Antiplatelet Therapy For Primary Prevention Research Articles

ANTIPLATELET THERAPY IN PRIMARY PREVENTION. OBSERVATIONAL STUDY AND SURVIVAL ANALYSIS IN HIGH CARDIOVASCULAR RISK PATIENTS.

Objective: Cardiovascular diseases are the leading cause of morbidity and mortality in industrialized countries. This was a retrospective observational study, evaluating clinical outcomes, metabolic consequences and survival rate resulting from prolonged antiplatelet therapy for primary prevention in patients with high CVR. Design and method: Overall, 516 patients were randomly selected from cardiovascular risk and metabolism consultations in a single center in Porto (Portugal). Sociodemographic, lifestyle and clinical characteristics were collected at baseline, including biochemical parameters, vascular risk scores and tests for heart and cardiovascular evaluation. In this follow-up with a median of 11 years, 287 patients received adjuvant antiplatelet therapy in primary prevention. Association between sex, observation time and treatments with LDLc and HDLc variations were assessed. Multiple linear regression was performed to evaluate which factors could explain the differences in HDLc and LDLc levels. Kaplan-Meier survival analysis was also conducted. Results: Therapy with statins was initiated early for metabolic compensation of dyslipidemia, according to clinical practice. Statistically significant reductions were found for almost all biochemical parameters, mean carotid intima-media thickness and lipid metabolism parameters, including triglycerides, total cholesterol and the respective fractions. Patients taking statins showed greater increased HDLc values and reduced LDLc values than those who were not. Additionally, women showed a more favorable evolution regarding HDLc increase compared to men. Survival rate was estimated at 77.5% with 22 years as the maximum observed time. The median time of survival was not computed, since more than half of the patients (77.5%) were alive after 22 years. No bleeding episodes were recorded during this long period of observation.In fact, 99.0% of patients were alive after 10 years and the percentage of patients alive remained over 90% at 17 years. After 18 years of observation, 88.6% of patients were alive, and at 20 years 77.5% were alive without major cardiovascular events (MACE). Conclusions: Antiplatelet therapy should always be considered in primary prevention in patients with high CVR. There were no cases of hemorrhage or MACE. The survival rate estimated for the study population was 77.5% over 22 years.

Internal Carotid Artery Dissection – A Case for Antithrombotic Therapy in the Era of (Minimally) Invasive Procedures

Objectives: Carotid artery dissection represents a common cause of stroke among people aged 30-45. We present two clinical cases and a review of the literature concerning the management of internal carotid artery dissections (ICADs). Materials and methods: The two patients are a 54-year-old male and a 40-year-old female. The first patient presented to our Neurology Department for one-week-old intense occipital headache. His clinical examination revealed left-sided miosis and upper eyelid ptosis. He underwent cerebral-cervical computed tomography (CT) and computed tomography angiography (CTA) scans and the latter revealed hemodynamically significant narrowing of both ICAs (right C1-C5 and left C1-C2 segments). Transcranial Doppler ultrasonography and Doppler ultrasonography (DUS) of the cervical-cerebral arteries showed right ICA occlusion at its origin (dissection fold and intraluminal thrombosis). Cervical magnetic resonance imaging (MRI) and time-of-flight magnetic resonance angiography (MRA) revealed a semilunar-shaped T2-weighted hypersignal present in the walls of the C1-C5 segments of the right ICA and of the C1-C2 segments of the left ICA, with bilaterally reduced intraluminal flow (right more than left). These findings indicated the presence of bilateral ICA intramural hematomas caused by subacute bilateral ICAD. The second patient presented to our Neurology Department for recurrent episodes of headache and lateral cervical pain on both sides. She underwent transcranial DUS and DUS of the cervicalcerebral arteries. They revealed right ICAD fold in its upper cervical segments. The CTA scan of the supra-aortic trunks showed hemodynamically significant narrowing with subsequent diminished blood flow in the upper cervical segments of right ICA. The patient was diagnosed with right ICAD. Results:Both patients were treated using antiplatelet therapy for primary prevention of ischaemic events. Follow-up at seven months and at six months, respectively, by means of CTA of the supra-aortic trunks or MRA of the cervical region, revealed the restoration of arterial patency with subsequent normal blood flow in both cases. Conclusions: The long-term outcomes of ICADs should be kept in mind when assigning medical or endovascular management on a case-by-case basis. Antiplatelet or anticoagulant therapy is a safe and effective first-line strategy in such patients, especially in cases that do not warrant particular management.

Update of Antiplatelet Therapy in Patients Without Known Cardiovascular Disease

AbstractPlatelet activation and aggregation play a critical role in thrombosis, a fundamental pathophysiologic event responsible for the acute clinical manifestations of atherothrombotic events such as acute coronary syndrome, myocardial infarction, ischemic stroke/transient ischemic attack and peripheral artery disease. Dual antiplatelet therapy (low-dose aspirin plus ADP-P2Y12 receptor blockers) has become the cornerstone of therapy for the management of acute and chronic coronary artery disease and the prevention of ischemic complications associated with percutaneous coronary intervention. However, dual antiplatelet therapy in primary prevention of cardiovascular disease in patients without known cardiovascular disease did not significantly reduce the risk of cardiovascular events, such as myocardial infarction, stroke or death, but significantly increased the rate of bleeding. Furthermore, despite multiple randomized controlled trials evaluating the efficacy and safety of aspirin use in patients without known cardiovascular disease, its role in primary prevention is still unclear, especially in patients with a higher risk of cardiovascular disease (non-diabetic individuals with >2 risk factors for coronary artery disease, elderly >60 years with additional risk factors, and patients with diabetes). Currently, there are four ongoing randomized controlled trials aiming to fill the missing gap in the efficacy and safety of aspirin therapy for primary prevention in these patients. The current European and United States Guidelines agree that primary prevention of cardiovascular disease is essential, but there are some substantial differences in risk estimation and treatment strategies among patients without known cardiovascular disease. This short review is focused on these differences and practical treatment approach to these patients based on present European and United States recommendations.

Assessment of NICE and USPSTF guidelines for identifying women at high risk of pre-eclampsia for tailoring aspirin prophylaxis in pregnancy: An individual participant data meta-analysis

To assess the accuracy of the National Institute of Health and Care Excellence (NICE) and United States Preventive Services Task Force (USPSTF) guidelines for predicting pre-eclampsia in pregnancy to guide aspirin prophylaxis. We conducted an individual participant data meta-analysis using the Perinatal Antiplatelet Review of International Studies (PARIS) dataset. This dataset includes randomised controlled trials (RCTs) of antiplatelet therapy for primary prevention of pre-eclampsia conducted in international antenatal care settings. RCTs were eligible if they enrolled pregnant women up to 28 weeks'gestation, reported risk factors, and assessed pre-eclampsia. Women assigned to the control arm (no antiplatelet agent) were included. Both guidelines recommend aspirin if ≥1 high-risk factors or ≥2 moderate-risk factors. Two moderate-risk factors (body mass index and pregnancy interval) were unavailable. Pre-eclampsia was the primary outcome. The secondary outcomes were pre-eclampsia defined by gestational age at delivery (<37 weeks versus ≥37 weeks; <34 weeks versus ≥34 weeks). We assessed the performance of the NICE and USPSTF approaches for parous and nulliparous women by estimating sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for predicting pre-eclampsia, the number-needed-to-screen (NNS) and the number-needed-to-treat (NNT) to prevent one pre-eclampsia event. Three RCTs were eligible (4524 women, 221 pre-eclampsia cases). Using the NICE guidelines, 9.4% of 1020 parous women were classified as screen-positive with a sensitivity of 26.4% (95% confidence interval 16.4-39.6%), specificity 91.5% (89.6-93.1%), PPV 14.6% (8.9-23.0%) and NPV 95.8% (94.3-96.9%). The NNS was 729 and NNT 69. For 3504 nulliparous women, 3% were classified as screen-positive with a sensitivity of 8.9% (5.5-14.4%), specificity 97.2% (96.6-97.8%), PPV 14.2% (8.7-21.9%), NPV 95.5% (94.8-96.1%). The NNS was 2336 and NNT 71. The USPSTF approach demonstrated similar performance. The NICE and USPSTF guidelines offer a simple and specific approach for recommending aspirin prophylaxis for women at high-risk of pre-eclampsia where more advanced screening methods are not available. However, the low detection rate limits its value in clinical practice, in particular for nulliparous women, and raises the need for development of an improved simple risk prediction tool.

The Role of Antiplatelet Therapy in Primary Prevention. A Review.

The efficacy of antiplatelet therapy for the secondary prevention of cardiovascular disease after an ischemic event is well established. However, the role for antiplatelet therapy for the primary prevention of cardiovascular disease is more complex because of the interplay of efficacy vs safety in individuals without established cardiovascular disease who have a relatively low, but linear trajectory of cardiovascular risk. Several large randomized trials have investigated the efficacy and safety of antiplatelet therapy (primarily aspirin) for patients without established cardiovascular disease. The pharmacological profile of the most commonly used primary prevention antiplatelet agent, aspirin, has been delineated by randomized clinical trials and showcased in practice guidelines for reducing cardiovascular risk. For this indication, aspirin has been consistently shown to reduce the risk of non-fatal myocardial infarction with little impact on cardiovascular death, but with a consistent increased risk of bleeding. These divergent results have contributed to differences in the recommendations from international practice guidelines and highlight controversy at the forefront of considerations for anti-platelet therapy for primary prevention. However, further studies in specific sub-groups of patients without established cardiovascular disease such as those with Diabetes Mellitus, chronic kidney disease, or the elderly may clarify which patient groups will benefit the most from aspirin treatment for the primary prevention of a cardiovascular event.

POSSIBILITY OF THE PRIMARY PREVENTION OF STROKE: DEVELOPING AT THE POPULATION LEVEL

Review is devoted to primary prevention of stroke. Detailed analysed the prevalence of stroke and its contribution to the development of complications and deaths. The basic principles for the prevention of stroke are proved. The article presents the current international recommendations for correction of risk factors (hypertension, smoking, lipid metabolism, diabetes, atrial fibrillation). The significance of asymptomatic carotid artery stenosis as a predictor of stroke presented separately. Modern methods of diagnosis and treatment of carotid artery stenosis are presented. We consider the appropriateness of hormone replacement therapy in postmenopausal women for the prevention of stroke, as well as antiplatelet therapy for primary prevention of stroke, particularly aspirin, which can be used only when there is a high risk of cardiovascular complications. According to the authors, the success of prevention of stroke depends on the implementation of comprehensive and long-term national programs.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las Guías Europeas de Prevención Cardiovascular 2012

Based on the two main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions — such as smoking ban in public areas or the elimination of trans fatty acids from the food chain — are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las Guías Europeas de Prevención Cardiovascular 2012

Based on the two main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions — such as smoking ban in public areas or the elimination of trans fatty acids from the food chain — are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las Guías Europeas de Prevención Cardiovascular 2012

Based on the two main frameworks for evaluating scientific evidence (SEC and GRADE) European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions) led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions — such as smoking ban in public areas or the elimination of trans fatty acids from the food chain — are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure within the 130-139/80-85mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Comentarios del Comité Español Interdisciplinario de Prevención Cardiovascular (CEIPC) a las guías europeas de prevención cardiovascular 2012

Based on the two main frameworks for evaluating scientific evidence--SEC and GRADE--European cardiovascular prevention guidelines recommend interventions across all life stages using a combination of population-based and high-risk strategies with diet as the cornerstone of prevention. The evaluation of cardiovascular risk (CVR) incorporates HDL levels and psychosocial factors, a very high risk category, and the concept of age-risk. They also recommend cognitive-behavioural methods (e.g., motivational interviewing, psychological interventions, led by health professionals and with the participation of the patient's family, to counterbalance psychosocial stress and reduce CVR through the institution of positive habits such as a healthy diet, physical activity, smoking cessation, and adherence to treatment. Additionally, public health interventions--such as smoking ban in public areas or the elimination of trans fatty acids from the food chain--are also essential. Other innovations include abandoning antiplatelet therapy in primary prevention and the recommendation of maintaining blood pressure (BP) within the 130-139/80-85 mmHg range in diabetic patients and individuals with high CVR. Finally, due to the significant impact on patient progress and medical costs, special emphasis is given to the low therapeutic adherence levels observed. In sum, improving cardiovascular prevention requires a true partnership among the political class, public administrations, scientific and professional associations, health foundations, consumer associations, patients and their families. Such partnership would promote population-based and individual strategies by taking advantage of the broad spectrum of scientific evidence available, from clinical trials to observational studies and mathematical models to evaluate population-based interventions, including cost-effectiveness analyses.

Antithrombotic drugs in women: should we worry more about bleeding?

Since the mid '90s, the concept of evidence-based medicine has grown exponentially, contributing to the advancement of personalized medicine, which considers the "female gender" as an extremely important area of customization, but orphan of targeted research. Strong evidence do exists demonstrating gender differences in bleeding risk associated with antithrombotic treatment, mostly related to lower values of body mass, organ size and renal function in women than men. Across clinical studies, the search for the specific risk of bleeding in the female vs male gender has gained attention only recently; therefore, data from different studies and relatively limited meta-analyses should be assessed carefully. As for antiplatelet therapy for primary prevention, the risk of major bleeding events, such as cerebral hemorrhage, is lower for women than for men. Conversely, in acute situations in which antithrombotic drugs are given in association, the risk of bleeding is greater for women, in particular for combination therapies with heparin or low molecular weight heparin or thrombolytic agents. Numerous studies in the literature evaluated the incidence of minor and major bleeding during oral anticoagulant therapy in relation to gender, but the results are not entirely consistent and appear to vary over the years. In summary, there are some aspects of guidance in the complex spectrum of the bleeding risk related to antithrombotic treatment, with indications of a lower bleeding risk in women than men related to long-term preventive single antithrombotic drug treatments. In addition, hormonal effects and use of outprescribed drugs may also play a significant role in modulating hemostasis.

Optimization of Vitamin D Status as an Alternative Strategy for Primary Prevention of Cardiovascular Events in Type 2 Diabetes Mellitus

To the Editor: The documentation of significantly (P=.001) greater cardiovascular mortality in men and women aged 50 to 75 with 25(OH) vitamin D levels 30.6±6.9 nmol/L or less,1 potentially attributable to the association between 25(OH) vitamin D deficiency and endothelial dysfunction (as well as its association with increased lipid peroxidation)2 raises the possibility that optimization of vitamin D status might be a more-advantageous strategy than antiplatelet therapy for primary prevention of cardiovascular events in people with type 2 diabetes mellitus. Although aspirin doses of 81 to 100 mg/day have a more-favorable gastrointestinal risk profile than higher doses of aspirin,3 they have proved ineffective for primary prevention of atherosclerotic events in patients with type 2 diabetes mellitus,4 at least in part because of persistent platelet activation in the presence of such doses5 and because glycosylated hemoglobin of 8% or greater is significantly (P=.002) associated with aspirin resistance.6 Furthermore, in type 2 diabetes mellitus, the 46% (95% confidence interval=22–75) greater risk of serious bleeding associated with aspirin use in patients with diabetes mellitus without cardiovascular disease7 may offset the nonsignificant reduction in cardiovascular events associated with the use of aspirin 100 mg/day for primary prevention.8 Optimization of vitamin D status, alternatively, carries no such risk, and the results of in vitro9 and in vivo2 studies document vitamin D–related beneficial effects on macrophages obtained from vitamin D–deficient subjects with diabetes mellitus with 25-hydroxyvitamin D levels less than 80 nmol/L9 and beneficial effects on endothelial function after replacement therapy, in vitamin D–deficient subjects with 25 hydroxy vitamin D levels less than 25 nmol/L.2 In the in vitro context, 1,25 dihydroxyvitamin D suppresses foam cell formation by reducing uptake of acetylated or oxidized low-density lipoprotein cholesterol.9 In the in vivo study, when administered to asymptomatic vitamin D subjects with 25-hydroxyvitamin D levels less than 25 nmol/L, vitamin D replacement significantly (P=.002) improved endothelial function.2 In addition, in that study, posttreatment values of thiobarbituric acid–reactive substances (which are a measure of the degree of lipid peroxidation) were significantly (P=.001) lower than pretreatment levels.2 Accordingly, optimization of vitamin D status might be a strategy to surmount the difficulty that “the antiplatelet effects of aspirin in diabetic subjects are overwhelmed by aspirin insensitive mechanisms of platelet activation and thrombus formation thus making the balance between benefits and harms of aspirin treatment unfavourable.”7 Optimization of vitamin D status might, arguably, also enhance the successful use of multifactorial interventions to reduce cardiovascular disease in type 2 diabetes mellitus.10 In conclusion, the potential role of vitamin D therapy in older adults with diabetes mellitus warrants further investigation in observational studies and prospective clinical trials. Conflict of Interest: The editor in chief has reviewed the conflict of interest checklist provided by the author and has determined that the author has no financial or any other kind of personal conflicts with this paper. Author Contributions: The author is the sole contributor to this letter. Sponsor's Role: None.

Role of Antiplatelet Agents in the Primary and Secondary Prevention of Atherothrombotic Events in High Risk-Patients

Atherothrombosis describes the superimposition of a thrombus on a ruptured atherosclerotic plaque, and is the primary cause of acute ischemic events. Atherothrombosis is a generalized and progressive process with an inflammatory component. Patients with disease in one vascular bed are at risk of disease in another, a concept known as "cross-risk." Platelet adhesion, activation, and aggregation in the final stage of atherothrombosis are ultimately responsible for arterial occlusion and consequent ischemia. Therefore, antiplatelet therapy is an effective treatment choice for secondary prevention. Clopidogrel, an adenosine diphosphate receptor antagonist, given alone or in combination with aspirin, may benefit secondary prevention of ischemic events. Current treatment guidelines suggest the use of a combination of these two agents for secondary prevention where appropriate. However, data conflict regarding the efficacy of antiplatelet therapy for primary prevention. A recent meta-analysis demonstrated that aspirin significantly reduces the risk of first myocardial infarction in both men and women. The recent Clopidogrel for High Atherothrombotic Risk and Ischemic Stabilization, Management, and Avoidance trial, which evaluated the effects of clopidogrel plus aspirin compared with aspirin alone, seems to support the use of dual antiplatelet therapy in secondary prevention, but suggests that it may not be more effective than aspirin alone in primary prevention.

Clopidogrel and risk for acute coronary events

Clopidogrel bisulfate is a potent adenosine diphosphate receptor blocker that irreversibly inhibits platelet aggregation by preventing the activation of the glycoprotein IIb/IIIa pathway. This helps to prevent thrombus formation and resultant ischemic or thrombotic complications. Clopidogrel was proven to be superior to aspirin in the treatment of atherothrombotic diseases. Clopidogrel plus aspirin, known as dual antiplatelet therapy, is highly effective in patients with acute coronary syndromes or undergoing percutaneous coronary intervention. There is no apparent benefit of dual antiplatelet therapy in primary prevention. In this article, we review the benefits of clopidogrel as an antiplatelet agent and its role in the management of acute coronary syndromes and following percutaneous coronary intervention.

Antiplatelet therapy for primary prevention in diabetes

Aspirin is currently recommended by ADA (American Diabetes Association) for the diabetic patients over 40 years of age and without cardiovascular disease. This recommendation is at odds with drug approval for aspirin. The main explanation is the absence of appropriate trials assessing the usefulness of aspirin in such patients. Two assumptions, central to these guidelines are that diabetes is a coronary risk equivalent, and that aspirin benefit/risk ratio is similar in diabetic patients than in coronary disease patients. Unfortunately, vascular risk level is variable in diabetic patients. Patients with new onset diabetes have lower cardiovascular risk than patients with established cardiovascular disease. Smoking habits markedly increase the risk. Benefits may be lower in diabetic patients since aspirin resistance is common in these patients. Haemorrhagic risk may be higher since diabetes is a risk factor for haemorrhagic stroke. Awaiting trial evidence, aspirin therapy should be considered in diabetic patients with a very high risk, such as smokers, patients with long diabetes duration, or atherosclerotic plaques at echography.