Risk of Another Event Remains High for Years After TIA, Minor Stroke

The risk of a subsequent stroke remains high for at least the next decade for patients who have had a TIA or minor stroke, according to a comprehensive review of cohort studies from the PERSIST group.

The incidence of additional strokes was 12.5% by 5 years and 19.8% by 10 years, Faizan Khan, PhD (University of Calgary, Canada), and colleagues report in a study published Wednesday in JAMA. Half of future strokes occurred more than a year after the initial event, and roughly one out of every 10 were fatal.

While it’s not surprising that these patients have a greater risk of subsequent stroke several years after a TIA or minor stroke, “what was surprising to us is actually the magnitude of that risk beyond 90 days,” said Khan, lead author of the writing committee for the PERSIST collaborators. “Given that most secondary prevention clinics only follow their patients for the first 90 days, we hope that our findings will . . . raise attention to this persistently high risk. And second, we hope our findings will provide a benchmark upon which to improve current practice on long-term stroke prevention.”

Over the past 25 years or so, research and clinical practice has focused mostly on secondary stroke prevention in the 3 months after a TIA or minor stroke, a period during which an elevated risk is well described, Khan told TCTMD. Beyond that time point, evidence is mixed regarding how much the risk of a subsequent stroke is elevated, and for how long.

“There is that one clinical uncertainty that we don’t really know what the long-term prognosis of these patients looks like, both in terms of the main outcome of having a more severe stroke after a TIA or minor stroke, but also some other outcomes, including all-cause mortality, other vascular events like MI . . . as well as disability,” Khan said.

To get a better idea of the risks these patients face in the years after a TIA or minor stroke—with implications touching on patient counseling, risk stratification, long-term treatment and surveillance, and the design of future prevention trials—the PERSIST group performed a systematic review and meta-analysis of prospective and retrospective cohort studies.

Given that most secondary prevention clinics only follow their patients for the first 90 days, we hope that our findings will . . . raise attention to this persistently high risk. Faizan Khan

The analysis included 171,068 patients (median age 69 years; median proportion of men 57%) from 38 studies of TIA and/or minor stroke (NIHSS score of up to 5). Most studies (22) came from Europe, with another seven from Asia, five from North America, one from Australia, and three from multiple continents. Twenty-seven studies included patients recruited in 2007 or later, a cut point chosen because there were multiple landmark studies on the urgent management of TIA published that year.

The pooled rate of any stroke per 100 person-years was 5.94 in the first year after TIA or minor stroke, falling to 1.80 in years 2 to 5 and 1.72 in years 6 to 10. Within the first year, most of the repeat strokes (61.7%) occurred in the first 90 days, reflecting the known high risk in that initial period.

Stroke risk remained elevated for up to 10 years, however, with cumulative incidences of ischemic, hemorrhagic, and fatal strokes of 17.8%, 2.8%, and 3.2%, respectively. The pooled case-fatality rate of subsequent stroke was 10.4%.

The cumulative 10-year incidence of disability among patients who didn’t have a subsequent stroke was 42.6%, with rates of all-cause mortality and MI among the overall cohorts of 35.1% and 5.9%, respectively. Of the deaths, 12.6% were attributed to stroke.

Risk of subsequent stroke varied based on certain study characteristics, with higher risks seen in studies conducted in North America and Asia (versus Europe), in those that included only patients with TIA or first-ever index events (versus unselected populations), and in those using active versus passive ascertainment of outcomes.

Of note, studies conducted in 2007 or later demonstrated higher risks of subsequent stroke, despite the use of more-aggressive preventive measures in that time period. That’s surprising, Khan said. “Over time, as more and more aggressive secondary prevention strategies are implemented in practice, one would hypothesize that maybe we’re doing better and stroke risk is declining over time.”

That finding “is possibly due to better awareness and better diagnostic strategies that are available now, imaging modalities that are available now, that are picking up stroke outcomes,” Khan said. “But at the same time, I think that finding should prompt further evaluation of what is happening in the modern era with respect to stroke prevention.”

Indeed, it could be that earlier cohorts may have had true events diluted by stroke mimics like migraine, senior author Michael Hill, MD (University of Calgary), told TCTMD. “And I think the other thing to consider is that there are some other counterbalancing phenomena,” he added, pointing to rises in obesity and diabetes in recent years. “It could really be that people are at higher risk now than they were 20 years ago. We just don’t know.”

Whatever the explanation, it’s clear that attention to reducing stroke risk needs to be carried out beyond just the first 90 days after a TIA or minor stroke, a responsibility that can’t fall on the medical community alone, Hill indicated, citing the important role of patients themselves.

When a TIA or minor stroke occurs, it provides a sign that steps should be taken to avoid the devastating effects of a more serious subsequent stroke. “This is the time to pay attention and fix it, and fix it for good,” Hill said.