OBJECTIVES: The Triple Therapy Prevention of Recurrent Intracerebral Disease Events Trial (TRIDENT) aims to determine the effects of a novel SPC "Triple Pill," three generic antihypertensive drugs with demonstrated efficacy and complementary mechanisms of action at half standard dose (telmisartan 20 mg, amlodipine 2.5 mg, and indapamide 1.25 mg), with placebo for the prevention of recurrent stroke, cardiovascular events, and cognitive impairment after ICH.
DESIGN: An international, double-blind, placebo-controlled, randomized trial in adults with ICH and mild-moderate hypertension (systolic BP: 130-160 mmHg), who are not taking any Triple Pill component drug at greater than half-dose. A total of 1500 randomized patients provide 90% power to detect a hazard ratio of 0.5, over an average follow-up of 3 years, according to a total primary event rate (any stroke) of 12% in the control arm and other assumptions. Secondary outcomes include recurrent ICH, cardiovascular events, and safety.
RESULTS: Recruitment started 28 September 2017. Up to 31 October 2021, 821 patients were randomized at 54 active sites in 10 countries. Triple Pill adherence after 30 months is 86%. The required sample size should be achieved by 2024.
CONCLUSION: Low-dose Triple Pill BP lowering could improve long-term outcome from ICH.
AIMS: We sought to investigate recent trends in stroke outcomes at hospital discharge among first-ever stroke patients.
METHODS: This was an analysis of data from the Malaysia National Stroke Registry. Patients aged 18 years or older documented as having a first episode of stroke in the registry were recruited. Subsequently, the comparison of proportions for overall and sex-specific stroke outcomes between years (from 2009 to 2017) was conducted. The primary outcome was modified Rankin Scale score, which was assessed at hospital discharge, and each patient was categorized as follows: 1) functional independence, 2) functional dependence, or 3) death for analysis.
RESULTS: This study included 9361 first-ever stroke patients. Approximately 36.2% (3369) were discharged in an independence state, 53.1% (4945) experienced functional dependence, and 10.8% (1006) patients died at the time of hospital discharge. The percentage of patients who were discharged independently increased from 23.3% in 2009 to 46.5% in 2017, while that of patients discharged in a disabled state fell from 56.0% in 2009 to 45.6% in 2017. The percentage of death at discharge was reduced from 20.7% in 2009 to 7.8% in 2017. These findings suggest that the proportions of stroke outcomes at hospital discharge have changed significantly over time (p stroke outcomes at hospital discharge following first stroke episode (p stroke outcomes over the past nine years in Malaysia. This information ought to be considered in ongoing efforts of tertiary stroke prevention.
OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH).
DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial.
SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK).
PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset.
EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy 4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK.
CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events.
FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed.
TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214.
FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland.
METHODS: We did an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage from acute stroke units at 124 hospital sites in 12 countries. Participants were randomly assigned (1:1) to receive 1 g intravenous tranexamic acid bolus followed by an 8 h infusion of 1 g tranexamic acid or a matching placebo, within 8 h of symptom onset. Randomisation was done centrally in real time via a secure website, with stratification by country and minimisation on key prognostic factors. Treatment allocation was concealed from patients, outcome assessors, and all other health-care workers involved in the trial. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale, using ordinal logistic regression with adjustment for stratification and minimisation criteria. All analyses were done on an intention-to-treat basis. This trial is registered with the ISRCTN registry, number ISRCTN93732214.
FINDINGS: We recruited 2325 participants between March 1, 2013, and Sept 30, 2017. 1161 patients received tranexamic acid and 1164 received placebo; the treatment groups were well balanced at baseline. The primary outcome was assessed for 2307 (99%) participants. The primary outcome, functional status at day 90, did not differ significantly between the groups (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the tranexamic acid group (101 [9%] deaths in the tranexamic acid group vs 123 [11%] deaths in the placebo group; aOR 0·73, 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (250 [22%] vs 249 [21%]; adjusted hazard ratio 0·92, 95% CI 0·77-1·10, p=0·37). Fewer patients had serious adverse events after tranexamic acid than after placebo by days 2 (379 [33%] patients vs 417 [36%] patients), 7 (456 [39%] vs 497 [43%]), and 90 (521 [45%] vs 556 [48%]).
INTERPRETATION: Functional status 90 days after intracerebral haemorrhage did not differ significantly between patients who received tranexamic acid and those who received placebo, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect.
FUNDING: National Institute of Health Research Health Technology Assessment Programme and Swiss Heart Foundation.
Methods: We recruited independent patients with clinically confirmed lacunar ischaemic stroke without cognitive impairment to a prospective randomised clinical trial, LACunar Intervention-1 (LACI-1). We randomised patients using a central web-based system, 1:1:1:1 with minimisation, to masked ISMN 25 mg bd, cilostazol 100 mg bd, both ISMN and cilostazol started immediately, or both with start delayed. We escalated doses to target over two weeks, sustained for eight weeks. Primary outcome was the proportion achieving target dose. Secondary outcomes included symptoms, safety (haemorrhage, recurrent vascular events), cognition, haematology, vascular function, and neuroimaging. LACI-1 was powered (80%, alpha 0.05) to detect 35% (90% versus 55%) difference between the proportion reaching target dose on one versus both drugs at 55 patients. Registration ISRCTN12580546.
Findings: LACI-1 enrolled 57 participants between March 2016 and August 2017: 18 (32%) females, mean age 66 (SD 11, range 40-85) years, onset-randomisation 203 (range 6-920) days. Most achieved full (64%) or over half (87%) dose, with no difference between cilostazol vs ISMN, single vs dual drugs. Headache and palpitations increased initially then declined similarly with dual versus single drugs. There was no between-group difference in BP, pulse-wave velocity, haemoglobin or platelet function, but pulse rate was higher (mean difference, MD, 6.4, 95%CI 1.2-11.7, p = 0.02), platelet count higher (MD 35.7, 95%CI 2.8, 68.7, p = 0.03) and white matter hyperintensities reduced more (Chi-square p = 0.007) with cilostazol versus no cilostazol.
Interpretation: Cilostazol and ISMN are well tolerated when the dose is escalated, without safety concerns, in patients with lacunar stroke. Larger trials with longer term follow-up are justified.
Funding: Alzheimer's Society (AS-PG-14-033).
BACKGROUND: Drug eluting stent (DES) implantation is the treatment of choice for coronary artery disease (CAD) leaving only marginal indications for the use of bare metal stents (BMS). However, selected treatment populations with DES contraindications such as patients who cannot sustain 6-12 months of dual antiplatelet therapy (DAPT) remain candidates for BMS implantations.
METHODS: Thin strut bare metal stenting in a priori defined subgroups were investigated in a non-randomized, international, multicenter «all comers» observational study. Primary endpoint was the 9-month TLR rate whereas secondary endpoints included the 9-month MACE and procedural success rates.
RESULTS: A total of 783 patients of whom 98 patients had AF underwent BMS implantation. Patient age was 70.4 ± 12.8 years. Cardiovascular risk factors in the overall population were male gender (78.2%, 612/783), diabetes (25.2%, 197/783), hypertension (64.1%, 502/783), cardiogenic shock (4.9%, 38/783) and end stage renal disease (4.9%, 38/783). In-hospital MACE was 4.1% (30/783) in the overall population. The 9-month TLR rate was 4.5% (29/645) in the non-AF group and 3.3% (3/90) in the AF group (P = 0.613). At 9 months, the MACE rate in the AF-group and non-AF group was not significantly different either (10.7%, 69/645 vs. 6.7%, 6/90; P = 0.237). Accumulated stroke rates were 0.3% (2/645) in the non-AF subgroup at baseline and 1.1% (1/90) in the AF subgroup (P = 0.264).
CONCLUSION: Bare metal stenting in AF patients delivered acceptably low TLR and MACE rates while having the benefit of a significantly shorter DAPT duration in a DES dominated clinical practice. © 2015 Wiley Periodicals, Inc.
OBJECTIVE: This study aimed to translate and validate the CAFU instrument into the Malay language and test the validity and reliability of the CAFU among informal stroke caregivers in Malaysia.
METHODS: A standard forward-backward translation method was employed to translate CAFU. Subsequently, 10 expert panels were included in the validation process, and thereafter reliability testing was conducted among 51 stroke caregivers. The validation of the instrument was determined by computing the content validity indices (CVIs), and we used the Cronbach's alpha method to explore the internal consistency of the overall score and subscales scores of the Malay-CAFU. Finally, the explanatory factor analysis used principal component extraction and a varimax rotation to examine construct validity.
RESULTS: All items of the Malay-CAFU had satisfactory item-level CVI (I-CVI), with values greater than 0.80, and the scale-level CVI (S-CVI) was 0.95. These results indicate that the Malay-CAFU had good relevancy. The internal consistency for the reliability test showed a Cronbach's alpha value of 0.95 for the overall score. The eigenvalues and scree plot supported a two-factor structural model of the instrument. From the explanatory factor analysis, the factor loadings ranged from 0.82 to 0.90 and 0.56 to 0.83, respectively.
CONCLUSION: The Malay-CAFU questionnaire is a valid and reliable instrument to assess the dependence level of stroke survivors and the upset level of informal stroke caregivers in Malaysia.
OBJECTIVES: To ascertain whether therapy-based rehabilitation services can influence outcome one year or more after stroke.
SEARCH STRATEGY: We searched the trials registers of the following Cochrane Review Groups: Stroke Group (last searched September 2007), Effective Practice and Organisation of Care Group (last searched October 2006) and Dementia and Cognitive Improvement Group (last searched October 2006). We also searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library Issue 4, 2006), MEDLINE (1966 to October 2006), EMBASE (1980 to October 2006), CINAHL (1982 to October 2006), AMED (1985 to October 2006), PEDro (1952 to October 2006), British Nursing Index (1993 to October 2006), DARE (1994 to October 2006), HMIC (1979 to October 2006) and NHS EED (1991 to October 2006). We also searched dissertation databases and ongoing trials and research registers, scanned reference lists and contacted researchers and experts in the field.
SELECTION CRITERIA: All randomised controlled trials of community-based stroke patients, in which at least 75% were recruited one year after stroke and received a therapy-based rehabilitation intervention that was compared with conventional care.
DATA COLLECTION AND ANALYSIS: Two review authors independently selected trials and extracted data on a number of pre-specified outcomes. The primary outcomes were the proportion of participants who had deteriorated or were dependent in personal activities of daily living at the end of scheduled follow up.
MAIN RESULTS: We identified five trials of 487 participants that were eligible for the review. Overall, there was inconclusive evidence as to whether therapy-based rehabilitation intervention one year after stroke was able to influence any relevant patient or carer outcome. Trials varied in design, type of interventions provided, quality, and outcomes assessed.
AUTHORS' CONCLUSIONS: This review highlights the dearth of evidence investigating long-term therapy-based rehabilitation interventions for patients with stroke.