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      Risk and Secondary Prevention of Stroke Recurrence : A Population-Base Cohort Study

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          Abstract

          Supplemental Digital Content is available in the text.

          Abstract

          Background and Purpose:

          With recent advances in secondary prevention management, stroke recurrence rates may have changed substantially. We aim to estimate risks and trends of stroke recurrence over the past 2 decades in a population-based cohort of patients with stroke.

          Methods:

          Patients with a first-ever stroke between 1995 and 2018 in South London, United Kingdom (n=6052) were collected and analyzed. Rates of recurrent stroke with 95% CIs were stratified by 5-year period of index stroke and etiologic TOAST (Trial of ORG 10172 in Acute Stroke Treatment) subtype. Cumulative incidences were estimated and multivariate Cox models applied to examine associations of recurrence and recurrence-free survival.

          Results:

          The rate of stroke recurrence at 5 years reduced from 18% (95% CI, 15%–21%) in those who had their stroke in 1995 to 1999 to 12% (10%–15%) in 2000 to 2005, and no improvement since. Recurrence-free survival has improved (35%, 1995–1999; 67%, 2010–2015). Risk of recurrence or death is lowest for small-vessel occlusion strokes and other ischemic causes (36% and 27% at 5 years, respectively). For cardioembolic and hemorrhagic index strokes around half of first recurrences are of the same type (54% and 51%, respectively). Over the whole study period a 54% increased risk of recurrence was observed among those who had atrial fibrillation before the index stroke (hazard ratio, 1.54 [1.09–2.17]).

          Conclusions:

          The rate of recurrence reduced until mid-2000s but has not changed over the last decade. The majority of cardioembolic or hemorrhagic strokes that have a recurrence are stroke of the same type indicating that the implementation of effective preventive strategies is still suboptimal in these stroke subtypes.

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          Most cited references21

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          Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.

          (2002)
          To determine the effects of antiplatelet therapy among patients at high risk of occlusive vascular events. Collaborative meta-analyses (systematic overviews). Randomised trials of an antiplatelet regimen versus control or of one antiplatelet regimen versus another in high risk patients (with acute or previous vascular disease or some other predisposing condition) from which results were available before September 1997. Trials had to use a method of randomisation that precluded prior knowledge of the next treatment to be allocated and comparisons had to be unconfounded-that is, have study groups that differed only in terms of antiplatelet regimen. 287 studies involving 135 000 patients in comparisons of antiplatelet therapy versus control and 77 000 in comparisons of different antiplatelet regimens. "Serious vascular event": non-fatal myocardial infarction, non-fatal stroke, or vascular death. Overall, among these high risk patients, allocation to antiplatelet therapy reduced the combined outcome of any serious vascular event by about one quarter; non-fatal myocardial infarction was reduced by one third, non-fatal stroke by one quarter, and vascular mortality by one sixth (with no apparent adverse effect on other deaths). Absolute reductions in the risk of having a serious vascular event were 36 (SE 5) per 1000 treated for two years among patients with previous myocardial infarction; 38 (5) per 1000 patients treated for one month among patients with acute myocardial infarction; 36 (6) per 1000 treated for two years among those with previous stroke or transient ischaemic attack; 9 (3) per 1000 treated for three weeks among those with acute stroke; and 22 (3) per 1000 treated for two years among other high risk patients (with separately significant results for those with stable angina (P=0.0005), peripheral arterial disease (P=0.004), and atrial fibrillation (P=0.01)). In each of these high risk categories, the absolute benefits substantially outweighed the absolute risks of major extracranial bleeding. Aspirin was the most widely studied antiplatelet drug, with doses of 75-150 mg daily at least as effective as higher daily doses. The effects of doses lower than 75 mg daily were less certain. Clopidogrel reduced serious vascular events by 10% (4%) compared with aspirin, which was similar to the 12% (7%) reduction observed with its analogue ticlopidine. Addition of dipyridamole to aspirin produced no significant further reduction in vascular events compared with aspirin alone. Among patients at high risk of immediate coronary occlusion, short term addition of an intravenous glycoprotein IIb/IIIa antagonist to aspirin prevented a further 20 (4) vascular events per 1000 (P<0.0001) but caused 23 major (but rarely fatal) extracranial bleeds per 1000. Aspirin (or another oral antiplatelet drug) is protective in most types of patient at increased risk of occlusive vascular events, including those with an acute myocardial infarction or ischaemic stroke, unstable or stable angina, previous myocardial infarction, stroke or cerebral ischaemia, peripheral arterial disease, or atrial fibrillation. Low dose aspirin (75-150 mg daily) is an effective antiplatelet regimen for long term use, but in acute settings an initial loading dose of at least 150 mg aspirin may be required. Adding a second antiplatelet drug to aspirin may produce additional benefits in some clinical circumstances, but more research into this strategy is needed.
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            Classification and natural history of clinically identifiable subtypes of cerebral infarction.

            We describe the incidence and natural history of four clinically identifiable subgroups of cerebral infarction in a community-based study of 675 patients with first-ever stroke. Of 543 patients with a cerebral infarct, 92 (17%) had large anterior circulation infarcts with both cortical and subcortical involvement (total anterior circulation infarcts, TACI); 185 (34%) had more restricted and predominantly cortical infarcts (partial anterior circulation infarcts, PACI); 129 (24%) had infarcts clearly associated with the vertebrobasilar arterial territory (posterior circulation infarcts, POCI); and 137 (25%) had infarcts confined to the territory of the deep perforating arteries (lacunar infarcts, LACI). There were striking differences in natural history between the groups. The TACI group had a negligible chance of good functional outcome and mortality was high. More than twice as many deaths were due to the complications of immobility than to direct neurological sequelae of the infarct. Patients in the PACI group were much more likely to have an early recurrent stroke than were patients in other groups. Those in the POCI group were at greater risk of a recurrent stroke later in the first year after the index event but had the best chance of a good functional outcome. Despite the small anatomical size of the infarcts in the LACI group, many patients remained substantially handicapped. The findings have important implications for the planning of stroke treatment trials and suggest that various therapies could be directed specifically at the subgroups.
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              Risk and cumulative risk of stroke recurrence: a systematic review and meta-analysis.

              Estimates of risk of stroke recurrence are widely variable and focused on the short- term. A systematic review and meta-analysis was conducted to estimate the pooled cumulative risk of stroke recurrence. Studies reporting cumulative risk of recurrence after first-ever stroke were identified using electronic databases and by manually searching relevant journals and conference abstracts. Overall cumulative risks of stroke recurrence at 30 days and 1, 5, and 10 years after first stroke were calculated, and analyses for heterogeneity were conducted. A Weibull model was fitted to the risk of stroke recurrence of the individual studies and pooled estimates were calculated with 95% CI. Sixteen studies were identified, of which 13 studies reported cumulative risk of stroke recurrence in 9115 survivors. The pooled cumulative risk was 3.1% (95% CI, 1.7-4.4) at 30 days, 11.1% (95% CI, 9.0-13.3) at 1 year, 26.4% (95% CI, 20.1-32.8) at 5 years, and 39.2% (95% CI, 27.2-51.2) at 10 years after initial stroke. Substantial heterogeneity was found at all time points. This study also demonstrates a temporal reduction in 5-year risk of stroke recurrence from 32% to 16.2% across the studies. The cumulative risk of recurrence varies greatly up to 10 years. This may be explained by differences in case mix and changes in secondary prevention over time However, methodological differences are likely to play an important role and consensus on definitions would improve future comparability of estimates and characterization of groups of stroke survivors at increased risk of recurrence.
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                Author and article information

                Journal
                Stroke
                Stroke
                STR
                Stroke
                Lippincott Williams & Wilkins (Hagerstown, MD )
                0039-2499
                1524-4628
                10 July 2020
                August 2020
                : 51
                : 8
                : 2435-2444
                Affiliations
                [1 ]King’s College London, School of Population Health and Environmental Sciences, United Kingdom (C.F., W.M., C.D.A.W., A.B., A.D.).
                [2 ]National Institute for Health Research Applied Research Collaboration (ARC) South London (C.D.A.W., A.D.), Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London, United Kingdom.
                [3 ]Department of Ageing Health and Stroke (A.B.), Guy’s and St Thomas’ National Health Service Foundation Trust and King’s College London, United Kingdom.
                Author notes
                Correspondence to: Clare Flach, PhD, 4.07 Addison House, Guy’s Campus, King’s College London SE1 1UL, United Kingdom. Email clare.flach@ 123456kcl.ac.uk
                Article
                00021
                10.1161/STROKEAHA.120.028992
                7382537
                32646337
                d895361d-59b4-4dad-b011-58e68c65d3ea
                © 2020 The Authors and King’s College London.

                Stroke is published on behalf of the American Heart Association, Inc., by Wolters Kluwer Health, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution, and reproduction in any medium, provided that the original work is properly cited.

                History
                : 7 January 2020
                : 10 June 2020
                : 15 June 2020
                Categories
                10058
                10062
                10071
                10072
                Original Contributions
                Clinical and Population Sciences
                Custom metadata
                T
                TRUE

                atrial fibrillation,prevalence,risk factors,secondary prevention

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