scholarly journals Ischemic Benefit and Hemorrhage Risk Of Ticagrelor-Aspirin Versus Aspirin In Patients With Acute Ischemic Stroke Or TIA

Stroke ◽  
2021 ◽  
Author(s):  
S. Claiborne Johnston ◽  
Pierre Amarenco ◽  
Maria Aunes ◽  
Hans Denison ◽  
Scott Evans ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Clinical Impact ◽  
Major Hemorrhage ◽  
Safety Outcome ◽  
Efficacy Outcome ◽  
Ischemic Attack ◽  
Aspirin Group

Background and Purpose: In patients with acute mild-moderate ischemic stroke or high-risk transient ischemic attack (TIA), the Acute Stroke or Transient Ischemic Attack Treated with Ticagrelor and Aspirin for Prevention of Stroke and Death (THALES) trial demonstrated that when added to aspirin, ticagrelor reduced stroke or death but increased risk of severe hemorrhage compared with placebo. The primary efficacy outcome of THALES included hemorrhagic stroke and death, events also counted in the primary safety outcome. We sought to disentangle risk and benefit, assess their relative impact, and attempt to identify subgroups with disproportionate risk or benefit. Methods: In a randomized, placebo-controlled, double-blind trial of patients with mild-to-moderate acute noncardioembolic ischemic stroke or high-risk TIA, patients were randomized within 24 hours after symptom onset to a 30-day regimen of either ticagrelor plus aspirin or matching placebo plus aspirin. For the present analyses, we defined the efficacy outcome, major ischemic events, as the composite of ischemic stroke or non-hemorrhagic death, and defined the safety outcome, major hemorrhage, as intracranial hemorrhage or hemorrhagic death. Net clinical impact was defined as the combination of these two endpoints. Results: In 11 016 patients (5523 ticagrelor-aspirin and 5493 aspirin), a major ischemic event occurred in 294 patients (5.3%) in the ticagrelor-aspirin group and in 359 patients (6.5%) in the aspirin group (absolute risk reduction 1.19%, 95%CI 0.31%-2.07%). Major hemorrhage occurred in 22 patients (0.4%) in the ticagrelor-aspirin group and 6 patients (0.1%) in the aspirin group (absolute risk increase 0.29%, 95% CI, 0.10-0.48%). Net clinical impact favored ticagrelor-aspirin (absolute risk reduction 0.97%, 95% CI, 0.08%-1.87%). Findings were similar when different thresholds for disability were applied and over a range of predefined subgroups. Conclusions: In patients with mild-moderate ischemic stroke or high-risk TIA, ischemic benefits of 30-day treatment with ticagrelor-aspirin outweigh risks of hemorrhage. Registration: URL: http://www.clinicaltrials.gov; Unique identifier: NCT03354429

scholarly journals Time Course for Benefit and Risk of Clopidogrel and Aspirin After Acute Transient Ischemic Attack and Minor Ischemic Stroke

Circulation ◽  
2019 ◽  
Vol 140 (8) ◽  
pp. 658-664 ◽  
Author(s):  
S. Claiborne Johnston ◽  
Jordan J. Elm ◽  
J. Donald Easton ◽  
Mary Farrant ◽  
William G. Barsan ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Transient Ischemic Attack ◽  
Time Course ◽  
Hazard Ratio ◽  
Major Hemorrhage ◽  
Minor Ischemic Stroke ◽  
Ischemic Attack ◽  
Ischemic Events ◽  
Benefit And Risk

Background: In patients with acute minor ischemic stroke or high-risk transient ischemic attack enrolled in the POINT trial (Platelet-Oriented Inhibition in New TIA and Minor Ischemic Stroke [POINT] Trial), the combination of clopidogrel and aspirin for 90 days reduced major ischemic events but increased major hemorrhage in comparison to aspirin alone. Methods: In a secondary analysis of POINT (N=4881), we assessed the time course for benefit and risk from the combination of clopidogrel and aspirin. The primary efficacy outcome was a composite of ischemic stroke, myocardial infarction, or ischemic vascular death. The primary safety outcome was major hemorrhage. Risks and benefits were estimated for delayed times of treatment initiation using left-truncated models. Results: Through 90 days, the rate of major ischemic events was initially high then decreased markedly, whereas the rate of major hemorrhage remained low but relatively constant throughout. With the use of a model-based approach, the optimal change point for major ischemic events was 21 days (0–21 days hazard ratio 0.65 for clopidogrel-aspirin versus aspirin; 95% CI, 0.50–0.85; P =0.0015, in comparison to 22–90 days hazard ratio, 1.38; 95% CI, 0.81–2.35; P =0.24). Models showed benefits of clopidogrel-aspirin for treatment delayed as long as 3 days after symptom onset. Conclusions: The benefit of clopidogrel-aspirin occurs predominantly within the first 21 days, and outweighs the low, but ongoing risk of major hemorrhage. When considered with the results of the CHANCE trial (Clopidogrel in High-Risk Patients With Non-disabling Cerebrovascular Events), a similar trial treating with clopidogrel-aspirin for 21 days and showing no increase in major hemorrhage, these results suggest that limiting clopidogrel-aspirin use to 21 days may maximize benefit and reduce risk after high-risk transient ischemic attack or minor ischemic stroke. Clinical Trial Registration: URL: https://www.clinicaltrials.gov . Unique identifier: NCT00991029.

scholarly journals Dual Antiplatelet Therapy Using Cilostazol With Aspirin or Clopidogrel: Subanalysis of the CSPS.com Trial

Stroke ◽  
2021 ◽  
Author(s):  
Haruhiko Hoshino ◽  
Kazunori Toyoda ◽  
Katsuhiro Omae ◽  
Noriyuki Ishida ◽  
Shinichiro Uchiyama ◽  
...  
Keyword(s):  
Ischemic Stroke ◽  
High Risk ◽  
Dual Antiplatelet Therapy ◽  
Bleeding Risk ◽  
Primary Efficacy ◽  
Monotherapy Group ◽  
Unique Identifier ◽  
Primary Efficacy Outcome ◽  
Safety Outcome ◽  
Efficacy Outcome

Background and Purpose: Although dual antiplatelet therapy (DAPT) with aspirin and clopidogrel reduces the recurrence of ischemic stroke while significantly increasing the bleeding events compared with monotherapy, the CSPS.com trial (Cilostazol Stroke Prevention Study combination) showed that DAPT using cilostazol was more effective without the bleeding risk. In the CSPS.com trial, aspirin or clopidogrel was used as the underlying antiplatelet drug. The effectiveness and safety of each combination were examined and clarified. Methods: In the CSPS.com trial, a multicenter, open-label, randomized controlled study, patients with high-risk, noncardioembolic ischemic stroke 8 to 180 days after onset treated with aspirin or clopidogrel alone at the discretion of the physician in charge were recruited. Patients were randomly assigned to receive either monotherapy or DAPT using cilostazol and followed for 0.5 to 3.5 years. The primary efficacy outcome was first recurrence of ischemic stroke. The safety outcome was severe or life-threatening bleeding. The analysis was based on the underlying antiplatelet agents. Results: A total of 763 patients taking aspirin and 1116 taking clopidogrel were included in the intention-to-treat analysis. Although the clopidogrel group had more risk factors than the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the 2 groups. In the aspirin group, the primary efficacy outcome and safety outcome did not differ significantly between the DAPT group and the aspirin-monotherapy group. In the clopidogrel group, the primary end point occurred at a rate of 2.31 per 100 patient-years in the DAPT group and 5.19 per 100 patient-years in the clopidogrel-monotherapy group (hazard ratio, 0.447 [95% CI, 0.258–0.774]). Safety outcome did not differ significantly between groups (0.51 per 100 patient-years versus 0.71 per 100 patient-years, respectively; hazard ratio, 0.730 [95% CI, 0.206–2.588]). Conclusions: The combination of cilostazol and clopidogrel significantly reduced the recurrence of ischemic stroke without increasing the bleeding risk in noncardioembolic, high-risk patients. REGISTRATION: URL: http://www.clinicaltrials.gov ; Unique identifier: NCT01995370. URL: https://www.umin.ac.jp/ctr/ ; Unique identifier: UMIN000012180.

Abstract 392: Warfarin Versus Aspirin in Patients with Systolic Heart Failure and Normal Sinus Rhythm: Insights From a Meta-Analysis

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Rachit Shah ◽  
George Mueller ◽  
Dhavalkumar Patel ◽  
Janos Molnar ◽  
Kalpesh Patel ◽  
...  
Keyword(s):  
Heart Failure ◽  
Ischemic Stroke ◽  
Relative Risk ◽  
Sinus Rhythm ◽  
Systolic Heart Failure ◽  
Aspirin Therapy ◽  
Major Hemorrhage ◽  
Risk Of Death ◽  
Number Of Patients ◽  
Aspirin Group

Background: It is unknown whether warfarin or aspirin therapy is superior for the treatment of patients with systolic heart failure who are in sinus rhythm. Methods: We performed a systematic literature search for randomized trials comparing warfarin and aspirin in patients with systolic heart failure which provided the event rates for ischemic stroke, major hemorrhage and death in the two groups. Heterogeneity of the studies was analyzed by Q statistics. The studies were homogeneous for each outcome; therefore the fixed-effect model was used to compute the relative risk based on the number of events and total number of patients in each group. A two-sided alpha error of <0.05 was considered to be statistically significant (p<0.05). Results: We found 4 randomized clinical trials comparing warfarin and aspirin therapy in patients with systolic heart failure with a mean duration of follow up of 2.3 years enrolling a total of 3663 patients. The relative risk for ischemic stroke in patients treated with warfarin was 0.50 with 95% confidence interval (CI) of 0.33 - 0.75 (P= 0.001) while the relative risk for major hemorrhage was 1.94 with 95% CI of 1.40- 2.71 (P= 0.000) in comparison to the aspirin group. The relative risk of death was 1.01 with 95% CI of 0.89- 1.14 (P= 0.871) in the warfarin group compared to the aspirin group. Conclusion: Although warfarin therapy appears to reduce the risk of ischemic stroke in patients with systolic heart failure who are in sinus rhythm, the reduction comes at the cost of higher risk of bleeding and there is no evidence of an overall benefit on mortality.

scholarly journals The COMPASS Trial

Circulation ◽  
2020 ◽  
Vol 142 (1) ◽  
pp. 40-48 ◽  
Author(s):  
Jan Steffel ◽  
John W. Eikelboom ◽  
Sonia S. Anand ◽  
Olga Shestakovska ◽  
Salim Yusuf ◽  
...  
Keyword(s):  
High Risk ◽  
Absolute Risk ◽  
Absolute Risk Reduction ◽  
Cardiovascular Death ◽  
Hazard Ratio ◽  
Adverse Outcomes ◽  
Study Cohort ◽  
Unique Identifier ◽  
Intention To Treat ◽  
Fatal Bleeding

Background: Rivaroxaban 2.5 mg twice daily plus acetylsalicylic acid (aspirin; ASA) 100 mg reduced the risk of cardiovascular events as compared with ASA monotherapy in the COMPASS trial (Cardiovascular Outcomes for People Using Anticoagulation Strategies) but increased the risk of major bleedings. Analysis of net clinical benefit (NCB) is of key clinical relevance and represents an integrated measure of overall patient outcome. Methods: The current prespecified analysis was performed to assess the NCB of adding rivaroxaban 2.5 mg twice daily to ASA monotherapy in patients with chronic vascular disease in the COMPASS study cohort (intention-to-treat study population), with a specific focus on high-risk subgroups. The predefined NCB outcome was the composite of cardiovascular death, stroke, myocardial infarction, fatal bleeding, or symptomatic bleeding into a critical organ. Results: A lower number of NCB adverse outcomes was observed with rivaroxaban 2.5 mg twice daily plus ASA versus ASA alone (hazard ratio, 0.80 [95% CI, 0.70–0.91], P =0.0005), which became increasingly favorable with longer treatment duration. The main drivers of NCB outcomes were “efficacy” events, in particular stroke (0.5%/y versus 0.8%/y; hazard ratio, 0.58 [95% CI, 0.44–0.76], P <0.0001) and cardiovascular death (0.9%/y versus 1.2%/y; hazard ratio, 0.78 [95% CI, 0.64–0.96], P =0.02), whereas the bleeding components of the NCB, in particular fatal bleeding (0.09%/y versus 0.06%/y; hazard ratio, 1.49 [95% CI 0.67–3.33], P =0.32), only represented a minority of NCB events. In selected high-risk subgroups, including patients with polyvascular disease (≥2 vascular beds affected with atherosclerosis), impaired renal function, heart failure, and/or diabetes mellitus, a larger absolute risk reduction for experiencing a NCB event was observed. Conclusions: Compared with ASA monotherapy, the combination of rivaroxaban 2.5 mg twice daily plus ASA resulted in fewer NCB events primarily by preventing adverse efficacy events, particularly stroke and cardiovascular mortality, whereas severe bleedings were less frequent and with less clinical impact. The NCB was particularly favorable in high-risk subgroups and those with multiple risk characteristics. Registration: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT01776424.

Long-term Effects of Remote Ischemic Preconditioning on Kidney Function in High-risk Cardiac Surgery Patients

2017 ◽  
Vol 126 (5) ◽  
pp. 787-798 ◽  
Author(s):  
Alexander Zarbock ◽  
John A. Kellum ◽  
Hugo Van Aken ◽  
Christoph Schmidt ◽  
Mira Küllmar ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Cardiac Surgery ◽  
High Risk ◽  
Renal Dysfunction ◽  
Ischemic Preconditioning ◽  
Absolute Risk ◽  
Kidney Injury ◽  
Absolute Risk Reduction ◽  
Remote Ischemic Preconditioning ◽  
Major Adverse Kidney Events

Abstract Background In a multicenter, randomized trial, the authors enrolled patients at high-risk for acute kidney injury as identified by a Cleveland Clinic Foundation score of 6 or more. The authors enrolled 240 patients at four hospitals and randomized them to remote ischemic preconditioning or control. The authors found that remote ischemic preconditioning reduced acute kidney injury in high-risk patients undergoing cardiac surgery. The authors now report on the effects of remote ischemic preconditioning on 90-day outcomes. Methods In this follow-up study of the RenalRIP trial, the authors examined the effect of remote ischemic preconditioning on the composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction at 90 days. Secondary outcomes were persistent renal dysfunction and dialysis dependence in patients with acute kidney injury. Results Remote ischemic preconditioning significantly reduced the occurrence of major adverse kidney events at 90 days (17 of 120 [14.2%]) versus control (30 of 120 [25.0%]; absolute risk reduction, 10.8%; 95% CI, 0.9 to 20.8%; P = 0.034). In those patients who developed acute kidney injury after cardiac surgery, 2 of 38 subjects in the remote ischemic preconditioning group (5.3%) and 13 of 56 subjects in the control group (23.2%) failed to recover renal function at 90 days (absolute risk reduction, 17.9%; 95% CI, 4.8 to 31.1%; P = 0.020). Acute kidney injury biomarkers were also increased in patients reaching the major adverse kidney event endpoint compared to patients who did not. Conclusions Remote ischemic preconditioning significantly reduced the 3-month incidence of a composite endpoint major adverse kidney events consisting of mortality, need for renal replacement therapy, and persistent renal dysfunction in high-risk patients undergoing cardiac surgery. Furthermore, remote ischemic preconditioning enhanced renal recovery in patients with acute kidney injury.

Abstract 13117: Incorporation of High-Sensitivity Troponin Along With the AHA/ACC Cholesterol Guidelines for Improved Risk Stratification and Targeted PCSK9 Inhibition in Atherosclerotic Cardiovascular Disease

Circulation ◽  
2020 ◽  
Vol 142 (Suppl_3) ◽  
Author(s):  
Nicholas A Marston ◽  
Kazuma Oyama ◽  
Minao Tang ◽  
Petr Jarolim ◽  
Peter S Sever ◽  
...  
Keyword(s):  
High Risk ◽  
Risk Reduction ◽  
Lower Risk ◽  
Absolute Risk ◽  
High Sensitivity ◽  
Absolute Risk Reduction ◽  
Pcsk9 Inhibitors ◽  
High Sensitivity Troponin ◽  
Cholesterol Guidelines ◽  
Very High

Introduction: The 2018 AHA/ACC cholesterol guidelines only recommend PCSK9 inhibitors in patients with very high risk ASCVD. However, high-sensitivity troponin (hsTn) can reclassify some lower risk patients as very high risk, identifying a subgroup who may benefit from PCSK9 inhibitors. Methods: We performed a nested prospective biomarker substudy including 22,224 patients enrolled in the FOURIER trial, which tested the PCSK9 inhibitor evolocumab. Per the guidelines, patients were assigned to ASCVD risk categories of “very high risk” or “not very high risk” (lower risk), followed by classification based on hsTnI (Abbott ARCHITECT) using an a priori risk threshold of 6 ng/L. The primary endpoint was a composite of CV death, MI, stroke, unstable angina, or coronary revascularization. The median follow-up was 2.2 years. Results: Clinical ASCVD categories alone identified a gradient of risk from 7.1% to 12.3% (HR 1.83, p<0.0001). Adding hsTnI further risk stratified patients by 1.5- to 2-fold in both the lower and very high risk ASCVD categories (HR 1.73, p=0.017 & HR 1.81, P<0.0001). Among patients with lower risk ASCVD, 25% had an elevated hsTnI and carried a similar risk (10.5%) to patients with very high risk ASCVD and low hsTnI (9.8%). Very high risk ASCVD patients receiving evolocumab had an absolute risk reduction of 1.9% (0.98-2.72). A similar absolute risk reduction was seen in the 25% of patients in the lower risk group with elevated hsTnI (ARR 2.0%, Figure). Conclusions: Either hsTn or ASCVD clinical criteria can identify patients who benefit from evolocumab. Specifically, hsTnI identifies a significant cohort of nominally lower risk ASCVD patients who are actually at greater risk than appreciated and may derive absolute risk reductions on par with very high risk ASCVD patients.

Nonvitamin-K-antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and previous stroke or transient ischemic attack: An updated systematic review and meta-analysis of randomized controlled trials

2017 ◽  
Vol 12 (6) ◽  
pp. 589-596 ◽  
Author(s):  
George Ntaios ◽  
Vasileios Papavasileiou ◽  
Hans-Chris Diener ◽  
Konstantinos Makaritsis ◽  
Patrik Michel
Keyword(s):  
Atrial Fibrillation ◽  
Relative Risk ◽  
Risk Reduction ◽  
Relative Risk Reduction ◽  
Absolute Risk ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Absolute Risk Reduction ◽  
Number Needed To Treat ◽  
Ischemic Attack

Background In a previous systematic review and meta-analysis, we assessed the efficacy and safety of nonvitamin-K antagonist oral anticoagulants versus warfarin in patients with atrial fibrillation and stroke or transient ischemic attack. Since then, new information became available. Aim The aim of the present work was to update the results of the previous systematic review and meta-analysis. Methods We searched PubMed until 24 August 2016 for randomized controlled trials using the following search items: “atrial fibrillation” and “anticoagulation” and “warfarin” and “previous stroke or transient ischemic attack.” Eligible studies had to be phase III trials in patients with atrial fibrillation comparing warfarin with nonvitamin-K antagonist oral anticoagulants currently on the market or with the intention to be brought to the market in North America or Europe. The outcomes assessed in the efficacy analysis included stroke or systemic embolism, stroke, ischemic or unknown stroke, disabling or fatal stroke, hemorrhagic stroke, cardiovascular death, death from any cause, and myocardial infarction. The outcomes assessed in the safety analysis included major bleeding, intracranial bleeding, and major gastrointestinal bleeding. We performed fixed effects analyses on intention-to-treat basis. Results Among 183 potentially eligible articles, four were included in the meta-analysis. In 20,500 patients, compared to warfarin, nonvitamin-K antagonist oral anticoagulants were associated with a significant reduction of stroke/systemic embolism (relative risk reduction: 13.7%, absolute risk reduction: 0.78%, number needed to treat to prevent one event: 127), hemorrhagic stroke (relative risk reduction: 50.0%, absolute risk reduction: 0.63%, number needed to treat: 157), any stroke (relative risk reduction: 13.1%, absolute risk reduction: 0.7%, number needed to treat: 142), and intracranial hemorrhage (relative risk reduction: 46.1%, absolute risk reduction: 0.88%, number needed to treat: 113) over 1.8–2.8 years. Conclusions This updated meta-analysis in 20,500 atrial fibrillation patients with previous stroke or transient ischemic attack shows that compared to warfarin non-vitamin-K antagonist oral anticoagulants are associated with a significant reduction of stroke, stroke or systemic embolism, hemorrhagic stroke, and intracranial bleeding.

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