ticagrelor and Intracranial-Hemorrhages

Currently, it is still controversial to treat stroke with ticagrelor alone. The purpose of our study was to systematically review and analyze the efficacy and safety of ticagrelor on cerebrovascular outcomes in patients with vascular risk factors.. The PubMed, Cochrane Library, and Embase databases were systematically searched using the keywords stroke, ticagrelor, clopidogrel, and aspirin to identify randomized controlled trials (RCTs). Primary outcomes included reported stroke, ischemic stroke, and complex events; the secondary outcome was hemorrhagic stroke. The safety outcomes included major bleeding events, major or minor bleeding, and intracranial bleeding. The pooled odds ratio (OR), hazard ratios (HRs), and 95% confidence interval (CI) were calculated. We used I2 statistics to assess statistical heterogeneity.. This meta-analysis included 15 RCTs involving 63,865 patients. Compared to the control group, ticagrelor reduced the risk of stroke (OR: 0.90; 95% CI: 0.81-0.99, p = 0.03; I2 = 3%), ischemic stroke (OR: 0.81; 95% CI: 0.74-0.90, p < 0.0001; I2 = 0%). Ticagrelor was not associated with an increased risk of all-cause mortality (OR: 0.94; 95% CI: 0.84-1.06, p = 0.31; I2 = 62%), major bleeding (OR: 1.06; 95% CI: 0.97-1.15, p = 0.20; I2 = 17%), hemorrhagic strokes (OR: 1.22, 95% CI: 0.76-1.96, p = 0.41; I2 = 0%), and intracranial hemorrhage (OR: 1.06; 95% CI: 0.78-1.43, p = 0.71; I2 = 12%). There was an increased risk of major or minor bleeding with ticagrelor compared to the control group (OR: 1.40; 95% CI: 1.19-1.66, p < 0.0001; I2 = 56%). Additional analyses demonstrated that ticagrelor reduced the risk of incident recurrent stroke (HR: 0.83; 95% CI: 0.75-0.93, p = 0.0009; I2 = 0%), recurrent ischemic stroke (HR: 0.79; 95% CI: 0.71-0.89, p < 0.0001; I2 = 0%) among patients with a history of acute ischemic stroke (AIS) or transient ischemic attack (TIA). There were no significant differences in safety outcomes.. Ticagrelor is slightly better than clopidogrel and aspirin in preventing stroke, especially ischemic stroke, with significant safety risks. For patients with a history of AIS/TIA, the use of ticagrelor was superior to the use of clopidogrel or aspirin in reducing the risk of subsequent stroke. We believe that ticagrelor is a potential alternative to aspirin or clopidogrel in some cases, especially for patients with CYP2C19 deficiency.

Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Stroke; Ticagrelor; Treatment Outcome

In recent randomized controlled studies, the prevention of stroke and cognitive function of ticagrelor has been controversial. We conducted a meta-analysis to compare ticagrelor with other antiplatelet treatment in patients with vascular high-risk factors disease, defined as acute coronary syndrome, stroke or transient ischemic attack, coronary artery disease or peripheral artery disease.. We searched the PubMed, Embase, and Cochrane libraries for published randomized controlled trials and additional available data from ClinicalTrials.gov. The primary outcome was related adverse stroke events and the secondary outcome was cognitive function related adverse events. The outcomes were statistically analyzed using Peto odds ratio.. 12 RCTs with 105,654 patients were included in meta-analysis.. all stroke (OR 0.84, 95%CI 0.78-0.90, P < 0.001); Secondary outcomes: ischemic stroke (OR 0.83, 95%CI 0.77-0.90, P < 0.001), transient ischemic attack (OR 0.78, 95%CI 0.62-0.97, P = 0.029), intracranial hemorrhage (OR 1.33, 95%CI 1.09-1.61, P = 0.005), Parkinson's disease (OR 0.30, 95%CI 0.12-0.72, P = 0.007), dementia (OR 0.31, 95%CI 0.13-0.77, P = 0.012), dizziness (OR: 1.39, 95%CI 1.03-1.87, P = 0.032), insomnia (OR 1.45, 95%CI 1.05-2.00, P = 0.026).. Ticagrelor may provide more favorable outcomes for all stroke, ischemic stroke, and transient ischemic attack prevention in patients with vascular high-risk factors. However, this benefit may come with the cost of intracranial hemorrhage, dizziness and insomnia. Ticagrelor may reduce the risk of dementia and Parkinson's disease, although available data are limited.

Topics: Cognitive Dysfunction; Dementia; Dizziness; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Parkinson Disease; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Sleep Initiation and Maintenance Disorders; Stroke; Ticagrelor

Antiplatelet therapy is the cornerstone for acute ischemic stroke or transient ischemic attack (TIA). The purpose of this study was to conduct a meta-analysis to assess the efficacy and safety of P2Y12 receptor inhibitor plus aspirin versus aspirin alone treated within 24 h after acute noncardioembolic ischemic stroke or TIA.. We search Pubmed, EMBASE, CENTRAL and clinicaltrials.gov from January 1966 to January 2021. We included randomized trials which compared P2Y12 receptor inhibitor plus aspirin versus aspirin alone. Relative risk (RR) with 95% confidence (CI) was used as a measure of P2Y12 receptor inhibitor plus aspirin versus aspirin. The primary efficacy endpoint was recurrent stroke and the primary safety endpoint was severe bleeding.. The search identified 5 randomized trials comparing P2Y12 receptor inhibitor plus aspirin and aspirin with 21,808 individuals enrolled. Pooled results from these trials showed that P2Y12 receptor inhibitor plus aspirin compared with aspirin was associated with a lower risk of recurrent stroke (RR 0.75, 95% CI 0.68 to 0.83). Ticagrelor plus aspirin compared with aspirin was associated with increased risk of severe bleeding (RR 3.98, 95% CI 1.74 to 9.10) and intracranial hemorrhage (RR 3.32, 95% CI 1.33 to 8.25), whereas clopidogrel plus aspirin vs. aspirin had similar hemorrhagic risk.. P2Y12 receptor inhibitor plus aspirin vs aspirin given within 24 h after acute noncardioembolic ischemic stroke or TIA reduces the risk of subsequent stroke. However, the risk of severe bleeding, including intracranial hemorrhage, was higher with ticagrelor plus aspirin vs aspirin.. CRD42020203730.

Topics: Aspirin; Cerebral Infarction; Drug Therapy, Combination; Hemorrhage; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Ischemic Stroke; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Stroke; Ticagrelor

Ticagrelor is a novel antiplatelet agent that is frequently used for secondary prevention in coronary artery disease and has emerging evidence in stroke after the recent results of SOCRATES and THALES trials. The use of intravenous thrombolysis with alteplase in acute ischemic stroke (AIS) patients on ticagrelor is a topic of debate as the safety profile of ticagrelor in this setting is not well established.. We identified consecutive AIS patients taking ticagrelor who received intravenous alteplase at a comprehensive stroke center from January 2016 to December 2019. We then performed a literature search to capture all known published cases of intravenous thrombolysis in stroke patients on ticagrelor.. Of the 3896 patients who were treated for AIS at our local comprehensive stroke center during this time period, two patients received intravenous alteplase while on ticagrelor. Both patients had posterior circulation acute strokes and were successfully treated with intravenous alteplase without a systemic or intracranial bleeding event. Only five other cases of intravenous thrombolysis in AIS patients on ticagrelor have been reported in the literature. Among these cases, four of the five cases had a hemorrhagic complication.. Despite prior reports of hemorrhagic complications with use of IV alteplase in setting of pre-treatment with ticagrelor, we report the safe use of intravenous thrombolysis in two cases presenting with acute ischemic stroke. Until safety is established in large studies, decision for thrombolysis should be made on case-by-case basis.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Female; Fibrinolytic Agents; Humans; Infusions, Intravenous; Intracranial Hemorrhages; Ischemic Stroke; Male; Middle Aged; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Thrombolytic Therapy; Ticagrelor; Tissue Plasminogen Activator; Treatment Outcome

Administration of a P2Y 12 -receptor antagonist in addition to aspirin is mandatory in patients with acute coronary syndromes (ACS) or undergoing percutaneous coronary intervention (PCI) to reduce the occurrence of thrombotic events; however, their impact on mortality and stroke is unclear. We aimed to evaluate the influence of moderate (clopidogrel) or potent (prasugrel/ticagrelor) P2Y 12 -receptor inhibition on major cardiovascular outcomes among patients with ACS or undergoing PCI. Systematic literature search was performed to find randomised, controlled clinical trials comparing the clinical impact of clopidogrel with placebo or prasugrel/ticagrelor versus clopidogrel. Outcome measures included cardiovascular death, myocardial infarction (MI), total stroke and intracranial haemorrhage (ICH). Random-effects model with Mantel-Heanszel weighting was used to pool outcomes into a meta-analysis. Four studies comparing clopidogrel with placebo and five trials comparing clopidogrel with new P2Y 12 -receptor inhibitors were identified including a total of 107,473 patients. Compared to placebo, clopidogrel reduced the risk of cardiovascular death (odds ratio [OR]: 0.93; 95% confidence interval [CI]: 0.87-0.99, p=0.02), MI (OR 0.80; 95%CI 0.74-0.88, p<0.00001) and stroke (OR 0.84; 95%CI 0.72-0.97, p=0.02), without influencing risk for ICH (OR 0.96; 95%CI 0.69-1.33, p=0.79). Treatment with prasugrel/ticagrelor provided additional benefit over clopidogrel regarding cardiovascular mortality (OR 0.86; 95%CI 0.78-0.94, p=0.002) and MI (OR: 0.83; 95%CI 0.74-0.93, p<0.001), but no advantage in stroke (OR: 1.06; 95%CI 0.88-1.26, p=0.55) and in ICH (OR: 1.16; 95%CI 0.75-1.81; p=0.49) was observed. Increased potency of P2Y 12 -receptor inhibition is associated with decreased risk in cardiovascular death and MI; however, this association is not true in case of stroke, where potent P2Y 12 -receptor antagonists have no incremental benefit over clopidogrel.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Clopidogrel; Coronary Thrombosis; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Percutaneous Coronary Intervention; Piperazines; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Receptors, Purinergic P2Y12; Risk Assessment; Risk Factors; Stroke; Thiophenes; Ticagrelor; Ticlopidine; Treatment Outcome

Background and Purpose- Predictors of stroke and transient ischemic attack (TIA) in patients with peripheral artery disease (PAD) are poorly understood. The primary aims of this analysis were to (1) determine the incidence of ischemic/hemorrhagic stroke and TIA in patients with symptomatic PAD, (2) identify predictors of stroke in patients with PAD, and (3) compare the rate of stroke in ticagrelor- and clopidogrel-treated patients. Methods- EUCLID (Examining Use of Ticagrelor in Peripheral Artery Disease) randomized 13 885 patients with symptomatic PAD to receive monotherapy with ticagrelor or clopidogrel for the prevention of major adverse cardiovascular events (cardiovascular death, myocardial infarction, or ischemic stroke). Ischemic/hemorrhagic stroke and TIA were adjudicated and measured as incidence rates postrandomization and cumulative incidence (per patient-years). Post hoc multivariable competing risk hazards analyses were performed using baseline characteristics to determine factors associated with all-cause stroke in patients with PAD. Results- A total of 458 cerebrovascular events in 424 patients (317 ischemic strokes, 39 hemorrhagic strokes, and 102 TIAs) occurred over a median follow-up of 30 months, for a cumulative incidence of 0.87, 0.11, and 0.27 per 100 patient-years, respectively. Age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, geographic region, ankle-brachial index <0.60, prior amputation, and systolic blood pressure were independent baseline factors associated with the occurrence of all-cause stroke. After adjustment for baseline factors, the rates of ischemic stroke and all-cause stroke remained lower in patients treated with ticagrelor as compared with those receiving clopidogrel. There was no significant difference in the incidence of hemorrhagic stroke or TIA between the 2 treatment groups. Conclusions- In patients with symptomatic PAD, ischemic stroke and TIA occur frequently over time. Comorbidities such as age, prior stroke, prior atrial fibrillation/flutter, diabetes mellitus, higher blood pressure, prior amputation, lower ankle-brachial index, and geographic region were each independently associated with the occurrence of all-cause stroke. Use of ticagrelor, as compared with clopidogrel, was associated with a lower adjusted rate of ischemic and all-cause stroke. Further study is needed to optimize medical management and risk reduction of all-cause stroke in patients with PAD. Clinical Trial Registr

Topics: Aged; Clopidogrel; Double-Blind Method; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Peripheral Arterial Disease; Stroke; Ticagrelor

Patients with prior myocardial infarction (MI) and multivessel coronary disease (MVD) are at high risk for recurrent coronary events.. The authors investigated the efficacy and safety of ticagrelor versus placebo in patients with MVD in the PEGASUS-TIMI 54 (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis In Myocardial Infarction 54) trial.. Patients with a history of MI 1 to 3 years before inclusion in the PEGASUS-TIMI 54 trial were stratified in a pre-specified analysis based on the presence of MVD. The effect of ticagrelor (60 mg and 90 mg) on the composite of cardiovascular death, MI, or stroke (major adverse cardiovascular events [MACE]), as well as the composite of coronary death, MI, or stent thrombosis (coronary events), and on TIMI major bleeding, intracranial hemorrhage (ICH), and fatal bleeding were evaluated over a median of 33 months.. A total of 12,558 patients (59.4%) had MVD. In the placebo arm, compared with patients without MVD, those with MVD were at higher risk for MACE (9.37% vs. 8.57%, adjusted hazard ratio [HR. Patients with prior MI and MVD are at increased risk of MACE and coronary events, and experience substantial relative and absolute risk reductions in both outcomes with long-term ticagrelor treatment relative to those without MVD. Ticagrelor increases the risk of TIMI major bleeding, but not ICH or fatal bleeding. For patients with prior MI and MVD, ticagrelor is an effective option for long-term antiplatelet therapy. (Prevention of Cardiovascular Events [e.g., Death From Heart or Vascular Disease, Heart Attack, or Stroke] in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin [PEGASUS]; NCT01225562).

Topics: Aged; Coronary Artery Disease; Drug Administration Schedule; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Thrombosis; Ticagrelor

In the PEGASUS-TIMI 54 trial (Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin-Thrombolysis in Myocardial Infarction 54), ticagrelor reduced the risk of major adverse cardiovascular events when added to low-dose aspirin in stable patients with prior myocardial infarction, resulting in the approval of ticagrelor 60 mg twice daily for long-term secondary prevention. We investigated the incidence of stroke, outcomes after stroke, and the efficacy of ticagrelor focusing on the approved 60 mg twice daily dose for reducing stroke in this population.. Patients were followed for a median of 33 months. Stroke events were adjudicated by a central committee. Data from similar trials were combined using meta-analysis.. Of 14 112 patients randomly assigned to placebo or ticagrelor 60 mg, 213 experienced a stroke; 85% of these strokes were ischemic. A total of 18% of strokes were fatal and another 15% led to either moderate or severe disability at 30 days. Ticagrelor significantly reduced the risk of stroke (hazard ratio, 0.75; 95% confidence interval, 0.57-0.98; P=0.034), driven by a reduction in ischemic stroke (hazard ratio, 0.76; 95% confidence interval, 0.56-1.02). Hemorrhagic stroke occurred in 9 patients on placebo and 8 patients on ticagrelor. A meta-analysis across 4 placebo-controlled trials of more intensive antiplatelet therapy in 44 816 patients with coronary disease confirmed a marked reduction in ischemic stroke (hazard ratio, 0.66; 95% confidence interval, 0.54-0.81; P=0.0001).. High-risk patients with prior myocardial infarction are at risk for stroke, approximately one-third of which are fatal or lead to moderate-to-severe disability. The addition of ticagrelor 60 mg twice daily significantly reduced this risk without an excess of hemorrhagic stroke but with more major bleeding. In high-risk patients with coronary disease, more intensive antiplatelet therapy should be considered not only to reduce the risk of coronary events, but also of stroke.. URL: http://www.clinicaltrials.gov. Unique Identifier: NCT01225562.

Topics: Adenosine; Aged; Aspirin; Coronary Artery Disease; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Secondary Prevention; Stroke; Ticagrelor

The potential benefit of dual antiplatelet therapy beyond 1 year after a myocardial infarction has not been established. We investigated the efficacy and safety of ticagrelor, a P2Y12 receptor antagonist with established efficacy after an acute coronary syndrome, in this context.. We randomly assigned, in a double-blind 1:1:1 fashion, 21,162 patients who had had a myocardial infarction 1 to 3 years earlier to ticagrelor at a dose of 90 mg twice daily, ticagrelor at a dose of 60 mg twice daily, or placebo. All the patients were to receive low-dose aspirin and were followed for a median of 33 months. The primary efficacy end point was the composite of cardiovascular death, myocardial infarction, or stroke. The primary safety end point was Thrombolysis in Myocardial Infarction (TIMI) major bleeding.. The two ticagrelor doses each reduced, as compared with placebo, the rate of the primary efficacy end point, with Kaplan-Meier rates at 3 years of 7.85% in the group that received 90 mg of ticagrelor twice daily, 7.77% in the group that received 60 mg of ticagrelor twice daily, and 9.04% in the placebo group (hazard ratio for 90 mg of ticagrelor vs. placebo, 0.85; 95% confidence interval [CI], 0.75 to 0.96; P=0.008; hazard ratio for 60 mg of ticagrelor vs. placebo, 0.84; 95% CI, 0.74 to 0.95; P=0.004). Rates of TIMI major bleeding were higher with ticagrelor (2.60% with 90 mg and 2.30% with 60 mg) than with placebo (1.06%) (P<0.001 for each dose vs. placebo); the rates of intracranial hemorrhage or fatal bleeding in the three groups were 0.63%, 0.71%, and 0.60%, respectively.. In patients with a myocardial infarction more than 1 year previously, treatment with ticagrelor significantly reduced the risk of cardiovascular death, myocardial infarction, or stroke and increased the risk of major bleeding. (Funded by AstraZeneca; PEGASUS-TIMI 54 ClinicalTrials.gov number, NCT01225562.).

Topics: Adenosine; Aged; Aspirin; Cardiovascular Diseases; Double-Blind Method; Drug Administration Schedule; Drug Therapy, Combination; Female; Hemorrhage; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk; Secondary Prevention; Ticagrelor

Patients with acute coronary syndromes and history of stroke or transient ischemic attack (TIA) have an increased rate of recurrent cardiac events and intracranial hemorrhages.. We evaluated treatment effects of ticagrelor versus clopidogrel in patients with acute coronary syndrome with and without a history of prior stroke or TIA in the PLATelet inhibition and patient Outcomes (PLATO) trial. Of the 18 624 randomized patients, 1152 (6.2%) had a history of stroke or TIA. Such patients had higher rates of myocardial infarction (11.5% versus 6.0%), death (10.5% versus 4.9%), stroke (3.4% versus 1.2%), and intracranial bleeding (0.8% versus 0.2%) than patients without prior stroke or TIA. Among patients with a history of stroke or TIA, the reduction of the primary composite outcome and total mortality at 1 year with ticagrelor versus clopidogrel was consistent with the overall trial results: 19.0% versus 20.8% (hazard ratio, 0.87; 95% confidence interval, 0.66-1.13; interaction P=0.84) and 7.9% versus 13.0% (hazard ratio, 0.62; 95% confidence interval, 0.42-0.91). The overall PLATO-defined bleeding rates were similar: 14.6% versus 14.9% (hazard ratio, 0.99; 95% confidence interval, 0.71-1.37), and intracranial bleeding occurred infrequently (4 versus 4 cases, respectively).. Patients with acute coronary syndrome with a prior history of ischemic stroke or TIA had higher rates of clinical outcomes than patients without prior stroke or TIA. However, the efficacy and bleeding results of ticagrelor in these high-risk patients were consistent with the overall trial population, with a favorable clinical net benefit and associated impact on mortality.. URL: http://www.clinicatrials.gov. Unique identifier: NCT00391872.

Topics: Acute Coronary Syndrome; Adenosine; Aged; Brain Ischemia; Clopidogrel; Female; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Male; Middle Aged; Myocardial Infarction; Purinergic P2Y Receptor Antagonists; Risk Factors; Stroke; Ticagrelor; Ticlopidine

Given many emerging indications for endovascular interventions in ischemic strokes, a safe and effective adjuvant antiplatelet regimen for acute revascularization has become a subject of interest. Ticagrelor is a direct oral P2Y12 inhibitor that may achieve rapid platelet suppression than standard oral therapies. We report our experience of Ticagrelor use in revascularization of acute large arterial steno-occlusive disease, describing procedural post-procedure thrombotic events, major hemorrhages, and other clinical outcomes.. This was a single-center retrospective case series of large steno-occlusive disease requiring endovascular reperfusion with emergent adjuvant Ticagrelor, defined as 30 min of the procedure from skin puncture to closure of the arteriotomy. Major outcomes investigated were thromboembolism in the target artery, and symptomatic intracranial or extracranial major hemorrhages. Additional analyses were performed with respect to timing of the administration and use of rescue GPIIb/IIIa inhibitors if any.. 73 consecutive patients were identified, presenting with severe ischemic stroke (median NIHSS 16) of large artery origin. 67% required stent placement (45% cervical carotid, 22% intracranial artery), 9.5% angioplasty and 23% mechanical thrombectomy only. Two experienced symptomatic in-stent occlusion, and 7 experienced major hemorrhages (9.5%) including 3 fatal symptomatic intracranial hemorrhages (4.1%). Among 19 subjects (26%) who received pretreatment with Ticagrelor, there were fewer GPIIb/IIIa administration, angioplasty and stenting, without yielding benefit in functional outcome or mortality. GPIIb/IIIa was administered as rescue therapy in 45 subjects (62%), which was found associated with increased bleeding compared to patients receiving Ticagrelor only, in whom no bleeding complications were recorded (16% vs. 0%; p = 0.03).. We report our findings on Ticagrelor as an adjuvant antiplatelet therapy in ischemic stroke of large arterial origin requiring emergent revascularization. Effectiveness, safety, need for additional rescue treatment, and comparison to other commonly used oral antiplatelets should be investigated in future prospective studies.

Topics: Arterial Occlusive Diseases; Endovascular Procedures; Humans; Intracranial Hemorrhages; Ischemic Stroke; Reperfusion; Retrospective Studies; Stents; Stroke; Thrombectomy; Ticagrelor; Treatment Outcome

Stroke after acute coronary syndrome (ACS) can be devastating. It is uncertain whether the risks of ischaemic stroke or intracranial haemorrhage (ICH) are associated with different choices of P2Y12 inhibitors (potent P2Y12 inhibitors such as ticagrelor and prasugrel vs clopidogrel). Even though East Asians are known to have different thrombotic and haemorrhagic profiles from Caucasians, data on Chinese patients are sparse.. This was a retrospective cohort study conducting in Chinese patients with ACS who underwent first-ever percutaneous coronary intervention from 14 hospitals in Hong Kong between 2010 and 2017. The primary efficacy endpoint was ischaemic stroke. The secondary efficacy endpoint was a composite outcome of thrombotic events including all-cause mortality, non-fatal myocardial infarction and ischaemic stroke. The primary safety endpoint was ICH. The secondary safety endpoint was a composite of major bleeding events.. After adjustment of baseline characteristics by 1:1 propensity score matching, a total of 6220 patients (3110 on each group) were analysed. Compared with clopidogrel, potent P2Y12 inhibitors were associated with a lower risk of ischaemic stroke (HR 0.57; 95% CI 0.37 to 0.87; p=0.008) and a lower risk of thrombotic events (HR 0.77; 95% CI 0.66 to 0.90; p=0.001). Potent P2Y12 inhibitor was associated with similar risk of ICH (HR 0.65; 95% CI 0.34 to 1.25, p=0.20) and major bleeding (HR 0.83; 95% CI 0.68 to 1.01, p=0.069).. Potent P2Y12 inhibitors were associated with a lower adjusted risk of ischaemic stroke and thrombotic events, compared with clopidogrel. The risks of ICH and major bleeding were similar.

Topics: Acute Coronary Syndrome; Brain Ischemia; China; Clopidogrel; Hemorrhage; Hemorrhagic Stroke; Humans; Intracranial Hemorrhages; Ischemic Stroke; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Purinergic P2Y Receptor Antagonists; Retrospective Studies; Stroke; Ticagrelor

Preventive antiplatelet therapy is recommended for patients with cardiac or cerebrovascular atherosclerosis. Ticagrelor has an improved safety and efficacy profile in patients with acute coronary syndrome; however, data regarding stroke prevention remain controversial. We conducted a network meta-analysis to compare ticagrelor with other receptor antagonists (P2Y12) inhibitors and aspirin in monotherapy or combination in the treatment of patients with high risk for cardiovascular or cerebrovascular disease, defined as coronary artery disease, acute coronary syndrome, stroke or transient ischemic attack, or peripheral artery disease.. Systematic searches of MEDLINE, EMBASE, and the Cochrane Library were conducted until August 1, 2020. Search terms included ticagrelor, AZD 6140, and stroke. The risk of bias was assessed using the Cochrane Collaboration assessment tool. Random-effects model was used to combine risk estimates across trials and risk ratio with 95% CIs served as summary statistics. The influence of individual components was evaluated in an additive network meta-analysis model. The primary efficacy end point was the occurrence of stroke. The safety end points included bleeding and all-cause mortality.. Twenty-six randomized clinical trials comprising 124 495 patients were analyzed. When compared with controls, ticagrelor plus aspirin significantly reduced the risk of ischemic stroke by 20% (risk ratio, 0.80 [95% CI, 0.71–0.89]). Treatment with ticagrelor monotherapy did not significantly affect ischemic stroke (risk ratio, 0.88 [95% CI, 0.77–1.00]; P=0.05). Compared with aspirin alone, major bleeding was in similar ranges with antiplatelet monotherapies while the relative risk was twice higher with combined antiplatelet therapies. There was no considerable difference in the risk of mortality with ticagrelor plus aspirin (risk ratio, 0.99 [95% CI, 0.91–1.07]).. Ticagrelor on top of aspirin may provide more favorable outcomes on secondary stroke prevention in patients with vascular risk factors; however, this benefit may come with the price of increased bleeding risk including intracranial bleeding.

Topics: Acute Coronary Syndrome; Aspirin; Cerebrovascular Disorders; Coronary Artery Disease; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Network Meta-Analysis; Platelet Aggregation Inhibitors; Secondary Prevention; Stroke; Ticagrelor

Bleeding risk stratification is an unresolved issue in older adults. Anemia may reflect subclinical blood losses that can be exacerbated after percutaneous coronary intervention . We sought to prospectively determine the contribution of anemia to the risk of bleeding in 448 consecutive patients aged 75 or more years, treated by percutaneous coronary interventions without concomitant indication for oral anticoagulation. We evaluated the effect of WHO-defined anemia on the incidence of 1-year nonaccess site-related major bleeding. The prevalence of anemia was 39%, and 13.1% of anemic and 5.2% of nonanemic patients suffered a bleeding event (hazard ratio 2.75, 95% confidence interval 1.37 to 5.54, p = 0.004). Neither PRECISE-DAPT nor CRUSADE scores were superior to hemoglobin for the prediction of bleeding. In conclusion, anemia is a powerful predictor of bleeding with potential utility for simplifying tailoring therapies.

Topics: Acute Coronary Syndrome; Aged; Aged, 80 and over; Anemia; Angina, Unstable; Anticoagulants; Antithrombins; Aspirin; Cause of Death; Clopidogrel; Comorbidity; Coronary Artery Disease; Drug-Eluting Stents; Female; Gastrointestinal Hemorrhage; Hemorrhage; Heparin; Hirudins; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Myocardial Infarction; Peptide Fragments; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Postoperative Care; Postoperative Hemorrhage; Prasugrel Hydrochloride; Proportional Hazards Models; Prospective Studies; Recombinant Proteins; Risk Assessment; Stents; Ticagrelor; Urologic Diseases

Suboptimal platelet inhibition by clopidogrel (clopidogrel resistance) may be associated with high rates of stent thrombosis and ischemic events. Our objective was to determine if ticagrelor, a P2Y. A thromboelastography-platelet mapping assay was used in all patients undergoing neuroendovascular procedures requiring oral clopidogrel. In patients with suboptimal platelet inhibition (<60%) on clopidogrel, ticagrelor was imitated after an oral bolus of 180 mg followed by 90 mg twice daily and the platelet mapping assay was repeated. The primary endpoint was hemorrhagic complications classified as major (hemoglobin decrease >5 g/dL or intracranial hemorrhage with deficits), minor (hemoglobin decrease 3-5 g/dL or intracranial hemorrhage without residual deficits), or insignificant.. Suboptimal platelet inhibition on clopidogrel was seen in 70 of 106 patients undergoing neuroendovascular procedures. There was a significantly higher magnitude of platelet inhibition with ticagrelor compared with clopidogrel in patients with clopidogrel resistance (mean ± SD: 85.90 ± 10.74% vs. 29.26 ± 17.71%; P < .001); 50 of 70 patients showed optimal inhibition. Two patients had major (fatal) hemorrhagic events (both received either intravenous thrombolytics and/or eptifibatide infusion). Three patients had minor hemorrhagic events, and two patients had insignificant hemorrhagic events. Four of seven hemorrhagic events occurred in patients with optimal response to clopidogrel, two occurred in patients with suboptimal response to ticagrelor, and one occurred in a patient with optimal response to ticagrelor.. Oral ticagrelor can augment platelet inhibition in patients who have clopidogrel resistance.

Topics: Aged; Blood Platelets; Clopidogrel; Endovascular Procedures; Female; Humans; Intracranial Hemorrhages; Male; Middle Aged; Platelet Aggregation Inhibitors; Platelet Function Tests; Ticagrelor; Treatment Outcome

A poor ability of recommended risk scores for predicting in-hospital bleeding has been reported in elderly patients with acute coronary syndromes (ACS). No study assessed the prediction of post-discharge bleeding in the elderly. The new BleeMACS score (Bleeding complications in a Multicenter registry of patients discharged with diagnosis of Acute Coronary Syndrome), was designed to predict post-discharge bleeding in ACS patients. We aimed to assess the predictive ability of the BleeMACS score in elderly patients.. We assessed the incidence and characteristics of severe bleeding after discharge in ACS patients aged ≥ 75 years. Bleeding was defined as any intracranial bleeding or bleeding leading to hospitalization and/or red blood transfusion, occurring within the first year after discharge. We assessed the predictive ability of the BleeMACS score according to age by Fine-Gray proportional hazards regression analysis, calculating receiver-operating characteristic (ROC) curves and the area under the ROC curves (AUC).. Elderly patients with ACS had a significantly higher incidence of post-discharge bleeding. Despite a lower predictive ability in older patients, the BleeMACS score exhibited an acceptable performance in these patients.

Topics: Acute Coronary Syndrome; Age Factors; Aged; Asia; Brazil; Canada; Clopidogrel; Decision Support Techniques; Erythrocyte Transfusion; Europe; Female; Humans; Incidence; Intracranial Hemorrhages; Male; Middle Aged; Patient Discharge; Patient Readmission; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Prasugrel Hydrochloride; Predictive Value of Tests; Registries; Risk Assessment; Risk Factors; Ticagrelor; Time Factors; Treatment Outcome

Background and Purpose- Guidelines recommend dual antiplatelet treatment with ticagrelor instead of clopidogrel after acute myocardial infarction. Ticagrelor increases major and minor noncoronary artery bypass graft bleeding compared with clopidogrel, but whether the risk of intracranial hemorrhage (ICH) increases is unknown. We aimed to examine any association between ticagrelor and ICH and to identify predictors of ICH among unselected patients after acute myocardial infarction. Methods- Patients with acute myocardial infarction were identified using the Register of Information and Knowledge About Swedish Heart Intensive Care Admissions, and the data were combined with the Swedish National Patient Registry to identify ICH occurrence. To avoid obvious selection bias related to the choice of dual antiplatelet treatment, we divided the study cohorts into 2 time periods of similar length using the first prescription of ticagrelor as a cutoff point (December 20, 2011). The risk of ICH during the first period (100% clopidogrel treatment) versus the second period (52.1% ticagrelor and 47.8% clopidogrel treatment) was assessed using Kaplan-Meier analysis. Cox proportional-hazards regression analyses, with assessment of interactions between all significant variables, were used to identify predictors of ICH. Results- The analysis included 47 674 patients with acute myocardial infarction. The cumulative incidence of ICH during the first period was 0.59% (91 cases [95% CI, 0.49-0.69]) versus 0.52% (97 cases [95% CI, 0.43-0.61]) during the second period ( P=0.83). In multivariable Cox analysis, study period (second versus first period) was not predictive of ICH. Interaction analyses showed that age and prior cardiovascular morbidities were of importance in predicting the risk of ICH. Conclusions- The increased use of ticagrelor was not associated with ICH, whereas age and prior cardiovascular morbidities were related to the risk of ICH and interacted significantly.

Topics: Age Factors; Aged; Clopidogrel; Cohort Studies; Female; Humans; Intracranial Hemorrhages; Kaplan-Meier Estimate; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Practice Guidelines as Topic; Proportional Hazards Models; Secondary Prevention; Sweden; Ticagrelor

We describe a case of a 67-year-old man who required emergency surgery for acute intracranial bleeding after having received a loading dose of aspirin and ticagrelor for an acute ST-elevation myocardial infarction. Before and during the craniocervical decompression, the assessment of platelet function was performed using the Multiplate® analyzer. Biological evaluation of platelet function was consistent with the clinical impression, suggesting that platelet transfusion and desmopressin administration in the presence of ticagrelor had very little, if any, hemostatic effect.

Topics: Adenosine; Aged; Aspirin; Combined Modality Therapy; Deamino Arginine Vasopressin; Fatal Outcome; Hemostatics; Humans; Intracranial Hemorrhages; Male; Myocardial Infarction; Platelet Activation; Platelet Aggregation Inhibitors; Platelet Function Tests; Platelet Transfusion; Purinergic P2Y Receptor Antagonists; Ticagrelor

The PLATO trial revealed a remarkable advantage of ticagrelor over clopidogrel in ACS patients. Unless the regulatory authorities discover serious flaws with the study, which is unlikely, the drug may substantially change the present landscape of oral antiplatelet therapy, especially in high-risk patients. Despite a somewhat unfavourable safety profile, ticagrelor has a lot of room to compensate for these well-defined side effects based on a documented absolute mortality reduction, solid prevention of MI, and convincing pattern of benefit growing over time.

Topics: Acute Coronary Syndrome; Adenosine; Clinical Trials, Phase III as Topic; Clopidogrel; Humans; Intracranial Hemorrhages; Myocardial Infarction; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Ticlopidine; Treatment Outcome