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Current Vascular Pharmacology 2021Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clopidogrel monotherapy is guideline-recommended in symptomatic peripheral artery disease (PAD). The advent of new antithrombotic strategies prompts an updated analysis of available evidence on antiplatelet therapy for PAD.
METHODS
We searched MEDLINE, Embase and CENTRAL through January 2019 for randomised controlled trials and observational studies comparing antiplatelet therapies as monotherapy, dual therapy, or combination with anticoagulants. Efficacy (major adverse cardiovascular events, acute or chronic limb ischaemia, vascular amputation, peripheral revascularisation) and safety (all-cause mortality and overall bleeding) outcomes were evaluated via Bayesian network meta-analyses.
RESULTS
We analysed 26 randomised controlled trials. Clopidogrel (hazard ratio, HR, 0.78; 95% credible interval [CrI] 0.65-0.93) and ticagrelor (HR 0.80; 95% CrI 0.65-0.98) significantly reduced major adverse cardiovascular events risk compared with aspirin. No significant difference was observed for dual antiplatelet therapy with clopidogrel and aspirin. Vorapaxar significantly reduced limb ischaemia and revascularisation compared with placebo, while dual antiplatelet therapy with clopidogrel and aspirin showed a trend for reduced risk of amputation compared with aspirin (risk ratio 0.68; 95% CrI 0.43-1.04). For all-cause mortality, picotamide, vorapaxar, dipyridamole with aspirin, and ticlopidine showed a significantly lower risk of all-cause mortality vs aspirin. Clopidogrel and ticagrelor showed similar overall bleeding risk vs aspirin, while dual antiplatelet therapy with clopidogrel and aspirin significantly increased bleeding risk.
CONCLUSION
This updated network meta-analysis confirms that clopidogrel significantly decreases the risk of major adverse cardiovascular events compared with aspirin, without increasing bleeding risk. Clopidogrel should remain a mainstay of PAD treatment, at least in patients at higher bleeding risk.
Topics: Aspirin; Clopidogrel; Drug Therapy, Combination; Humans; Network Meta-Analysis; Peripheral Arterial Disease; Platelet Aggregation Inhibitors; Treatment Outcome
PubMed: 32819249
DOI: 10.2174/1570161118666200820141131 -
Annals of Translational Medicine Mar 2022It is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic...
BACKGROUND
It is still uncertain which antiplatelet regimen had the greatest net clinical benefit in patients who have suffered a transient ischemic attack or non-cardioembolic ischemic stroke, and it is necessary to choose the optimal regimen according to the clinical situation.
METHODS
We utilized 3 databases of Medline, Embase, and the Cochrane Central Register of Controlled Trials to find randomized controlled trials that met our criteria, and performed network meta-analyses in recurrent stroke, composite outcomes, major bleeding events, recurrent ischemic stroke, and all bleeding events. Three-dimensional clustered rank plots were used to obtain the net clinical benefit. Subgroup analyses were performed according to the symptom-onset-to-treatment time (<72 and >72 h), stroke subtypes (large artery atherosclerosis and small vessel occlusion), and dual antiplatelet agent treatment duration.
RESULTS
A total of 69 trials were enrolled. Cilostazol was associated with a lower risk of recurrent stroke, major bleeding events, composite outcomes, recurrent ischemic stroke, and all bleeding events compared to low to medium dose aspirin. The three-dimensional rank plot showed that cilostazol had the highest net clinical benefit. The combination of aspirin plus clopidogrel had greater efficacy in the <72 h after stroke onset and large artery atherosclerosis subgroups, and when it was restricted to1 month of use major bleeding risk was not higher than aspirin. The combination of aspirin plus dipyridamole had greater efficacy and safety comparable to aspirin in terms of small vessel occlusion.
CONCLUSIONS
The efficacy and safety profiles among antiplatelet regimens may differ according to clinical situation, although cilostazol, aspirin plus clopidogrel, and aspirin plus dipyridamole may be considered as preferable options.
PubMed: 35402589
DOI: 10.21037/atm-21-3748 -
The Cochrane Database of Systematic... Jul 2013Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimise this risk. An important issue is the effectiveness and safety of the latter strategy.
OBJECTIVES
This is an update of our previous review; the goal was to create a valid synthesis of all available, methodologically sound data to further assess the safety and efficacy of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulant monotherapy in patients with prosthetic heart valves.
SEARCH METHODS
We updated the previous searches from 2003 and 2010 on 16 January 2013 and searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 12), MEDLINE (OVID, 1946 to January Week 1 2013), and EMBASE (OVID, 1980 to 2013 Week 02). We have also looked at reference lists of individual reports, review articles, meta-analyses, and consensus statements. We included reports published in any language or in abstract form.
SELECTION CRITERIA
All reports of randomised controlled trials comparing standard-dose oral anticoagulation to standard-dose oral anticoagulation and antiplatelet therapy in patients with one or more prosthetic heart valves.
DATA COLLECTION AND ANALYSIS
Two review authors independently performed the search strategy, assessed trials for inclusion and study quality, and extracted data. We collected adverse effects information from the trials.
MAIN RESULTS
One new study has been identified and included in this update. In total, 13 studies involving 4122 participants were included in this review update. Years of publication ranged from 1971 to 2011. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P < 0.00001) and total mortality (OR 0.57, 95% CI 0.42 to 0.78; P = 0.0004). Aspirin and dipyridamole reduced these events similarly. The risk of major bleeding was increased when antiplatelet agents were added to oral anticoagulants (OR 1.58, 95% CI 1.14 to 2.18; P = 0.006).For major bleeding, there was no evidence of heterogeneity between aspirin and dipyridamole and in the comparison of trials performed before and after 1990, around the time when anticoagulation standardisation with the international normalised ratio was being implemented. A lower daily dose of aspirin (< 100 mg) may be associated with a lower major bleeding risk than higher doses.
AUTHORS' CONCLUSIONS
Adding antiplatelet therapy, either dipyridamole or low-dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events. The effectiveness and safety of low-dose aspirin (100 mg daily) appears to be similar to higher-dose aspirin and dipyridamole. In general, the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).
Topics: Administration, Oral; Anticoagulants; Aspirin; Dipyridamole; Drug Therapy, Combination; Heart Valve Prosthesis; Hemorrhage; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Thromboembolism
PubMed: 23839768
DOI: 10.1002/14651858.CD003464.pub2 -
Pharmacological Research Oct 2020Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk... (Meta-Analysis)
Meta-Analysis
CONTEXT
Ticagrelor was related to bradycardia in DISPERSE-II trial. This risk has been integrated into the European risk-management plan, and its use is warned in at-risk patients. Nevertheless, this risk was not systematically assessed nor measured.
OBJECTIVES
To estimate the risk of bradyarrhythmia associated with ticagrelor.
STUDY DESIGN
Systematic review and meta-analysis.
DATA-SOURCE
MEDLINE, Scopus, Cochrane Central Register of Controlled Trials, ISI web of Science, clinicaltrial.gov, clinicaltrialsregister.eu.
STUDY SELECTION
Randomized controlled trials (RCTs) and observational studies in patients treated with ticagrelor or comparator(s).
META-ANALYSIS
Risk of bias in each RCT was assessed using Cochrane tool. Relative Risks (RR) with 95 % confidence intervals (95 %CI) were calculated for each RCT, and pooled using fixed-effect or random-effects models, when appropriate. Subgroup and sensitivity analyses were performed. A potential publication bias was searched.
RESULTS
Among 82 eligible studies, event data were missing for 56 studies, due to detected reporting bias (i.e. inability to confirm zero events). Fifteen RCTs were selected and the combined RR of bradyarrhythmia was 1.15 (95 %CI 1.05-1.26), and 1.29 (1.02-1.65) for severe bradyarrhythmia. The risk appeared to be dose dependent. Restricting the analysis only to RCTs performed in patients without previous bradyarrhythmia resulted in a non-increased risk.
CONCLUSION
This meta-analysis confirmed the risk of bradyarrhythmia or severe bradyarrhythmia related to ticagrelor, and its use in patients without previous bradycardia was effective in preventing it. The evidence coming from this meta-analysis was low to moderate due to missing outcome in 2/3 of eligible studies. Waiting for access to these data, the use of ticagrelor in patients with risk factors of bradycardias should be avoided.
Topics: Aged; Bradycardia; Female; Heart Rate; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists; Risk Assessment; Risk Factors; Ticagrelor
PubMed: 32687950
DOI: 10.1016/j.phrs.2020.105089 -
The Cochrane Database of Systematic... 2003Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimize this risk. An important issue is the effectiveness and safety of the latter strategy.
OBJECTIVES
To compare the effectiveness and safety of adding antiplatelet therapy to standard oral anticoagulation among patients with prosthetic heart valves.
SEARCH STRATEGY
We searched the Cochrane Central Register of Controlled Trials (Cochrane Library Issue 2, 2003), MEDLINE (January 1966 to August 2002), EMBASE (January 1988 to July 2001) and reference lists of individual reports, review articles, meta-analyses, and consensus statements.
SELECTION CRITERIA
All reports of randomised controlled trials comparing standard dose oral anticoagulation to standard dose oral anticoagulation and antiplatelet therapy in patients with one or more prosthetic heart valves. We included reports published in any language or in abstract form.
DATA COLLECTION AND ANALYSIS
Two reviewers independently performed the search strategy, assessed trials for inclusion criteria, study quality, and extracted data. Adverse effects information was collected from the trials.
MAIN RESULTS
Eleven studies involving 2,428 subjects met the inclusion criteria. Year of publication ranged from 1971 to 2000. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio 0.39 (95% confidence interval 0.28 to 0.56; p<0.00001)) and total mortality (odds ratio 0.55 (95% confidence interval 0.40 to 0.77; p=0.0003)). Aspirin and dipyridamole reduced these events similarly. The risk of major bleeding was increased when antiplatelet agents were added to oral anticoagulants (odds ratio 1.66 (95% confidence interval 1.18 to 2.34; p=0.003)). For major bleeding, there was no evidence of heterogeneity between aspirin and dipyridamole and in the comparison of trials performed before and after 1990, around the time when anticoagulation standardization with the international normalized ratio was being implemented.
REVIEWER'S CONCLUSIONS
Adding antiplatelet therapy, either dipyridamole or low-dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events. The effectiveness and safety of low dose aspirin (100 mg daily) appears to be similar to higher dose aspirin and dipyridamole.
Topics: Anticoagulants; Aspirin; Dipyridamole; Heart Valve Prosthesis; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Thromboembolism
PubMed: 14583979
DOI: 10.1002/14651858.CD003464 -
Platelets 2015The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition... (Meta-Analysis)
Meta-Analysis Review
The majority of patients with ischaemic cerebrovascular disease (CVD) are not protected from further vascular events with antiplatelet therapy. Measurement of inhibition of platelet function ex vivo on antiplatelet therapy, using laboratory tests that correlate with the clinical effectiveness of these agents, would potentially enable physicians to tailor antiplatelet therapy to suit individuals. A systematic review of the literature was performed to collate all available data on ex vivo platelet function/reactivity in CVD patients, especially those treated with aspirin, dipyridamole or clopidogrel. Particular emphasis was paid to information from commonly available whole blood platelet function analysers (PFA-100®, VerifyNow® and Multiplate®). Data on pharmacogenetic mechanisms potentially influencing high on-treatment platelet reactivity (HTPR) on antiplatelet therapy in CVD were reviewed. Two-hundred forty-nine potentially relevant articles were identified; 93 manuscripts met criteria for inclusion. The prevalence of ex vivo HTPR in CVD varies between 3-62% with aspirin monotherapy, 8-61% with clopidogrel monotherapy and 56-59% when dipyridamole is added to aspirin in the early, subacute or late phases after TIA/stroke onset. The prevalence of HTPR on aspirin was higher on the PFA-100 than on the VerifyNow in one study (p < 0.001). Furthermore, the prevalence of HTPR on aspirin was lower when one used 'novel longitudinal' rather than 'cross-sectional, case-control' definitions of HTPR on the PFA early after TIA or stroke (p = 0.003; 1 study). Studies assessing the influence of genetic polymorphisms on HTPR in CVD patients are limited, and need validation in large multicentre studies. Available data illustrate that an important proportion of CVD patients have ex vivo HTPR on their prescribed antiplatelet regimen, and that the prevalence varies depending on the definition and assay used. Large, adequately-sized, prospective multicentre collaborative studies are urgently needed to determine whether comprehensive assessment of HTPR at high and low shear stress with a range of user-friendly whole blood platelet function testing platforms, in conjunction with pharmacogenetic data, improves our ability to predict the risk of recurrent vascular events in CVD patients, and thus enhance secondary prevention following TIA or ischaemic stroke.
Topics: Animals; Blood Platelets; Humans; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Platelet Function Tests; Prevalence; Stroke
PubMed: 26042726
DOI: 10.3109/09537104.2015.1049139 -
Annals of Internal Medicine Oct 2013Dual-antiplatelet regimens for prevention of recurrent stroke promote antithrombotic effects but may increase the risk for hemorrhage. (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Dual-antiplatelet regimens for prevention of recurrent stroke promote antithrombotic effects but may increase the risk for hemorrhage.
PURPOSE
To qualitatively and quantitatively examine the risk for recurrent stroke and intracranial hemorrhage (ICH) linked to long-term dual- and single-antiplatelet therapy among patients with ischemic stroke and transient ischemic attack.
DATA SOURCES
PubMed, EMBASE, and the Cochrane Central Register of Controlled Trials through March 2013 without language restrictions.
STUDY SELECTION
The search identified 7 randomized, controlled trials that involved a total of 39,574 participants and reported recurrent stroke and ICH as outcome measures.
DATA EXTRACTION
All data from eligible studies were independently abstracted by 2 investigators according to a standard protocol.
DATA SYNTHESIS
Recurrent stroke risk did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (relative risk [RR], 0.89 [95% CI, 0.78 to 1.01]) or clopidogrel monotherapy (RR, 1.01 [CI, 0.93 to 1.08]). Risk for ICH did not differ between patients receiving dual-antiplatelet therapy and those receiving aspirin monotherapy (RR, 0.99 [CI, 0.70 to 1.42]) but was greater among patients receiving dual-antiplatelet therapy than among those receiving clopidogrel monotherapy (RR, 1.46 [CI, 1.17 to 1.82]).
LIMITATION
Agents used in dual- and single-antiplatelet therapies varied across trials, and the relatively modest number of trials limited subgroup analysis.
CONCLUSION
Compared with monotherapy, dual-antiplatelet therapy lasting more than 1 year after an index ischemic stroke or transient ischemic attack is not associated with a greater reduction in overall recurrent stroke risk. However, long-term dual-antiplatelet therapy is linked to higher risk for ICH than clopidogrel monotherapy in this patient population.
PRIMARY FUNDING SOURCE
Chang Gung Memorial Hospital.
Topics: Anticoagulants; Aspirin; Brain Ischemia; Clopidogrel; Dipyridamole; Drug Therapy, Combination; Humans; Intracranial Hemorrhages; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Risk Assessment; Secondary Prevention; Stroke; Ticlopidine
PubMed: 24081287
DOI: 10.7326/0003-4819-159-7-201310010-00006 -
European Journal of Cardio-thoracic... Oct 2012Left ventricular assist devices (LVADs) are increasingly being used as a bridge to heart transplantation or destination therapy. It is unclear which antithrombotic... (Review)
Review
Left ventricular assist devices (LVADs) are increasingly being used as a bridge to heart transplantation or destination therapy. It is unclear which antithrombotic regimen should be used to reduce the risk of stroke. We systematically reviewed the literature on all types of antithrombotic regimens and stroke in patients with any type of LVADs. Our primary outcome measure was the mean incidence of any type of stroke. Twenty-six articles were selected as relevant, comprehending 1989 patients with a mean LVAD support of 200 days (range 30-621). The mean proportion of patients affected with stroke was 20% (range 0-55%), with a mean incidence of 0.74 (range 0-6.91) events/patient-year. Support with HeartMate II and a regimen of postoperative heparin converted to coumarins, acetylsalicylic acid (ASA) and dipyridamole resulted in 0.17 (mean; range 0.06-0.29) strokes/patient-year. HeartMate II support and the same regime without heparin was associated with 0.07 (mean; range 0.03-0.11) strokes/patient-year. A Novacor device with heparin, converted to coumarins, was associated with 3.82 (mean; range 1.03-6.91) strokes/patient-year, while ASA added to this regime resulted in 0.97 ischaemic strokes/patient-year (mean; range 0.53-1.48). Other combinations of assist devices and antithrombotic regimes were investigated in one or two studies only. This systematic review provides risk estimates for stroke for various LVADs and antithrombotic regimes. Our findings indicate that the postoperative use of heparin in HeartMate II patients is doubtful, and suggest an important role for antiplatelet drugs to prevent stroke in patients supported with a Novacor device.
Topics: Drug Administration Schedule; Drug Therapy, Combination; Fibrinolytic Agents; Heart-Assist Devices; Humans; Incidence; Postoperative Care; Postoperative Complications; Risk; Stroke
PubMed: 22659892
DOI: 10.1093/ejcts/ezs320 -
European Journal of Clinical... Jan 2023To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS). (Meta-Analysis)
Meta-Analysis
PURPOSE
To comprehensively compare the efficacy of different antiplatelet therapies for secondary prevention of lacunar stroke (LS).
METHODS
The relevant studies were identified by searching PubMed, EMBASE, Web of Science, and Cochrane Collaboration Database up to May 2022. Cardiovascular and cerebrovascular events were chosen to evaluate the efficacy of antiplatelet therapy for secondary prevention. Loop-specific approach and node-splitting analysis were used to evaluate consistency and inconsistency, respectively. The value of the surface under the cumulative ranking (SUCRA) was calculated and ranked. Funnel-plot symmetry was used to evaluate publication bias. The meta-analysis was performed by using STATA 16.0.
RESULTS
Thirteen studies with a total of 33,011 subjects were included in this network meta-analysis. Compared with placebo, aspirin, clopidogrel, cilostazol, ticlopidine, aspirin plus dipyridamole, and aspirin plus clopidogrel were associated with reducing cardiovascular and cerebrovascular events. The SUCRA estimated relative ranking of treatments showed that cilostazol may be the most effective (RR 0.56, 95% CI 0.42-0.74, SUCRA 95.8). No significant inconsistency or publication bias was found in the study.
CONCLUSIONS
This meta-analysis suggests that cilostazol may be a priority option for secondary prevention of patients with LS. These findings still need further study in the future.
Topics: Humans; Platelet Aggregation Inhibitors; Clopidogrel; Cilostazol; Secondary Prevention; Network Meta-Analysis; Stroke, Lacunar; Aspirin; Drug Therapy, Combination; Stroke
PubMed: 36342528
DOI: 10.1007/s00228-022-03413-z -
Stroke Apr 2012Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono... (Comparative Study)
Comparative Study Meta-Analysis Review
Dual or mono antiplatelet therapy for patients with acute ischemic stroke or transient ischemic attack: systematic review and meta-analysis of randomized controlled trials.
BACKGROUND AND PURPOSE
Antiplatelets are recommended for patients with acute noncardioembolic stroke or transient ischemic attack. We compared the safety and efficacy of dual versus mono antiplatelet therapy in patients with acute ischemic stroke or transient ischemic attack.
METHODS
Completed randomized controlled trials of dual versus mono antiplatelet therapy in patients with acute (≤3 days) ischemic stroke/transient ischemic attack were identified using electronic bibliographic searches. The primary outcome was recurrent stroke (ischemic, hemorrhagic, unknown; fatal, nonfatal). Comparison of binary outcomes between treatment groups was analyzed with random effect models and described using risk ratios (95% CI).
RESULTS
Twelve completed randomized trials involving 3766 patients were included. In comparison with mono antiplatelet therapy, dual therapy (aspirin+dipyridamole and aspirin+clopidogrel) significantly reduced stroke recurrence, dual 58 (3.3%) versus mono 91 (5.0%; risk ratio, 0.67; 95% CI, 0.49-0.93); composite vascular event (stroke, myocardial infarction, vascular death), dual 74 (4.4%) versus mono 106 (6%; risk ratio, 0.75; 95% CI, 0.56-0.99); and the combination of stroke, transient ischemic attack, acute coronary syndrome, and all death, dual 100 (1.7%) versus mono 136 (9.1%; risk ratio, 0.71; 95% CI, 0.56-0.91); dual therapy was also associated with a nonsignificant trend to increase major bleeding, dual 15 (0.9%) versus mono 6 (0.4%; risk ratio, 2.09; 95% CI, 0.86-5.06).
CONCLUSIONS
Dual antiplatelet therapy appears to be safe and effective in reducing stroke recurrence and combined vascular events in patients with acute ischemic stroke or transient ischemic attack as compared with mono therapy. These results need to be tested in prospective studies.
Topics: Acute Coronary Syndrome; Adult; Aged; Aged, 80 and over; Aspirin; Brain Ischemia; Clopidogrel; Databases, Factual; Dipyridamole; Disease-Free Survival; Drug Therapy, Combination; Female; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Recurrence; Stroke; Survival Rate; Ticlopidine
PubMed: 22282894
DOI: 10.1161/STROKEAHA.111.637686