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JAMA Neurology Feb 2022Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack... (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
Dual antiplatelet therapy (DAPT) with clopidogrel and aspirin is effective in preventing recurrent strokes after minor ischemic stroke or transient ischemic attack (TIA). However, there is emerging evidence for the use of ticagrelor and aspirin, and the 2 DAPT regimens have not been compared directly.
OBJECTIVE
To compare ticagrelor and aspirin with clopidogrel and aspirin in patients with acute minor ischemic stroke or TIA in the prevention of recurrent strokes or death.
DATA SOURCES
MEDLINE, Embase, and Cochrane from database inception until February 2021.
STUDY SELECTION
Randomized clinical trials that enrolled adults with acute minor ischemic stroke or TIA and provided the mentioned interventions within 72 hours of symptom onset, with a minimum follow-up of 30 days.
DATA EXTRACTION AND SYNTHESIS
PRISMA guidelines for network meta-analyses were followed. Two reviewers independently extracted data and appraised risk of bias. Fixed-effects models were fit using a bayesian approach to network meta-analysis. Between-group comparisons were estimated using hazard ratios (HRs) with 95% credible intervals (95% CrIs). Surface under the cumulative rank curve plots were produced.
MAIN OUTCOMES AND MEASURES
The primary outcome was a composite of recurrent stroke or death up to 90 days. Secondary outcomes include major bleeding, mortality, adverse events, and functional disability. A sensitivity analysis was performed at 30 days for the primary outcome.
RESULTS
A total of 4014 citations were screened; 5 randomized clinical trials were included. Data from 22 098 patients were analyzed, including 5517 in the clopidogrel and aspirin arm, 5859 in the ticagrelor and aspirin arm, and 10 722 in the aspirin arm. Both clopidogrel and aspirin (HR, 0.74; 95% CrI, 0.65-0.84) and ticagrelor and aspirin (HR, 0.79; 95% CrI, 0.68-0.91) were superior to aspirin in the prevention of recurrent stroke and death. There was no statistically significant difference between clopidogrel and aspirin compared with ticagrelor and aspirin (HR, 0.94; 95% CrI, 0.78-1.13). Both DAPT regimens had higher rates of major hemorrhage than aspirin alone. Clopidogrel and aspirin was associated with a decreased risk of functional disability compared with aspirin alone (HR, 0.82; 95% CrI, 0.74-0.91) and ticagrelor and aspirin (HR, 0.85; 95% CrI, 0.75-0.97).
CONCLUSIONS AND RELEVANCE
DAPT combining aspirin with either ticagrelor or clopidogrel was superior to aspirin alone, but there was no statistically significant difference found between the 2 regimens for the primary outcome.
Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Dual Anti-Platelet Therapy; Humans; Ischemic Attack, Transient; Ischemic Stroke; Network Meta-Analysis; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Ticagrelor
PubMed: 34870698
DOI: 10.1001/jamaneurol.2021.4514 -
Circulation Oct 2020The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term... (Meta-Analysis)
Meta-Analysis
BACKGROUND
The optimal duration of dual antiplatelet therapy (DAPT) after percutaneous coronary intervention with drug-eluting stents remains uncertain. We compared short-term (<6-month) DAPT followed by aspirin or P2Y12 inhibitor monotherapy; midterm (6-month) DAPT; 12-month DAPT; and extended-term (>12-month) DAPT after percutaneous coronary intervention with drug-eluting stents.
METHODS
Twenty-four randomized, controlled trials were selected using Medline, Embase, Cochrane library, and online databases through September 2019. The coprimary end points were myocardial infarction and major bleeding, which constituted the net clinical benefit. A frequentist network meta-analysis was conducted with a random-effects model.
RESULTS
In 79 073 patients, at a median follow-up of 18 months, extended-term DAPT was associated with a reduced risk of myocardial infarction in comparison with 12-month DAPT (absolute risk difference, -3.8 incident cases per 1000 person-years; relative risk, 0.68 [95% CI, 0.54-0.87]), midterm DAPT (absolute risk difference, -4.6 incident cases per 1000 person-years; relative risk, 0.61 [0.45-0.83]), and short-term DAPT followed by aspirin monotherapy (absolute risk difference, -6.1 incident cases per 1000 person-years; relative risk, 0.55 [0.37-0.83]), or P2Y12 inhibitor monotherapy (absolute risk difference, -3.7 incident cases per 1000 person-years; relative risk, 0.69 [0.51-0.95]). Conversely, extended-term DAPT was associated with a higher risk of major bleeding than all other DAPT groups. In comparison with 12-month DAPT, no significant differences in the risks of ischemic end points or major bleeding were observed with midterm or short-term DAPT followed by aspirin monotherapy, with the exception that short-term DAPT followed by P2Y12 inhibitor monotherapy was associated with a reduced risk of major bleeding. There were no significant differences with respect to mortality between the different DAPT strategies. In acute coronary syndrome, extended-term in comparison with 12-month DAPT was associated with a reduced risk of myocardial infarction without a significant increase in the risk of major bleeding.
CONCLUSIONS
The present network meta-analysis suggests that, in comparison with 12-month DAPT, short-term DAPT followed by P2Y12 inhibitor monotherapy reduces major bleeding after percutaneous coronary intervention with drug-eluting stents, whereas extended-term DAPT reduces myocardial infarction at the expense of more bleeding events.
Topics: Acute Coronary Syndrome; Aspirin; Drug-Eluting Stents; Humans; Incidence; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Randomized Controlled Trials as Topic
PubMed: 32795096
DOI: 10.1161/CIRCULATIONAHA.120.046308 -
Stroke Jul 2021Dual antiplatelet therapy (DAPT) after ischemic stroke or transient ischemic attack may reduce recurrent stroke but also increase severe bleeding compared with single... (Meta-Analysis)
Meta-Analysis
Benefits and Risks of Dual Versus Single Antiplatelet Therapy for Secondary Stroke Prevention: A Systematic Review for the 2021 Guideline for the Prevention of Stroke in Patients With Stroke and Transient Ischemic Attack.
BACKGROUND
Dual antiplatelet therapy (DAPT) after ischemic stroke or transient ischemic attack may reduce recurrent stroke but also increase severe bleeding compared with single antiplatelet therapy (SAPT). The American Heart Association/American Stroke Association convened an evidence review committee to perform a systematic review and meta-analysis of the benefits and risks of DAPT compared with SAPT for secondary ischemic stroke prevention.
METHODS
The Medline, Embase, and Cochrane databases were searched on December 5, 2019, to identify phase III or IV randomized controlled trials (n≥100) from December 1999 to December 2019. We calculated unadjusted relative risks (RRs) and performed meta-analyses of studies based on the duration of treatment (short [≤90 days] versus long [>90 days]).
RESULTS
Three short-duration randomized controlled trials were identified that enrolled mostly patients with minor stroke or high risk transient ischemic attack. In these trials, DAPT, compared with SAPT, was associated with a lower 90-day risk of recurrent ischemic stroke (pooled RR, 0.68 [95% CI, 0.55-0.83], =37.1%). There was no significant increase in major bleeding with DAPT in short-duration trials (pooled RR, 1.88 [95% CI, 0.93-3.83], =8.9%). In 2 long-duration treatment randomized controlled trials (mean treatment duration, 18-40 months), DAPT was not associated with a significant reduction in recurrent ischemic stroke (pooled RR, 0.89 [95% CI, 0.79-1.02], =1.4%), but was associated with a higher risk of major bleeding (pooled RR, 2.42 [95% CI, 1.37-4.30], =75.5%).
CONCLUSIONS
DAPT was more effective than SAPT for prevention of secondary ischemic stroke when initiated early after the onset of minor stroke/high-risk transient ischemic attack and treatment duration was <90 days. However, when the treatment duration was longer and initiated later after stroke or transient ischemic attack onset, DAPT was not more effective than SAPT for ischemic stroke prevention and it increased the risk of bleeding.
Topics: Dual Anti-Platelet Therapy; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Randomized Controlled Trials as Topic; Risk Assessment; Secondary Prevention; Stroke
PubMed: 34024115
DOI: 10.1161/STR.0000000000000377 -
The Cochrane Database of Systematic... Oct 2019Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Pre-eclampsia is associated with deficient intravascular production of prostacyclin, a vasodilator, and excessive production of thromboxane, a vasoconstrictor and stimulant of platelet aggregation. These observations led to the hypotheses that antiplatelet agents, low-dose aspirin in particular, might prevent or delay development of pre-eclampsia.
OBJECTIVES
To assess the effectiveness and safety of antiplatelet agents, such as aspirin and dipyridamole, when given to women at risk of developing pre-eclampsia.
SEARCH METHODS
For this update, we searched Cochrane Pregnancy and Childbirth's Trials Register, ClinicalTrials.gov, the WHO International Clinical Trials Registry Platform (ICTRP) (30 March 2018), and reference lists of retrieved studies. We updated the search in September 2019 and added the results to the awaiting classification section of the review.
SELECTION CRITERIA
All randomised trials comparing antiplatelet agents with either placebo or no antiplatelet agent were included. Studies only published in abstract format were eligible for inclusion if sufficient information was available. We would have included cluster-randomised trials in the analyses along with individually-randomised trials, if any had been identified in our search strategy. Quasi-random studies were excluded. Participants were pregnant women at risk of developing pre-eclampsia. Interventions were administration of an antiplatelet agent (such as low-dose aspirin or dipyridamole), comparisons were either placebo or no antiplatelet.
DATA COLLECTION AND ANALYSIS
Two review authors assessed trials for inclusion and extracted data independently. For binary outcomes, we calculated risk ratio (RR) and its 95% confidence interval (CI), on an intention-to-treat basis. For this update we incorporated individual participant data (IPD) from trials with this available, alongside aggregate data (AD) from trials where it was not, in order to enable reliable subgroup analyses and inclusion of two key new outcomes. We assessed risk of bias for included studies and created a 'Summary of findings' table using GRADE.
MAIN RESULTS
Seventy-seven trials (40,249 women, and their babies) were included, although three trials (relating to 233 women) did not contribute data to the meta-analysis. Nine of the trials contributing data were large (> 1000 women recruited), accounting for 80% of women recruited. Although the trials took place in a wide range of countries, all of the nine large trials involved only women in high-income and/or upper middle-income countries. IPD were available for 36 trials (34,514 women), including all but one of the large trials. Low-dose aspirin alone was the intervention in all the large trials, and most trials overall. Dose in the large trials was 50 mg (1 trial, 1106 women), 60 mg (5 trials, 22,322 women), 75mg (1 trial, 3697 women) 100 mg (1 trial, 3294 women) and 150 mg (1 trial, 1776 women). Most studies were either low risk of bias or unclear risk of bias; and the large trials were all low risk of bas. Antiplatelet agents versus placebo/no treatment The use of antiplatelet agents reduced the risk of proteinuric pre-eclampsia by 18% (36,716 women, 60 trials, RR 0.82, 95% CI 0.77 to 0.88; high-quality evidence), number needed to treat for one women to benefit (NNTB) 61 (95% CI 45 to 92). There was a small (9%) reduction in the RR for preterm birth <37 weeks (35,212 women, 47 trials; RR 0.91, 95% CI 0.87 to 0.95, high-quality evidence), NNTB 61 (95% CI 42 to 114), and a 14% reduction infetal deaths, neonatal deaths or death before hospital discharge (35,391 babies, 52 trials; RR 0.85, 95% CI 0.76 to 0.95; high-quality evidence), NNTB 197 (95% CI 115 to 681). Antiplatelet agents slightly reduced the risk of small-for-gestational age babies (35,761 babies, 50 trials; RR 0.84, 95% CI 0.76 to 0.92; high-quality evidence), NNTB 146 (95% CI 90 to 386), and pregnancies with serious adverse outcome (a composite outcome including maternal death, baby death, pre-eclampsia, small-for-gestational age, and preterm birth) (RR 0.90, 95% CI 0.85 to 0.96; 17,382 women; 13 trials, high-quality evidence), NNTB 54 (95% CI 34 to 132). Antiplatelet agents probably slightly increase postpartum haemorrhage > 500 mL (23,769 women, 19 trials; RR 1.06, 95% CI 1.00 to 1.12; moderate-quality evidence due to clinical heterogeneity), and they probably marginally increase the risk of placental abruption, although for this outcome the evidence was downgraded due to a wide confidence interval including the possibility of no effect (30,775 women; 29 trials; RR 1.21, 95% CI 0.95 to 1.54; moderate-quality evidence). Data from two large trials which assessed children at aged 18 months (including results from over 5000 children), did not identify clear differences in development between the two groups.
AUTHORS' CONCLUSIONS
Administering low-dose aspirin to pregnant women led to small-to-moderate benefits, including reductions in pre-eclampsia (16 fewer per 1000 women treated), preterm birth (16 fewer per 1000 treated), the baby being born small-for-gestational age (seven fewer per 1000 treated) and fetal or neonatal death (five fewer per 1000 treated). Overall, administering antiplatelet agents to 1000 women led to 20 fewer pregnancies with serious adverse outcomes. The quality of evidence for all these outcomes was high. Aspirin probably slightly increased the risk of postpartum haemorrhage of more than 500 mL, however, the quality of evidence for this outcome was downgraded to moderate, due to concerns of clinical heterogeneity in measurements of blood loss. Antiplatelet agents probably marginally increase placental abruption, but the quality of the evidence was downgraded to moderate due to low event numbers and thus wide 95% CI. Overall, antiplatelet agents improved outcomes, and at these doses appear to be safe. Identifying women who are most likely to respond to low-dose aspirin would improve targeting of treatment. As almost all the women in this review were recruited to the trials after 12 weeks' gestation, it is unclear whether starting treatment before 12 weeks' would have additional benefits without any increase in adverse effects. While there was some indication that higher doses of aspirin would be more effective, further studies would be warranted to examine this.
Topics: Aspirin; Female; Gestational Age; Humans; Infant, Newborn; Infant, Small for Gestational Age; Maternal Mortality; Platelet Aggregation Inhibitors; Pre-Eclampsia; Pregnancy; Premature Birth; Prenatal Care; Randomized Controlled Trials as Topic
PubMed: 31684684
DOI: 10.1002/14651858.CD004659.pub3 -
Stroke and Vascular Neurology Oct 2022Antiplatelet therapy is one of the mainstays for secondary stroke prevention. This narrative review aimed to highlight the current evidence and recommendations of... (Meta-Analysis)
Meta-Analysis
Antiplatelet therapy is one of the mainstays for secondary stroke prevention. This narrative review aimed to highlight the current evidence and recommendations of antiplatelet therapy for stroke prevention.We conducted advanced literature search for antiplatelet therapy. Landmark studies and randomised controlled trials evaluating antiplatelet therapy for secondary stroke prevention are reviewed. Results from Cochrane systematic review, pooled data analysis and meta-analysis are discussed.Single-antiplatelet therapy (SAPT) with aspirin, aspirin/extended-release dipyridamole or clopidogrel reduces the risk of recurrent ischaemic stroke in patients with non-cardioembolic ischaemic stroke or transient ischaemic attack (TIA). Dual-antiplatelet therapy (DAPT) with aspirin and clopidogrel or ticagrelor for 21-30 days is more effective than SAPT in patients with minor acute noncardioembolic ischaemic stroke or high-risk TIA. Prolonged use of DAPT is associated with higher risk of haemorrhage without reduction in stroke recurrence than SAPT. Compared with placebo, aspirin reduces the relative risk of recurrent stroke by approximately 22%. Aspirin/dipyridamole and cilostazol are superior to aspirin but associated with significant side effects. Cilostazol or ticagrelor might be more effective than aspirin or clopidogrel in patients with intracranial stenosis.SAPT is indicated for secondary stroke prevention in patients with non-cardioembolic ischaemic stroke or TIA. DAPT with aspirin and clopidogrel or ticagrelor for 21-30 days followed by SAPT is recommended for patients with minor acute noncardioembolic stroke or high-risk TIA. Selection of appropriate antiplatelet therapy should also be based on compliance, drug tolerance or resistance.
Topics: Humans; Aspirin; Brain Ischemia; Cilostazol; Clopidogrel; Dipyridamole; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor
PubMed: 35393359
DOI: 10.1136/svn-2021-001166 -
Drugs Aug 2022High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or... (Meta-Analysis)
Meta-Analysis
BACKGROUND
High-quality evidence from trials directly comparing single antiplatelet therapies in symptomatic peripheral arterial disease (PAD) to dual antiplatelet therapies or acetylsalicylic acid (ASA) plus low-dose rivaroxaban is lacking. Therefore, we conducted a network meta-analysis on the effectiveness of all antithrombotic regimens studied in PAD.
METHODS
A systematic search was conducted to identify randomized controlled trials. The primary endpoints were major adverse cardiovascular events (MACE) and major bleedings. Secondary endpoints were major adverse limb events (MALE) and acute limb ischaemia (ALI). For each outcome, a frequentist network meta-analysis was used to compare relative risks (RRs) between medication and ASA. ASA was the universal comparator since a majority of studies used ASA as in the reference group.
RESULTS
Twenty-four randomized controlled trials were identified including 48,759 patients. With regard to reducing MACE, clopidogrel [RR 0.78, 95% confidence interval (CI) 0.66-0.93], ticagrelor (RR 0.79, 95% CI 0.65-0.97), ASA plus ticagrelor (RR 0.79, 95% CI 0.64-0.97), and ASA plus low-dose rivaroxaban (RR 0.84, 95% CI 0.76-0.93) were more effective than ASA, and equally effective to one another. As compared to ASA, major bleedings occurred more frequently with vitamin K antagonists, rivaroxaban, ASA plus vitamin K antagonists, and ASA plus low-dose rivaroxaban. All regimens were similar to ASA concerning MALE, while ASA plus low-dose rivaroxaban was more effective in preventing ALI (RR 0.67, 95% CI 0.55-0.80). Subgroup analysis in patients undergoing peripheral revascularization revealed that ≥ 3 months after intervention, evidence of benefit regarding clopidogrel, ticagrelor, and ASA plus ticagrelor was lacking, while ASA plus low-dose rivaroxaban was more effective in preventing MACE (RR 0.87, 95% CI 0.78-0.97) and MALE (RR 0.89, 95% CI 0.81-0.97) compared to ASA. ASA plus clopidogrel was not superior to ASA in preventing MACE ≥ 3 months after revascularization. Evidence regarding antithrombotic treatment strategies within 3 months after a peripheral intervention was lacking.
CONCLUSION
Clopidogrel, ticagrelor, ASA plus ticagrelor, and ASA plus low-dose rivaroxaban are superior to ASA monotherapy and equally effective to one another in preventing MACE in PAD. Of these four therapies, only ASA plus low-dose rivaroxaban provides a higher risk of major bleedings. More than 3 months after peripheral vascular intervention, ASA plus low-dose rivaroxaban is superior in preventing MACE and MALE compared to ASA but again at the cost of a higher risk of bleeding, while other treatment regimens show non-superiority. Based on the current evidence, clopidogrel may be considered the antithrombotic therapy of choice for most PAD patients, while in patients who underwent a peripheral vascular intervention, ASA plus low-dose rivaroxaban could be considered for the long-term (> 3 months) prevention of MACE and MALE.
Topics: Aspirin; Clopidogrel; Fibrinolytic Agents; Hemorrhage; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Rivaroxaban; Ticagrelor; Vitamin K
PubMed: 35997941
DOI: 10.1007/s40265-022-01756-6 -
Cardiovascular Therapeutics 2019Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the... (Meta-Analysis)
Meta-Analysis
AIM
Though combination of clopidogrel added to aspirin has been compared to aspirin alone in patients with stroke or transient ischemic attack, limited data exists on the relative efficacy and safety between clopidogrel and aspirin monotherapy in patients with a recent ischemic stroke. We aimed to compare clopidogrel versus aspirin monotherapy in this population.
METHODS
PubMed, Embase, and CENTRAL databases were searched from inception to May 2018 to identify clinical trials and observational studies comparing clopidogrel versus aspirin for secondary prevention in patients with recent ischemic stroke within 12 months. Pooled effect estimates were calculated using a random effects model and were reported as risk ratios with 95% confidence intervals.
RESULTS
Five studies meeting eligibility criteria were included in the analysis. A total of 29,357 adult patients who had recent ischemic stroke received either clopidogrel ( = 14, 293) or aspirin ( = 15, 064) for secondary prevention. Pairwise meta-analysis showed a statistically significant risk reduction in the occurrence of major adverse cardiovascular and cerebrovascular events (risk ratio 0.72 [95% CI, 0.53-0.97]), any ischemic or hemorrhagic stroke (0.76 [0.58, 0.99), and recurrent ischemic stroke (0.72 [0.55, 0.94]) in patients who received clopidogrel versus aspirin. The risk of bleeding was also lower for clopidogrel versus aspirin (0.57 [0.45, 0.74]). There was no difference in the rate of all-cause mortality between the two groups.
CONCLUSIONS
The analysis showed lower risks of major adverse cardiovascular or cerebrovascular events, recurrent stroke, and bleeding events for clopidogrel monotherapy compared to aspirin. These findings support clinical benefit for single antiplatelet therapy with clopidogrel over aspirin for secondary prevention in patients with recent ischemic stroke.
Topics: Aspirin; Brain Ischemia; Clopidogrel; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Recurrence; Risk Assessment; Risk Factors; Secondary Prevention; Stroke; Time Factors; Treatment Outcome
PubMed: 31867054
DOI: 10.1155/2019/1607181 -
Stroke Jun 2021Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there... (Comparative Study)
Comparative Study Meta-Analysis
BACKGROUND AND PURPOSE
Antiplatelet therapy is key for preventing thrombotic events after transient ischemic attack or ischemic stroke. Although the role of aspirin is well established, there is emerging evidence for the role of short-term dual antiplatelet therapy (DAPT) in preventing recurrent stroke.
METHODS
We conducted a systematic review and study-level meta-analyses of randomized controlled trials comparing outcomes of early initiation of short-term DAPT (aspirin+P2Y12 inhibitor for up to 3 months) versus aspirin alone in patients with acute stroke or transient ischemic attack. Primary efficacy outcome was risk of recurrent stroke and primary safety outcome was incidence of major bleeding. Secondary outcomes studied were risk of any ischemic stroke, hemorrhagic stroke, major adverse cardiovascular events, and all-cause death. Pooled risk ratios (RRs) and CIs were calculated using a random-effects model.
RESULTS
Four trials with a total of 21 459 patients were included. As compared to aspirin alone, DAPT had a lower risk of recurrent stroke (RR, 0.76 [95% CI, 0.68–0.83]; P<0.001; I2=0%) but a higher risk of major bleeding events (RR, 2.22 [95% CI, 1.14–4.34], P=0.02, I2=46.5%). Patients receiving DAPT had a lower risk of major adverse cardiovascular events (RR, 0.76 [95% CI, 0.69–0.84], P<0.001, I2=0%) and recurrent ischemic events (RR, 0.74 [95% CI, 0.67–0.82], P<0.001, I2=0%).
CONCLUSIONS
As compared to aspirin alone, short-term DAPT within 24 hours of high-risk transient ischemic attack or mild-moderate ischemic stroke reduces the risk of recurrent stroke at the expense of higher risk of major bleeding.
Topics: Aspirin; Dual Anti-Platelet Therapy; Hemorrhage; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Time-to-Treatment
PubMed: 33902301
DOI: 10.1161/STROKEAHA.120.033033 -
JAMA Aug 2022The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear. (Comparative Study)
Comparative Study Meta-Analysis
IMPORTANCE
The role of ticagrelor with or without aspirin after coronary artery bypass graft surgery remains unclear.
OBJECTIVE
To compare the risks of vein graft failure and bleeding associated with ticagrelor dual antiplatelet therapy (DAPT) or ticagrelor monotherapy vs aspirin among patients undergoing coronary artery bypass graft surgery.
DATA SOURCES
MEDLINE, Embase, and Cochrane Library databases from inception to June 1, 2022, without language restriction.
STUDY SELECTION
Randomized clinical trials (RCTs) comparing the effects of ticagrelor DAPT or ticagrelor monotherapy vs aspirin on saphenous vein graft failure.
DATA EXTRACTION AND SYNTHESIS
Individual patient data provided by each trial were synthesized into a combined data set for independent analysis. Multilevel logistic regression models were used.
MAIN OUTCOMES AND MEASURES
The primary analysis assessed the incidence of saphenous vein graft failure per graft (primary outcome) in RCTs comparing ticagrelor DAPT with aspirin. Secondary outcomes were saphenous vein graft failure per patient and Bleeding Academic Research Consortium (BARC) type 2, 3, or 5 bleeding events. A supplementary analysis included RCTs comparing ticagrelor monotherapy with aspirin.
RESULTS
A total of 4 RCTs were included in the meta-analysis, involving 1316 patients and 1668 saphenous vein grafts. Of the 871 patients in the primary analysis, 435 received ticagrelor DAPT (median age, 67 years [IQR, 60-72 years]; 65 women [14.9%]; 370 men [85.1%]) and 436 received aspirin (median age, 66 years [IQR, 61-73 years]; 63 women [14.5%]; 373 men [85.5%]). Ticagrelor DAPT was associated with a significantly lower incidence of saphenous vein graft failure (11.2%) per graft than was aspirin (20%; difference, -8.7% [95% CI, -13.5% to -3.9%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001) and was associated with a significantly lower incidence of saphenous vein graft failure per patient (13.2% vs 23.0%, difference, -9.7% [95% CI, -14.9% to -4.4%]; OR, 0.51 [95% CI, 0.35 to 0.74]; P < .001). Ticagrelor DAPT (22.1%) was associated with a significantly higher incidence of BARC type 2, 3, or 5 bleeding events than was aspirin (8.7%; difference, 13.3% [95% CI, 8.6% to 18.0%]; OR, 2.98 [95% CI, 1.99 to 4.47]; P < .001), but not BARC type 3 or 5 bleeding events (1.8% vs 1.8%, difference, 0% [95% CI, -1.8% to 1.8%]; OR, 1.00 [95% CI, 0.37 to 2.69]; P = .99). Compared with aspirin, ticagrelor monotherapy was not significantly associated with saphenous vein graft failure (19.3% vs 21.7%, difference, -2.6% [95% CI, -9.1% to 3.9%]; OR, 0.86 [95% CI, 0.58 to 1.27]; P = .44) or BARC type 2, 3, or 5 bleeding events (8.9% vs 7.3%, difference, 1.7% [95% CI, -2.8% to 6.1%]; OR, 1.25 [95% CI, 0.69 to 2.29]; P = .46).
CONCLUSIONS AND RELEVANCE
Among patients undergoing coronary artery bypass graft surgery, adding ticagrelor to aspirin was associated with a significantly decreased risk of vein graft failure. However, this was accompanied by a significantly increased risk of clinically important bleeding.
Topics: Aged; Aspirin; Coronary Artery Bypass; Female; Graft Occlusion, Vascular; Hemorrhage; Humans; Male; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Saphenous Vein; Ticagrelor; Treatment Outcome
PubMed: 35943473
DOI: 10.1001/jama.2022.11966 -
European Stroke Journal Mar 2024A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor...
A quarter of ischaemic strokes are lacunar subtype, typically neurologically mild, usually resulting from intrinsic cerebral small vessel pathology, with risk factor profiles and outcome rates differing from other stroke subtypes. This European Stroke Organisation (ESO) guideline provides evidence-based recommendations to assist with clinical decisions about management of lacunar ischaemic stroke to prevent adverse clinical outcomes. The guideline was developed according to ESO standard operating procedures and Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) methodology. We addressed acute treatment (including progressive lacunar stroke) and secondary prevention in lacunar ischaemic stroke, and prioritised the interventions of thrombolysis, antiplatelet drugs, blood pressure lowering, lipid lowering, lifestyle, and other interventions and their potential effects on the clinical outcomes recurrent stroke, dependency, major adverse cardiovascular events, death, cognitive decline, mobility, gait, or mood disorders. We systematically reviewed the literature, assessed the evidence and where feasible formulated evidence-based recommendations, and expert concensus statements. We found little direct evidence, mostly of low quality. We recommend that patients with suspected acute lacunar ischaemic stroke receive intravenous alteplase, antiplatelet drugs and avoid blood pressure lowering according to current acute ischaemic stroke guidelines. For secondary prevention, we recommend single antiplatelet treatment long-term, blood pressure control, and lipid lowering according to current guidelines. We recommend smoking cessation, regular exercise, other healthy lifestyle modifications, and avoid obesity for general health benefits. We cannot make any recommendation concerning progressive stroke or other drugs. Large randomised controlled trials with clinically important endpoints, including cognitive endpoints, are a priority for lacunar ischaemic stroke.
Topics: Humans; Brain Ischemia; Cerebral Small Vessel Diseases; Lipids; Platelet Aggregation Inhibitors; Stroke; Stroke, Lacunar
PubMed: 38380638
DOI: 10.1177/23969873231219416