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Biomedicines Apr 2023Major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke and cardiovascular death, cause substantial morbidity and mortality. This review... (Review)
Review
Major adverse cardiovascular events (MACE), including myocardial infarction (MI), stroke and cardiovascular death, cause substantial morbidity and mortality. This review assessed the incidence rate of MACE and the association with modifiable risk factors (diabetes, hypertension) and medication use (aspirin, statins) in patients with unrepaired abdominal aortic aneurysm (AAA). Electronic databases were searched systematically for observational studies reporting the incidence of MI, stroke or cardiovascular death in patients with unrepaired AAAs. The primary outcome was cardiovascular death reported as an incidence rate (events per 100 person-years (PY)). Fourteen studies, including 69,579 participants with a mean follow-up time of 5.4 years, were included. Meta-analysis revealed the overall incidence of cardiovascular death, MI and stroke of 2.31 per 100 PY (95% CI, 1.63-3.26; I = 98%), 1.65 per 100 PY (95% CI, 1.01-2.69, I = 88%) and 0.89 per 100 PY (95% CI, 0.53-1.48, I = 87.0%), respectively. The mean rates of statin and aspirin prescriptions were 58.1% and 53.5%, respectively. In conclusion, there is a substantial incidence of MACE in patients with unrepaired AAA, but the prescription of preventative medication is suboptimal. Greater emphasis should be placed on secondary prevention in this population.
PubMed: 37189797
DOI: 10.3390/biomedicines11041178 -
ARYA Atherosclerosis May 2023Ticagrelor monotherapy after short-term (1-3 months) dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events...
Cardiovascular and Bleeding Events of Ticagrelor Monotherapy after Short-term Dual Antiplatelet Therapy (DAPT) in Diabetics and Non-Diabetics Patients Undergoing Percutaneous Coronary Intervention: A Systematic Review and Meta-Analysis.
INTRODUCTION
Ticagrelor monotherapy after short-term (1-3 months) dual antiplatelet therapy (DAPT) with aspirin and ticagrelor can reduce bleeding without increasing ischemic events after percutaneous coronary intervention (PCI). However, its effect in diabetic and non-diabetic individuals has not been evaluated as a meta-analysis so far.
METHOD
This systematic review and meta-analysis were conducted covering PubMed, ISI Web of Science, and Scopus without date restrictions for English published clinical trials. The authors searched the mentioned databases, wherein the screening led to 151 studies, of which 40 were assessed for eligibility, and finally, three studies were included. These trials compared ticagrelor monotherapy after a short duration of aspirin plus ticagrelor with conventional 12 months DAPT.
RESULTS
The results showed that the risk of major bleeding (based on Bleeding Academic Research Consortium (BARC) type 3 or 5) for ticagrelor monotherapy subjects was lower in both diabetics and non-diabetics. It was especially significant in non-diabetic patients (HR 95%CI: 0.79(0.64, 0.98); p=0.029). In cardiovascular events assessment, the pooled estimate on cardiac deaths was significantly lower in diabetic subjects treated by ticagrelor monotherapy (HR 95%CI: 0.71(0.51, 1); p=0.05), while this reduction was not significant for non-diabetics (p=0.843) in comparison to patients treated by 12 months DAPT. However, there was no significant decrease or rise in myocardial infarction (MI) and ischemic stroke in patients treated by short-term DAPT strategy.
CONCLUSION
In conclusion, discontinuing aspirin after short-duration DAPT could minimize the incidence of cardiac death and BARC type 3 or 5 bleeding in diabetic and non-diabetic patients who underwent PCI, with no increase in MI and ischemic stroke.
PubMed: 38881589
DOI: 10.48305/arya.2022.26680.2821 -
Cardiology 2023The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing... (Comparative Study)
Comparative Study Meta-Analysis
Safety and Efficacy of Ticagrelor versus Clopidogrel in East Asian Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention Treated with Dual Antiplatelet Therapy: A Meta-Analysis of Randomized Controlled Trials.
INTRODUCTION
The treatment strategy for dual antiplatelet therapy (DAPT) with ticagrelor has been controversial in East Asian patients with acute coronary syndrome (ACS) undergoing percutaneous coronary intervention (PCI). Our meta-analysis aimed to demonstrate whether intensified antithrombotic regimens with ticagrelor plus aspirin have more beneficial effects and fewer adverse events compared to those of clopidogrel plus aspirin in East Asian patients with ACS undergoing PCI.
METHODS
We searched PubMed, Embase, Web of Science, ScienceDirect, Clinical Trials, Cochrane Library, and Chinese Clinical Trial Registry for randomized controlled trials (RCTs) comparing the efficacy of DAPT with ticagrelor or clopidogrel plus aspirin for secondary prevention of ACS in East Asian patients undergoing PCI. Risk ratios (RRs) and 95% confidence intervals (CIs) were used as the metrics of choice for assessing treatment effects. The primary endpoint was bleeding events, and the secondary endpoints were major adverse cardiovascular and cerebrovascular events (MACCEs, including cardiovascular death, nonfatal myocardial infarction [MI], and stroke), all-cause death, and definite/probable/possible stent thrombosis. The I2 index was used to assess heterogeneity.
RESULTS
Six RCTs involving a total of 2,725 patients met the inclusion criteria. The incidence of all bleeding events with ticagrelor was higher than that with clopidogrel (RR, 1.65; 95% CI, 1.31-2.07), but the incidence of MACCE was not significantly different between the two groups (RR, 1.08; 95% CI, 0.54-2.16). All-cause death (RR, 1.10; 95% CI, 0.67-1.79), cardiovascular death (RR, 1.42; 95% CI, 0.68-2.98), nonfatal MI (RR, 0.92; 95% CI, 0.48-1.78), stroke (RR, 1.00; 95% CI, 0.40-2.50), and stent thrombosis (RR, 0.76; 95% CI, 0.19-2.98) were not statistically different between the two groups.
CONCLUSION
Ticagrelor increased the risk of bleeding and did not increase treatment efficacy compared to that of clopidogrel in the East Asian population who have ACS treated with PCI.
Topics: Humans; Acute Coronary Syndrome; Aspirin; Clopidogrel; East Asian People; Hemorrhage; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Randomized Controlled Trials as Topic; Stroke; Ticagrelor; Treatment Outcome
PubMed: 37094558
DOI: 10.1159/000530602 -
Frontiers in Cardiovascular Medicine 2023Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and... (Review)
Review
BACKGROUD
Antithrombotic therapy is the cornerstone of chronic coronary syndrome (CCS) management. However, the best treatment option that optimally balances bleeding risk and efficacy remains undefined. Our objective was to evaluate the effectiveness and safety of antithrombotic options and identify the optimal treatment option for patients with CCS.
METHODS
We used the MEDLINE, CENTRAL and Embase databases to search for randomized controlled trials with follow-up periods longer than 12 months that compared aspirin (ASA) monotherapy with other antithrombotic therapies in patients with CCS. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were used. Extracted data [hazard ratios (HR)] were pooled using Bayesian fixed-effect models, allowing the estimation of credible intervals (CrI) and posterior probabilities of benefit, harm, and practical equivalence. Confidence in the results was assessed with the Confidence In Network Meta-Analysis (CINeMA) tool. The primary efficacy and safety outcomes were major adverse cardiovascular events (MACE) and primary bleeding, respectively. Secondary outcomes were acute myocardial infarction, ischemic stroke, all-cause, and cardiovascular-specific mortality.
RESULTS
Five trials with a total of 80,605 patients were included. Mean patient age ranged from 61 to 69 years, while 20.3% to 31.4% were women. The reference treatment was ASA monotherapy. ASA + prasugrel 10 mg and clopidogrel 75 mg monotherapy presented the greatest benefit for MACE [HR 0.52 (95% CrI, 0.39-0.71); and 0.68 (95% CrI, 0.54-0.88)]. There was a probability of 98.8% that ASA + ticagrelor was practically equivalent to ASA monotherapy. Regarding the primary bleeding outcome, clopidogrel 75 mg monotherapy performed best [HR 0.64 (0.42, 0.99)]. There was a probability of 97.4% that ASA + Prasugrel 10 mg increases bleeding (HR > 1.0). Secondary outcome results followed a similar treatment ranking pattern as in primary outcomes. Overall, CINeMA confidence ratings were judged as either low or very low.
CONCLUSIONS
These results revealed that clopidogrel monotherapy might provide the best risk-benefit balance in treating CCS. However, low CINeMA confidence ratings may preclude more forceful conclusions. Our analysis suggests that current guidelines recommending ASA as first-line therapy for CCS management need to be revised to include additional pharmacological options.
PubMed: 37089879
DOI: 10.3389/fcvm.2023.1040936 -
European Neurology 2023Currently, 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... (Meta-Analysis)
Meta-Analysis
INTRODUCTION
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.
METHODS
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.
RESULTS
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.
CONCLUSION
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: Humans; Aspirin; Clopidogrel; Ticagrelor; Ischemic Attack, Transient; Platelet Aggregation Inhibitors; Drug Therapy, Combination; Stroke; Hemorrhage; Intracranial Hemorrhages; Ischemic Stroke; Treatment Outcome
PubMed: 37068471
DOI: 10.1159/000530504 -
Chinese Medical Journal Apr 2023Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Many nutritional supplements and pharmacological agents have been reported to show preventive effects on colorectal adenoma and colorectal cancer (CRC). We performed a network meta-analysis to summarize such evidence and assess the efficacy and safety of these agents.
METHODS
We searched PubMed, Embase, and the Cochrane Library for studies published in English until October 31, 2021 that fit our inclusion criteria. We performed a systematic review and network meta-analysis to assess the comparative efficacy and safety of candidate agents (low-dose aspirin [Asp], high-dose Asp, cyclooxygenase-2 inhibitors [coxibs], calcium, vitamin D, folic acid, ursodeoxycholic acid [UDCA], estrogen, and progesterone, alone or in combination) for preventing colorectal adenoma and CRC. Cochrane risk-of-bias assessment tool was employed to evaluate the quality of each included study.
RESULTS
Thirty-two randomized controlled trials (278,694 participants) comparing 13 different interventions were included. Coxibs significantly reduced the risk of colorectal adenoma (risk ratio [RR]: 0.59, 95% confidence interval [CI]: 0.44-0.79, six trials involving 5486 participants), advanced adenoma (RR: 0.63, 95% CI: 0.43-0.92, four trials involving 4723 participants), and metachronous adenoma (RR: 0.58, 95% CI: 0.43-0.79, five trials involving 5258 participants) compared with placebo. Coxibs also significantly increased the risk of severe adverse events (RR: 1.29, 95% CI: 1.13-1.47, six trials involving 7109 participants). Other interventions, including Asp, folic acid, UDCA, vitamin D, and calcium, did not reduce the risk of colorectal adenoma in the general and high-risk populations compared with placebo.
CONCLUSIONS
Considering the balance between benefits and harms, regular use of coxibs for prevention of colorectal adenoma was not supported by the current evidence. Benefit of low-dose Asp for chemoprevention of colorectal adenoma still requires further evidence.
REGISTRATION
PROSPERO, No. CRD42022296376.
Topics: Humans; Cyclooxygenase 2 Inhibitors; Calcium; Network Meta-Analysis; Vitamins; Colorectal Neoplasms; Chemoprevention; Aspirin; Adenoma; Vitamin D
PubMed: 37027286
DOI: 10.1097/CM9.0000000000002514 -
European Cardiology 2024Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A... (Review)
Review
Dual-pathway Inhibition with Low-dose Aspirin and Rivaroxaban versus Aspirin Monotherapy in Patients with Coronary Artery Disease and Peripheral Artery Disease: Systematic Literature Review and Meta-analysis.
BACKGROUND
Low-dose aspirin lowers cardiovascular event risk; dual-pathway inhibition (DPI) using low-dose aspirin with low-dose rivaroxaban may reduce this risk further. A systematic literature review and meta-analysis compared the efficacy, safety and net clinical benefit (NCB) of DPI with aspirin.
METHODS
PubMed and Embase were searched for randomised controlled trials reporting clinical efficacy, safety and NCB of DPI compared with aspirin alone in patients with coronary artery disease (CAD) and/or peripheral artery disease. Six articles representing four trials were included.
RESULTS
DPI versus aspirin alone significantly reduced major adverse cardiovascular events (HR 0.77; 95% CI [0.69-0.87]; p<0.01), increased International Society on Thrombosis and Haemostasis major bleeding events (HR 1.67; 95% CI [1.37-2.02]; p<0.01) and resulted in a significant NCB (HR 0.79; 95% CI [0.70-0.90]; p<0.01).
CONCLUSION
These results underscore the potential benefit of DPI in patients with CAD, including those in the immediate post-acute coronary syndrome stage and with established CAD, as well as patients with peripheral artery disease.
PubMed: 38708371
DOI: 10.15420/ecr.2023.40 -
Frontiers in Physiology 2023Preeclampsia is a progressive, multisystem pregnancy disorder. According to the time of onset or delivery, preeclampsia has been subclassified into early-onset...
Preeclampsia is a progressive, multisystem pregnancy disorder. According to the time of onset or delivery, preeclampsia has been subclassified into early-onset (<34 weeks) and late-onset (≥34 weeks), or preterm (<37 weeks) and term (≥37 weeks). Preterm preeclampsia can be effectively predicted at 11-13 weeks well before onset, and its incidence can be reduced by preventively using low-dose aspirin. However, late-onset and term preeclampsia are more prevalent than early forms and still lack effective predictive and preventive measures. This scoping review aims to systematically identify the evidence of predictive biomarkers reported in late-onset and term preeclampsia. This study was conducted based on the guidance of the Joanna Briggs Institute (JBI) methodology for scoping reviews. The Preferred Reporting Items for Systematic Reviews and Meta-Analysis extension for scoping reviews (PRISMA-ScR) was used to guide the study. The following databases were searched for related studies: PubMed, Web of Science, Scopus, and ProQuest. Search terms contain "preeclampsia," "late-onset," "term," "biomarker," or "marker," and other synonyms combined as appropriate using the Boolean operators "AND" and "OR." The search was restricted to articles published in English from 2012 to August 2022. Publications were selected if study participants were pregnant women and biomarkers were detected in maternal blood or urine samples before late-onset or term preeclampsia diagnosis. The search retrieved 4,257 records, of which 125 studies were included in the final assessment. The results demonstrate that no single molecular biomarker presents sufficient clinical sensitivity and specificity for screening late-onset and term preeclampsia. Multivariable models combining maternal risk factors with biochemical and/or biophysical markers generate higher detection rates, but they need more effective biomarkers and validation data for clinical utility. This review proposes that further research into novel biomarkers for late-onset and term preeclampsia is warranted and important to find strategies to predict this complication. Other critical factors to help identify candidate markers should be considered, such as a consensus on defining preeclampsia subtypes, optimal testing time, and sample types.
PubMed: 36969613
DOI: 10.3389/fphys.2023.1143543 -
Kidney360 May 2023Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the... (Meta-Analysis)
Meta-Analysis
Postprocedural bleeding is the main complication of percutaneous kidney biopsy (PKB). Therefore, aspirin is routinely withheld in patients undergoing PKB to reduce the bleeding risk. The authors aimed to examine the association between aspirin use and bleeding during PKB. This systematic review and meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The article search was performed on MEDLINE and Scopus using queries specific to each database. Article inclusion was limited to primary studies. The meta-analysis compared the risk of major bleeding events between the aspirin-exposed versus nonexposed group. Pooled effect estimate was examined using random effects presented as odds ratio with 95% confidence intervals. Heterogeneity was assessed through Cochrane I 2 test statistics. Sensitivity and subgroup analyses were also performed according to kidney type. Ten studies were included in the review and four studies were included in the meta-analysis, reviewing a total of 34,067 PKBs. Definitions for significant aspirin exposure were inconsistent between studies, limiting comparisons. Studies with broader definitions for aspirin exposure mostly showed no correlation between aspirin use and postbiopsy bleeding. Studies with strict definitions for aspirin exposure found an increased risk of hemorrhagic events in the aspirin-exposed group. No significant differences were found between the aspirin-exposed and comparison groups regarding major bleeding events (odds ratio 1.72; 95% confidence interval 0.50 to 5.89, I 2 =84%). High-quality evidence on the effect of aspirin on the bleeding risk is limited. Our meta-analysis did not show a significantly increased risk of major bleeding complications in aspirin-exposed patients. Further studies are needed to define a more comprehensive approach for clinical practice.
Topics: Humans; Aspirin; Hemorrhage; Kidney; Biopsy
PubMed: 36951435
DOI: 10.34067/KID.0000000000000091 -
Frontiers in Endocrinology 2023Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Clopidogrel is a cornerstone antiplatelet drug used in cardiovascular, cerebrovascular, and peripheral artery diseases. The sulfhydryl group of clopidogrel metabolite could induce insulin autoimmune syndrome (IAS) with hypoglycemia as the major symptom. Discontinuing clopidogrel and substituting it with ticagrelor has been revealed as an effective treatment in previous studies. Since hypoglycemia serves as a risk factor for cardiovascular and cerebrovascular events, we aimed to determine the association between hypoglycemia/IAS and clopidogrel and to investigate whether clopidogrel is a modifiable and causal risk factor of hypoglycemia/IAS.
METHODS
MEDLINE, Embase, Cochrane databases, and clinical trial registries were searched for randomized controlled trials (RCTs) of clopidogrel from inception to 28 February 2022. RCTs comparing clopidogrel with placebo or other antiplatelet drugs were eligible if meeting the inclusion criteria: 1) clopidogrel was administrated 75 mg qd orally as a long-term antiplatelet prescription at least for months, and 2) hypoglycemia-inducible drugs were not used in the control arm. One investigator abstracted articles and performed a quality assessment. Uncertainties were resolved by discussions with two investigators independently. Odds ratio (OR) and risk difference (RD) were calculated and performed with subgroup analyses. The pre-specified protocol was registered in PROSPERO (CRD42022299622).
RESULTS
Six trials with 61,399 participants in total fulfilled the criteria and were included in the meta-analysis. Clopidogrel might not be associated with higher hypoglycemia odds (OR 0.95, 95% CI 0.65 to 1.40). However, Asian participants (p = 0.0437) seemed more likely to develop clopidogrel-associated hypoglycemia. Clopidogrel-associated hypoglycemia occurred at the highest rate of 0.03% (RD -0.00023, 95% CI -0.00077 to 0.00031), and this increased to 0.91% (RD 0.00210, 95% CI -0.00494 to 0.00914) in an aging population and to 0.18% (RD 0.00040, 95% CI -0.00096 to 0.00177) when Asian ratio of the population was elevated.
CONCLUSIONS
We raise the concern that clopidogrel might be a modifiable and causal risk factor of hypoglycemia. The Asian population might be more vulnerable and need additional care.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/prospero, identifier CRD42022299622.
Topics: Humans; Aged; Clopidogrel; Aspirin; Ticlopidine; Platelet Aggregation Inhibitors; Hypoglycemia
PubMed: 36926026
DOI: 10.3389/fendo.2023.1091933