high rupture risk underwent surgical or endovascular interventions; thus there's a selection bias for the low-risk aneurysms, thus possibly leading to an artifically lower rupture rate in the observation group.
- Selection bias of older, sicker patients --  The 5 year KM mortality in this group was 12.7% -- you would expect <1% in an age-matched control cohort. The observation group was likely enriched for poor surgical (and poor mid-90s era endovascular) candidates -- many died from cancer, heart disease, etc; About half of the patients died from intracranial hemorrhage events, many of which were NOT counted as rupture events but as censored -- patients who died from intracranial hemorrhage that could not be definitively attributed to the aneurysm were counted as censored. Another group (I can't remember which, but I think it was the TEAM group) re-analyzed the data counting all these censorship events as rupture events and found the overall annual rupture rate to be 1.2% vs 0.8% - a 50% difference although a small absolute difference.
- 32% censorship/crossover for treatment  -- enough said.
- <22% with >4 years of fu -- enough said.

- Included cavernous carotid aneurysms - which are known to have a very, very low rupture rate.