Which risk factors predict rupture of intracranial aneurysms? Towards more refined cost-effectiveness analyses and individualized risk estimates

Background Subarachnoid haemorrhage (SAH) from a ruptured intracranial (cerebral) aneurysm is a serious type of stroke that carries high case-fatality (35%) and morbidity (20%) rates. It represents only 5% of all strokes, but because of the early age it occurs (mean age 55 yrs) and the poor prognosis, the loss of productive life-years from SAH in the population is as large as that from ischaemic stroke. Unruptured intracranial aneurysms are relatively common: aneurysms are detected to be present in approximately 2% of the population. With the ongoing improvement of imaging techniques, the chance that an asymptomatic intracranial aneurysm is detected has increased. Preventive aneurysm occlusion seems an attractive option to reduce the risk of future SAH, but then the dilemma arises whether the risk associated with preventive surgical or endovascular occlusion of the aneurysm is outweighed by the risk of death or disability from rupture of the untreated aneurysms sometime later in life. Furthermore, uncertainty still exists in the estimation of individual aneurysmal rupture risk. Identifying prognostic factors that predict the risk of rupture appears to be difficult, because individual studies are too small for valid and reliable analyses and multivariable analysis cannot be performed with aggregated data available from the literature. Collaborative efforts with pooled analysis of individual patient data are needed to identify independent risk factors for aneurysm rupture. With such an approach reliable individual rupture risk estimates based on patient and aneurysm characteristics will become available. By means of decision analysis it is possible to translate these results into a framework that provides the best possible insight in the balance of risks and benefits of preventive aneurysm treatment. Aim With the proposed project we aim: 1) to develop a simple and practical prediction tool which predicts the risk of rupture for each individual patient with an unruptured intracranial aneurysm, and 2) to better characterize individual patients with an unruptured intracranial aneurysm for whom preventive treatment (surgical repair or endovascular repair) is (cost-)effective. Methods We will conduct an individual patient data (IPD) meta-analysis of all observational studies that investigated the long-term natural history of unruptured intracranial aneurysms prospectively (a total of 2924 patients with 4212 unruptured aneurysms; 114 aneurysms ruptured during follow-up). This dataset will provide the unique opportunity to study predictors of risk of aneurysm rupture with Cox regression analysis. Based on and building on previously performed studies (ZonMW 6120.0019 - Prevention 2, prof. dr A. Algra) a modelling study will be conducted to determine the optimal treatment of unruptured aneurysms. A previously developed Markov model designed to evaluate the cost-effectiveness of surgical and endovascular treatment of unruptured aneurysms will be adapted. Expected results The ultimate aim is to develop a practically applicable risk score that enables clinicians to estimate an individuals’ aneurysm rupture risk that can be used to target preventive aneurysm treatment to those individuals who are likely to benefit and to avoid it in those with little chance of benefit (i.e. the risks of preventive treatment are too high to outweigh the risk of future SAH).