Aspirin Therapy For Primary Prevention Research Articles

Aspirin for primary prevention of cardiovascular disease.

Although aspirin has a well-established role in preventing adverse events in patients with known cardiovascular disease (CVD), its benefit in patients without a history of CVD remains under scrutiny. Current data have provided insight into the risks of aspirin use, particularly bleeding, compared with its benefits in primary CVD prevention. Although aspirin is inexpensive and widely available, especially in developing countries, there is lack of evidence that the benefits outweigh the adverse events with continuous aspirin use in primary CVD prevention. Therefore, the decision to initiate aspirin therapy should be an individual clinical judgment that weighs the absolute benefit in reducing the risk of a first cardiovascular event against the absolute risk of major bleeding, and tailored to the patient’s CVD risk. This risk must be calculated, based on accurate and cost-benefit locally developed risk assessment tools, the most discriminating threshold be identified. Additionally, patients preferences should be taken into account when making the decision to initiate aspirin therapy in primary prevention of CVD or not. Physicians should continuously be trained to calculate their patients CVD risk, and concomitant strategies be emphasized.

Which people should take aspirin for primary prevention of cardiovascular disease?

Dear editor A single trial, ISIS-2,1 in 1988, demonstrated the utility of daily aspirin in the setting of acute myocardial infarction, reducing the risk of vascular death by 23%. In addition, aspirin has also proven effective in the setting of acute ischemic stroke.2 Thus, for a subset of the general population, aspirin may help to prevent heart attacks and strokes. In fact, at low doses, in the range of 75 to 100 mg per day, aspirin prevents the progression of existing cardiovascular disease (CVD), including coronary heart disease, stroke and peripheral arterial disease, and reduces the frequency of cardiovascular events in patients with history of CVD,3,4 referred to as secondary prevention. Although the benefits of aspirin for secondary prevention of CVD are well known, its use in primary prevention of CVD, defined as prevention of the first occurrence of CVD for all patients without clinical CVD, including those with diabetes mellitus and those without clinical evidence of atherosclerotic disease who are at higher CVD risk, is less clear and controversial results have been obtained. In fact, the results of several studies using aspirin for primary prevention of CVD have generally shown more modest reductions of major vascular events compared with secondary prevention (12% vs 23%).3,5 In this regard, the health study of women,6 the hypertension optimal treatment (HOT) study,7,8 the primary prevention project,9,10 the health study research group,11 the British doctors’ trial,12 and the thrombosis prevention trial,13 indicate that aspirin therapy is associated with a significant reduction of 19% in the risk of stroke and no reduction in the risk of myocardial infarction in women; and a significant reduction of 32% in the risk of myocardial infarction and a non-significant increase in the risk of stroke in men. However, in all cases, aspirin significantly increased the risk of bleeding, as the main important side effect.14 In this context, because fatal and non-fatal thrombotic events (eg, stroke and/or myocardial infarction events) are usually prevented by aspirin, in an order of magnitude lower than in secondary prevention, and overall risk for bleeding events (eg, intracranial and/or subarachnoid hemorrhage events) are generally increased by aspirin, in an order of magnitude equal to secondary prevention, aspirin appears to offer little benefit for the primary prevention of CVD. Moreover, in the vast majority of primary prevention studies, the overall risk level for CVD events was very low5 and the events rate was much lower than expected, leading to studies with less power to detect differences in the primary prevention of CVD. In addition to this, it must add a greater use in general population of preventive medications for different atherosclerotic risk factors, such as antihypertensive and lipid-lowering drugs, and other preventive measures, which together result in fewer events than expected.15 Accordingly, it was more difficult to achieve an overall risk reduction of cardiovascular events than in secondary prevention,2,3,5 and most studies concluded that low-dose aspirin does not significantly reduce the risk of cardiovascular death, non-fatal stroke (ischemic or hemorrhagic) or non-fatal myocardial infarction in subjects without prior CVD.16 Thus, using aspirin, in a cost-effective manner and with a good risk–benefit balance, for primary prevention of CVD, we must consider that patients are affected by different atherosclerotic risk factors (eg, hypertension, dyslipidemia, and diabetes mellitus) and, therefore, the preventive effects of aspirin on CVD will be heterogeneous. So, it will be necessary to study these preventive effects, for each type of individual cardiovascular event (eg, ischemic or hemorrhagic stroke, fatal or non-fatal myocardial infarction) among the different subgroups of patients, stratified according to cardiovascular risk factors studied, eg, hypertension, dyslipidemia, diabetes mellitus, sex, age, smoking, family history of premature CVD, blood pressure (<120/75 mmHg, 120–129/75–84 mmHg, 130–139/85–89 mmHg, and $140/$90 mmHg), body mass index (<25.0, 25.0–29.9, and $30.0) and/or 10-year cardiovascular risk of 6%–10%.16 This would be the case for the following ongoing clinical trials: the ASCEND study, involving aspirin for patients 40 years and older with type 1 or type 2 diabetes;17 the ARRIVE study, testing aspirin in middle aged and older patients who are at moderate risk based on the presence of multiple risk factors for CVD;18 and the ASPREE study, testing aspirin in individuals older than 70 years.19 With these data, it will be possible to demonstrate the presence or absence of a preventive effect of low-dose aspirin and, consequently, the benefit of aspirin treatment for primary prevention in certain types of patients. However, so long as clinical trials are conducted and until completion, the use of aspirin for primary prevention of CVD should target patients at high cardiovascular risk: physicians should evaluate the risks and benefits of aspirin therapy for primary prevention and incorporate patient preferences.

Inappropriate use of aspirin for primary prevention

Finer points Current guidelines vary slightly in their exact recommendations for aspirin use in the primary prevention setting. However, most consider aspirin appropriate for primary prevention when the 10-year CV risk is 6% or more. To determine the frequency of inappropriate use of aspirin in the primary prevention setting, researchers examined a cohort of patients receiving aspirin for primary prevention who were enrolled in the American College of Cardiology’s National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence (PINNACLE) registry. Inappropriate aspirin use was characterized as use in patients with a 10-year CV risk of less than 6% by the Framingham CV risk assessment tool. A total of 68,808 patients were identi ed from 119 medical practices across the United States from January 2008 to June 2013. Of the 68,808 patients reviewed, 7,972 (11.6%) were classi ed as inappropriately receiving aspirin therapy for primary prevention. The mean 10-year CV risk in the inappropriate-use group was 4% compared with 24.5% in the appropriate-use group (P < 0.001). An assessment of individual practices revealed substantial variation for inappropriate aspirin use across practices, ranging from 0% to 71.8% (median 10.1%). However, only modest regional variations were observed in the northeast, midwest, south, and west.

Reducing Cardiovascular and Cancer Risk: How to Address Global Primary Prevention in Clinical Practice.

Emerging evidence suggesting the possibility that interventions able to prevent cardiovascular disease (CVD) may also be effective in the prevention of cancer have recently stimulated great interest in the medical community. In particular, data from both experimental and observational studies have demonstrated that aspirin may play a role in preventing different types of cancer. Although the use of aspirin in the secondary prevention of CVD is well established, aspirin in primary prevention is not systematically recommended because the absolute cardiovascular event reduction is similar to the absolute excess in major bleedings. By adding to its cardiovascular prevention benefits, the potential beneficial effect of aspirin in reducing the incidence of mortality and cancer could tip the balance between risks and benefits of aspirin therapy in primary prevention in favor of the latter and broaden the indication for treatment with aspirin in populations at average risk. Prospective and randomized studies are currently investigating the effect of aspirin in prevention of both cancer and CVD; however, clinical efforts at the individual level to promote the use of aspirin in global (or total) primary prevention already could be made on the basis of a balanced evaluation of the benefit/risk ratio.

Preventing Cardiovascular Disease in Patients with Diabetes: Use of Aspirin for Primary Prevention

Diabetics are at high risk for atherosclerotic cardiovascular disease (ASCVD) and are considered a coronary heart disease risk equivalent. The utility of aspirin in primary prevention of ASCVD in diabetic patients has been widely studied and is still debated. Overall, the current evidence suggests a modest benefit for reduction in ASCVD events with the greatest benefit among those with higher baseline risk, but at the cost of increased risk of gastrointestinal bleeding. Diabetic patients at higher risk (with 10-year ASCVD risk >10%) are generally recommended for aspirin therapy if bleeding risk is felt to be low. A patient-provider discussion is recommended before prescribing aspirin therapy. Novel markers such as coronary artery calcium scores and high-sensitivity C-reactive protein may help refine ASCVD risk prediction and guide utility for aspirin therapy. This article will review the literature for the most up-to-date studies evaluating aspirin therapy for primary prevention of ASCVD in patients with diabetes.

Frequency and Practice-Level Variation in Inappropriate Aspirin Use for the Primary Prevention of Cardiovascular Disease: Insights From the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence Registry

BackgroundAmong patients without cardiovascular disease (CVD) and low 10-year CVD risk, the risks of gastrointestinal bleeding and hemorrhagic strokes associated with aspirin use outweigh any potential atheroprotective benefit. According to the guidelines on primary prevention of CVD, aspirin use is considered appropriate only in patients with 10-year CVD risk ≥6% and inappropriate in patients with 10-year CVD risk <6%. ObjectivesThe goal of this study was to examine the frequency and practice-level variation in inappropriate aspirin use for primary prevention in a large U.S. nationwide registry. MethodsWithin the National Cardiovascular Disease Registry’s Practice Innovation and Clinical Excellence registry, we assessed 68,808 unique patients receiving aspirin for primary prevention from 119 U.S. practices. The frequency of inappropriate aspirin use was determined for primary prevention (aspirin use in those with 10-year CVD risk <6%). Using hierarchical regression models, the extent of practice-level variation using the median rate ratio (MRR) was assessed. ResultsInappropriate aspirin use frequency was 11.6% (7,972 of 68,808) in the overall cohort. There was significant practice-level variation in inappropriate use (range 0% to 71.8%; median 10.1%; interquartile range 6.4%) for practices; adjusted MRR was 1.63 (95% confidence interval [CI]: 1.47 to 1.77). Results remained consistent after excluding 21,052 women age ≥65 years (inappropriate aspirin use 15.2%; median practice-level inappropriate aspirin use 13.8%; interquartile range 8.2%; adjusted MRR 1.61 [95% CI: 1.46 to 1.75]) and after excluding patients with diabetes (inappropriate aspirin use 13.9%; median practice-level inappropriate aspirin use 12.4%; interquartile range 7.6%; adjusted MRR 1.55 [95% CI: 1.41 to 1.67]). ConclusionsMore than 1 in 10 patients in this national registry were receiving inappropriate aspirin therapy for primary prevention, with significant practice-level variations. Our findings suggest that there are important opportunities to improve evidence-based aspirin use for the primary prevention of CVD.

Abstract 226: Adherence to Aspirin Therapy for Primary Prevention of Coronary Artery Disease and Cerebrovascular Accidents

Cardiovascular disease is the leading cause of death in the United States. One simple, overlooked, and easily available therapy can reduce this risk: aspirin. Low dose aspirin reduces the risk of first time myocardial infarction (MI) in men and ischemic stroke (CVA) in women. The American Heart Association recommends anti-platelet therapy for those with an ASCVD (atherosclerotic cardiovascular disease) risk score&gt; 7.5%. The aim of our study was to determine adherence to guidelines regarding aspirin therapy for primary prevention of myocardial infarction and stroke in our resident clinic. A retrospective chart review of randomized patients with risk factors for CAD and CVA seen at Ambulatory Center in Newark, NJ, between 5/1/12 and 10/29/13 was conducted. Those with contraindications to aspirin therapy were excluded. Over 400 charts were reviewed; 281 met inclusion criteria. Per chart review, only 30% (84/281) of all at-risk patients were taking aspirin. When assessing various risk factors, 44.9% (35/78) of males ages 45-79; 24% (28/116) of females ages 55-79 (95% Confidence Interval [CI] = +-5.9%); 35.7% (51/143) of those with 10-year ASCVD risk score greater than 7.5% (95% CI = +-7.9%); 36.1% (39/108) of diabetic patients (95% CI 95% = +-9.2%); 32.8% (66/201) of those on anti-hypertensive medication (95% CI = +- 6.5%) and 29.3% (36/123) of those with a smoking history were taking aspirin (95% CI = +-8.2%). Of note, the number of women taking aspirin was statistically low as compared to men across all risk factors except for ASCVD score (p&lt;0.01). This study revealed poor adherence to guidelines with regards to use of aspirin for primary prevention of cardiovascular disease and stroke in our resident clinic. In particular, adherence to aspirin therapy for women was strikingly low. However, our estimate may be somewhat low due to improper documentation of over the counter medications. We are implementing interventions to increase awareness of aspirin use such as educational campaigns for patients, mini-lectures for ambulatory resident cohorts, automated EMR reminders and adding aspirin therapy to health maintenance smart texts to achieve our goal of 100% compliance.

Effects of Changing Guidelines on Prescribing Aspirin for Primary Prevention of Cardiovascular Events

The use of low-dose aspirin for primary prevention of cardiovascular events in patients at elevated risk for cardiovascular disease (CVD) is increasingly being questioned. Aspirin may not benefit this population and may increase the risk of major bleeding events. Data support aspirin use in patients with known CVD. This is a secondary analysis of de-identified electronic health record (EHR) data from 131,050 individuals with known CVD or elevated risk for CVD as determined by diagnostic, demographic, and clinical data collected from 33 primary care practices in 11 different clinical organizations across 6 states. The percentage of the population of each cohort with aspirin recorded on their medication list, created through risk base analysis, was observed across 4 time periods. From 2007 to 2011, aspirin usage reflected in the EHR increased for the entire population and for each individual high-risk diagnosis. The percentage of the population initiating aspirin therapy for primary prevention within a year of diagnosis of CVD risk factors or CVD "equivalency" increased between 2007 and 2011. Among those with a new diagnosis of CVD, aspirin usage also steadily increased over the 4-year period, indicating no negative impact from new negative primary prevention studies. Primary care clinicians have a central role in providing evidence-based preventive services and should integrate revised information into their practice to improve outcomes. Even with new evidence against the use of aspirin for primary prevention, it is difficult to change beliefs about the effectiveness and safety of aspirin, as reflected in the behavior of physicians and patients.

Reinitiating Aspirin Therapy for Primary Prevention of Cardiovascular Events in a Patient Post—Aspirin-Induced Upper Gastrointestinal Bleed: A Case Report and Review of Literature

To describe a case of continued aspirin use for primary prevention of a cardiovascular event in a patient post-aspirin-induced upper gastrointestinal (GI) bleed and evaluate published evidence to determine whether reinitiating aspirin therapy for this patient was appropriate. A 65-year-old man had been taking chronic low-dose (81 mg/day) aspirin therapy since 2002 for primary prevention of a cardiovascular event. He developed an upper GI bleed with lowered hemoglobin (9 mg/dL) and hematocrit (26.3%) after concomitantly taking 2 doses of naproxen (220 mg each). An objective causality assessment with the Naranjo probability scale revealed a probable adverse reaction of an upper GI bleed associated with concomitant naproxen and aspirin use. No further naproxen was taken. Aspirin was discontinued and pantoprazole was started, with resolution of the bleeding. Aspirin was restarted 2.5 months after pantoprazole was initiated, and no further bleeding occurred. Upper GI bleeds associated with aspirin therapy are well described in the literature. The management of cardiovascular event prophylaxis after a GI bleed is often controversial; consensus in regard to the optimal method of management does not exist. We evaluated GI protection strategies for patients with a history of aspirin-induced GI bleeding requiring cardiovascular prophylaxis. We found that the benefit of aspirin for the primary prevention of cardiovascular events needs to be carefully balanced with the risks associated with its use. The current literature supports that the best approach to prevent recurrent aspirin-induced GI bleeding is to administer a proton pump inhibitor with aspirin therapy. The benefit of aspirin for primary prevention of cardiovascular events needs to be carefully balanced with the risks associated with its use. Based on the current literature, the best approach to preventing recurrent aspirin-induced GI bleeds is to administer a proton pump inhibitor concomitantly with aspirin therapy.

Aspirin for Primary Prevention of Cardiovascular Disease Events

Aspirin has been used for the prevention and treatment of cardiovascular disease (CVD) for several decades. The efficacy of aspirin for secondary prevention of cardiovascular disease is well established, but the clinical benefit of aspirin for primary prevention of CVD is less clear. The primary literature suggests that aspirin may provide a reduction in CVD events, but the absolute benefit is small and accompanied by an increase in bleeding. For aspirin to be beneficial for an individual patient, the risk of a future CVD event must be large enough to outweigh the risk of bleeding. The estimation of CVD risk is multifaceted and can involve numerous risk scores and assessments of concomitant comorbidities that confer additional CVD risk. Numerous guidelines provide recommendations for the use of aspirin for primary prevention, but they often contradict one another despite being based on the same clinical trials. Additional literature suggests that the presence of comorbidities that increase CVD risk, such as diabetes mellitus, asymptomatic peripheral arterial disease, or chronic kidney disease, does not ensure that aspirin therapy will be beneficial. Ongoing clinical trials may provide additional insight, but until more data are available, an individualized assessment of CVD risk with careful evaluation of risk and benefit should be performed before recommending aspirin therapy for primary prevention of CVD.

Clinical Use of Aspirin in Ischemic Heart Disease: Past, Present and Future

Aspirin is an antiplatelet drug, inhibiting the cyclooxygenase activity of platelet prostaglandin H synthase-1 and almost complete suppressing platelet capacity to generate the prothrombotic and proatherogenic thromboxane A2. Antiplatelet therapy with aspirin reduces the risk of serious vascular events by about a quarter in patients who are at high risk because they already have occlusive vascular disease. However, the inhibition of thromboxane-dependent platelet function by aspirin is effective for the prevention of thrombosis, but is also associated with excess bleeding, although the absolute increase in major gastrointestinal or other major extracranial bleeds is an order of magnitude smaller. For secondary prevention of vascular events, the benefits of aspirin therapy substantially exceed the risks. Therefore, aspirin is a cornerstone of antithrombotic therapy in acute coronary syndromes, in chronic ischemic heart disease and in percutaneous coronary intervention. On the other hand, the role of aspirin in primary prevention remains uncertain and it is still debated, because the absolute risk of vascular complications is the major determinant of the absolute benefit of antiplatelet prophylaxis and the reduction in vascular events needs to be weighed against any increase in major bleeds. Future data from ongoing studies will help us to identify people at high vascular risk who take advantage from aspirin therapy for primary prevention or will indicate if specific category of high risk patients, like patients with diabetes, could be better protected from an increase in the frequency of aspirin administration.

Cost-Effectiveness Model of Use of Genetic Testing as an Aid in Assessing the Likely Benefit of Aspirin Therapy for Primary Prevention of Cardiovascular Disease

BackgroundAspirin use for the primary prevention of cardiovascular disease (CVD) is controversial because of the need to balance the risk of major bleeding events caused by aspirin with the benefit of CVD events prevented by aspirin. The United States Preventive Services Task Force (USPSTF) proposed guidelines that use CVD risk thresholds, based on the Framingham Risk Score, to identify patients likely to benefit from aspirin use. Genetic information could be used to modify this CVD risk assessment; for example, 2 variants of the LPA gene, which encodes apolipoprotein(a), are associated with increased risk of CVD. ObjectivesTo estimate the incremental cost-effectiveness of using genetic test results for 2 LPA variants to derive modified Framingham Risk Score estimates and to use these estimates to identify patients likely to benefit from aspirin use according to USPSTF guidelines for aspirin use in the primary prevention of CVD. MethodsA cost-effectiveness model of 1 million patients representative of the US population was developed based on the association of 2 LPA variants (rs3798220 and rs10455872) with CVD. The cost of testing was estimated for patients whose 10-year CVD risk would exceed the USPSTF treatment threshold if they were to test positive for the LPA variants. Patient utility estimates for myocardial infarction and stroke, and cost estimates (using a 3.5% annual discount rate) for myocardial infarction, stroke, and gastrointestinal bleeding events were based on published estimates. ResultsRecommending aspirin to patients whose CVD risk surpassed the risk threshold when LPA information was included in their risk assessment would prevent an estimated 65 CVD events over 10 years. At a genetic test cost of $150, the incremental cost-utility of testing for LPA variants is estimated at $24,942 per quality-adjusted life-year. ConclusionsLPA genotyping in the context of the aspirin use guidelines for primary prevention of CVD could be cost-effective.

Aspirin Therapy in Primary Prevention

Aspirin Therapy in Primary Prevention

Personalizing Evidence-Based Primary Prevention With Aspirin

One of the unfortunate side consequences of evidence-based medicine (EBM) is that sometimes there is no escaping how small the benefit of any individual treatment may seem. In the “days of the giants,” doctors saved lives; now we can consult league tables that bloodlessly inform us how many patients—10, 50, or 200—must receive a treatment to avert even a single bad outcome,1 EBM's venerable number needed to treat. Article see p 268 The number needed to treat is, of course, based only on average treatment effects. A limitation of EBM is that we study groups of patients, whereas we treat individuals. This mismatch can be partially addressed by the use of statistical models to calculate the important risks that determine a more “personalized” probability of benefit. When this is done, it turns out, the degree of benefit for an intervention in any typical patient is often even less than the overall average.2 This is because benefits are determined by the baseline risk, which is usually highly skewed, such that a few high-risk patients may account for most of the benefit, whereas most patients have baseline risks (and therefore potential benefit) considerably less than the average.3 This is true particularly when the overall risk of the outcome of interest is low because there is a lower bound for risk at 0%, creating a “floor effect.” In this issue of Circulation: Cardiovascular Quality and Outcomes , Sussman et al4 describe the “personalized” risks and benefits of aspirin therapy for primary prevention of cardiovascular diseases, a rather extreme exemplar of the pattern described above. The number needed to treat to prevent a single ischemic event for any typical patient in a primary prevention population can easily exceed 1000 per year but may vary substantially, depending on individualized risk. Because …

A Variant of the LPA Gene Predicts Cardiovascular Event Reduction by Aspirin Therapy in a Primary Prevention Setting

Synopsis: The risk/benefit ratio of aspirin therapy in primary prevention of cardiovascular disease does not justify the use of aspirin. The 4399Met variant of the LPA gene—a gene that encodes apolipoprotein(a)—can help identify those who may have an acceptable risk/benefit ratio for aspirin therapy in a primary prevention setting. Purpose: To investigate the association of the LPA 4399Met variant (rs3798220) with risk of coronary events and with differential response to aspirin therapy. Methods: We used regression models to investigate the association between LPA 4399Met carrier status and coronary events and the effect of aspirin therapy on event reduction on carriers and non-carriers of 4399Met in 2 settings: 1) The Women's Health Study (WHS)—a study of more than 25,000 initially healthy women who were randomized to low-dose aspirin or placebo, and 2) self-reported nonusers (n = 5330) and regular users (n = 1422) of aspirin in the Atherosclerosis Risk in Communities (ARIC) study. We investigated the effect of aspirin therapy according to LPA 4399Met carrier status in WHS. Results: Carriers of the 4399Met allele of the LPA gene, compared with non-carriers, had increased levels of plasma lipoprotein(a) (P < .0001) and over 2-fold increased risk for major cardiovascular events in the placebo group of WHS (age-adjusted hazard ratio (HR) = 2.21; 95% CI, 1.39–3.52). This excess risk was essentially eliminated by aspirin therapy: for aspirin compared with placebo the age-adjusted HR was 0.44 (95% CI, 0.20–0.94). The risk of major cardiovascular events was not significantly reduced among non-carriers (age-adjusted HR, 0.91; 95% CI, 0.77–1.08). Consistent with these findings, among nonusers of aspirin in ARIC, carriers of the 4399Met allele compared with noncarriers had increased risk of coronary heart disease (HR, 1.57; 90% CI, 1.00–2.46; 1-sided P = .049), after adjusting for age and sex. However, carriers of the 4399Met allele did not have increased risk of CHD among nonusers of aspirin (HR, 0.86; 90% CI, 0.43–1.71; P = .36). Conclusions: Carriers of the LPA 4399Met allele are at increased risk of coronary heart disease. This excess risk is ameliorated by aspirin therapy.

Aspirin for primary prevention of cardiovascular events in patients with diabetes: A meta-analysis

Background To systematically review trials concerning the benefit and risk of aspirin therapy for primary prevention of cardiovascular events in patients with diabetes mellitus. Methods We searched MEDLINE, EMBASE and the Cochrane Central Register of Controlled Trials. Eligible studies were prospective, randomized controlled trials of aspirin therapy for primary cardiovascular prevention in patients with diabetes with follow-up duration at least 12 months. Results 7 trials included 11,618 individuals with diabetes. Aspirin therapy was not associated with a statistically significant reduction in major cardiovascular events (relative risk [RR] 0.92, 95% confidence interval [CI] 0.83–1.02, p = 0.11). Aspirin use also did not significantly reduce all-cause mortality (0.95, 95% CI 0.85–1.06; p = 0.33), cardiovascular mortality (0.95, 95% CI 0.71–1.27; p = 0.71), stroke (0.83, 95% CI 0.63–1.10; p = 0.20), or myocardial infarction (MI) (0.85, 95% CI 0.65–1.11; p = 0.24). There was no significant increased risk of major bleeding in aspirin group (2.46, 95% CI 0.70–8.61; p = 0.16). Meta-regression suggested that aspirin agent could reduce the risk of stroke in women and MI in men. Conclusions In patients with diabetes, aspirin therapy did not significantly reduce the risk of cardiovascular events without an increased risk of major bleeding, and showed sex-specific effects on MI and stroke.

Platelet Function and Response to Aspirin: Gender-Specific Features and Implications for Female Thrombotic Risk and Management

This article reviews gender-specific differences in platelet function and response to aspirin. In contrast with men, women under 65 years of age do not benefit from aspirin therapy in primary prevention of coronary artery disease. Furthermore, the overall mortality after myocardial infarction is higher among women, which cannot simply be explained by age or individual treatment. Platelets play a central role in thrombo-ischemic events leading to myocardial infarction and ischemic stroke. Gender differences in platelet reactivity and "aspirin resistance" have been reported. Several studies using female platelets have shown increased platelet reactivity at baseline and a less effective inhibition of platelet aggregation by aspirin. The mechanisms underlying these differences are still to be elucidated, but influences of female sex hormones may play an important role. As a consequence, inhibition of platelet aggregation in women treated with aspirin may be insufficient, and female patients might benefit from higher maintenance dosages or the use of alternative antiplatelet medications. A potential future role of pharmacogenomics and laboratory monitoring of antiplatelet medications in predicting individual responsiveness is likely. Overall, primary prevention of myocardial infarction in women should be correlated with the individual risk score of the female patient. More studies focused on women are needed to optimize gender-specific therapy and, therefore, to improve clinical outcomes in women with atherosclerosis.

Underutilization of aspirin in hemodialysis patients for primary and secondary prevention of cardiovascular disease

Patients on hemodialysis are at high risk for cardiovascular disease (CVD). Aspirin is an established therapy for primary and secondary prevention of CVD that may be underutilized in hemodialysis patients. To better understand the use of aspirin in hemodialysis patients, we examined the experience of an urban hemodialysis center. Guidelines for use as well as associated risks and benefits are reviewed. Medical records for patients receiving hemodialysis treatment at our center (New York City, USA) in May 2004 were reviewed for aspirin use, presence of CVD, and potential contraindications to aspirin therapy. CVD was defined as a history of coronary artery disease, ischemic stroke, transient ischemic attack, or peripheral vascular disease. Potential contraindications to aspirin therapy included history of clinically significant bleeding or increased risk of bleeding, aspirin allergy and routine treatment with other anticoagulants. 176 patients were eligible for the study and 172 (98%) were included. Although 74 patients had a history of CVD, only 38 (51 %) of these were treated with aspirin. Among patients with a history of CVD who were not treated with aspirin, 19 (53%) had no identifiable contraindications to aspirin therapy for secondary prevention of CVD. Ninetyeight patients had no history of CVD, and 18 (18%) of these were treated with aspirin. Of patients without a history of CVD who were not treated with aspirin, 57 (71%) had no identifiable contraindications to aspirin therapy for primary prevention of CVD. Aspirin is underutilized in hemodialysis patients for the primary and secondary prevention of CVD. Given the high risk of CVD in hemodialysis patients, therapy with aspirin may be of significant benefit and prospective studies of aspirin therapy are needed.

Aspirin for the Primary Prevention of Cardiovascular Disease: A Comprehensive Review

Aspirin use for the primary prevention of cardiovascular disease should be targeted to patients with a high cardiovascular risk. Physicians should assess the risks and benefits of aspirin therapy for primary prevention and incorporate patient preferences.

Prevention of aspirin-induced gastroduodenal damage: H. pylori infection eradication versus proton pump inhibitors or both

Low-dose aspirin is the most important antiplatelet agent, which is recommended in all clinical conditions where antiplatelet prophylaxis has a favourable benefit/risk profile in secondary prevention (e.g. ≥3% of vascular event per annum) [ [1] Patrono C. Bachmann F. Baigent C. Bode C. De Caterina R. Charbonier B. et al. Expert consensus document on the use of antiplatelet agents. Eur. Heart J. 2004; 25: 166-181 Crossref PubMed Scopus (388) Google Scholar ]. The benefits of aspirin in this therapeutic approach are reduced because low-dose aspirin is associated with increased risk of side effects, especially gastrointestinal (GI) bleeding [ [2] Lanas A. Hirschowitz B.I. Toxicity of NSAIDs in the stomach and duodenum. Eur. J. Gastroenterol. Hepatol. 1999; 11: 375-381 Crossref Scopus (46) Google Scholar ]. In this context, the benefits of aspirin therapy in primary prevention of vascular occlusive diseases and/or when the risk of cardiovascular events is less than 1% per annum is outweighed by the risks associated with aspirin use [ [1] Patrono C. Bachmann F. Baigent C. Bode C. De Caterina R. Charbonier B. et al. Expert consensus document on the use of antiplatelet agents. Eur. Heart J. 2004; 25: 166-181 Crossref PubMed Scopus (388) Google Scholar ]. However, unlike NSAIDs, the available information regarding GI toxicity associated with low-dose aspirin is poor [ [3] Lanas A.I. Current approaches to reducing gastrointestinal toxicity of low-dose aspirin. Am. J. Med. 2001; 110: 70S-73S Abstract Full Text Full Text PDF PubMed Google Scholar ]. Only very recently has new information been reported and some gaps are being filled.