what is the action of aspirin in relation to prevention of disease?

April 09, 2022 Post a Comment

Both globally and in the United States, atherosclerotic cardiovascular disease (ASCVD) represents the leading cause of death and inability.^one,ii Aspirin has been the cornerstone of the antithrombotic management of patients with ASCVD for >3 decades.^3,4 It exerts its biological action mainly past inhibition of cyclooxygenase (COX)-1 activity, and consequently of thromboxane A₂ synthesis, leading to irreversible suppression of platelet activation and aggregation.^five Clinical practice guidelines recommend long-term aspirin therapy for the secondary prevention treatment of patients with established ASCVD but provide alien recommendations for primary prevention in patients with an increased hazard of developing ASCVD (Table 1).^6–12

**Table 1.** Summary of Guidelines Recommendations for Aspirin in Primary Prevention of Atherosclerotic Cardiovascular Diseases
Guidelines	Recommendation	Level of Evidence
2019 American College of Cardiology/American Heart Association Guideline on the Principal Prevention of Cardiovascular Disease^six	Depression-dose aspirin (75–100 mg/d orally) might be considered amid select adults twoscore to 70 years of historic period who are at college ASCVD take chances but not at increased bleeding gamble	IIb, A: weak recommendation; high-quality show from more than than 1 RCT or meta-analyses of high-quality RCTs or 1 or more RCTs corroborated by high-quality registry studies
	Low-dose aspirin (75–100 mg/d orally) should not be administered on a routine basis for the principal prevention of ASCVD amidst adults >lxx years of age	3, B-R: harm; moderate-quality evidence from one or more than RCTs, or meta-analyses of moderate-quality RCTs
	Depression-dose aspirin (75–100 mg/d orally) should not be administered for the primary prevention of ASCVD among adults of any age who are at increased gamble of bleeding	Three, C-LD: harm; randomized or nonrandomized observational or registry studies with limitations of blueprint or execution or meta-analyses of such studies or physiological or mechanistic studies in human subjects
American Diabetes Association Standards of Medical Care in Diabetes 2019^xi	Aspirin 75–162 mg daily for patients with diabetes mellitus at increased cardiovascular chance (who practise not have known CVD)	Class C: supportive evidence from poorly controlled or uncontrolled studies
United states Preventive Services Task Force 2016 Recommendations for Primary Care Practice⁸	Depression-dose aspirin for adults 50–59 years old without CVD just with a ≥10% x-yr CVD take a chance	B: Loftier certainty that the net benefit is moderate, or moderate certainty that the net benefit is moderate to substantial
	Low-dose aspirin for adults lx–69 years old without CVD but with a ≥10% 10-year CVD risk	C: At least moderate certainty that the net benefit is pocket-sized
	No recommendation for patients <50 or ≥70 years old without CVD	I: Current evidence is insufficient
European Society of Cardiology 2016 Guidelines on Cardiovascular Disease Prevention in Clinical Practise^ix	Aspirin non recommended in individuals without CVD	III, B: Treatment not recommended, information derived from a single randomized clinical trial or large nonrandomized studies
American Center Association Effectiveness-Based Guidelines for the Prevention of Cardiovascular Illness in Women—2011 Update¹²	Routine use of aspirin in healthy women <65 years of age without CVD is non recommended to forbid myocardial infarction	Iii, C: Procedure/test not helpful or handling has no proven do good, procedure/test backlog cost without benefit or harmful or handling harmful to patients; based on skillful opinion, case studies, or standard of care
	Aspirin therapy (75–325 mg/d) is reasonable to use in women with diabetes mellitus without known CVD unless contraindicated	IIa, B: weight of evidence/opinion is in favor of usefulness/efficacy; express prove from single randomized trial or other nonrandomized studies
	Aspirin therapy tin be useful in women ≥65 y of age without known CVD (81 mg/d or 100 mg every other twenty-four hour period) if blood pressure is controlled and benefit for ischemic stroke and myocardial infarction prevention is likely to outweigh risk of gastrointestinal haemorrhage and hemorrhagic stroke	IIa, B: weight of bear witness/opinion is in favor of usefulness/efficacy; limited evidence from single randomized trial or other nonrandomized studies
	Aspirin (81 mg/d or 100 mg every other day) may be reasonable for women <65 y without known CVD for ischemic stroke prevention	IIb, B: usefulness/efficacy is less well established by evidence/opinion; limited evidence from unmarried randomized trial or other nonrandomized studies
Canadian Cardiovascular Society Antiplatelet Guidelines^7,10	Aspirin not routinely recommended for patients without CVD	III, A: evidence that the treatment is not useful and, in some cases, may be harmful; data derived from multiple randomized clinical trials or meta-analyses
	Aspirin 75–162 mg daily recommended for patients without CVD, if high vascular risk and low bleeding risk^ten	IIb, C: Conflicting evidence and/or a divergence of opinion about the usefulness/efficacy of the treatment with the usefulness/efficacy less well established; consensus of opinion by experts and/or small studies, retrospective studies, and registries

Until recently, the supportive evidence underlying guidelines recommendations in favor of aspirin in principal prevention were based on meta-analyses of trials enrolling heterogeneous patient populations, postal service hoc subgroup analyses of randomized controlled trials (RCT), or price-utility analyses.^xiii–18 Although this level of evidence can be sufficient to support low-grade recommendations, they exercise not comply with evidentiary standards to support a characterization indication. The Usa Food and Drug Administration voiced reservations with the use of data from studies that were non initially intended to be pooled to support primary prevention claims.^xix Their position is echoed by the Eye for Disease Control'southward 1000000 Hearts® Initiative, and by the National Heart, Lung, and Blood Institute.

The standards of intendance for the management of cardiovascular risk factors for patients without established ASCVD, including diabetes mellitus, lipids, hypertension, smoking cessation, and lifestyle interventions, have evolved substantially in the contemporary era.^xi,20 While the pivotal role of aspirin as a long-term secondary prevention therapy for patients with established ASCVD has not diminished over the past decades, findings from 3 big-scale RCTs including >47 000 patients call into question its net clinical benefits when used for primary prevention in iii cardinal patient populations: patients with diabetes mellitus, community-dwelling elderly individuals, and patients without diabetes mellitus who are at intermediate risk for time to come atherosclerotic events.^21–23 In this article, we revisit the role of aspirin in primary prevention, critically review the key scientific literature, highlight areas of uncertainties for future research, and propose a decisional framework for clinicians to back up prescription of aspirin in master prevention.

Contemporary Trials Evaluating Aspirin for Principal Prevention of ASCVD

Several meta-analyses of RCTs evaluating the function of aspirin in primary prevention accept demonstrated significant benefits in the prevention of vascular events compared with placebo, mainly driven by lower rates of nonfatal myocardial infarctions. Notwithstanding, findings were inconsistent with respect to the issue of aspirin on all-crusade bloodshed, and major bleeding issue rates were invariably increased.^24–27 A timeline of the major RCTs evaluating aspirin for the primary prevention of ASCVD is shown in Figure one. In 2018, iii large-scale RCTs have been published, including the Get in trial (Aspirin to Reduce Gamble of Initial Vascular Events),²¹ the Ascend trial (A Study of Cardiovascular Events in Diabetes),²² and the ASPREE trial (Aspirin in Reducing Events in the Elderly).²³

Figure 1. — **Effigy i.** **Timeline of major randomized controlled trials of aspirin in primary prevention of atherosclerotic cardiovascular diseases.** ACCEPT-D indicates Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes²⁸; Arrive, Aspirin to Reduce Risk of Initial Vascular Events²¹; ASCEND, A Study of Cardiovascular Events in Diabetes²²; ASPREE, Aspirin in Reducing Events in the Elderly²³; HOT, Hypertension Optimal Handling¹⁷; JPAD, Japanese Chief Prevention of Atherosclerosis With Aspirin for Diabetes¹⁴; JPPP, Japanese Primary Prevention Project¹³; Peto et al¹⁵; PHS, Physician's Health Written report^xviii; and WHS, Women'southward Health Study.¹⁶

Summary and Implications of the ARRIVE Trial: Aspirin in the Master Prevention of ASCVD in Nondiabetic Patients at Moderate Risk of Cardiovascular Diseases

In the double-blind, multicenter, international Arrive trial, 12 546 participants from 6 European countries and the U.s., with an estimated 10% to xx% 10-yr risk of developing coronary artery disease, were randomized to aspirin 100 mg daily vs placebo, and followed for an average of v years. The primary endpoint, divers equally time to myocardial infarction, stroke, cardiovascular expiry, unstable angina, or transient ischemic set on, occurred in 269 (iv.29%) participants in the aspirin group vs. 281 (4.48%) in the placebo grouping (take a chance ratio [HR], 0.96; 95% CI, 0.81–1.xiii; P=0.6038). These results were consequent in prespecified subgroups, and in that location was no pregnant divergence in the frequency of the individual components of the primary endpoint or in all-crusade death. Gastro-intestinal haemorrhage events occurred in <1% of patients in each group and were predominantly mild merely were more than frequent for those assigned to aspirin (Hour, 2.xi; 95% CI, 1.36–3.28; P=0.0007). A major limitation of the ARRIVE trial was that the observed event rates were lower than anticipated, providing less power to detect a difference between the groups than originally planned. The primary composite endpoint was modified during the trial by adding transient ischemic attack and unstable angina every bit component endpoints, and the neutral results were consistent for both definitions of the primary endpoint. Every bit such, the function of aspirin in principal prevention of cardiovascular events in patients with at least a moderate future risk of developing ASCVD remains uncertain.

Summary and Implications of the ASCEND Trial: Aspirin in the Primary Prevention of ASCVD in Diabetic Patients

In the ASCEND trial, conducted in the Great britain, 15 480 patients ≥xl years old with diabetes mellitus without established ASCVD were randomized to aspirin 100 mg daily or placebo. After a hateful follow-up of vii.4 years, the frequency of the primary endpoint (blended of nonfatal myocardial infarction, nonfatal stroke or transient ischemic attack, or death from any vascular cause), was eight.five% with aspirin and 9.vi% with placebo (60 minutes, 0.88; 95% CI, 0.79–0.97; P=0.01). This salutary outcome of aspirin came at the expense of more than major bleeding events (rate ratio, 1.29; 95% CI, i.09–i.52; P=0.003). Fatal and intracranial bleeding events were observed in <1% of participants with no significant between-grouping difference. Similarly to the ARRIVE trial, transient ischemic assault was added to the primary endpoint composite during the course of the trial, and only a not-meaning trend was observed in favor of aspirin when transient ischemic attack was excluded from the primary endpoint (HR, 0.92; 95% CI, 0.82–1.03). The accept-home message is that among patients with diabetes mellitus without established ASCVD, aspirin was associated with a modest subtract in the risk of ischemic events, merely these findings were balanced by an increased risk of major haemorrhage events.

Despite some limitations, the ASCEND trial provides high-quality evidence given the large sample size, the long length of follow-upwardly, and the pragmatism of the trial eligibility criteria (only 5 inclusion and exclusion criteria altogether). However, the lack of pregnant benefit of aspirin observed using the original prespecified primary endpoint and the small magnitude of clinical consequence (one.1% absolute risk reduction), betoken that aspirin does not have a definitive indication in primary prevention for patients with diabetes. In contrast, a shared decision-making arroyo involving clinicians and patients should be encouraged, in which the tradeoff between ischemic consequence reduction and increased haemorrhage risk with aspirin can exist considered.¹¹ According to the 2019 American Diabetes Association Standards of Medical Care in Diabetes, aspirin should exist considered in certain cardiovascular risk categories.^eleven Modest relative risk reduction with aspirin in patients with diabetes translate into increasingly higher absolute reductions as the overall cardiovascular run a risk category increases, based on available run a risk calculators.^9,20,29 Practical algorithms take been proposed to guide aspirin therapy use in principal prevention in patients with diabetes mellitus, incorporating an estimation of the ASCVD risk.²⁹

Summary and Implications of the ASPREE Trial: Aspirin in Primary Prevention in Community-Dwelling Elderly Patients

In the ASPREE trial, 19 114 participants from Australia or the United States anile ≥70 years old (≥65 years former for Hispanic and African American patients within the United states) without life-limiting chronic illness, dementia, physical inability or documented cardiovascular or cerebrovascular affliction, were randomized to aspirin 100 mg daily or placebo.²³ After a median follow-upwards of 4.vii years, the trial was stopped prematurely based on futility. The primary endpoint of disability-free survival (survival free from dementia or persistent physical disability) occurred in 21.five per m patient-years in the aspirin grouping and 21.two per 1000 patient-years in the placebo group (HR, 1.01; 95% CI, 0.92–one.xi; P=0.79), with significantly more major bleeding events with aspirin (8.6 vs. six.2 per m patient-years; Hr, 1.38, 95% CI, ane.18–1.62; P<0.001). The incidence rate of cardiovascular illness was also similar between written report groups.^thirty Although the latter cardiovascular endpoint was not specified every bit the principal endpoint, it remains unlikely that the trial missed a significant benign effect of aspirin to forbid major adverse cardiovascular events, given ASPREE's large sample size and the consistency of the results among the relevant prespecified subgroups. A higher risk of all-crusade mortality was observed with aspirin, mainly driven by cancer-related mortality, although this signal disappeared afterward statistical correction for multiple comparisons. In summary, the ASPREE trial did non show any benefit of aspirin in terms of disability-gratuitous survival in elderly patients without documented cardiovascular disease merely demonstrated higher major bleeding rates and a point for higher all-cause mortality. These findings thus call into question the employ of aspirin in main prevention in customs-dwelling elderly patients in the contemporary era.

A summary of the Make it, Ascend, and ASPREE trials are provided in Tabular array 2. An updated meta-analysis including these three trials did not demonstrate pregnant survival benefits with aspirin in principal prevention (adventure ratio, 0.98; 95% CI, 0.93–1.02; P=0.xxx), and confirmed the heightened risks of major bleeding (risk ratio, 1.47; 95% CI, 1.31–1.65; P<0.0001).³¹ These findings were consequent among trials including loftier-run a risk and diabetic patients.³¹

**Table 2.** Summary of the Recent Trials on Aspirin for the Primary Prevention of Atherosclerotic Cardiovascular Disease
	Get in		ASCEND		ASPREE
Study population	Men ≥55 years and 2–4 chance factors; women ≥sixty years and ≥iii hazard factors from Europe and the Us		≥40 years erstwhile with type I or blazon Ii diabetes mellitus without known cardiovascular disease from the United Kingdom		≥70 years old (≥65 years for Hispanic and African American patients) in Commonwealth of australia or the United States without life-limiting chronic illness, dementia, physical inability or documented cardiovascular or cerebrovascular illness
Age, y	63.ix (mean)		63.3 (mean)		74 years (median)
Sample size	12 546 patients		15 480 patients		19 114 patients
Median follow-up fourth dimension, y	5		7.4		four.7
Written report interventions	Enteric-coated aspirin 100 mg daily versus placebo		Enteric-coated aspirin 100 mg daily versus placebo		Enteric-coated aspirin 100 mg daily versus placebo
Primary endpoint	Composite of time to myocardial infarction, stroke, cardiovascular death, unstable angina, or transient ischemic attack Results: Aspirin versus placebo: iv.3% versus 4.5%; hazard ratio, 0.96 (95% CI, 0.81–1.thirteen; P=0.6038)		Serious vascular event (composite of nonfatal myocardial infarction, nonfatal stroke (excluding confirmed intracranial hemorrhage) or transient ischemic attack, or death from any vascular crusade (excluding confirmed intracranial hemorrhage) Results: Aspirin versus placebo: viii.v% versus 9.6%; hazard ratio, 0.88; 95% CI (0.79–0.97; P=0.01)		Disability-free survival, defined as survival free from dementia or persistent physical disability Results: Aspirin: 21.v per 100 patient-year; placebo: 21.two per 100 patient-twelvemonth (P=0.79)
All-cause mortality	Aspirin, 2.6%; placebo, 2.6%; hazard ratio, 0.99 (95% CI, 0.eighty–1.24; P=0.9459)		Aspirin, nine.7%; placebo, x.two%; charge per unit ratio, 0.94 (95% CI, 0.85–ane.04)		Aspirin, 12.7 per 100 patient-yr; placebo, 11.1 per 100 patient-yr; take chances ratio, 1.14 (95% CI, ane.01–1.29)
Bleeding endpoints	Gastrointestinal bleeding events	Aspirin: 0.97%; placebo: 0.46%; hazard ratio, 2.11 (95% CI, 1.36–3.28; P=0.0007)	Major haemorrhage events	Aspirin: four.ane%; placebo: 3.ii%; charge per unit ratio, i.29 (95% CI, 1.09–1.52)	Major hemorrhagic events	Aspirin: eight.half-dozen per yard person-yr; placebo: vi.2 per grand person-year; hazard ratio, 1.38 (95% CI, i.eighteen–i.62)

Fundamental Residual Questions

Tailoring Aspirin Dosing and Formulation

Whether testing college doses of aspirin in primary prevention would uncover significant cardiovascular benefits in the electric current era remains uncertain. The proportional dose-relationship of aspirin to define bleeding risk is well established, but the clinical equipoise surrounding aspirin dosing has been reflected by the variability of clinical practice patterns.³² Prior post hoc analyses of RCTs, meta-analyses, and a single, short-term RCT of depression-dose vs loftier-dose aspirin (CURRENT-Oasis 7) take not definitively established the efficacy and safety profiles of different aspirin dosing regimens in secondary prevention.^4,33,34

Mechanistic knowledge of the pharmacodynamic targets of aspirin tin contribute to explain the heightened thrombotic risk occasionally observed with higher doses. Doses in the lower range (75–162 mg) are sufficient to saturate COX-1 acetylation, leading to maximal thromboxane A_ii suppression required for adequate platelet inhibition. Increasing the dose over this range does non provide incremental pharmacodynamic reward through this pathway, but rather augments dose-dependent COX-2 inhibition, leading to suppression of prostacyclin synthesis. This prostaglandin has established platelet aggregation inhibition and vasodilatory properties, potentially underpinning a paradoxical prothrombotic event of aspirin with higher doses.

Inter-individual variability of COX-1 recovery post-obit one time-daily aspirin administration, with some patients having faster thromboxane B_ii renormalization during the 12- to 24-hour period after administration, can be counteracted by twice-daily regimens.³⁵ A dose-escalating pharmacodynamic written report suggested that twice-daily aspirin administration was associated with meliorate platelet inhibition than increasing the in one case daily dose in patients with diabetes mellitus.³⁶ Attributable to aspirin pseudoresistance observed in patients with diabetes mellitus, partly explained by accelerated thrombopoiesis and platelet turnover, its net clinical benefits might improve with dosing regimens different from once-daily administration in this population.²⁹ The potential benefits of extended-release formulations or of twice-daily administration remains to be studied in stage III trials in patients with diabetes mellitus and in those with faster COX-1 recovery (Table 3).

**Table 3.** Key Areas of Residual Dubiousness for the Use of Aspirin for the Chief Prevention of Atherosclerotic Cardiovascular Affliction
Areas of Dubiety	Rationale	Proposed Potential Study
Optimal drug formulation	Increased platelet turnover in patients with diabetes mellitus³⁶ Interindividual variability of cyclooxygenase-1 recovery can be overcome past twice-daily aspirin³⁵	Randomized trial comparing twice-daily aspirin and/or extended-release formulation to placebo, preferably in patients with diabetes mellitus
Optimal drug formulation	In patients with diabetes mellitus, the number of nonresponders is significantly higher with enteric-coated aspirin compared with other formulations³⁷ Definitive evidence for bleeding hazard mitigation with enteric-coated aspirin is lacking³⁸	Randomized trial comparing evidently aspirin and/or modified-release lipid-based aspirin to placebo, preferably in patients with diabetes mellitus
Interplay between torso weight and aspirin dosing	A meta-assay of randomized trials suggests an interaction betwixt trunk weight and treatment response according to the dose of aspirin In Ascend, only patients weighing ≥seventy kg benefited significantly from low-dose aspirin	Randomized trial comparing a weight-based aspirin dosing strategy versus placebo, in which randomization is stratified by weight
Decision support tools	Tools to predict the net clinical do good of aspirin in primary prevention of ASCVD are lacking	Derivation and external validation of risk prediction scores to identify patients for trial inclusion who are predicted to be the most likely to derive internet positive benefits from aspirin
Interaction between sex and aspirin	Evidence suggests that aspirin reduces the take a chance of myocardial infarction only in men, and the take a chance of ischemic strokes just in women³⁹	Randomized trial of aspirin in primary prevention stratified past sex, with both strata sufficiently powered to detect a significant treatment effect
Cancer chemoprevention	The United states Preventive Services Task Force recommends aspirin for the prevention of colorectal cancer, and family unit history of gastrointestinal cancer has been advocated as a variable to take into account in the risk/do good assessment for aspirin prescription^viii,29,40	Randomized trials specifically evaluating the effect of aspirin on cancer-related endpoints. The ADD-ASPIRIN trial (URL: https://world wide web.clinicaltrials.gov; unique identifier: NCT02804815) is currently ongoing to address this question⁴¹

Furthermore, enteric-coated aspirin was used in the ARRIVE, Ascend, and ASPREE trials, merely recent pharmacodynamic and pharmacokinetic insights have shown that half of patients with diabetes mellitus are nonresponders to this formulation.³⁷ This proportion is significantly reduced if plain aspirin or a modified-release lipid-based aspirin formulations are used.³⁷ This observation was mediated past lower absorption with enteric-coated aspirin, translating into decreased bioavailability. In the absence of definitive evidence for haemorrhage risk mitigation with enteric-coated aspirin,³⁸ the use of this formulation in the recent large-scale trials might have led to suboptimal bioavailability of the drug, undermining the evaluation of the full potential of aspirin to prevent ASCVD, especially in participants with diabetes mellitus.

Coaction Between Body Weight and Treatment Effect

Emerging show suggests that the anti-platelet activity of aspirin is influenced by body weight. Findings from a contempo meta-assay including more than 100 000 patients with established ASCVD from nine previous aspirin clinical trials suggested that patients weighing ≥70 kg did not derive benefit with low-dose (≤100 mg daily) aspirin (Hr, 0.95; 95% CI, 0.86–1.04; P for interaction=0.0072), that patients weighing <70 kg did not derive benefits with doses of aspirin ≥300 to 325 mg (P for interaction=0.017), and that a putative dose-response relationship with higher doses of aspirin demonstrating greater do good with increasing body weight may exist present.⁴² The results of this meta-analysis advise that the efficacy of aspirin to foreclose cardiovascular events may vary according to body weight (and probable drug exposure) and that a more personalized approach to aspirin dosing could be helpful. The apparent interaction between aspirin dose and trunk weight observed in the meta-analysis contrasts with the results from the ASCEND trial, which suggested that only patients with weighting ≥70kg or with a body mass index ≥30 seemed to benefit from low-dose aspirin. Body mass index was not an effect modifier in the ASPREE and the ARRIVE trials. Because none of the findings regarding body weight and aspirin handling outcome were the results of a priori hypotheses before the development of the datasets, they tin can simply be considered as hypothesis generating. Dedicated trials focusing on a personalized approach with the apply of aspirin tailored to body weight are required. Results from the Adaptable trial (Aspirin Dosing: A Patient-Centric Trial Assessing Benefits and Long-Term Effectiveness) that is evaluating low-dose (81 mg) vs. high-dose (325 mg) aspirin for patients with established ASCVD should provide more definitive evidence regarding optimization of aspirin dose but targeted just toward secondary prevention.⁴³

Predicting Future Cardiovascular and Bleeding Run a risk in the Primary Prevention Population

Results from both the ARRIVE and ASCEND trials demonstrate the difficulties with accurately predicting the risk of future ischemic cardiovascular events in patients without established ASCVD, given that event rates were lower than expected, similarly to previous trials evaluating cardiometabolic therapies.^44,45 Over the past decade, the direction of known cardiovascular take chances factors has evolved considerably based on several developments in the risk stratification and treatment of dyslipidemia, hypertension, and diabetes,^eleven,20 accounting for the overestimation of the risk of ASCVD using available tools. This current landscape pb the ACC/AHA to movement away from recommending the utilise of a specific chance threshold based on the validated pooled cohort equations in the decision to prescribe aspirin in primary prevention.⁶ Rather, the guidelines encourage clinicians to weigh the totality of the available testify in their decision to prescribe aspirin in chief prevention, which includes traditional comorbidities in add-on to chance-enhancing factors.

Longitudinal prediction hazard scores have been derived and validated to inform the selection of dual antiplatelet therapy duration in secondary prevention.^46–48 However, tools to predict the take chances/benefit ratio of aspirin in main prevention of ASCVD are lacking. Chance tables take been developed to judge bleeding off-aspirin in a accomplice of 359 166 patients without cardiovascular illness, but they exercise not inform on the bleeding risk on aspirin treatment.⁴⁹ In the era of precision medicine, evolution of conclusion back up tools leveraging real-world information reflecting patients treated in routine practice more accurately than the more narrowly divers clinical trial populations is desirable to inform cyberspace clinical benefits of aspirin initiation in master prevention. This existent-earth data tin can incorporate multisource technologies including electronic health records and digital mobile health applications. Recently, a gamble score incorporating 17 variables was developed and internally validated to predict bleeding risk in a accomplice of 385 191 patients without cardiovascular illness in New Zealand.^fifty Still, the result of this score for clinical practice is limited because it does not inform on the expected ischemic benefits, its generalizability in the Us population is unknown, and it does not apply to patients with diabetes, which were excluded from the development cohort.

Interplay Between Sex and Response to Aspirin

How the sex-based biologic differences in the pharmacodynamic response to aspirin should affect the patterns of prescription is another primal unresolved issue. In their guidelines for the prevention of cardiovascular diseases in women, the American Center Clan established specific recommendations for aspirin in main prevention targeted toward women (Table 1).¹² Even if low-dose aspirin suppresses the direct COX-ane activation pathway similarly between both genders, a meta-analysis of six RCTs suggested that aspirin reduced the hazard of myocardial infarction only in men, and the risk of ischemic strokes just in women, while the effect on mortality was neutral for both men and women.³⁹ Aspirin increased significantly the gamble of bleeding for both genders.³⁹ This meta-analysis is limited by the fact that 3 of the included trials only involved men, and 1 only involved women, implying that male men and women populations included in the pooled analysis were not comparable. In the Women's Health Study, the only trial focusing exclusively on women (northward=39 876), the rates of major cardiovascular events was similar between those who were randomized to aspirin 100 mg on alternate days and placebo, but aspirin was associated with a significant relative 17% risk reduction in strokes. In the Make it, ASCEND, or ASPREE trials, at that place was no significant interaction between sex and handling upshot of aspirin.^21–23 Collectively, in the absence of trial in which randomization was stratified by sex, the available show does not support a sex-based personalization of aspirin therapy in principal prevention of ASCVD.

Conclusion

The positioning of aspirin as a handling option for the primary prevention of cardiovascular events has been informed past the recent results of three large-scale RCTs that collectively question its role for the treatment of patients without established ASCVD. A decisional framework for clinicians to support prescription of aspirin in main prevention is presented in Figure 2. Key unresolved questions regarding the part of aspirin in main prevention include the optimal drug conception, dosing schedule, weight-based dose choice, and interplay between sex activity and treatment response. Given the want expressed past regulatory authorities to explore the use of real-globe information sources in RCTs, creative approaches are needed in future trials of aspirin in chief prevention. For instance, evaluation of the validity and utility of gamble calculators derived from existent-globe data could be conducted to enable their use to inform modeling of eligibility criteria. In the current era, most patients without established ASCVD should not be prescribed aspirin in the absence of established evidence for definitive risk reduction and of determination back up tools to tailor patient option according to the expected net clinical benefits. Rather, ambitious management of comorbidities tailored to the expected cardiovascular risk needs to be emphasized. Informed shared conclusion making between clinicians and patients regarding the employ of aspirin for primary prevention of cardiovascular events is a suitable and commendable approach going forrard.¹¹

Figure 2. — **Figure two.** **Suggested decisional pathway for the apply of aspirin in primary prevention of atherosclerotic cardiovascular disease** (**ASCVD) for gimmicky practice.** CV indicates cardiovascular.

Sources of Funding

Dr Marquis-Gravel received a grant from the Canadian Institute of Wellness Research, Ottawa, Ontario, Canada.

Disclosures

Dr Marquis-Gravel is in the master panel of the 2018 Canadian Cardiovascular Society/Canadian Association of Interventional Cardiology Focused Update of the Guidelines for the Use of Antiplatelet Therapy (unpaid) and receives salary grant support from the Canadian Institute of Health Research, Ottawa, Ontario, Canada (Grant #395851); Dr Roe receives research funding from the American College of Cardiology, American Eye Association, AstraZeneca, Familial Hypercholesterolemia Foundation, Ferring Pharmaceuticals, Myokardia, Janssen Pharmaceuticals, the Patient-Centered Outcomes Research Institute, and Sanofi-Aventis. Dr Roe also receives consulting or other fees from Amgen, Ardea Biosciences, AstraZeneca, Eli Lilly & Company, Flatiron, Janssen Pharmaceuticals, Novo Nordisk, Pfizer, Regeneron, Roche-Genentech, Sanofi-Aventis, and Betoken Path. Dr Harrington acknowledges research grants to Stanford University in his name from Apple tree, AstraZeneca, Bristol-Myers Squibb, Commonwealth Serum Laboratories, Janssen, The Medicines Company, Novartis, Portola, and Sanofi. Dr Harrington also belongs to the consulting and advisory boards at Amgen, Bayer, Chemical element Science, Gilead, MyoKardia, and WebMD; and belongs to the board of directors at the American Center Association (unpaid), Scanadu, Signal Path, and Stanford HealthCare (unpaid). Dr Munoz is associated with the writing group of the American Heart Association/American Higher of Cardiology Guideline on Main Prevention of Cardiovascular Disease. Dr Hernandez receives research funding from American Regent, AstraZeneca, Daiichi, GlaxoSmithKline, Janssen, Merck, Novartis, and Verily. Dr Munoz is also a consultant to Amgen, AstraZeneca, Bayer, Boehringer Ingelheim, Boston Scientific, Eidos, Intercept, Merck, Novartis, and Pfizer. Dr Jones acknowledges a inquiry grant from the Patient-Centered Outcomes Research Found.

Footnotes

References

1. James Due south, Abate D, Abate KH, Abay SM, Abbafati C, Abbasi N, Abbastabar H, Abd-Allah F, Abdela J, Abdelalim A, et al. . Global, regional, and national incidence, prevalence, and years lived with inability for 354 diseases and injuries for 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet . 2018; 392:1789–1858. doi: 10.1016/S0140-6736(eighteen)32279-sevenCrossrefMedlineGoogle Scholar
2. Centers for Disease Control and Prevention. National Eye for Health Statistics. Deaths and Bloodshed . May 3, 2017. https://world wide web.cdc.gov/nchs/fastats/deaths.htm. Accessed April 18, 2019.Google Scholar
3. Théroux P, Ouimet H, McCans J, Latour JG, Joly P, Lévy G, Pelletier East, Juneau One thousand, Stasiak J, deGuise P, et al. . Aspirin, heparin, or both to treat acute unstable angina. N Engl J Med . 1988; 319:1105–1111. doi: 10.1056/NEJM198810273191701CrossrefMedlineGoogle Scholar
4. Baigent C, Sudlow C, Collins R and Peto R. Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of expiry, myocardial infarction, and stroke in loftier risk patients. BMJ . 2002; 324:71–86. doi: x.1136/bmj.324.7329.71CrossrefMedlineGoogle Scholar
v. Patrono C, Garcia Rodriguez LA, Landolfi R and Baigent C. Low-dose aspirin for the prevention of atherothrombosis. Due north Eng J Med . 2005; 353:2373–2383. doi: 10.1056/NEJMra052717CrossrefMedlineGoogle Scholar
6. Arnett DK, Blumenthal RS, Albert MA, Buroker AB, Goldberger ZD, Hahn EJ, Himmelfarb CD, Khera A, Lloyd-Jones D, McEvoy JW, Michos ED, Miedema Dr., Muñoz D, Smith SC, Virani SS, Williams KA, Yeboah J, Ziaeian B. 2019 ACC/AHA guideline on the chief prevention of cardiovascular disease: a study of the American College of Cardiology/American Center Association Task Force on Clinical Practice Guidelines. Circulation . 2019; 140:e596–e646. doi: 10.1161/CIR.0000000000000678.LinkGoogle Scholar
7. Mehta Southward, Bainey Yard, Cantor W, Lordkipanidzé K, Marquis-Gravel G, Robinson S, Sibbald M, So D, Wong G, Abunassar J, et al. . 2018 Canadian Cardiovascular Society (CCS)/Canadian Clan of Interventional Cardiology (CAIC) focused update of the guidelines for the use of antiplatelet therapy. Can J Cardiol . 2018; 34:214–233. doi: x.1016/j.cjca.2017.12.012CrossrefMedlineGoogle Scholar
8. Bibbins-Domingo 1000. Aspirin utilize for the primary prevention of cardiovascular disease and colorectal cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med . 2016; 164:836–845. doi: 10.7326/M16-0577CrossrefMedlineGoogle Scholar
ix. Piepoli MF, Hoes AW, Agewall S, Albus C, Brotons C, Catapano AL, Cooney MT, Corra U, Cosyns B, Deaton C, et al. . 2016 European Guidelines on cardiovascular disease prevention in clinical practice: The Sixth Articulation Chore Forcefulness of the European Order of Cardiology and Other Societies on Cardiovascular Disease Prevention in Clinical Practise (constituted past representatives of 10 societies and past invited experts)Developed with the special contribution of the European Association for Cardiovascular Prevention & Rehabilitation (EACPR). Eur Heart J . 2016; 37:2315–2381. doi: 10.1093/eurheartj/ehw106CrossrefMedlineGoogle Scholar
x. Bell Ad, Roussin A, Cartier R, Chan WS, Douketis JD, Gupta A, Kraw ME, Lindsay TF, Dear MP, Pannu N, et al. ; Canadian Cardiovascular Society. The use of antiplatelet therapy in the outpatient setting: Canadian Cardiovascular Society guidelines. Tin can J Cardiol . 2011; 27 Suppl A:S1–59. doi: 10.1016/j.cjca.2010.12.015CrossrefMedlineGoogle Scholar
11. American Diabetes Association. 10. Cardiovascular Disease and Take chances Management: Standards of Medical Care in Diabetes - 2019. Diabetes Intendance . 2019; 42:S103–123. doi: 10.2337/dc19-S010CrossrefMedlineGoogle Scholar
12. Mosca 50, Benjamin EJ, Berra Thou, Bezanson JL, Dolor RJ, Lloyd-Jones DM, Newby LK, Piña IL, Roger VL, Shaw LJ, et al. . Effectiveness-based guidelines for the prevention of cardiovascular disease in women–2011 update: a guideline from the american heart association. Circulation . 2011; 123:1243–1262. doi: ten.1161/CIR.0b013e31820faaf8LinkGoogle Scholar
thirteen. Ikeda Y, Shimada K, Teramoto T, Uchiyama Southward, Yamazaki T, Oikawa Southward, Sugawara M, Ando K, Murata One thousand, Yokoyama K, et al. . Low-dose aspirin for primary prevention of cardiovascular events in Japanese patients 60 years or older with atherosclerotic gamble factors: a randomized clinical trial. JAMA . 2014; 312:2510–2520. doi: 10.1001/jama.2014.15690CrossrefMedlineGoogle Scholar
14. Ogawa H, Nakayama One thousand, Morimoto T, Uemura Due south, Kanauchi Chiliad, Doi N, Jinnouchi H, Sugiyama S, Saito Y; Japanese Primary Prevention of Atherosclerosis With Aspirin for Diabetes (JPAD) Trial Investigators. Low-dose aspirin for primary prevention of atherosclerotic events in patients with type two diabetes: a randomized controlled trial. JAMA . 2008; 300:2134–2141. doi: 10.1001/jama.2008.623CrossrefMedlineGoogle Scholar
15. Peto R, Grayness R, Collins R, Wheatley K, Hennekens C, Jamrozik Yard, Warlow C, Hafner B, Thompson E, Norton South. Randomised trial of prophylactic daily aspirin in British male doctors. Br Med J (Clin Res Ed) . 1988; 296:313–316. doi: 10.1136/bmj.296.6618.313CrossrefMedlineGoogle Scholar
16. Ridker PM, Cook NR, Lee IM, Gordon D, Gaziano JM, Manson JE, Hennekens CH, Buring JE. A randomized trial of low-dose aspirin in the primary prevention of cardiovascular disease in women. Northward Engl J Med . 2005; 352:1293–1304. doi: 10.1056/NEJMoa050613CrossrefMedlineGoogle Scholar
17. Hansson Fifty, Zanchetti A, Carruthers SG, Dahlöf B, Elmfeldt D, Julius Due south, Ménard J, Rahn KH, Wedel H, Westerling Southward. Furnishings of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: main results of the Hypertension Optimal Handling (HOT) randomised trial. HOT Study Group. Lancet . 1998; 351:1755–1762. doi: 10.1016/s0140-6736(98)04311-6CrossrefMedlineGoogle Scholar
eighteen. Steering Committee of the Physicians' Health Study Research K. Final report on the aspirin component of the ongoing Physicians' Health Study. North Engl J Med . 1989; 321:129–135. doi: 10.1056/NEJM198907203210301CrossrefMedlineGoogle Scholar
xix. Regulations.gov. Citizen Petition Denial Response from FDA to Bayer Healthcare, LLC. May 2,2014. https://www.regulations.gov/document?D=FDA-1977-N-0018-0101. Accessed April 18, 2019.Google Scholar
20. Grundy SM, Stone NJ, Bailey AL, Beam C, Birtcher KK, Blumenthal RS, Braun LT, deFerranti South, Faiella-Tommasino J, Forman DE, et al. . 2018 AHA/ACC/AACVPR/AAPA/ABC/ACPM/ADA/AGS/APhA/ASPC/NLA/PCNA guideline on the direction of blood cholesterol. A report of the American College of Cardiology/American Heart Association Task Force on Clinical Exercise Guidelines. Apportionment . 2018;Epub ahead of print. DOI: x.1161/CIR.0000000000000625.Google Scholar
21. Gaziano JM, Brotons C, Coppolecchia R, Cricelli C, Darius H, Gorelick PB, Howard M, Pearson TA, Rothwell PM, Ruilope LM, et al. ; Get in Executive Committee. Use of aspirin to reduce take a chance of initial vascular events in patients at moderate gamble of cardiovascular affliction (ARRIVE): a randomised, double-blind, placebo-controlled trial. Lancet . 2018; 392:1036–1046. doi: 10.1016/S0140-6736(18)31924-XCrossrefMedlineGoogle Scholar
22. Bowman L, Mafham M, Wallendszus K, Stevens W, Cadet G, Barton J, Murphy One thousand, Aung T, Haynes R, Cox J, et al. . Furnishings of aspirin for primary prevention in persons with diabetes mellitus. N Engl J Med . 2018; 379:1529–1539. doi: 10.1056/NEJMoa1804988CrossrefMedlineGoogle Scholar
23. McNeil JJ, Wood RL, Nelson MR, Reid CM, Kirpach B, Wolfe R, Storey E, Shah RC, Lockery JE, Tonkin AM, et al. ; ASPREE Investigator Group. Effect of Aspirin on Disability-complimentary Survival in the Healthy Elderly. N Engl J Med . 2018; 379:1499–1508. doi: ten.1056/NEJMoa1800722CrossrefMedlineGoogle Scholar
24. Guirguis-Blake JM, Evans CV, Senger CA, O'Connor EA, Whitlock EP. Aspirin for the principal prevention of cardiovascular events: a systematic evidence review for the U.S. Preventive Services Chore Forcefulness. Ann Intern Med . 2016; 164:804–813. doi: 10.7326/M15-2113CrossrefMedlineGoogle Scholar
25. Xie K, Shan Z, Zhang Y, Chen Southward, Yang Westward, Bao West, Rong Y, Yu X, Hu FB, Liu Fifty. Aspirin for primary prevention of cardiovascular events: meta-analysis of randomized controlled trials and subgroup analysis by sex and diabetes status. PLoS Ane . 2014; ix:e90286. doi: ten.1371/journal.pone.0090286CrossrefMedlineGoogle Scholar
26. Baigent C, Blackwell L, Collins R, Emberson J, Godwin J, Peto R, Buring J, Hennekens C, Kearney P, Meade T, et al. . Aspirin in the primary and secondary prevention of vascular disease: collaborative meta-assay of private participant data from randomised trials. Lancet . 2009; 373:1849–1860. doi: 10.1016/S0140-6736(09)60503-1CrossrefMedlineGoogle Scholar
27. Zheng SL, Roddick AJ. Association of Aspirin Apply for Primary Prevention With Cardiovascular Events and Bleeding Events: A Systematic Review and Meta-assay. JAMA . 2019; 321:277–287. doi: 10.1001/jama.2018.20578CrossrefMedlineGoogle Scholar
28. De Berardis G, Sacco M, Evangelista V, Filippi A, Giorda CB, Tognoni 1000, Valentini U, Nicolucci A; ACCEPT-D Study Group. Aspirin and Simvastatin Combination for Cardiovascular Events Prevention Trial in Diabetes (ACCEPT-D): blueprint of a randomized study of the efficacy of low-dose aspirin in the prevention of cardiovascular events in subjects with diabetes mellitus treated with statins. Trials . 2007; eight:21. doi: 10.1186/1745-6215-8-21MedlineGoogle Scholar
29. Capodanno D, Angiolillo DJ. Aspirin for Primary Cardiovascular Risk Prevention and Beyond in Diabetes Mellitus. Circulation . 2016; 134:1579–1594. doi: ten.1161/CIRCULATIONAHA.116.023164LinkGoogle Scholar
30. McNeil JJ, Wolfe R, Woods RL, Tonkin AM, Donnan GA, Nelson MR, Reid CM, Lockery JE, Kirpach B, Storey E, et al. ; ASPREE Investigator Group. Effect of aspirin on cardiovascular events and bleeding in the salubrious elderly. N Engl J Med . 2018; 379:1509–1518. doi: 10.1056/NEJMoa1805819CrossrefMedlineGoogle Scholar
31. Mahmoud AN, Gad MM, Elgendy AY, Elgendy IY, Bavry AA. Efficacy and safe of aspirin for primary prevention of cardiovascular events: a meta-analysis and trial sequential analysis of randomized controlled trials. Eur Middle J . 2019; forty:607–617. doi: 10.1093/eurheartj/ehy813CrossrefMedlineGoogle Scholar
32. Hall HM, de Lemos JA, Enriquez JR, McGuire DK, Peng SA, Alexander KP, Roe MT, Desai North, Wiviott SD, Das SR. Contemporary patterns of discharge aspirin dosing later on acute myocardial infarction in the United States: results from the National Cardiovascular Data Registry (NCDR). Circ Cardiovasc Qual Outcomes . 2014; 7:701–707. doi: x.1161/CIRCOUTCOMES.113.000822LinkGoogle Scholar
33. Mehta SR, Tanguay JF, Eikelboom JW, Jolly SS, Joyner CD, Granger CB, Faxon DP, Rupprecht HJ, Budaj A, Avezum A, et al. ; CURRENT-Oasis 7 trial investigators. Double-dose versus standard-dose clopidogrel and high-dose versus low-dose aspirin in individuals undergoing percutaneous coronary intervention for acute coronary syndromes (CURRENT-Haven 7): a randomised factorial trial. Lancet . 2010; 376:1233–1243. doi: 10.1016/S0140-6736(10)61088-4CrossrefMedlineGoogle Scholar
34. Peters RJ, Mehta SR, Fox KA, Zhao F, Lewis BS, Kopecky SL, Diaz R, Commerford PJ, Valentin V, Yusuf S; Clopidogrel in Unstable angina to prevent Recurrent Events (CURE) Trial Investigators. Furnishings of aspirin dose when used lonely or in combination with clopidogrel in patients with acute coronary syndromes: observations from the Clopidogrel in Unstable angina to preclude Recurrent Events (CURE) study. Circulation . 2003; 108:1682–1687. doi: 10.1161/01.CIR.0000091201.39590.CBLinkGoogle Scholar
35. Rocca B, Santilli F, Pitocco D, Mucci L, Petrucci G, Vitacolonna E, Lattanzio Southward, Mattoscio D, Zaccardi F, Liani R, et al. . The recovery of platelet cyclooxygenase activeness explains interindividual variability in responsiveness to depression-dose aspirin in patients with and without diabetes. J Thromb Haemost . 2012; 10:1220–1230. doi: 10.1111/j.1538-7836.2012.04723.10CrossrefMedlineGoogle Scholar
36. Capodanno D, Patel A, Dharmashankar Thousand, Ferreiro JL, Ueno M, Kodali One thousand, Tomasello SD, Capranzano P, Seecheran N, Darlington A, et al. . Pharmacodynamic effects of different aspirin dosing regimens in type 2 diabetes mellitus patients with coronary avenue disease. Circ Cardiovasc Interv . 2011; iv:180–187. doi: 10.1161/CIRCINTERVENTIONS.110.960187LinkGoogle Scholar
37. Bhatt DL, Grosser T, Dong JF, Logan D, Jeske W, Angiolillo DJ, Frelinger AL, Lei 50, Liang J, Moore JE, et al. . Enteric coating and aspirin nonresponsiveness in patients with type 2 diabetes mellitus. J Am Coll Cardiol . 2017; 69:603–612. doi: ten.1016/j.jacc.2016.11.050CrossrefMedlineGoogle Scholar
38. Kelly JP, Kaufman DW, Jurgelon JM, Sheehan J, Koff RS, Shapiro S. Risk of aspirin-associated major upper-gastrointestinal haemorrhage with enteric-coated or buffered product. Lancet . 1996; 348:1413–1416. doi: 10.1016/S0140-6736(96)01254-viiiCrossrefMedlineGoogle Scholar
39. Berger JS, Roncaglioni MC, Avanzini F, Pangrazzi I, Tognoni G, Brownish DL. Aspirin for the main prevention of cardiovascular events in women and men: a sex-specific meta-assay of randomized controlled trials. JAMA . 2006; 295:306–313. doi: 10.1001/jama.295.3.306CrossrefMedlineGoogle Scholar
twoscore. Patrignani P, Patrono C. Aspirin and Cancer. J Am Coll Cardiol . 2016; 68:967–976. doi: 10.1016/j.jacc.2016.05.083CrossrefMedlineGoogle Scholar
41. Coyle C, Cafferty FH, Rowley S, MacKenzie G, Berkman L, Gupta S, Pramesh CS, Gilbert D, Kynaston H, Cameron D, et al. ; Add together-Aspirin investigators. ADD-ASPIRIN: A phase 3, double-blind, placebo controlled, randomised trial assessing the effects of aspirin on illness recurrence and survival after primary therapy in common not-metastatic solid tumours. Contemp Clin Trials . 2016; 51:56–64. doi: 10.1016/j.cct.2016.10.004CrossrefMedlineGoogle Scholar
42. Rothwell PM, Cook NR, Gaziano JM, Price JF, Belch JFF, Roncaglioni MC, Morimoto T, Mehta Z. Effects of aspirin on risks of vascular events and cancer according to bodyweight and dose: analysis of individual patient data from randomised trials. Lancet . 2018; 392:387–399. doi: ten.1016/S0140-6736(18)31133-4CrossrefMedlineGoogle Scholar
43. Hernandez AF, Fleurence RL, Rothman RL. The ADAPTABLE trial and PCORnet: shining light on a new research paradigm. Ann Intern Med . 2015; 163:635–636. doi: 10.7326/M15-1460CrossrefMedlineGoogle Scholar
44. Wiviott SD, Raz I, Bonaca MP, Mosenzon O, Kato ET, Cahn A, Silverman MG, Zelniker TA, Kuder JF, Murphy SA, et al. ; DECLARE–TIMI 58 Investigators. Dapagliflozin and cardiovascular outcomes in type ii diabetes. N Engl J Med . 2019; 380:347–357. doi: x.1056/NEJMoa1812389CrossrefMedlineGoogle Scholar
45. Bhatt DL, Steg PG, Miller Yard, Brinton EA, Jacobson TA, Ketchum SB, Doyle RT, Juliano RA, Jiao L, Granowitz C, et al. ; REDUCE-Information technology Investigators. Cardiovascular risk reduction with icosapent ethyl for hypertriglyceridemia. Due north Engl J Med . 2019; 380:11–22. doi: 10.1056/NEJMoa1812792CrossrefMedlineGoogle Scholar
46. Baber U, Mehran R, Giustino G, Cohen DJ, Henry TD, Sartori S, Ariti C, Litherland C, Dangas G, Gibson CM, et al. . coronary thrombosis and major bleeding after PCI with drug-eluting stents: risk scores from PARIS. J Am Coll Cardiol . 2016; 67:2224–2234. doi: ten.1016/j.jacc.2016.02.064CrossrefMedlineGoogle Scholar
47. Costa F, van Klaveren D, James Southward, Heg D, Räber L, Feres F, Pilgrim T, Hong MK, Kim HS, Colombo A, et al. ; PRECISE-DAPT Study Investigators. Derivation and validation of the predicting haemorrhage complications in patients undergoing stent implantation and subsequent dual antiplatelet therapy (PRECISE-DAPT) score: a pooled analysis of individual-patient datasets from clinical trials. Lancet . 2017; 389:1025–1034. doi: 10.1016/S0140-6736(17)30397-5CrossrefMedlineGoogle Scholar
48. Yeh RW, Secemsky EA, Kereiakes DJ, Normand SL, Gershlick AH, Cohen DJ, Spertus JA, Steg PG, Cutlip DE, Rinaldi MJ, et al. ; DAPT Study Investigators. Development and validation of a prediction rule for benefit and harm of dual antiplatelet therapy beyond i year afterwards percutaneous coronary intervention. JAMA . 2016; 315:1735–1749. doi: 10.1001/jama.2016.3775CrossrefMedlineGoogle Scholar
49. Selak 5, Kerr A, Poppe Grand, Wu B, Harwood M, Greyness C, Jackson R, Wells South. Annual gamble of major bleeding amongst persons without cardiovascular affliction not receiving antiplatelet therapy. JAMA . 2018; 319:2507–2520. doi: 10.1001/jama.2018.8194CrossrefMedlineGoogle Scholar
50. Selak V, Jackson R, Poppe 1000, Wu B, Harwood M, Grey C, Pylypchuk R, Mehta S, Kerr A, Wells S. Predicting bleeding take a chance to guide aspirin use for the primary prevention of cardiovascular disease. A cohort written report. Ann Intern Med . 2019; 170:357–368.CrossrefMedlineGoogle Scholar

abbottobselp.blogspot.com

Source: https://www.ahajournals.org/doi/10.1161/CIRCULATIONAHA.119.040205

Abbott Obselp