Aspirin use in patients with elevated lipoprotein(a): Impact on cardiovascular events and bleeding.

The role of aspirin in cardiovascular primary prevention remains controversial. There are physiological reasons to explore its potential benefits in patients with high levels of lipoprotein(a) [Lp(a)], mainly due to its antifibrinolytic properties and interactions with platelets. The primary objective of this systematic review was to evaluate the cardiovascular benefits and bleeding risks associated with aspirin use in patients who have elevated Lp(a) levels but no history of cardiovascular disease. This systematic review was conducted following PRISMA guidelines. We performed a literature search to identify studies assessing the cardiovascular benefits and bleeding risks of aspirin use in patients with elevated Lp(a) levels (or a related genetic variant) who have no history of cardiovascular disease. Five studies (49,871 individuals) were considered for this systematic review. Three studies assessed the impact of aspirin use in relation to genetic variants associated with elevated Lp(a) levels (SNP rs379822), while the remaining two studies directly measured plasma levels of Lp(a). The endpoints evaluated varied among the studies. Overall, the findings consistently show that carriers of the apolipoprotein(a) variant or patients with Lp(a) levels > 50 mg/dL experience a reduction in cardiovascular risk with aspirin use. No significant bleeding issues were observed, although such events were reported in only two studies. This systematic review suggests that aspirin use in patients with elevated Lp(a) levels and no prior cardiovascular history may reduce cardiovascular risk. The available data on bleeding risk is insufficient.

Dual Antiplatelet Therapy vs Alteplase in Adult Patients with Acute Minor Ischemic Stroke: A Systematic Review and Meta-Analysis.

The efficacy and safety of dual antiplatelet therapy (DAPT) relative to intravenous (IV) alteplase in patients with acute minor ischemic stroke are insufficiently established. Therefore, we aimed to perform a meta-analysis to compare DAPT with IV alteplase in patients with acute minor stroke. MEDLINE, Embase, and Cochrane were searched for studies comparing DAPT with IV alteplase in patients with minor stroke. Functional and safety outcomes in 90 days were analyzed. Statistical analysis was performed using Rstudio 4.3.1. Subanalyses were performed restricted to non-disabling minor strokes and NIHSS score ≤ 3. PROSPERO (CRD42023440986). We included five studies with a total of 6,340 patients, of whom 4,050 (63.9%) received DAPT. The follow-up period for all included studies was 90 days. There was no significant difference for individual outcomes of mRS 0-1 (OR 1.26; 95% CI 0.85-1.89; p = 0.25), mRS 0-2 (OR 0.99; 95% CI 0.69-1.43; p = 0.97), or all-cause mortality (OR 0.80; 95% CI 0.20-3.13; p = 0.75) between groups. Symptomatic intracranial hemorrhage (sICH) was significantly lower (OR 0.11; 95% CI 0.003-0.36; p < 0.001) in patients treated with DAPT compared with IV alteplase. In terms of mRS 0-1 and mRS 0-2, we found no significant difference in both subgroup analyses. We found no statistically significant difference between DAPT and IV alteplase regarding functional outcome (mRS scores of 0-1 and 0-2) or all-cause mortality at 90 days in patients with minor ischemic stroke. Additionally, DAPT was associated with a significantly lower rate of sICH.

Ticagrelor versus clopidogrel in dual antiplatelet therapy after minor stroke or transient ischemic attack: an updated network meta-analysis.

BACKGROUND: Dual antiplatelet therapy (DAPT) with clopidogrel plus aspirin is a well-established practice after a minor stroke or transient ischemic attack (TIA). However, ticagrelor plus aspirin may be an alternative. AIMS: We systematically searched PubMed, Embase, and Cochrane Central from inception to January 2024. We included randomized controlled trials (RCTs) enrolling adults with acute minor stroke or TIA within 72 hours of the onset of the symptoms. RESULTS: A total of 8 RCTs were included in our meta-analysis. Ticagrelor plus aspirin (RR, 0.70; 95% CrI 0.52, 0.91) and clopidogrel plus aspirin (RR, 0.79; 95% CrI 0.64, 0.98) were superior to aspirin in preventing stroke recurrence in overall analysis. Excluding studies with dual antiplatelet up to 90 days, ticagrelor plus aspirin was the only strategy that maintained superiority compared with aspirin regarding stroke recurrence (RR, 0.70; 95% CrI 0.51, 0.95) and ischemic stroke (RR, 0.68; 95% CrI 0.47, 0.94). There was no significant difference between treatment groups regarding hemorrhagic stroke, functional disability, and mortality. CONCLUSIONS: DAPTs were superior to aspirin in preventing recurrence or ischemic stroke. Although no significant difference was observed between DAPTs, ticagrelor plus aspirin may be related to worse major bleeding results, including intracranial bleeding. Ticagrelor plus aspirin is a considerable option for patients after a minor stroke or TIA.

Uso de aspirina en prevención primaria cardiovascular: es tiempo de cambiar el paradigma / Aspirin use for primary cardiovascular prevention: time for a paradigm shift

La Aspirina es una droga ampliamente utilizada con un protagonismo indiscutido en el escenario de la prevención secundaria. Sin embargo, el rol de este medicamento en prevención primaria es aún motivo de discusión. Los primeros ensayos que evaluaron la Aspirina en prevención primaria sugerían reducciones en el infarto agudo al miocardio y el accidente cerebrovascular -aunque no en la mortalidad- con un riesgo no despreciable de hemorragia mayor. Esto llevó a diversas sociedades científicas a recomendar su prescripción sólo en aquellos individuos con alto riesgo de eventos cardiovasculares. Desde el año 2018 en adelante, surgen diversos ensayos aleatorizados que han cuestionado estas indicaciones, mostrando beneficios clínicos muy discretos o ausentes. El objetivo de esta revisión es realizar un análisis histórico de la evidencia sobre el rol de la Aspirina en prevención primaria y resumir las recomendaciones actuales en este escenario.

Aspirin is widely used with a clear role in secondary prevention of cardiovascular diseases. However, its benefit in primary prevention is still a matter of discussion. The first trials evaluating Aspirin for primary prevention suggested reductions in acute myocardial infarction and stroke (although not in mortality) but with a non-negligible risk of major bleeding. This led to aspirin being recommended by various scientific societies, albeit limited to individuals at high risk of cardiovascular events. Since 2018 various randomized trials in primary prevention showed minimal or no beneficial effects of aspirin thus questioning its indication for this purpose. The aim of this review is to make an historical analysis of the evidence for the role of Aspirin in primary prevention and suggest modified recommendations for these subjects.

Sangramiento posextracción dentaria y medidas para su control en pacientes tratados con antiagregantes plaquetarios / Bleeding after tooth extraction and measures for its control in patients treated with antiplatelet agents

Introducción: El desarrollo de las ciencias médicas trae consigo un incremento en la expectativa de vida, junto a la detección temprana de un gran número de enfermedades crónicas como las cerebrovasculares y cardiovasculares, que son tratadas rutinariamente con medicamentos antiagregantes plaquetarios. El conocimiento del manejo de estos pacientes ante los procedimientos quirúrgicos estomatológicos constituye un reto en la práctica diaria profesional. Objetivo: Determinar el nivel de sangramiento posextracción dentaria en pacientes con enfermedad cardiovascular y cerebrovascular, según el tipo de antiagregantes plaquetarios y grupo dentario, así como la frecuencia de utilización de las medidas para su control. Métodos: Se efectuó un estudio observacional, descriptivo, longitudinal y prospectivo con un universo de 136 pacientes de más de 20 años, remitidos por su cardiólogo y que necesitaban realizarse extracciones dentarias sin modificar su tratamiento con antiagregantes plaquetarios. Las variables estudiadas fueron la enfermedad sistémica, el tipo de antiagregante plaquetario, el nivel de sangramiento, grupo dentario intervenido y método hemostático utilizado. Resultados: La mitad de los pacientes estudiados no presentó sangramiento posextracción dentaria. En los pacientes tratados con aspirina o clopidogrel predominaron los sujetos sin sangramiento para un 84,3 por ciento y 62,5 por ciento, respectivamente. En los de doble antiagregación prevaleció el sangramiento moderado con un 46,3 por ciento. Los grupos dentarios incisivo, canino y premolar no presentaron episodios de sangramiento para un 64,1 por ciento, 51,6 por ciento y 53,3por ciento, respectivamente. El método hemostático más utilizado fue la compresión de las corticales y termoterapia fría (47,8 por ciento). Conclusiones: La mitad de los pacientes con enfermedades cardiovasculares y cerebrovasculares no presentaron sangramiento posextracción dentaria(AU)

Introduction: The development of medical sciences brings with it an increase in life expectancy, together with the early detection of a large number of chronic diseases such as cerebrovascular and cardiovascular diseases, which are routinely treated with antiplatelet aggregation drugs. Knowledge on the treatment of these patients before stomatological surgical procedures constitutes a challenge in daily professional practice. Objective: To determine the level of bleeding after tooth extraction in patients with cardiovascular and cerebrovascular disease, according to the type of antiplatelet agents and dental group, as well as the frequency of use of measures for their control. Methods: An observational, descriptive, longitudinal and prospective study was carried out with a universe of 136 patients over 20 years of age, referred by their cardiologist, who needed dental extractions without modifying their treatment with antiplatelet agents. The variables studied were systemic disease, type of antiplatelet agent, level of bleeding, dental group treated and hemostatic method used. Results: Half of the patients studied did not present bleeding after tooth extraction. In patients treated with aspirin or clopidogrel, 84.3 percent and 62.5por ciento, respectively, had no bleeding. In those with double antiplatelet therapy, modera te bleeding prevailed with 46.3 The incisor, canine and premolar tooth groups did not present bleeding episodes (64.1 percent, 51.6and 53.3 percent respectively). The most commonly used hemostatic method was cortical compression and cold thermotherapy (47.8%). Conclusions: Half of the patients with cardiovascular and cerebrovascular diseases did not present bleeding after tooth extraction(AU)

Profilaxis farmacológica para la prevención de la enfermedad tromboembólica en paciente con enfermedad cerebrovascular / Pharmacological prophylaxis for the prevention of thromboembolic disease in patients with cerebrovascular disease

INTRODUCCIÓN: La enfermedad cerebrovascular es un conjunto de alteraciones atribuidas a lesiones agudas y focales en el sistema nervioso central, en su mayoría secundaria a aterosclerosis DESARROLLO: En la prevención de la enfermedad cerebrovascular, existen dos grandes grupos farmacológicos, los antitromboticos y los anti plaquetarios, los cuales impactan en la calidad de vida de estos pacientes mejorando el pronóstico de los mismos. CONCLUSIONES: La enfermedad cerebrovascular comparte factores de riesgo de enfermedad tromboembólica, por lo que se recomienda iniciar profilaxis.

INTRODUCTION: Cerebrovascular disease is a group of alterations attributed to acute and focal lesions in the central nervous system, mostly secondary to atherosclerosis. DEVELOPMENT: In the prevention of cerebrovascular disease, there are two major pharmacological groups, antithrombotics and antiplatelet drugs. , which impact the quality of life of these patients, improving their prognosis. CONCLUSIONS: Cerebrovascular disease shares risk factors for thromboembolic disease, so it is recommended to start prophylaxis.

Platelet Reactivity in Patients With Acute Coronary Syndromes Awaiting Surgical Revascularization.

BACKGROUND: Dual antiplatelet therapy is recommended for patients with acute coronary syndromes (ACS). Approximately 10% to 15% of these patients will undergo coronary artery bypass graft (CABG) surgery for index events, and current guidelines recommend stopping clopidogrel at least 5 days before CABG. This waiting time has clinical and economic implications. OBJECTIVES: This study aimed to evaluate if a platelet reactivity-based strategy is noninferior to standard of care for 24-h post-CABG bleeding. METHODS: In this randomized, open label noninferiority trial, 190 patients admitted with ACS with indications for CABG and on aspirin and P2Y12 receptor inhibitors, were assigned to either control group, P2Y12 receptor inhibitor withdrawn 5 to 7 days before CABG, or intervention group, daily measurements of platelet reactivity by Multiplate analyzer (Roche Diagnostics GmbH, Vienna, Austria) with CABG planned the next working day after platelet reactivity normalization (pre-defined as ≥46 aggregation units). RESULTS: Within the first 24 h of CABG, the median chest tube drainage was 350 ml (interquartile range [IQR]: 250 to 475 ml) and 350 ml (IQR: 255 to 500 ml) in the intervention and control groups, respectively (p for noninferiority <0.001). The median waiting period between the decision to undergo CABG and the procedure was 112 h (IQR: 66 to 142 h) and 136 h (IQR: 112 to 161 h) (p < 0.001), respectively. In the intention-to-treat analysis, a 6.4% decrease in the median in-hospital expenses was observed in the intervention group (p = 0.014), with 11.2% decrease in the analysis per protocol (p = 0.003). CONCLUSIONS: A strategy based on platelet reactivity-guided is noninferior to the standard of care in patients with ACS awaiting CABG regarding peri-operative bleeding, significantly shortens the waiting time to CABG, and decreases hospital expenses. (Evaluation of Platelet Aggregability in the Release of CABG in Patients With ACS With DAPT; NCT02516267).

Risk of Early Bleeding with Dual Antiplatelet Therapy in Acute Stroke and Transient Ischemic Attack Regardless of NIHSS Admission.

BACKGROUND: Dual antiplatelet therapy (DAT) is a therapeutic option for patients with minor ischemic stroke (IS) or transient ischemic attack (TIA). No study has evaluated the incidence of early bleeding in patients with moderate to major ischemic stroke. The current study aimed to analyze both the frequency of early bleeding and hospital morbidity related to DAT for either acute IS or TIA regardless of admission National Institute of Health Stroke Scale (NIHSS) score. METHODS: This was a retrospective analysis based on data collected from a prospective data bank of a single center. We included patients who underwent DAT in the first 24 hours of symptom onset with a loading dose (aspirin 300 mg + clopidogrel 300 mg) on the first day, followed by a maintenance dose (aspirin 100 mg + clopidogrel 75 mg). We analyzed intracranial and/or extracranial hemorrhage that had occurred during the hospital admission, symptomatic bleeding, modified Rankin Scale (mRS) score at discharge, and death rates as outcomes. RESULTS: Of the 119 patients analyzed, 94 (79 %) had IS and 25 (21 %) had TIA. Hemorrhage occurred in 11 (9.2 %) and four (3.4 %) patients with TIA or NIHSS ≤ 3, respectively, although none were symptomatic. Patients with bleeding as a complication had higher admission NIHSS [4 (3-7) vs. 2 (1-4), p = 0.044] and had higher mRS at discharge (mRS 2 [1-5] vs. mRS 1 [0-2], p = 0.008). These findings did not indicate increased mortality, as one (9 %) patient died from bleeding and two (1.8 %) patients died without bleeding (p = 0.254). CONCLUSION: DAT seems to be a safe therapy in patients regardless of admission NIHSS if started within the first 24 h after symptom onset because only 1.6 % of patients had symptomatic bleeding.

Treatment of distal unruptured intracranial aneurysms using a surface-modified flow diverter under prasugrel monotherapy: a pilot safety trial.

BACKGROUND: Flow diverters (FDs) are effective in the treatment of carotid aneurysms. Compared with carotid aneurysms, the treatment of distal intracranial aneurysms with FDs has been associated with a relatively high incidence of complications. Low thrombogenic modified-surface FDs may reduce ischemic complications and allow for the use of a single antiplatelet medication. The aim of this study was to assess the safety and efficacy of the p48 MW HPC Flow Modulation Device (Phenox GmbH, Bochum, Germany) to treat distal intracranial aneurysms used in combination with prasugrel monotherapy. METHODS: This was a single-center, prospective, pivotal, open, single-arm study. Patients were included in this study from December 2019 to September 2020. The primary endpoints were the incidence of any neurologic deficit after treatment until 1 month of follow-up, defined as National Institutes of Health Stroke Scale (NIHSS) ≥1, and the incidence of acute ischemic lesions in magnetic resonance imagin (MRI) images 48 hours after treatment. The secondary endpoint was the rate of complete occlusion of the aneurysms at the 1-month follow-up. RESULTS: Twenty-one patients harboring 27 distal aneurysms of the anterior circulation were included. Mean age was 57.8 (SD 9.7) years, and 16 patients were female (80%). No patient had neurologic symptoms at the 1-month follow-up. Four patients (20%) had asymptomatic acute brain ischemic lesions on MRI. Complete aneurysm occlusion occurred in 9/27 (33.3%) aneurysms at the 1-month follow-up. CONCLUSION: In this pilot safety trial, treatment of distal intracranial aneurysms with p48 MW HPC under monotherapy with prasugrel appeared to be safe.

Aspirin monotherapy in the treatment of distal intracranial aneurysms with a surface modified flow diverter: a pilot study.

BACKGROUND: Flow diverters (FDs) result in high occlusion rates of aneurysms located distally to the carotid artery. However, the complications reported are not negligible. New modified surface FDs have low thrombogenic properties that may reduce ischemic complications related to the treatment. In addition, a modified surface FD may allow for the use of a single antiplatelet medication to reduce hemorrhagic risk during the procedure. The aim of this study was to assess the safety and efficacy of the p48 MW HPC (phenox, Bochum, Germany) to treat distal intracranial aneurysms under the use of aspirin monotherapy. METHODS: The primary endpoint was the incidence of any neurologic deficit after treatment after 6 months of follow-up. The secondary endpoint was the rate of the complete occlusion of the aneurysms at the 6-month follow-up. Enrollment of 20 patients was planned, but after inclusion of seven patients the study was stopped due to safety issues. RESULTS: Seven patients with eight aneurysms were included. Among the seven patients, three (42.8%) had ischemic complications on the second day after FD deployment. Two patients experienced complete recovery at discharge (National Institutes of Health Stroke Scale (NIHSS) score=0), while one patient maintained mild dysarthria at discharge (NIHSS score=1) which improved after 6 months (NIHSS score=0). All three patients had no new symptoms during the 6-month follow-up. Complete aneurysm occlusion occurred in six (75%) of the eight aneurysms at the 6-month follow-up. CONCLUSIONS: Antiplatelet monotherapy with aspirin for the treatment of distal intracranial aneurysms with this modified surface FD resulted in a significant incidence of ischemic complications after treatment.

Anticoagulantes, Antiplaquetarios y sus implicaciones en cirugía: una revisión de la literatura / Anticoagulants, Anti-platelets, and their implications in Surgery: A Literature review

All health care providers should be aware of the impact of bleeding disorders on their patients during any surgical procedures. The knowledge of the mechanisms of hemostasis and optimized management are very important. Initial recognition of a bleeding disorder, in such patients with a systemic pathologic process, may occur in surgical practice. The surgical treatment of those patients might be complicated during the surgery due to the use of anticoagulant and/or antiplatelet medications raises a challenge in the daily practice of surgical professionals. Adequate hemostasis is critical for the success of any surgical procedure because bleeding problems can give rise to complications associated with important morbidity-mortality. Besides, prophylactic, restorative, and surgical care of patients with any bleeding disorders is handled skillfully by practitioners who are well educated regarding the pathology, complications which could arise, and surgical options associated with these conditions. The purpose of this paper is to review common bleeding disorders and their effects on the surgical aspect. Many authors consider that patient medication indicated for the treatment of background disease should not be altered or suspended unless so indicated by the prescribing physician. Local hemostatic measures have been shown to suffice for controlling possible bleeding problems resulting from surgery.

Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk.

Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados. Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Aspirina en la prevención primaria. Metaanálisis estratificado por riesgo cardiovascular basal / Aspirin in primary prevention. Meta-analysis stratified by baseline cardiovascular risk

Resumen Introducción: La utilidad de la aspirina en la prevención primaria es todavía objeto de controversia. Los avances médicos y la variabilidad del riesgo cardiovascular podrían explicar la heterogeneidad de los estudios publicados, y las poblaciones de alto riesgo tendrían mayor beneficio. Objetivo: Analizar los efectos de la aspirina en pacientes sin antecedentes cardiovasculares y evaluar los resultados de acuerdo con el riesgo cardiovascular de las poblaciones. Métodos: Se incluyeron estudios que evaluaron el uso de la aspirina en comparación con placebo en la prevención primaria. Se analizó la combinación de muerte cardiovascular, infarto agudo de miocardio (IAM) y accidente cerebrovascular (ACV) isquémico. El punto final de seguridad fue la combinación de ACV hemorrágico y sangrado mayor. Se clasificaron los estudios en riesgo bajo y moderado/ alto, de acuerdo con el número de episodios en la rama de placebo. Resultados: Se evaluaron 13 estudios (n = 164,225), ocho de riesgo cardiovascular bajo (n = 118,455) y cinco de moderado/alto (n = 45,770). Se observó una reducción del punto final combinado en el grupo de aspirina (OR 0.90; IC 95%, 0.85-0.94), sin diferencias en mortalidad cardiovascular (OR 0.94; IC 95%, 0.86-1.04). No se identificaron diferencias entre los subgrupos de riesgo. Se reconocieron mayores complicaciones hemorrágicas en el grupo de aspirina (OR 1.45; IC 95%, 1.32-1.60), sin diferencias entre los subgrupos de riesgo. Conclusión: La aspirina se relacionó con una leve disminución de IAM y ACV isquémico en términos absolutos, sin diferencias en la mortalidad cardiovascular. Esto, junto con el aumento de las complicaciones hemorrágicas, se traduce en una ausencia de beneficio clínico neto. El riesgo cardiovascular basal de la población no modificó los resultados.

Abstract Background: The usefulness of aspirin in primary prevention continues to be the subject of debate. Medical advances and the variability of cardiovascular risk could explain the heterogeneity of the published studies. High risk populations would have greater benefit. Objective: Analyzing the effects of aspirin in patients without cardiovascular disease and evaluating the results according to the cardiovascular risk of the populations. Methods: Studies evaluating aspirin versus placebo in primary prevention were included. The primary endpoint was the combined cardiovascular death, acute myocardial infarction (AMI) and ischemic stroke. The final safety point was the combination of hemorrhagic stroke and major bleeding. The studies were classified into low and moderate/high risk, according to the number of events in the placebo arm. Results: Thirteen studies were evaluated (n = 164,225), eight of low cardiovascular risk (n = 118,455) and five of moderate/high risk (n = 45,770). There was a reduction of the combined endpoint in the aspirin group (odds ratio [OR] 0.90; 95% confidence interval [CI], 0.85-0.94), without differences in cardiovascular mortality (OR 0.94; 95% CI, 0.86-1.04). No differences were observed when comparing the risk subgroups. Greater hemorrhagic complications were observed in the aspirin group (OR 1.45; 95% CI, 1.32-1.60), without differences between the risk subgroups. Conclusion: Aspirin was associated with a slight decrease in AMI and ischemic stroke in absolute terms, with no differences in cardiovascular mortality. This accompanied by the increase in hemorrhagic complications, results in an absence of net clinical benefit. The baseline cardiovascular risk of the population did not affect the results.

Safety and Efficacy of Oral Anticoagulants Therapies in Patients With Atrial Fibrillation Undergoing Percutaneous Coronary Intervention: A Network Meta-Analysis.

BACKGROUND: Different antithrombotic treatments, from vitamin K antagonists to direct oral anticoagulants (DOACs), are available to reduce ischemic risks in patients with atrial fibrillation (AF) after percutaneous coronary intervention (PCI). Objective: To synthetize evidence about the benefit-risk ratio of antithrombotic treatments and their combinations in patients with AF and PCI. METHODS: A network meta-analysis and a stochastic multicriteria acceptability analysis (SMAA) were performed including randomized controlled trials (RCT) that evaluate antithrombotic treatments in adults with AF and PCI. Searches were conducted in PubMed and Scopus (updated November-2019). Outcomes compared included bleeding, stroke, and death (Prospero registration: CRD42019146813). RESULTS: Five RCTs were included (11 532 patients). Vitamin K antagonists + dual antiplatelet therapy was associated with major bleeding (odds ratio: 0.52 [95% CI: 0.32-0.86]) compared to DOAC + P2Y12. No statistical differences were found among DOAC regimens for the main outcomes, including bleeding, stroke, and death. Surface under the cumulative ranking curve analysis (SUCRA) and SMAA demonstrated edoxaban 60 mg + P2Y12 inhibitor as the worst option (28%). Apixaban 5 mg + P2Y12 inhibitor was the safest alternative (63%) in all scenarios. CONCLUSIONS: Insufficient evidence on the clinical superiority among anticoagulant regimens exists, although apixaban slightly stands out. Edoxaban was associated with more adverse events. To strength this evidence, well-designed, low risk of bias clinical trials are needed. Cost-minimization analyses are required to provide further information for clinical decision-making.

Impact of the ACOG guideline regarding low-dose aspirin for prevention of superimposed preeclampsia in women with chronic hypertension.

BACKGROUND: Patients with chronic hypertension are at increased risk for superimposed preeclampsia. The 2016 American College of Obstetricians and Gynecologists guideline recommended initiating 81 mg of daily aspirin for all pregnant women with chronic hypertension to prevent superimposed preeclampsia. OBJECTIVE: (1) To evaluate the rates of implementation of the 2016 American College of Obstetricians and Gynecologists guideline over time; and (2) to evaluate the effectiveness of aspirin for the prevention of superimposed preeclampsia and other adverse maternal and neonatal outcomes in women with chronic hypertension before and after this guideline. STUDY DESIGN: This is a retrospective study of women with chronic hypertension who delivered at Thomas Jefferson University Hospital from January 2014 through June 2018. This cohort of women with chronic hypertension was divided into 2 groups, before and after the American College of Obstetricians and Gynecologists recommendation published in September 2016. Daily 81 mg of aspirin was initiated between 12 and 16 weeks. We excluded multiple gestations and incomplete records. The primary outcome was incidence of superimposed preeclampsia, and secondary outcomes were incidence of superimposed preeclampsia with or without severe features, small for gestational age, and preterm birth <37 weeks. Subgroup analysis based on risk stratification was evaluated in women with chronic hypertension requiring antihypertensive medication, history of preeclampsia, and pregestational diabetes. RESULTS: We identified 457 pregnant women with chronic hypertension, 203 in the post-American College of Obstetricians and Gynecologists group and 254 in the pre-American College of Obstetricians and Gynecologists group. Aspirin 81 mg was offered to 142 (70%) in the post-American College of Obstetricians and Gynecologists group and 18 (7.0%) in the pre-American College of Obstetricians and Gynecologists group. Maternal demographics were not significantly different. The overall incidence of superimposed preeclampsia was not significantly different: 87 (34.3%) vs 72 (35.5%), P=.79, in the pre- and post-American College of Obstetricians and Gynecologists guideline groups, respectively. Superimposed preeclampsia with severe features significantly increased: 32 (12.6%) vs 9 (4.4%), P<.01, whereas superimposed preeclampsia without severe features significantly decreased: 55 (21.7%) vs 63 (31.0%), P=.03. There were no significant differences in small for gestational age neonates or preterm birth <37 weeks incidences between groups. There were no significant differences in the subgroup analysis based on the severity of chronic hypertension requiring antihypertensive medication, history of preeclampsia, or pregestational diabetes. CONCLUSION: After the adoption of the American College of Obstetricians and Gynecologists guidelines in 70% of the cohort, superimposed preeclampsia, small for gestational age, and preterm birth were not significantly decreased after implementation of aspirin 81 mg initiated between 12 and 16 weeks of gestation.

Multicap to improve adherence after acute coronary syndromes: results of a randomized controlled clinical trial.

BACKGROUND: Adherence to treatment after a myocardial infarction (MI) is poor, even in the early postinfarction period. Combining evidence-based drugs into a multicap could improve adherence in this population. No previous randomized trial assessing fixed-dose combination therapy has included patients early after a MI. We aimed to assess if a multicap containing four secondary prevention drugs increases adherence to treatment at 6 months after MI hospitalization. The study was designed as a randomized, parallel, open-label, controlled trial. METHODS: Patients were randomized within 7 days of a MI to either multicap or control group. The multicap group received a capsule containing aspirin, atenolol, ramipril, and simvastatin. The control group received each drug in separate pills. The primary outcome was adherence at 6 months. We also measured blood pressure, heart rate, serum cholesterol levels, C-reactive protein, and platelet aggregation. RESULTS: The study was stopped prematurely when 100 patients were included for futility. At 6 months, 92 (95.8%) patients were adherent to medical treatment: 98.0% in the multicap group and 93.5% in the control group [relative risk (RR) 1.05; 95% confidence interval (CI) 0.96-1.14; p = 0.347]. There were no differences between groups in systolic blood pressure (p = 0.662), diastolic blood pressure (p = 0.784), heart rate (p = 0.533), total cholesterol (p = 0.760), LDL-c (p = 0.979), C-reactive protein (p = 0.399), or in the proportion of patients with adequate platelet aggregation inhibition (p = 0.600). CONCLUSIONS: The study did not find any improvement in the adherence at 6 months after a MI with a multicap-based strategy (Multicap for Increase Adherence After Acute Myocardial Infarction; [ ClinicalTrials.gov identifier: NCT02271178]).

Case Report: Malignant Ventricular Arrhythmias Mimicking Acute Coronary Syndrome in Chagas Disease.

Chronic Chagas heart disease has different clinical manifestations including arrhythmias, heart failure, and stroke. Chest pain is one of the most common symptoms and when associated with changes in the electrocardiogram, such as T-wave changes, electrically inactive areas, and segmental wall motion abnormalities, may lead to a misdiagnosis of acute coronary syndrome (ACS). Here, we describe two patients with Chagas heart disease and syncope due to sustained ventricular tachycardia who were misdiagnosed with ACS, and discuss the role of novel imaging modalities in the differential diagnosis and risk stratification.

Morphine and Cardiovascular Outcomes Among Patients With Non-ST-Segment Elevation Acute Coronary Syndromes Undergoing Coronary Angiography.

BACKGROUND: Mechanistic studies have shown that morphine blunts the antiplatelet effects of oral adenosine diphosphate receptor blockers. However, the clinical relevance of this interaction is controversial. OBJECTIVES: This study sought to explore the association between morphine and ischemic events in 5,438 patients treated with concomitant clopidogrel presenting with non-ST-segment elevation acute coronary syndromes (NSTEACS) in the EARLY ACS (Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome) trial. Patients not treated with clopidogrel (n = 3,462) were used as negative controls. METHODS: Endpoints were the composite of death, myocardial infarction (MI), recurrent ischemia, or thrombotic bailout at 96 h (4-way endpoint) and the composite of death or MI at 30 days. RESULTS: In patients treated with clopidogrel, morphine use was associated with higher rates of the 4-way endpoint at 96 h (adjusted odds ratio [OR]: 1.40; 95% confidence interval [CI]: 1.04 to 1.87; p = 0.026). There was a trend for higher rates of death or MI at 30 days (adjusted OR: 1.29; 95% CI: 0.98 to 1.70; p = 0.072), driven by events in the first 48 h (adjusted hazard ratio: 1.54; 95% CI: 1.07 to 2.23; p = 0.021). In patients not treated with clopidogrel, morphine was not associated with either the 4-way endpoint at 96 h (adjusted OR: 1.05; 95% CI: 0.74 to 1.49; p = 0.79; pinteraction = 0.36 ) or death or MI at 30 days (adjusted OR: 1.07; 95% CI: 0.77 to 1.48; p = 0.70; pinteraction = 0.46). CONCLUSIONS: When used concomitantly with clopidogrel pre-treatment, morphine was associated with higher rates of ischemic events in patients with NSTEACS. (EARLY ACS: Early Glycoprotein IIb/IIIa Inhibition in Patients With Non-ST-Segment Elevation Acute Coronary Syndrome; NCT00089895).

Effect of Cilostazol-Loaded PCL/PEG Nanocapsules on Abdominal Aortic Tunics and Lipid Profile of Wistar Rats

Abstract Cilostazol (CLZ) is a phosphodiesterase III inhibitor with antiplatelet and vasodilator properties. It has been recently verified that CLZ plays a significant role in the arteries by inhibiting the proliferation and growth of muscle cells, increasing the release of nitric oxide by the endothelium and promoting angiogenesis. Considering these promising effects, the use of nanocapsules may be an interesting strategy to optimize its pharmacokinetics and pharmacodynamics at the vascular level for preventing atherosclerosis. The aim of this study was to evaluate the effect of cilostazol-loaded nanocapsules in the abdominal aortic tunics and on the lipid profile of Wistar rats in order to investigate its potential role in the prevention of atherosclerosis. Thirty-two animals were divided into four groups of eight animals, with 30-day treatment. Group 1 received nanoencapsulated CLZ; Group 2, control nanocapsules with no drug; Group 3, propylene glycol and water; and Group 4, a solution of CLZ in propylene glycol and water. After 30 days, there was no statistically significant difference between the groups regarding the cellularity and thickness of the arterial tunics of the abdominal aorta. However, the group that received nanoencapsulated CLZ (Group 1) had an improvement in HDL-c and triglyceride values compared to unloaded nanocapsules (Group 2).