ASA For Primary Prevention Research Articles

Kyselina acetylsalicylová v primární prevenci kardiovaskulárních onemocnění

Acetylsalicylic acid is an effective and widely accepted essential drug in the secondary prevention of ischemic events. Its role in primary prevention has been studied for several decades and still remains controversial. Initial studies showed a reduction in both myocardial infarctions and ischemic strokes, without affecting overall or cardiovascular mortality, but the enrolled subjects were not treated with modern drugs and procedures in primary preventive care as they do today. Recently published studies have also not shown a mortality benefit, but in some sub-populations and groups of patients, the clinical benefit of aspirin continues to outweigh the risks associated with its long-term use. This review article will discuss the development of ASA in primary prevention, the results of the latest studies of the year 2018 and their meta-analyses, current indications for ASA treatment, as well as future perspectives.

Primary Prevention of CVD with Aspirin: Benefits vs Risks.

Low-dose aspirin (acetylsalicylic acid [ASA]; 75 to 100 mg/d) is widely used in the prevention of cardiovascular (CV) events based on the results of large-scale studies supporting a benefit. However, questions remain regarding the benefit-risk relationship in certain settings since long-term use of ASA is not devoid of risk. Incontrovertible evidence supports the benefits of ASA treatment, which exceed the risks, in patients who have had a previous CV event (myocardial infarction, stroke, unstable angina, or transient ischemic attack). Nonetheless, the question remains for those patients who have not had a previous event (primary prevention), where the risk of CV events is lower and, consequently, the absolute benefit is also lower than in patients who have a history of a CV event or its equivalent (secondary prevention). Recent evidence from large-scale clinical trials shows that administration of low-dose ASA is associated with a reduced risk of CV events with a corresponding small absolute increase in the risk of major bleeding (eg, gastrointestinal bleeding and hemorrhagic stroke). Although the benefit and the risk of low-dose ASA in primary prevention are numerically similar, the clinical consequences of an increased risk of bleeding and a decreased risk of a CV event may not be equivalent. If these data are applied to patients with higher levels of CV outcome risk, more patients may potentially benefit from aspirin use in primary prevention.

ASA - from cardiovascular to cancer prevention

Cardiovascular disease and cancer are the leading causes of morbidity and mortality worldwide. Low-dose ASA has been shown to effectively prevent about one fifth of atherothrombotic vascular complications in patients with previous myocardial infarction, peripheral arterial occlusive disease (PAOD), or stroke 2. In secondary prevention, the benefits of antiplatelet therapy substantially exceed its risk 2. By contrast, recommendations for the use of ASA in primary prevention are still a matter of controversy. The aim of this article is to review the current evidence for the efficacy of low-dose ASA in primary and secondary prevention of cardiovascular diseases as well as to discuss its potential additional chemopreventive action.

Perioperative management of antiplatelet therapy

Worldwide, cardiovascular events represent the major cause of morbidity and mortality. A key role in the pathogenesis of these events is played by platelets. Interventional procedures, with placement of coronary and vascular stents, often represent the preferred therapeutic strategy. Antiplatelet medications are considered first-line therapy in preventing cardiovascular thrombotic events. A wide array of antiplatelet agents is available, each with different pharmacological properties. When patients on antiplatelet agents present for surgery, the perioperative team must design an optimal strategy to manage antiplatelet medications. Each patient is stratified according to risk of developing a cardiovascular thrombotic event and inherent risk of surgical bleeding. After risk stratification analysis, various therapeutic pathways include continuing or discontinuing all antiplatelet agents or maintaining one antiplatelet agent and discontinuing the other. This review focuses on the pharmacological and pharmacokinetic properties of both older and novel antiplatelet drugs, and reviews current literature and guidelines addressing options for perioperative antiplatelet management.

Aspirin for the primary prevention of cardiovascular diseases

BackgroundFor secondary prevention of fatal and non-fatal cardio-vascular events, benefits of aspirin (ASA) are well defined,and form the basis for current clinical practice [1–4]. Inpatients without a history of cardiovascular diseases(CVD), in contrast, the picture is not clear: several meta-analyses [5, 6] and the individual data meta-analysis ofthe antithrombotic trialists’ (ATT) collaboration [7] showthat the efficacy of ASA in reducing the risks of acutemyocardial infarction (MI) and ischemic stroke does notoutweigh the associated increased risk of bleeding. Theconflicting recommendations from guidelines panels reflectthis uncertainty [3, 8, 9]. After the publication of ATTstudy in 2009 [7], three more randomized controlledstudies (RCT) evaluating the use of ASA in primary pre-vention were published [10–12]. Recently, three nearlycontemporaneous meta-analyses [13–15] combined old andnewest trials’ results.SummaryWe discuss three meta-analyses published between January2011 and 2012 that evaluated trials in primary cardiovas-cular prevention and involved a randomized comparison ofASA versus placebo or control [13–15].The first was carried out by Berger et al., who searchedelectronic databases (MEDLINE, the Cochrane CentralRegister of Controlled Trials, and EMBASE) for RCTspublished up to 2011 [13]. The occurrence of a majorcardiovascular event (MCE), i.e. non-fatal MIs, non-fatalstrokes, all-cause and cardiovascular mortality, was chosenas primary outcome. As primary safety outcomes, theauthors included major bleedings as defined by each study.All outcomes were analysed using the data reported in theoriginal publications. Random effect meta-analysis wasexecuted, using risk ratio (RR) as efficacy measure. Sen-sitivity analysis was performed and specific subsets ofstudies were analysed (removing one by one trials enrollingpatients with diabetes or subclinical atherosclerosis andthose including extended or controlled release aspirin).Meta-regression was applied to evaluate potential effectmodifiers (year of study publication, baseline cardiovas-cular risk, mean age and sex of trial’s participants, and doseof ASA). Potential publication biases were examined byconstructing a funnel plot. Nine prospective randomizedtrials involving 102,621 participants (52,145 allocated toaspirin, 50,476 to placebo/control) were identified forinclusion and meta-analysed.The same nine trials were incorporated in the meta-analysis by Raju et al. [14]. Medline, Cinahl, Embase andthe Cochrane Library databases were sought up to May2010, bibliographies of journal articles were hand-sear-ched and experts were contacted to identify unpublishedstudies. Raju et al. considered the following outcomes

019 Who receives asa for primary prevention in canada?: Insight from the primary care audit of global risk management (PARADIGM) study

stolic and untreated 145 / 13 mmHg systolic and 91 / 9 mmHg diastolic. Of the untreated subjects 56%, 13%, 2% and 19% had[M1] Stage 1, 2, 3, or isolated systolic hypertension. CV risk factors included past/current smoking (36%), family history of CVD (27%), abdominal obesity (63%) and dyslipidemia (33%). Median LDL cholesterol was 3.6 / 0.8 mmol/L, hsCRP 3.7 / 5[M2] mg/L, andHbA1C0.06 / 0.01.Using the totalCVFramingham Risk Score, 20%, 41% and 39% of subjects were in the low, intermediate and high risk categories respectively. Mean creatinine was 80 / 17 umol/L, eGFR 76 / 17; a higher proportion of untreated patientshadaurineMACR 2mg/mmol (50%vs.30%,P 0.05). In treated subjects, 47% and 39% were receiving either mono or dual antihypertensive therapy, with 14% receiving drugs. In monotherapy the use of ACEi was 39%, ARB 30%, diuretics 17% and CCB 7%. The most common combination therapies were ARB/ diuretic (39.4%), ACEi/diuretic (32.9%), BB/diuretic (6.2%), ACEi/CCB (6.2%) and ARB/CCB (5.2%). The use of ACEi/ARB was negligible (0.3%) The most commonly used triple therapy was RAS blocker/CCB/diuretic (60%) and RAS blocker/BB/diuretic (29%). CONCLUSION: In this contemporary analysis of otherwise healthy Canadians with HT, additional CV risk factors are common, particularly abdominal obesity. Treated BP levels were within recommended ranges. Despite the absence of diabetes or vascular disease, 80% of subjects had intermediate to high FRS, a large proportion of whom likely qualify for statin therapy. The use of RAS-based monotherapy is high. Combination therapy with RAS/ diuretic is still favoured over RAS/ CCB.

C-B4-04: Underuse of Aspirin in Women for Primary and Secondary Prevention of Cardiovascular Disease Events

Background and Aims: Cardiovascular disease (CVD) is the leading cause of death among women. Consistent with studies documenting that aspirin (ASA) use decreases the risk of CVD events in certain groups, the American Heart Association (AHA) published specific evidence based guidelines for ASA use in women. This paper evaluates the self-reported use of ASA among women and examined characteristics of those most likely to be adhering to clinical guidelines. Methods: Data from 127 healthcare centers across the U.S. using a commercial, web-based CVD risk assessment tool (HeartAware™) were analyzed. Volunteer respondents answered questions about their CVD risk factors, the presence or absence of coronary, cerebral, peripheral arterial disease, diabetes, and medication use including daily ASA. Individuals who, based on the AHA 2007 guidelines should be taking ASA (for primary and secondary prevention) were included in the analysis. Univariate and multivariate logistic regression analyses were performed to identify factors significantly associated with ASA intake. Results: Of the 21,199 women who should be on ASA based on guideline information, only 42% reported the use for primary prevention and 68% for secondary prevention. Multivariate regression analysis found that African Americans (OR = 0.61, 95% CI 0.53–0.70, p<0.0001) and Hispanics (OR = 0.67, 95% CI 0.53–0.83, p=0.0004) were less likely than Caucasians to be taking ASA. Other factors that contributed significantly (p<0.001) to ASA use were a relationship with a PCP or cardiologist, taking blood pressure medications, past history of smoking, a family history of heart disease, and a family history of high cholesterol. Conclusions: Findings from a large cross-sectional cohort revealed that 58% of women who should be taking ASA for primary prevention and 32% of women who should be taking ASA for secondary prevention of CVD events were not following national guidelines. Individuals from racial/ethnic minorities were less likely to be taking ASA compared with Caucasians suggesting targets for intervention. These findings emphasize the need for ASA education among clinicians to provide guidance for targeting educational efforts that can improve CVD outcomes in women.

Report from the 100th Cardiovascular and Renal Drugs Advisory Committee meeting: US Food and Drug Administration: December 8-9, 2003 Gaithersburg, MD.

The Committee was asked, through a citizen petition filed by Bayer Healthcare, to evaluate amending the professional labeling for the use of aspirin (ASA) to include primary prevention of myocardial infarction (MI). They cited evidence from 5 studies germane to this issue. Specifically, the request was to expand the current cardiovascular indications for daily ASA (75 to 325 mg) to include asymptomatic individuals with a 10% or greater risk of coronary heart disease over 10 years. The Food and Drug Administration (FDA) and the Advisory Committee considered the use of ASA in primary prevention in 1998, when the Physicians Health Study (PHS) and the British Doctors Study (BDS) were reviewed. At that time, the FDA concluded that the data were insufficient to warrant a change identical to that requested in the current application. Since then, 3 new studies have been conducted and were provided for the current review: (1) the Thrombosis Prevention Trial (TPT), (2) the Hypertension Optima Trial (HOT), and (3) the Primary Prevention Project (PPP). Overall, these 5 trials represent data from more than 55 000 patients in placebo-controlled trials from heterogeneous patient populations, using differing doses and formulations of ASA, and aimed towards differing primary end points. The 2 previously reviewed studies in male doctors account for more than 27 000 patients within the new pooled analysis supporting the claim. TPT, conducted …