People who suffer a stroke caused by bleeding in the brain can take antiplatelet drug without raising their risk of another stroke

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People who suffer a stroke caused by bleeding in the brain – known as brain haemorrhage – can take common medicines without raising their risk of another stroke, a major clinical trial has found.

Researchers say the findings are reassuring for the thousands of people who take the medicines to reduce their risk of heart attack and another common type of stroke caused by blood clots in the brain.

These everyday treatments – known as antiplatelet medicines – work by slowing or stopping blood from clotting.

They are often prescribed to older people because they can lower risk of heart attack and stroke caused by a blood clot.

Doctors had thought the medicines – which include aspirin and clopidogrel – might make people with stroke due to brain haemorrhage more likely to suffer another bleed in the brain.

Researchers led by the University of Edinburgh tracked outcomes from 537 people from across the UK who had suffered a brain haemorrhage while they were taking medicines to stop blood clotting.

Patients were randomly assigned to either start taking antiplatelet treatment or avoid it for up to five years.

The team found that people who took antiplatelet medicines experienced fewer recurrences of brain haemorrhage compared with those who did not take these treatments.

Some 12 people suffered a brain bleed while taking the medication compared with 23 people who did not.

This may suggest the treatments reduce rather than increase risk of further bleeding in the brain, the researchers say, but further studies are needed to confirm this.

Around half of the participants underwent an additional brain scan using MRI at the beginning of the study.

These scans are often used by doctors to check for the presence of tiny blood deposits in the brain, known as microbleeds, which can be a warning sign of future strokes.

The researchers found treatment with antiplatelet medication was not more hazardous for people who already had microbleeds in their brain.

Experts say this provides further reassurance that brain haemorrhage survivors can safely continue to take antiplatelet medicines to reduce their risk of future heart attacks or strokes.

It also suggests that patients do not need to undergo an MRI scan before starting treatment.

This is important because older people are often unable to have an MRI.

The study – called RESTART – is published in The Lancet and The Lancet Neurology.

It was funded by the British Heart Foundation.

Findings are being presented at the European Stroke Organisation Conference in Milan.

Professor Rustam Salman, of the University of Edinburgh’s Centre for Clinical Brain Sciences, said:

“The results of the RESTART trial are reassuring for survivors of brain haemorrhage who need to take antiplatelet medicines to prevent heart attacks and strokes.

I am keen to investigate the possibility that these medicines might halve the risk of brain haemorrhage happening again.”

Professor Metin Avkiran, Associate Medical Director at the British Heart Foundation (BHF), said:

“Around a third of people who suffer a brain haemorrhage, also known as haemorrhagic stroke, do so when they are taking an antiplatelet medicine such as aspirin to reduce the risk of a heart attack or an ischaemic stroke.

We now have a strong indication they can carry on taking these potentially life-saving medicines after the brain haemorrhage without increasing the risk of another one, which is crucial new information for both patients and doctors.

“Although some developments have been made, the options at our disposal for treating and preventing strokes are still far too limited.

Around 36,000 people die each year in the UK after having a stroke, most commonly an ischaemic stroke. Every advance from important research such as this takes us a step closer to better stroke prevention and management.”


Approximately 795 000 people in the United States have a stroke each year, ≈610 000 of whom have had first attacks, resulting in 6.8 million stroke survivors >19 years of age.1 

Stroke ranks as the fourth-leading cause of death in the United States.2 

Globally, over the past 4 decades, stroke incidence rates have fallen by 42% in high-income countries and increased by >100% in low- and middle-income countries.3 

Stroke incidence rates in low- and middle-income countries now exceed those in high-income countries.3

Stroke is a leading cause of functional impairment.

For patients who are ≥65 years of age, 6 months after stroke, 26% are dependent in their activities of daily living, and 46% have cognitive deficits.1

Stroke changes the lives not only of those who experience a stroke but also of their family and other caregivers.

A major stroke is viewed by more than half of those at risk as being worse than death.4 

Despite the advent of reperfusion therapies for selected patients with acute ischemic stroke, effective prevention remains the best approach for reducing the burden of stroke.57 

Primary prevention is particularly important because >76% of strokes are first events.1

Fortunately, there are enormous opportunities for preventing stroke.

An international case-control study of 6000 individuals found that 10 potentially modifiable risk factors explained 90% of the risk of stroke.8 

As detailed in the sections that follow, stroke-prone individuals can readily be identified and targeted for effective interventions.

This guideline summarizes the evidence on established and emerging stroke risk factors and represents an update of the last American Heart Association (AHA) statement on this topic, published in 2011.9 

Targets for stroke prevention have been reordered to align with the AHA’s public health campaign for ideal cardiovascular health known as Life’s Simple 7.10 

As with the earlier document, the guideline addresses prevention of both hemorrhagic and ischemic stroke.

The traditional definition of ischemic stroke as a clinical event is used in most instances out of necessity because of the design of most stroke prevention studies; however, where permitted by the evidence, the Writing Group has adopted the updated tissue-based definition of ischemic stroke as infarction of central nervous system tissue.11

Differences in stroke risk among men and women are well recognized, and certain risk factors are specific to women’s health (eg, oral contraceptives [OCs] and hormone replacement therapy).

To increase awareness of these important issues and to provide sufficient coverage of the topic, the AHA has issued a guideline on the prevention of stroke in women.11a 

Key recommendations are summarized in the current document but not reiterated in full. Readers are encouraged to review the new guideline.

The committee chair nominated Writing Group members on the basis of their previous work in relevant topic areas.

The AHA Stroke Council’s Scientific Statement Oversight Committee and the AHA’s Manuscript Oversight Committee approved all Writing Group members.

In consultation with 2 research librarians, we developed individual search strategies for each topic section and for each database to identify potentially relevant studies from the PubMed, Ovid MEDLINE, Ovid Cochrane Database of Systematic Reviews, and Ovid Central Register of Controlled Trials databases.

The Internet Stroke Center/Clinical Trials Registry (http://www.strokecenter.org/trials/) and National Guideline Clearinghouse (http://guideline.gov/) were also searched.

Articles included were limited to those that were randomized, controlled trials; systematic reviews; meta-analyses; and in some cases, cohort studies.

The database searches were also limited to articles with English-language citations, with human subjects, and published between January 1, 2009, and varying end dates, (between October 2, 2012, and December 6, 2012).

Medical subject headings (MeSH) and key words, including stroke; ischemic attack, transient; cerebral infarction; cerebral hemorrhage; ischemia; and cerebrovascular disorders, in addition to select MeSH and key words on each topic, were used in the search strategy.

The writers used systematic literature reviews covering the time period since the last review published in 2011 to October 2012.

They also reviewed contemporary published evidence-based guidelines, personal files, and published expert opinion to summarize existing evidence, to indicate gaps in current knowledge, and, when appropriate, to formulate recommendations using standard AHA criteria (Tables 1 and ​and2).2).

All members of the Writing Group had the opportunity to comment on the recommendations and approved the final version of this document.

The guideline underwent extensive peer review, including review by the Stroke Council Leadership and Scientific Statements Oversight Committees, before consideration and approval by the AHA Science Advisory and Coordinating Committee.

Because of the diverse nature of the topics covered, it was not possible to provide a systematic, uniform summary of the magnitude of the effect associated with each of the recommendations.

As with all therapeutic recommendations, patient preferences must be considered.

Risk factors, which directly increase disease probability and if absent or removed reduce disease probability, or risk markers, which are attributes or exposures associated with increased probability of disease but are not necessarily causal12 of a first stroke, were classified according to their potential for modification.7 

Although this distinction is somewhat subjective, risk factors considered both well documented and modifiable were those with clear, supportive epidemiological evidence and evidence of risk reduction when modified in the context of randomized clinical trials.

Less well-documented or potentially modifiable risk factors were those either with less clear epidemiological evidence or without evidence from randomized clinical trials demonstrating a reduction of stroke risk when modified.

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Table 1
Applying Classification of Recommendations and Level of Evidence
A recommendation with Level of Evidence B or C does not imply that the recommendation is weak. Many important clinical questions addressed in the guidelines do not lend themselves to clinical trials. Although randomized trials are unavailable, there may be a very clear clinical consensus that a particular test or therapy is useful or effective.
*Data available from clinical trials or registries about the usefulness/efficacy in different subpopulations, such as sex, age, history of diabetes, history of prior myocardial infarction, history of heart failure, and prior aspirin use.
For comparative effectiveness recommendations (Class I and IIa; Level of Evidence A and B only), studies that support the use of comparator verbs should involve direct comparisons of the treatments or strategies being evaluated.

Table 2

Definition of Classes and Levels of Evidence Used in AHA/ASA Recommendations

Class IConditions for which there is evidence for and/or general agreement that the procedure or treatment is useful and effective.
Class IIConditions for which there is conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of a procedure or treatment.
 Class IIaThe weight of evidence or opinion is in favor of the procedure or treatment.
 Class IIbUsefulness/efficacy is less well established by evidence or opinion.
Class IIIConditions for which there is evidence and/or general agreement that the procedure or treatment is not useful/effective and in some cases may be harmful.
Therapeutic recommendations
 Level of Evidence AData derived from multiple randomized clinical trials or meta-analyses
 Level of Evidence BData derived from a single randomized trial or nonrandomized studies
 Level of Evidence CConsensus opinion of experts, case studies, or standard of care
Diagnostic recommendations
 Level of Evidence AData derived from multiple prospective cohort studies using a reference standard applied by a masked evaluator
 Level of Evidence BData derived from a single grade A study or one or more case-control studies, or studies using a reference standard applied by an unmasked evaluator
 Level of Evidence CConsensus opinion of experts

More information: Colin Baigent et al, Effects of antiplatelet therapy after stroke due to intracerebral haemorrhage (RESTART): a randomised, open-label trial, The Lancet (2019). DOI: 10.1016/S0140-6736(19)30840-2

Journal information: The Lancet , Lancet Neurology
Provided by University of Edinburgh

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