Discussion

In the current study, we were able to analyze rates of stroke and mortality up to 1 year after a TIA and observed that long-term stroke occurrence and mortality after TIA significantly declined from 2003 to 2015 in an Ontario-wide hospital-based cohort, with a 32% reduction in stroke and 61% reduction in mortality at 1 year. The high risk of early stroke remains, with the majority of strokes occurring in the first 7 d (Figure 4). This is further illustrated by the fact that the slopes of each line from 2003 to 2015 for the first 30 d following a TIA have not changed significantly (Figure 4). However, the risk of stroke decreased from 1.9% in 2003 to 1.7% in 2015 for 48-hour risk, and from 6.0% to 3.4% for 1-year risk.

Over the past 15 years, public health initiatives, knowledge translation efforts, diagnostic strategies, primary and emergency care, and organized secondary prevention after TIA have significantly improved. Few previous studies have evaluated the impact of improved TIA management at a provincial level over time; most assess risk in specialized stroke centers. ^{Reference Wu, McLaughlin, Lorenzetti, Hill, Manns and Ghali6,Reference Giles and Rothwell7} In 2014, Sundararajan et al. conducted a population-based study in Australia and reported an overall 90-day stroke risk of 2.9%. ^{Reference Sundararajan, Thrift, Phan, Choi, Clissold and Srikanth30} In addition, after adjusting for age and sex, the risk of stroke at 90 d after a TIA decreased by 3% per year over a 10-year period. However, it remains unclear whether treatment is merely delaying stroke, or truly reducing occurrence in the longer term.

Ontario’s universal healthcare system provides public funding for doctor and hospital visits and has had an organized stroke care system, which began in 2000 and was fully implemented in 2005. Using data from the Ontario Stroke Registry from 2000, Gladstone et al. ^{Reference Gladstone, Kapral, Fang, Laupacis and Tu2} reported a 30-day risk of stroke at 5%. In our larger population-based sample, we found a lower rate of stroke at day 30 in 2003 (3.8%) and decline over the next decade to 2.7% in 2015. It is likely that rates were already decreasing between 2000 and 2003. In addition, two previous registry-based studies have evaluated stoke risk at 1 year after TIA and reported risk at 6.1% ^{Reference Park, Kim and Han9} and 5.1%. ^{Reference Amarenco, Lavallée and Labreuche8}

Comparisons of the earlier hospital-, registry- and community-based studies to more recent studies illustrate similar trends. Two meta-analyses of previous studies between 1973 and 2007 reported pooled risk of stroke at 2 d of 3.1 ^{Reference Giles and Rothwell7} –3.5%, ^{Reference Wu, McLaughlin, Lorenzetti, Hill, Manns and Ghali6} and 5.2%, ^{Reference Giles and Rothwell7} 8.0%, ^{Reference Wu, McLaughlin, Lorenzetti, Hill, Manns and Ghali6} and 9.2% ^{Reference Wu, McLaughlin, Lorenzetti, Hill, Manns and Ghali6} at 7, 30, and 90 days, respectively. A more recent meta-analysis including interventional studies (with an urgent assessment and management strategy) from 2007 to 2015 suggests that the risk of stroke has reduced by almost half ^{Reference Valls, Peiro-Chamarro, Cambray, Molina-Seguin, Benabdelhak and Purroy31} ; with pooled stroke risks of 1.4%, 2.1%, 2.8%, and 3.4% at 2, 7, 30, and 90 days, respectively. This 50% reduction seen in the registry- and hospital-based cohorts directly mirrors the population-based results reported here.

Compared to these studies, that included patients from specialized centers, we observed a lower risk of stroke (3.4%) among TIA patients in Ontario. It is possible that administrative codes may have less specificity than registry-based/clinic-based studies which could increase the number of lower risk TIA patients and may underestimate the risk of stroke; ^{Reference Lavallée, Meseguer and Abboud20–Reference Kapral, Hall and Fang22} however, the time-curves of stroke rates were nearly identical to those seen in the analysis by Gladstone et al., ^{Reference Gladstone, Kapral, Fang, Laupacis and Tu2} Johnston et al. ^{Reference Johnston, Rothwell and Nguyen-Huynh32} (ABCD2) and others. ^{Reference Lovett, Dennis, Sandercock, Bamford, Warlow and Rothwell33} In addition, if more low-risk patients were being diagnosed with TIA, we would expect to see the rates of early stroke decrease and the slopes of the initial part of the curves in Figure 4 flatten over time, however, this was not observed. While our study limits sampling biases, studies based on administrative databases may have lower specificity for TIA diagnoses. ^{Reference Goldstein34–Reference Benesch, Witter, Wilder, Duncan, Samsa and Matchar36} However, data by Yu et al., suggest that administrative codes for TIA have good specificity (92.5%) and positive predictive value (PPV) of 76.0%, ^{Reference Yu, Quan, McRae, Wagner, Hill and Coutts37} and that coding accuracy is associated with physician documentation. ^{Reference Yu, Quan, McRae, Wagner, Hill and Coutts38} ICD-10 codes for ischemic stroke and TIA are also well-validated in the Canadian administrative databases. ^{Reference Kokotailo and Hill28} Furthermore, we were able to use the same methodology over a 13-year period, in a publicly funded system, without changes to hospital or physician remuneration based on identifying TIA/stroke. This helps to increase confidence that the findings reported here are attributable to changes in care, rather than greater identification and labeling of low-risk patients. This is, especially, important when considering that 1-year mortality is now a fraction of what it was in 2003 (70 deaths, 1.3%), with only 16 deaths in 2015.

Our study has some limitations. We did not have access to patient-level data such as past medical history, vascular risk factors, medications, carotid surgery, or treatment adherence. In addition, due to large time span that we analyzed, we could not account for the effect of improved access to stroke imaging modalities such as MRI and the effect of the endorsement of the “tissue-based definition” of TIA in 2009. ^{Reference Easton, Saver and Albers39,Reference Albers, Caplan and Easton40} Imaging studies of TIA patients have found that around one-third of patients presenting with transient symptoms were found to have an abnormality in diffusion-weighted imaging (DWI). ^{Reference Easton, Saver and Albers39,Reference Kidwell, Alger and Di Salle41,Reference Brazzelli, Chappell and Miranda42} Ovibiagele et al. ^{Reference Ovbiagele, Kidwell and Saver43} estimated that adopting a tissue-based definition of TIA could result in a 33% reduction in the incidence of TIAs and a 7% increase in ischemic stroke annually. In our data, we did not observe significant changes in the number of TIA diagnoses per year. It is unknown how much this would influence our data given that MRI is more costly and time-consuming in the acute setting compared to CT imaging and is not widely available across the province. ^{Reference Kapral, Hall and Gozdyra44} The effect of the tissue-based definition on TIA diagnoses will therefore depend on both the timing of clinical evaluation and access to DWI. ^{Reference Degan, Ornello and Tiseo45} There was a significant amount of missing data on MRI utilization in our study, which hindered our ability to examine the potential impact of MRI on TIA diagnoses. In addition, our study was underpowered to examine trends over time for rates of stroke and mortality in patients coded with a “query” prefix, given that data was only available starting 2008. We were also unable to control for age and sex in our regression models examining trends over time; given that data was available only for 13 time points, there was insufficient power to account for the effect of additional variables.

The observed reduction in stroke and mortality could be attributed to numerous potential factors. One factor could be improved management of TIA facilitated by the Ontario Stroke Strategy. ^{Reference Kapral, Fang and Silver21} Improved early diagnostic strategies, such as assessment of the intracranial vasculature using CTA, ^{Reference Coutts, Modi and Patel13} and greater awareness of stroke symptoms resulting in faster hospital arrival has improved acute treatment. From 2008 to 2013, the proportion of TIA patients referred to secondary stroke prevention services after ED discharge increased from 62.3% to 79.6%, highlighting increased awareness of the importance of timely specialized follow-up. ^{Reference Hall, Khan and O’Callaghan46} Moreover, management guidelines for hypertension, ^{Reference Nerenberg, Zarnke and Leung47} atrial fibrillation ^{Reference Andrade, Verma and Mitchell48} diabetes ⁴⁹ and dyslipidemia ^{Reference Anderson, Grégoire and Pearson50} as well as changes to secondary prevention treatment guidelines resulting from pivotal clinical trials (CHANCE, ^{Reference Wang, Wang and Zhao51} SPARCL, ^{Reference Amarenco, Bogousslavsky and Callahan52} ESPRIT ^{Reference Rouhl and Lodder53} ) may have led to improvements in treatment strategies. Moreover, awareness initiatives such as the Cardiovascular Health Awareness Program (CHAP) ^{Reference Kaczorowski, Chambers and Dolovich54} and early management of TIA by primary and emergency care physicians ^{Reference Edwards, Fletcher and Deller15} may also be contributing to this trend.

These reductions could also be a result of the changing demographic of patients in 2015 compared to 2003. Stroke is becoming increasingly common among young adults, ^{Reference Béjot, Delpont and Giroud55} likely due to increasing prevalence of classic vascular risk factors and emerging risk factors, and lifestyle changes, among younger adults. Younger patients may be at a lower risk of stroke compared to older, ^{Reference Putaala, Haapaniemi and Metso56} and represent a greater proportion of our sample in 2015 compared to 2003; however, the proportion of young adults (<50 years) increased only from 6.5% to 7.4%, and thus is unlikely, in isolation, to account for a 50% drop in stroke incidence. Our results could also partly be explained by changing the incidence of stroke etiologies, such as the decreasing rate of large artery atherosclerosis, given improvements in controlling hypertension and hyperlipidemia, ^{Reference Bogiatzi, Hackam, McLeod and Spence57} and management of atrial fibrillation. ^{Reference Amarenco, Lavallée and Labreuche8,Reference Gladstone, Spring and Dorian58–Reference Mensah, Wei and Sorlie64} Many of these factors may have synergistically contributed to the reduction in stroke incidence and mortality observed in this study.

The economic benefit of this reduction in stroke could be substantial. Previous studies have estimated that comprehensive and optimal stroke care in Canada could be associated with a cost avoidance of up to $682 million annually. ^{Reference Krueger, Lindsay, Cote, Kapral, Kaczorowski and Hill65} In 2004, the average 1-year direct costs of managing TIA and ischemic stroke in Canada were $17,769 and $53,576, respectively. ^{Reference Goeree, Blackhouse, Petrovic and Salama66} The number of strokes within 1 year has reduced from 312 in 2003 to 166 in 2015 and this is estimated to have saved at least $7.8 million (based on the 1-year cost of stroke determined in 2004). Actual savings would be greater, given increases in cost; investment in organized stroke care strategies could reduce both the personal and economic burden of stroke and TIA in the long term.

Despite organized stroke care, many patients are not treated in specialized TIA clinics and the extent of improved care for those treated in the hospital or in general practitioner care requires further evaluation. Additionally, geographic differences and regional differences remain, even in publicly-funded systems. ^{Reference Kapral, Austin and Jeyakumar67} Further work examining inequities in care, and ways to improve the implementation of best practices in community and primary care settings, are needed. Ongoing advances in secondary prevention after TIA ^{Reference Wang, Wang and Zhao51,Reference Johnston, Easton and Farrant68} may contribute to further reductions in stroke. However, future clinical trials must be sufficiently powered to account for the reduced event rates seen with modern, aggressive secondary prevention strategies. Efforts to further improve the short- and long-term risk of stroke following a TIA, and advances in the implementation of best practices across populations are needed to reduce the global burden of stroke.