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Expert Opinion on Drug Safety Mar 2009Antiplatelet therapy is critical in the management of coronary artery disease. For patients undergoing coronary artery bypass graft surgery (CABG), controversy remains... (Review)
Review
BACKGROUND
Antiplatelet therapy is critical in the management of coronary artery disease. For patients undergoing coronary artery bypass graft surgery (CABG), controversy remains regarding the safety of preoperative antiplatelet therapy and the optimal postoperative antiplatelet regimen to maintain graft patency and reduce ischemic complications.
OBJECTIVE
The goal of this systematic review is to evaluate the risks and benefits of preoperative aspirin and clopidogrel therapy, to identify the optimal timing and dose of aspirin following CABG, and to assess the role of postoperative clopidogrel therapy.
METHODS
A systematic review was performed to retrieve relevant articles from the Medline database published between 1978 and 2008.
RESULTS
With respect to aspirin, the published data suggest that it should be held for 7 - 10 days preoperatively in patients undergoing elective CABG. However, in the current era of routine antifibrinolytic therapy and the high prevalence of patients with extensive atherosclerotic disease, this practice has been put into question. Clopidogrel should be held for at least 5 days before CABG to avoid perioperative bleeding complications. Following surgery, extensive evidence supports the use of aspirin, in doses of 100 - 325 mg daily, to be administered in 48 h postoperatively and continued indefinitely. Less is known regarding the use of clopidogrel following CABG, although it is now recommended as postoperative antiplatelet therapy in patients with recent acute coronary syndromes.
CONCLUSION
Despite > 30 years of experience with antiplatelet agents during CABG, questions remain regarding their perioperative safety and efficacy. The results of continuing randomized controlled trials should further clarify the role of perioperative aspirin and clopidogrel therapy and help redefine the modern antiplatelet management of coronary artery bypass patients.
Topics: Aspirin; Clopidogrel; Coronary Artery Bypass; Drug Administration Schedule; Drug Therapy, Combination; Humans; Meta-Analysis as Topic; Perioperative Care; Platelet Aggregation Inhibitors; Postoperative Complications; Postoperative Period; Randomized Controlled Trials as Topic; Risk Assessment; Ticlopidine
PubMed: 19309245
DOI: 10.1517/14740330902797081 -
International Journal of Stroke :... Feb 2014Heart failure is an independent risk factor for stroke. Anticoagulation is effective for prevention of cardio-embolic stroke secondary to atrial fibrillation or... (Meta-Analysis)
Meta-Analysis Review
Efficacy and safety of warfarin vs. antiplatelet therapy in patients with systolic heart failure and sinus rhythm: a systematic review and meta-analysis of randomized controlled trials.
BACKGROUND AND PURPOSE
Heart failure is an independent risk factor for stroke. Anticoagulation is effective for prevention of cardio-embolic stroke secondary to atrial fibrillation or mechanical heart valves but is of uncertain benefit in heart failure patients. We performed this meta-analysis to obtain the best estimates of the efficacy and safety of warfarin as compared with antiplatelet therapy in patients with systolic heart failure who are in sinus rhythm.
METHODS AND RESULTS
A systematic search was performed using PubMed and Central Register of Controlled Trials databases for all randomized controlled trials, which compare warfarin with antiplatelet therapy given for at least one-month in heart failure patients with sinus rhythm and report at least one of the following outcomes: ischemic stroke, death, myocardial infarction, hospitalization due to worsening heart failure, intracranial hemorrhage, and major hemorrhage. Four randomized controlled trials involving adjusted-dose warfarin (4187 subjects) were included. When compared with antiplatelet therapy, warfarin reduced ischemic stroke by 0·74% per year (RR 0·49; 95% CI: 0·32-0·73: P = 0·0006; Number needed to treat = 135) but increased major hemorrhage by 0·99% per year (RR 2·15; 95% CI: 1·55-2·99: P < 0·00001; Number needed to harm = 101). Warfarin did not significantly affect the risk of death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage as compared with antiplatelet therapy.
CONCLUSIONS
Warfarin as compared with antiplatelet therapy reduces risk of ischemic stroke, does not significantly affect death, myocardial infarction, hospitalization due to heart failure or intracranial hemorrhage and increases major hemorrhage in heart failure patients who are in sinus rhythm.
Topics: Anticoagulants; Heart Failure, Systolic; Heart Rate; Humans; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Warfarin
PubMed: 23506160
DOI: 10.1111/ijs.12036 -
BMC Musculoskeletal Disorders Mar 2016Femoral neck fractures in the elderly make up a large proportion of Orthopaedic surgical admissions each year. Operating on patients with clopidogrel poses a challenge... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Femoral neck fractures in the elderly make up a large proportion of Orthopaedic surgical admissions each year. Operating on patients with clopidogrel poses a challenge because of the risk of bleeding and the difficulty deciding the optimal timing of surgery. The aim of this systematic review is to examine the published evidence to establish a set of guidelines for approaching neck of femur patients who are on clopidogrel.
METHODS
All comparative studies with an intervention group and a control group were considered. Data on patient blood transfusion exposures, units transfused, haemoglobin concentration and drop in haemoglobin were extracted and pooled using the fixed effects model. Heterogeneity of the intervention effect was assessed with the I (2) statistic.
RESULTS
A total of 4219 studies were identified. After removal of duplicates and after exclusion criteria were applied, there were 14 studies to be included. All 14 were case series with controls. There was no significant heterogeneity amongst the studies. Pooled odds ratio for transfusion exposures was 1.24 (95 % confidence interval 0.91 to 1.71) however this was not statistically significant (p = 0.14). No significant mean differences were found for other primary outcome measures.
CONCLUSIONS
On the available evidence, we recommend that these patients can be managed by normal protocols with early surgery. Operating early on patients on clopidogrel is safe and does not appear to confer any clinically significant bleeding risk. As reported in other studies, we believe clopidogrel, if possible, should not be withheld throughout the perioperative period due to increased risk of cardiovascular events associated with stopping clopidogrel. Care should be taken intraoperatively to minimise blood loss due to the increased potential for bleeding.
TRIAL REGISTRATION
This systematic review and meta-analysis has been registered on Research Registry on July 16, 2015. The Review Registry Unique Identifying Number is: reviewregistry61 .
Topics: Blood Loss, Surgical; Chi-Square Distribution; Clopidogrel; Drug Administration Schedule; Femoral Neck Fractures; Fracture Fixation; Humans; Odds Ratio; Platelet Aggregation Inhibitors; Risk Assessment; Risk Factors; Ticlopidine; Treatment Outcome
PubMed: 27005816
DOI: 10.1186/s12891-016-0988-9 -
Journal of Cardiovascular Pharmacology Jun 2021Dual antiplatelet therapy (DAPT) and proton pump inhibitors (PPIs) are widely used in clinical treatment. However, the pharmacokinetic interaction between PPIs and DAPT... (Meta-Analysis)
Meta-Analysis
Systematic Review and Meta-analysis: The Effects of Prophylactic Proton Pump Inhibitor Treatment in Patients With Coronary Heart Disease Receiving Dual Antiplatelet Therapy.
Dual antiplatelet therapy (DAPT) and proton pump inhibitors (PPIs) are widely used in clinical treatment. However, the pharmacokinetic interaction between PPIs and DAPT is still unclear in patients with cardiovascular disease. This systematic review and meta-analysis aimed to evaluate the risks and benefits of the combination of PPI and DAPT in patients with coronary heart disease. The PubMed, EMBASE, Cochrane, and Web of Science databases were systematically searched from inception to April 1, 2020, for eligible studies. The outcomes investigated in this study included major adverse cardiovascular events, myocardial infarction, all-cause death, gastrointestinal complications, and platelet function testing. Studies were excluded from the review if other gastrointestinal medication or aspirin or P2Y12 receptor inhibitor monotherapy was administered. The review included 52 studies, and data from 40 studies were extracted for meta-analysis. No association was found between the risk of adverse clinical outcomes and the combination of PPI and DAPT based on the randomized controlled trial data (risk ratio: 0.98; 95% confidence interval: 0.87-1.09; P = 0.877; I2 = 0%). However, an increased risk of adverse clinical outcomes due to the use of PPIs was observed in patients treated with DAPT based on the data from observational studies (risk ratio: 1.259; 95% confidence interval: 1.079-1.468; P = 0.003; I2 = 67.8%), although the heterogeneity of these studies was high. In conclusion, this systematic review and meta-analysis demonstrated that pharmacokinetic interactions between PPI and DAPT do not lead to adverse clinical outcomes.
Topics: Coronary Disease; Drug Interactions; Dual Anti-Platelet Therapy; Humans; Platelet Aggregation Inhibitors; Proton Pump Inhibitors; Randomized Controlled Trials as Topic
PubMed: 34057160
DOI: 10.1097/FJC.0000000000001014 -
Clinical Neurology and Neurosurgery Oct 2017Flow diversion with the Pipeline Embolization Device (PED) is reported as a safe and efficient treatment for patients with intracranial aneurysms; however, literature... (Review)
Review
Flow diversion with the Pipeline Embolization Device (PED) is reported as a safe and efficient treatment for patients with intracranial aneurysms; however, literature discussing the antiplatelet (APT) regimen used before and after the PED is limited. Our aim was to systematically review and summarize available data regarding the APT regimen and the platelet function test (PFT) that was used. We also sought to provide an overview of the aneurysm morphologies and adverse event rates associated with the PED use. This systematic review was conducted according to the PRISMA statement and eligible studies were identified through search of the PubMed and Cochrane databases. We reviewed 28 studies, involving 1556 patients that underwent aneurysm treatment with the PED. The preprocedural aspirin (ASA) 300- 325mg (2-14days) combined with clopidogrel 75mg (3 to >10days) were used as a treatment strategy in 61.7% of patients and ASA 81mg with clopidogrel 75mg for 5-10days for 27%. Patients who received low versus high dose pre-PED ASA, were at less risk for a hemorrhagic event (0.7% versus 3.3%, p=0.053); however no statistical significance was reached. There was also lack of relationship between patients that received low versus high preprocedural ASA in terms of thromboembolic events. Regarding postprocedural APT, ASA (>6months) and clopidogrel (3- 12 months) was the regimen of choice for 93% of patients. Most studies conducted at least one PFT, most common being the VerifyNow. The most frequently reported target P2Y12 Reaction unit (PRU) and Aspirin Reaction Unit (ARU) values were <230 and <550 respectively. There was no statistically demonstrable difference in regards to thrombotic events between centers that conducted at least one PFT and centers that did not test their patients with a PFT. The overall rates of symptomatic thrombotic episodes were 6.6% and hemorrhagic were 3%. The pre- and post-PED APT dose and duration varies across different institutions. More prospective studies are needed to compare the efficacy of different APT agents and reach conclusions regarding use of PFT and platelet reaction values in order to decrease hemorrhagic and thromboembolic complications associated with the PED.
Topics: Cerebrovascular Circulation; Embolization, Therapeutic; Humans; Intracranial Aneurysm; Platelet Aggregation Inhibitors
PubMed: 28863286
DOI: 10.1016/j.clineuro.2017.08.003 -
The Journal of Urology Oct 2014Given the lack of urology specific directives for the periprocedural management of anticoagulant and antiplatelet medications, the AUA (American Urological Association)... (Review)
Review
PURPOSE
Given the lack of urology specific directives for the periprocedural management of anticoagulant and antiplatelet medications, the AUA (American Urological Association) and ICUD (International Consultation on Urological Disease) named an international multidisciplinary panel to develop consensus based recommendations.
MATERIALS AND METHODS
A systematic literature review was queried by a methodologist for 3 questions. 1) When and in whom can anticoagulant/antiplatelet prophylaxis be stopped in preparation for surgery? 2) What procedures can be safely performed without discontinuing anticoagulant/antiplatelet prophylaxis? 3) What periprocedural strategies can adequately balance the risk of major surgical bleeding vs the risk of major thrombotic event? Hematology and cardiology guidelines, and 79 articles were selected for full review.
RESULTS
Multidisciplinary management of anticoagulant/antiplatelet medications for patients with recent thromboembolic events, mechanical cardiac valves, atrial fibrillation and cardiac stents would reduce the high morbidity and mortality of inexpertly discontinuing or modifying these lifesaving therapies. No elective procedures requiring interruption of dual antiplatelet therapies should be performed with a recent bare metal or drug eluting stent. The risk of significant bleeding complications is low for patients who require continuation of aspirin for ureteroscopy, transrectal prostate biopsies, laser prostate outlet procedures and percutaneous renal biopsy. Open extirpative prostate and renal procedures can be performed with a low risk of significant hemorrhage for patients on aspirin and those requiring heparin based bridging strategies. The current literature does not give direction on the timing of the resumption of anticoagulant/antiplatelet prophylaxis other than that it be resumed as soon as the risk of bleeding has decreased.
CONCLUSIONS
A total of 2,674 nonredundant article abstracts were obtained and assessed for relevance to key questions outlined by the panel. Overall 106 articles were selected for full text review and accepted or rejected based on the relation to the topic, quality of information and key questions. A total of 79 articles were accepted. Reasons for rejection (27 articles) included abstract only (12), insufficient information or unrelated to topic (13) and redundancy (2). We extracted study design, patient population, followup period and results from accepted articles, which serve as the evidence base.
Topics: Anticoagulants; Humans; Platelet Aggregation Inhibitors; Postoperative Complications; Thromboembolism; Urologic Diseases; Urologic Surgical Procedures; Urology
PubMed: 24859439
DOI: 10.1016/j.juro.2014.04.103 -
The Cochrane Database of Systematic... Feb 2022Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney... (Review)
Review
BACKGROUND
Antiplatelet agents are widely used to prevent cardiovascular events. The risks and benefits of antiplatelet agents may be different in people with chronic kidney disease (CKD) for whom occlusive atherosclerotic events are less prevalent, and bleeding hazards might be increased. This is an update of a review first published in 2013.
OBJECTIVES
To evaluate the benefits and harms of antiplatelet agents in people with any form of CKD, including those with CKD not receiving renal replacement therapy, patients receiving any form of dialysis, and kidney transplant recipients.
SEARCH METHODS
We searched the Cochrane Kidney and Transplant Register of Studies up to 13 July 2021 through contact with the Information Specialist using search terms relevant to this review. Studies in the Register are identified through searches of CENTRAL, MEDLINE, and EMBASE, conference proceedings, the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.
SELECTION CRITERIA
We selected randomised controlled trials of any antiplatelet agents versus placebo or no treatment, or direct head-to-head antiplatelet agent studies in people with CKD. Studies were included if they enrolled participants with CKD, or included people in broader at-risk populations in which data for subgroups with CKD could be disaggregated.
DATA COLLECTION AND ANALYSIS
Four authors independently extracted data from primary study reports and any available supplementary information for study population, interventions, outcomes, and risks of bias. Risk ratios (RR) and 95% confidence intervals (CI) were calculated from numbers of events and numbers of participants at risk which were extracted from each included study. The reported RRs were extracted where crude event rates were not provided. Data were pooled using the random-effects model. Confidence in the evidence was assessed using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach.
MAIN RESULTS
We included 113 studies, enrolling 51,959 participants; 90 studies (40,597 CKD participants) compared an antiplatelet agent with placebo or no treatment, and 29 studies (11,805 CKD participants) directly compared one antiplatelet agent with another. Fifty-six new studies were added to this 2021 update. Seven studies originally excluded from the 2013 review were included, although they had a follow-up lower than two months. Random sequence generation and allocation concealment were at low risk of bias in 16 and 22 studies, respectively. Sixty-four studies reported low-risk methods for blinding of participants and investigators; outcome assessment was blinded in 41 studies. Forty-one studies were at low risk of attrition bias, 50 studies were at low risk of selective reporting bias, and 57 studies were at low risk of other potential sources of bias. Compared to placebo or no treatment, antiplatelet agents probably reduces myocardial infarction (18 studies, 15,289 participants: RR 0.88, 95% CI 0.79 to 0.99, I² = 0%; moderate certainty). Antiplatelet agents has uncertain effects on fatal or nonfatal stroke (12 studies, 10.382 participants: RR 1.01, 95% CI 0.64 to 1.59, I² = 37%; very low certainty) and may have little or no effect on death from any cause (35 studies, 18,241 participants: RR 0.94, 95 % CI 0.84 to 1.06, I² = 14%; low certainty). Antiplatelet therapy probably increases major bleeding in people with CKD and those treated with haemodialysis (HD) (29 studies, 16,194 participants: RR 1.35, 95% CI 1.10 to 1.65, I² = 12%; moderate certainty). In addition, antiplatelet therapy may increase minor bleeding in people with CKD and those treated with HD (21 studies, 13,218 participants: RR 1.55, 95% CI 1.27 to 1.90, I² = 58%; low certainty). Antiplatelet treatment may reduce early dialysis vascular access thrombosis (8 studies, 1525 participants) RR 0.52, 95% CI 0.38 to 0.70; low certainty). Antiplatelet agents may reduce doubling of serum creatinine in CKD (3 studies, 217 participants: RR 0.39, 95% CI 0.17 to 0.86, I² = 8%; low certainty). The treatment effects of antiplatelet agents on stroke, cardiovascular death, kidney failure, kidney transplant graft loss, transplant rejection, creatinine clearance, proteinuria, dialysis access failure, loss of primary unassisted patency, failure to attain suitability for dialysis, need of intervention and cardiovascular hospitalisation were uncertain. Limited data were available for direct head-to-head comparisons of antiplatelet drugs, including prasugrel, ticagrelor, different doses of clopidogrel, abciximab, defibrotide, sarpogrelate and beraprost.
AUTHORS' CONCLUSIONS
Antiplatelet agents probably reduced myocardial infarction and increased major bleeding, but do not appear to reduce all-cause and cardiovascular death among people with CKD and those treated with dialysis. The treatment effects of antiplatelet agents compared with each other are uncertain.
Topics: Humans; Platelet Aggregation Inhibitors; Proteinuria; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 35224730
DOI: 10.1002/14651858.CD008834.pub4 -
Annals of Cardiac Anaesthesia 2016Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality... (Meta-Analysis)
Meta-Analysis Review
AIM
Platelet function is intricately linked to the pathophysiology of critical Illness, and some studies have shown that antiplatelet therapy (APT) may decrease mortality and incidence of acute respiratory distress syndrome (ARDS) in these patients. Our objective was to understand the efficacy of APT by conducting a meta-analysis.
MATERIALS AND METHODS
We conducted a meta-analysis using PubMed, Central, Embase, The Cochrane Central Register, the ClinicalTrials.gov Website, and Google Scholar. Studies were included if they investigated critically ill patients receiving antiplatelet therapy and mentioned the outcomes being studied (mortality, duration of hospitalization, ARDS, and need for mechanical ventilation).
RESULTS
We found that there was a significant reduction in all-cause mortality in patients on APT compared to control (odds ratio [OR]: 0.83; 95% confidence interval [CI]: 0.70-0.97). Both the incidence of acute lung injury/ARDS (OR: 0.67; 95% CI: 0.57-0.78) and need for mechanical ventilation (OR: 0.74; 95% CI: 0.60-0.91) were lower in the antiplatelet group. No significant difference in duration of hospitalization was observed between the two groups (standardized mean difference: -0.02; 95% CI: -0.11-0.07).
CONCLUSION
Our meta-analysis suggests that critically ill patients who are on APT have an improved survival, decreased incidence of ARDS, and decreased need for mechanical ventilation.
Topics: Acute Lung Injury; Critical Care; Critical Illness; Hospital Mortality; Humans; Platelet Aggregation Inhibitors; Respiration, Artificial
PubMed: 27716693
DOI: 10.4103/0971-9784.191576 -
Heart, Lung & Circulation Mar 2022Polycythaemia vera (PV) is a condition that may potentially put patients undergoing cardiac surgery at an increased risk of bleeding and thrombosis; however, there is... (Review)
Review
OBJECTIVES
Polycythaemia vera (PV) is a condition that may potentially put patients undergoing cardiac surgery at an increased risk of bleeding and thrombosis; however, there is currently a paucity of literature regarding the management of these patients. We aim to examine the literature in this systematic review to indicate the interventions that may be considered to minimise complications.
METHODS
We conducted a literature search using keywords and MeSH terms to identify articles discussing PV and cardiac surgery. The studies were identified and qualitatively analysed using the Preferred Reporting Items for Systematic Reviews and Meta-analysis (PRISMA) protocol.
RESULTS
In total, 10 case reports representing 11 patients were identified for this systematic review and were included in qualitative analysis. 63.6% of patients had preoperative intermittent phlebotomy, and the majority of patients received postoperative therapy that involved one antiplatelet agent and one anticoagulant. Generous perioperative fluid management, phlebotomy, preservation of core body temperature, early extubation, monitoring of myocardial ischaemia, infarction and vascular events, intense chest physiotherapy and patient mobilisation are important to consider to reduce the risk of complications arising from surgery.
CONCLUSION
These considerations should be systematically discussed in a multidisciplinary team, where the acute surgical need can be balanced appropriately against the risk of haemorrhage and thrombosis.
Topics: Anticoagulants; Coronary Artery Bypass; Humans; Platelet Aggregation Inhibitors; Polycythemia Vera; Thrombosis
PubMed: 34794873
DOI: 10.1016/j.hlc.2021.10.012 -
European Heart Journal Jun 2013Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Oral anticoagulation in addition to antiplatelet treatment after an acute coronary syndrome might reduce ischaemic events but increase bleeding risk. We performed a meta-analysis to evaluate the efficacy and safety of adding direct thrombin or factor-Xa inhibition by any of the novel oral anticoagulants (apixaban, dabigatran, darexaban, rivaroxaban, and ximelagatran) to single (aspirin) or dual (aspirin and clopidogrel) antiplatelet therapy in this setting.
METHODS AND RESULTS
All seven published randomized, placebo-controlled phase II and III studies of novel oral anticoagulants in acute coronary syndromes were included. The database consisted of 30 866 patients, 4135 (13.4%) on single, and 26 731 (86.6%) on dual antiplatelet therapy, with a non-ST- or ST-elevation acute coronary syndrome within the last 7-14 days. We defined major adverse cardiovascular events (MACEs) as the composite of all-cause mortality, myocardial infarction, or stroke; and clinically significant bleeding as the composite of major and non-major bleeding requiring medical attention according to the study definitions. When compared with aspirin alone the combination of an oral anticoagulant and aspirin reduced the incidence of MACE [hazard ratio (HR) and 95% confidence interval 0.70; 0.59-0.84], but increased clinically significant bleeding (HR: 1.79; 1.54-2.09). Compared with dual antiplatelet therapy with aspirin and clopidogrel, adding an oral anticoagulant decreased the incidence of MACE modestly (HR: 0.87; 0.80-0.95), but more than doubled the bleeding (HR: 2.34; 2.06-2.66). Heterogeneity between studies was low, and results were similar when restricting the analysis to phase III studies.
CONCLUSION
In patients with a recent acute coronary syndrome, the addition of a new oral anticoagulant to antiplatelet therapy results in a modest reduction in cardiovascular events but a substantial increase in bleeding, most pronounced when new oral anticoagulants are combined with dual antiplatelet therapy.
Topics: Acute Coronary Syndrome; Administration, Oral; Aged; Anticoagulants; Clinical Trials, Phase I as Topic; Clinical Trials, Phase II as Topic; Drug Combinations; Female; Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Treatment Outcome
PubMed: 23470494
DOI: 10.1093/eurheartj/eht049