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Clinical Medicine & Research Aug 2020Aspirin has demonstrated a clear benefit in secondary prevention of coronary syndrome, while aspirin's effect in primary prevention is unclear. This report will explore... (Review)
Review
Aspirin has demonstrated a clear benefit in secondary prevention of coronary syndrome, while aspirin's effect in primary prevention is unclear. This report will explore the role of aspirin as primary prevention for various vascular events. It strives to provide a clear guide for clinicians on whether or not to prescribe aspirin for their patients for primary prevention. Current guidelines and recent trials failed to show clear benefit against primary prevention, with risks outweighing benefits in moderate to high risk patients. A thoughtful discussion between patients and their doctors should be conducted before beginning aspirin use. More studies are needed to gain a better understanding of aspirin use in primary prevention.
Topics: Aspirin; Cardiovascular Diseases; Humans; Primary Prevention; Risk Factors
PubMed: 32580960
DOI: 10.3121/cmr.2020.1548 -
British Journal of Haematology Jun 2017The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an... (Review)
Review
The story of the discovery of aspirin stretches back more than 3500 years to when bark from the willow tree was used as a pain reliever and antipyretic. It involves an Oxfordshire clergyman, scientists at a German dye manufacturer, a Nobel Prize-winning discovery and a series of pivotal clinical trials. Aspirin is now the most commonly used drug in the world. Its role in preventing cardiovascular and cerebrovascular disease has been revolutionary and one of the biggest pharmaceutical success stories of the last century.
Topics: Anti-Inflammatory Agents, Non-Steroidal; Antipyretics; Aspirin; Cardiovascular Diseases; Drug Discovery; Forecasting; Hematologic Diseases; Hemorrhage; History, 18th Century; History, 19th Century; History, 20th Century; History, 21st Century; History, Ancient; Plant Bark; Platelet Aggregation Inhibitors; Salix
PubMed: 28106908
DOI: 10.1111/bjh.14520 -
Drugs Nov 2017Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are,... (Review)
Review
Aspirin is currently the most widely prescribed treatment in the prevention of cardiovascular complications. The indications for the use of aspirin during pregnancy are, however, the subject of much controversy. Since the first evidence of the obstetric efficacy of aspirin in 1985, numerous studies have tried to determine the effect of low-dose aspirin on the incidence of preeclampsia, with very controversial results. Large meta-analyses including individual patient data have demonstrated that aspirin is effective in preventing preeclampsia in high-risk patients, mainly those with a history of preeclampsia. However, guidelines regarding the usage of aspirin to prevent preeclampsia differ considerably from one country to another. Screening modalities, target population, and aspirin dosage are still a matter of debate. In this review, we report the pharmacodynamics of aspirin, its main effects according to dosage and gestational age, and the evidence-based indications for primary and secondary prevention of preeclampsia.
Topics: Aspirin; Female; Humans; Incidence; Pre-Eclampsia; Pregnancy; Primary Prevention; Risk Factors; Secondary Prevention
PubMed: 29039130
DOI: 10.1007/s40265-017-0823-0 -
Open Biology Sep 2022Evidence on aspirin and cancer comes from two main sources: (1) the effect of aspirin upon biological mechanisms in cancer, and (2) clinical studies of patients with... (Review)
Review
Evidence on aspirin and cancer comes from two main sources: (1) the effect of aspirin upon biological mechanisms in cancer, and (2) clinical studies of patients with cancer, some of whom take aspirin. A series of systematic literature searches identified published reports relevant to these two sources. The effects of aspirin upon biological mechanisms involved in cancer initiation and growth appear to generate reasonable expectations of effects upon the progress and mortality of cancer. Clinical evidence on aspirin appears overall to be favourable to the use of aspirin, but evidence from randomized trials is limited, and inconsistent. The main body of evidence comes from meta-analyses of observational studies of patients with a wide range of cancers, about 25% of whom were taking aspirin. Heterogeneity is large but, overall, aspirin is associated with increases in survival and reductions in metastatic spread and vascular complications of different cancers. It is important that evaluations of aspirin used as an adjunct cancer treatment are based upon all the available relevant evidence, and there appears to be a marked harmony between the effects of aspirin upon biological mechanisms and upon the clinical progress of cancer.
Topics: Aspirin; Cardiovascular Diseases; Humans; Neoplasms
PubMed: 36099932
DOI: 10.1098/rsob.220124 -
The New England Journal of Medicine Aug 2017Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy... (Comparative Study)
Comparative Study Randomized Controlled Trial
BACKGROUND
Preterm preeclampsia is an important cause of maternal and perinatal death and complications. It is uncertain whether the intake of low-dose aspirin during pregnancy reduces the risk of preterm preeclampsia.
METHODS
In this multicenter, double-blind, placebo-controlled trial, we randomly assigned 1776 women with singleton pregnancies who were at high risk for preterm preeclampsia to receive aspirin, at a dose of 150 mg per day, or placebo from 11 to 14 weeks of gestation until 36 weeks of gestation. The primary outcome was delivery with preeclampsia before 37 weeks of gestation. The analysis was performed according to the intention-to-treat principle.
RESULTS
A total of 152 women withdrew consent during the trial, and 4 were lost to follow up, which left 798 participants in the aspirin group and 822 in the placebo group. Preterm preeclampsia occurred in 13 participants (1.6%) in the aspirin group, as compared with 35 (4.3%) in the placebo group (odds ratio in the aspirin group, 0.38; 95% confidence interval, 0.20 to 0.74; P=0.004). Results were materially unchanged in a sensitivity analysis that took into account participants who had withdrawn or were lost to follow-up. Adherence was good, with a reported intake of 85% or more of the required number of tablets in 79.9% of the participants. There were no significant between-group differences in the incidence of neonatal adverse outcomes or other adverse events.
CONCLUSIONS
Treatment with low-dose aspirin in women at high risk for preterm preeclampsia resulted in a lower incidence of this diagnosis than placebo. (Funded by the European Union Seventh Framework Program and the Fetal Medicine Foundation; EudraCT number, 2013-003778-29 ; Current Controlled Trials number, ISRCTN13633058 .).
Topics: Adult; Aspirin; Double-Blind Method; Female; Humans; Incidence; Infant, Newborn; Intention to Treat Analysis; Kaplan-Meier Estimate; Pre-Eclampsia; Pregnancy; Pregnancy Complications; Pregnancy Outcome; Risk
PubMed: 28657417
DOI: 10.1056/NEJMoa1704559 -
JAMA Jan 2019The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk. (Meta-Analysis)
Meta-Analysis
IMPORTANCE
The role for aspirin in cardiovascular primary prevention remains controversial, with potential benefits limited by an increased bleeding risk.
OBJECTIVE
To assess the association of aspirin use for primary prevention with cardiovascular events and bleeding.
DATA SOURCES
PubMed and Embase were searched on Cochrane Library Central Register of Controlled Trials from the earliest available date through November 1, 2018.
STUDY SELECTION
Randomized clinical trials enrolling at least 1000 participants with no known cardiovascular disease and a follow-up of at least 12 months were included. Included studies compared aspirin use with no aspirin (placebo or no treatment).
DATA EXTRACTION AND SYNTHESIS
Data were screened and extracted independently by both investigators. Bayesian and frequentist meta-analyses were performed.
MAIN OUTCOMES AND MEASURES
The primary cardiovascular outcome was a composite of cardiovascular mortality, nonfatal myocardial infarction, and nonfatal stroke. The primary bleeding outcome was any major bleeding (defined by the individual studies).
RESULTS
A total of 13 trials randomizing 164 225 participants with 1 050 511 participant-years of follow-up were included. The median age of trial participants was 62 years (range, 53-74), 77 501 (47%) were men, 30 361 (19%) had diabetes, and the median baseline risk of the primary cardiovascular outcome was 9.2% (range, 2.6%-15.9%). Aspirin use was associated with significant reductions in the composite cardiovascular outcome compared with no aspirin (57.1 per 10 000 participant-years with aspirin and 61.4 per 10 000 participant-years with no aspirin) (hazard ratio [HR], 0.89 [95% credible interval, 0.84-0.95]; absolute risk reduction, 0.38% [95% CI, 0.20%-0.55%]; number needed to treat, 265). Aspirin use was associated with an increased risk of major bleeding events compared with no aspirin (23.1 per 10 000 participant-years with aspirin and 16.4 per 10 000 participant-years with no aspirin) (HR, 1.43 [95% credible interval, 1.30-1.56]; absolute risk increase, 0.47% [95% CI, 0.34%-0.62%]; number needed to harm, 210).
CONCLUSIONS AND RELEVANCE
The use of aspirin in individuals without cardiovascular disease was associated with a lower risk of cardiovascular events and an increased risk of major bleeding. This information may inform discussions with patients about aspirin for primary prevention of cardiovascular events and bleeding.
Topics: Aspirin; Cardiovascular Diseases; Diabetes Complications; Diabetes Mellitus; Female; Hemorrhage; Humans; Male; Platelet Aggregation Inhibitors; Primary Prevention; Risk
PubMed: 30667501
DOI: 10.1001/jama.2018.20578 -
Methodist DeBakey Cardiovascular Journal 2021Aspirin's antithrombotic effects have a long-established place in the prevention of cardiovascular disease (CVD), and its traditional use as a core therapy for secondary... (Review)
Review
Aspirin's antithrombotic effects have a long-established place in the prevention of cardiovascular disease (CVD), and its traditional use as a core therapy for secondary prevention of CVD is well recognized. However, with the advent of newer antiplatelet agents and an increasing understanding of aspirin's bleeding risks, its role across the full spectrum of modern CVD prevention has become less certain. As a consequence, recent trials have begun investigating aspirin-free strategies in secondary prevention. For example, a contemporary metanalysis of trials that assessed P2Y inhibitor monotherapy versus prolonged (≥ 12 months) dual antiplatelet therapy (which includes aspirin) after percutaneous coronary intervention reported a lower risk of major bleeding and no increase in stent thrombosis, all-cause mortality, myocardial infarction (MI), or stroke in the P2Y monotherapy group. In contrast to secondary prevention, aspirin's role in primary prevention has always been more controversial. While historical trials reported a reduction in MI and stroke, more contemporary trials have suggested diminishing benefit for aspirin in this setting, with no reduction in hard outcomes, and some primary prevention trials have even indicated a potential for harm. In this review, we discuss how changing population demographics, enhanced control of lipids and blood pressure, changes in the definition of outcomes like MI, evolution of aspirin formulations, and updated clinical practice guidelines have all impacted the use of aspirin for primary and secondary CVD prevention.
Topics: Aspirin; Cardiovascular Diseases; Humans; Myocardial Infarction; Percutaneous Coronary Intervention; Platelet Aggregation Inhibitors; Purinergic P2Y Receptor Antagonists
PubMed: 34824680
DOI: 10.14797/mdcvj.293 -
Nature Reviews. Cancer Mar 2016Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis.... (Review)
Review
Aspirin (acetylsalicylic acid) has become one of the most commonly used drugs, given its role as an analgesic, antipyretic and agent for cardiovascular prophylaxis. Several decades of research have provided considerable evidence demonstrating its potential for the prevention of cancer, particularly colorectal cancer. Broader clinical recommendations for aspirin-based chemoprevention strategies have recently been established; however, given the known hazards of long-term aspirin use, larger-scale adoption of an aspirin chemoprevention strategy is likely to require improved identification of individuals for whom the protective benefits outweigh the harms. Such a precision medicine approach may emerge through further clarification of aspirin's mechanism of action.
Topics: Aspirin; Chemoprevention; Colorectal Neoplasms; Humans; Precision Medicine
PubMed: 26868177
DOI: 10.1038/nrc.2016.4 -
Lancet (London, England) Sep 2018The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in... (Randomized Controlled Trial)
Randomized Controlled Trial
Use of aspirin to reduce risk of initial vascular events in patients at moderate risk of cardiovascular disease (ARRIVE): a randomised, double-blind, placebo-controlled trial.
BACKGROUND
The use of aspirin in the primary prevention of cardiovascular events remains controversial. We aimed to assess the efficacy and safety of aspirin versus placebo in patients with a moderate estimated risk of a first cardiovascular event.
METHODS
ARRIVE is a randomised, double-blind, placebo-controlled, multicentre study done in seven countries. Eligible patients were aged 55 years (men) or 60 years (women) and older and had an average cardiovascular risk, deemed to be moderate on the basis of the number of specific risk factors. We excluded patients at high risk of gastrointestinal bleeding or other bleeding, or diabetes. Patients were randomly assigned (1:1) with a computer-generated randomisation code to receive enteric-coated aspirin tablets (100 mg) or placebo tablets, once daily. Patients, investigators, and others involved in treatment or data analysis were masked to treatment allocation. The primary efficacy endpoint was a composite outcome of time to first occurrence of cardiovascular death, myocardial infarction, unstable angina, stroke, or transient ischaemic attack. Safety endpoints were haemorrhagic events and incidence of other adverse events, and were analysed in the intention-to-treat population. This study is registered with ClinicalTrials.gov, number NCT00501059.
FINDINGS
Between July 5, 2007, and Nov 15, 2016, 12 546 patients were enrolled and randomly assigned to receive aspirin (n=6270) or placebo (n=6276) at 501 study sites. Median follow-up was 60 months. In the intention-to-treat analysis, the primary endpoint occurred in 269 (4·29%) patients in the aspirin group versus 281 (4·48%) patients in the placebo group (hazard ratio [HR] 0·96; 95% CI 0·81-1·13; p=0·6038). Gastrointestinal bleeding events (mostly mild) occurred in 61 (0·97%) patients in the aspirin group versus 29 (0·46%) in the placebo group (HR 2·11; 95% CI 1·36-3·28; p=0·0007). The overall incidence rate of serious adverse events was similar in both treatment groups (n=1266 [20·19%] in the aspirin group vs n=1311 [20·89%] in the placebo group. The overall incidence of adverse events was similar in both treatment groups (n=5142 [82·01%] vs n=5129 [81·72%] in the placebo group). The overall incidence of treatment-related adverse events was low (n=1050 [16·75%] vs n=850 [13·54%] in the placebo group; p<0·0001). There were 321 documented deaths in the intention-to-treat population (n=160 [2·55%] vs n=161 [2·57%] of 6276 patients in the placebo group).
INTERPRETATION
The event rate was much lower than expected, which is probably reflective of contemporary risk management strategies, making the study more representative of a low-risk population. The role of aspirin in primary prevention among patients at moderate risk could therefore not be addressed. Nonetheless, the findings with respect to aspirin's effects are consistent with those observed in the previously published low-risk primary prevention studies.
FUNDING
Bayer.
Topics: Aged; Aspirin; Double-Blind Method; Female; Gastrointestinal Hemorrhage; Humans; Intention to Treat Analysis; Longitudinal Studies; Male; Middle Aged; Myocardial Infarction; Platelet Aggregation Inhibitors; Proportional Hazards Models; Risk Factors; Stroke
PubMed: 30158069
DOI: 10.1016/S0140-6736(18)31924-X -
Biomedicine & Pharmacotherapy =... Nov 2022Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and... (Review)
Review
Gastric mucosal injury is the initial stage of the occurrence and development of gastric diseases. Oxidative stress and ferroptosis caused by the imbalance of redox and iron dynamics in gastric mucosal epithelial cells are present throughout the occurrence and development of gastric mucosal injury. Therefore, the inhibition of oxidative stress and ferroptosis is a potential target for the treatment of the gastric mucosal injury. Xiaojianzhong decoction (XJZ), which consists of six Chinese herbal medicines and extracts, is used for the treatment of diseases related to gastrointestinal mucosal injury; however, its specific mechanism of action has yet to be clarified. In this study, we clarified the protective effect of XJZ on gastric mucosa and revealed its underlying mechanism. We established a gastric mucosal injury model using aspirin and administered XJZ. Furthermore, we systematically evaluated the mucosal injury and examined the expression of genes related to oxidative stress, ferroptosis, and inflammation. The study found that XJZ significantly counteracted aspirin-induced gastric mucosal injury and inhibited oxidative stress and ferroptosis in mice. Upon examining SQSTM1/p62(p62)/Kelch-like ECH-associated protein 1 (Keap1)/Nuclear Factor erythroid 2-Related Factor 2 (Nrf2), a well-known signaling pathway involved in the regulation of oxidative stress and ferroptosis, we found that its activation was significantly inhibited by aspirin treatment and that this signaling pathway was activated after XJZ intervention. Our study suggests that XJZ may inhibit aspirin induced oxidative stress and ferroptosis via the p62/Keap1/Nrf2 signaling pathway, thereby attenuating gastric mucosal injury.
Topics: Animals; Mice; Aspirin; Ferroptosis; Gastric Mucosa; Iron; Kelch-Like ECH-Associated Protein 1; NF-E2-Related Factor 2; Oxidative Stress; Sequestosome-1 Protein; Signal Transduction; Stomach Diseases
PubMed: 36122518
DOI: 10.1016/j.biopha.2022.113631