Receiving Aspirin Therapy Research Articles

Diverticular bleeding in the third part of the duodenum as a cause of overt obscure gastrointestinal bleeding.

A 65-year-old man with a history of chronic renal failure and ischemic heart disease who was receiving aspirin therapy was admitted for recurrent melena. Initial evaluation revealed severe anemia. Other than a diverticulum in the third part of the duodenum, the findings of upper and lower gastrointestinal endoscopies and computed tomography were unremarkable. Capsule endoscopy detected altered blood in the ileum; however, balloon-assisted enteroscopy found no definitive source of bleeding. Three years later, he presented with recurrent melena and hemorrhagic shock. Upper gastrointestinal endoscopy identified Dieulafoy's lesion within the duodenal diverticulum. Hemostasis was achieved using hemoclips. No recurrence of bleeding was observed during 4 years of follow-up. The findings from this case highlight the diagnostic and therapeutic challenges of managing obscure gastrointestinal bleeding due to Dieulafoy's lesion in a diverticulum in the third part of the duodenum. Duodenal diverticular bleeding should be included in the differential diagnoses for patients with obscure gastrointestinal bleeding.

Hereditary haemorrhagic telangiectasias with recurrent ischemic stroke hinted by manganese deposition in the basal ganglia: a case report and literature review

BackgroundHereditary hemorrhagic telangiectasia (HHT) is a rare autosomal dominant inherited vascular disorder that can involve multiple organs, thus can be associated with so many clinical departments that proper screening and diagnosis of HHT are needed for providing better management of both patients and their family members.Case presentationWe present a 58-year-old female patient with recurrent paradoxical brain embolism due to HHT. She received aspirin therapy and underwent pulmonary arteriovenous malformation embolization, recovering well and discharged 3 days postoperatively. Though ischemic stroke caused by HHT-induced vascular disorders has been reported, our patient presented with both recurrent paradoxical brain embolisms and radiologic findings of bilateral globus pallidus manganese deposition at the same time, a combination rarely reported. We also review the literature on the clinical features and management of HHT for prompt diagnosis of this genetic disease behind paradoxical embolism.ConclusionsWhen patients with ischemic stroke, especially recurrent ischemic stroke, have combined arteriovenous malformations (AVMs) in single or multiple organs, or clues for AVMs like manganese deposition in globus pallidus, genetic diseases such as HHT may be the reason for ischemic stroke and shouldn’t be missed in the evaluation of embolic sources.

Aspirin Resistance in Vascular Disease: A Review Highlighting the Critical Need for Improved Point-of-Care Testing and Personalized Therapy.

Aspirin resistance describes a phenomenon where patients receiving aspirin therapy do not respond favorably to treatment, and is categorized by continued incidence of adverse cardiovascular events and/or the lack of reduced platelet reactivity. Studies demonstrate that one in four patients with vascular disease are resistant to aspirin therapy, placing them at an almost four-fold increased risk of major adverse limb and adverse cardiovascular events. Despite the increased cardiovascular risk incurred by aspirin resistant patients, strategies to diagnose or overcome this resistance are yet to be clinically validated and integrated. Currently, five unique laboratory assays have shown promise for aspirin resistance testing: Light transmission aggregometry, Platelet Function Analyzer-100, Thromboelastography, Verify Now, and Platelet Works. Newer antiplatelet therapies such as Plavix and Ticagrelor have been tested as an alternative to overcome aspirin resistance (used both in combination with aspirin and alone) but have not proven to be superior to aspirin alone. A recent breakthrough discovery has demonstrated that rivaroxaban, an anticoagulant which functions by inhibiting active Factor X when taken in combination with aspirin, improves outcomes in patients with vascular disease. Current studies are determining how this new regime may benefit those who are considered aspirin resistant.

Risk of bleeding after percutaneous native kidney biopsy in patients receiving low-dose aspirin: a single-center retrospective study.

Although discontinuation of antiplatelet agents at least 5days before kidney biopsy is commonly recommended, the evidence behind this practice is of low level. Indeed, few non-randomized studies previously showed an equivalent risk of bleeding in patients receiving aspirin therapy. We conducted a single center retrospective study comparing the risk of complications after percutaneous native kidney biopsy in patients who received low-dose aspirin (ASA) within 5days from biopsy and those who did not. The main outcome was the difference in the incidence of major complications (red blood cell transfusion, need for selective arterial embolization, surgery, nephrectomy). Secondary outcomes included difference in minor complications, comparison between patients who received ASA within 48h or within 3-5days, identification of independent factors predictive of major complications. We analyzed data on 750 patients, of whom 94 received ASA within 5days from biopsy. There were no significant differences in the proportion of major complications in patients receiving or not receiving ASA (2.59% and 3.19%, respectively, percentage point difference 1%, 95% CI - 3 to 4%, p = 0.74). Groups were also comparable for minor complications; among patients receiving ASA, there were no differences in major bleeding between those who received ASA within 48h or 3-5days from biopsy. Significant baseline predictors of major bleeding in our cohort were platelet count lower than 120*103/microliter, higher diastolic blood pressure and higher blood urea. Treatment with low-dose ASA within 5days from kidney biopsy did not increase the risk of complicationsafter the procedure.

ESSENTIAL THROMBOCYTHEMIA AS A CAUSE OF SEVERE CHEST PAIN: CASE REPORT

Essential thrombocythemia is a myeloproliferative dise­ase that is characterized by elevated platelet count, speci­fic changes of megakaryocyte lineage in bone marrow as well as non-specific clinical symptoms. This case report presents a 40-year-old female complaining of episodic chest pain and shortness of breath. Cardiologists ruled out cardiovascular pathologies after performing electrocar­diography (ECG), echocardiography, a complete blood count, and a treadmill test. After a recurring episode of chest pain, the patient was sent to the emergency depar­tment on suspicion of acute coronary syndrome or pul­monary embolism but routine tests (ECG, troponin I, D-dimers, computed tomography pulmonary angiography) excluded these diagnoses. Essential thrombocythemia was diagnosed based on bone marrow trephine biopsy results and positive genetic testing for JAK2 mutation. The patient was assigned to the low-risk group, there­fore, she received aspirin therapy as well as correction of cardiovascular risk factors.

Factors Impacting Stent Thrombosis in Patients With Percutaneous Coronary Intervention and Coronary Stenting: A Systematic Review and Meta-Analysis.

Stent thrombosis (ST) is a frequently reported complication in cardiac patients with percutaneous coronary intervention (PCI) that adversely impacts their prognostic outcomes. Medical literature reveals several baseline characteristics of PCI patients that may predict their predisposition to ST and its potential complications. Our systematic review and meta-analysis aimed to determine the diagnostic significance of these baseline parameters in terms of determining the risk of ST among adult patients with PCI. We statistically evaluated 18 baseline characteristics of more than 15,500 PCI patients to delineate their stent thrombosis attribution. We included a number of articles focusing on baseline parameters in-stent thrombosis-related PCI scenarios. We explored the articles of interest based on inclusion/exclusion parameters across PubMed, JSTOR, Cochrane library, Google Scholar, and Embase. Medical subject headings (MeSH) words included “stent thrombosis,” “percutaneous coronary intervention,” and “coronary stenting.” We extracted the research articles published between 2005 and 2021 on April 20, 2021. The included studies also focused on procedures and clinical factors concerning their association with PCI-related ST.Our findings ruled out the progression of abnormal left ventricular ejection fraction (LVEF)-related stent thrombosis in PCI patients (odds ratio {OR}: 9.68, 95% CI: 1.88-49.90, p=0.007). We found an insignificant clinical correlation between stent thrombosis and PCI in the setting of acute coronary syndrome (ACS). Our study outcomes further revealed the absence of stent thrombosis in PCI patients with antiplatelet prescription (OR: 32.42, 95% CI: 21.28-49.39). The findings affirmed the absence of ST in PCI patients receiving aspirin therapy (OR: 32.77, 95% CI: 18.73-57.34; OR: 4.59, 95% CI: 1.97-10.73). The majority of the included studies negated the clinical correlation of stent thrombosis with diabetes mellitus in the setting of PCI (OR: 0.49, 95% CI: 0.06-3.78). Our study did not reveal statistically significant results based on stent thrombosis in PCI patients with drug-eluting stents (OR: 2.91, 95% CI: 0.35-24.49). The findings also did not reveal the impact of cardiac biomarker elevation on stent thrombosis in PCI patients (OR: 8.42, 95% CI: 2.54-27.98, p=0.0005). Eight studies revealed a statistically insignificant correlation between myocardial infarction and stent thrombosis in PCI scenarios (OR: 2.69, 95% CI: 0.89-8.11, p=0.08). The clinical correlation between PCI and stent thrombosis/major bleeding in the setting of hypertension also proved statistically insignificant at 0.67 (OR: 1.31, 95% CI: 0.38-4.51, p=0.97). The study findings did not correlate mean body mass index and multivessel coronary artery disease with ST in PCI scenarios (OR: 1.98, 95% CI: 0.02-239.58, p=0.78; OR: 1.09, 95% CI: 0.58-2.04, p=0.80). Only two studies revealed statistically significant results confirming stent thrombosis in PCI patients with a prior history of PCI (OR: 0.49, 95% CI: 0.23-1.06; OR: 0.33, 95% CI: 0.02-5.59; p=0.03).Our findings question the clinical significance of baseline characteristics in terms of predicting stent thrombosis in PCI patients. The results support the requirement of future studies to investigate complex interactions between procedural, medicinal, genetic, and patient-related factors contributing to the development of stent thrombosis in PCI patients.

The effect of aspirin therapy on the increasing of Barthel Index score in stroke patients

Stroke, a disorder of nervous system function, is caused by impaired blood circulation to the brain. Post-stroke patients often receive aspirin therapy, yet many still require assistance from others for daily activities. This study aimed to evaluate the impact of aspirin therapy on functional improvement in stroke patients at RSUD Dr. Soekardjo Tasikmalaya, using the Barthel Index score as a measure of patients' ability to perform activities of daily living. A retrospective, descriptive observational approach was employed, analyzing data from stroke patients who underwent aspirin therapy between February and May 2019. The study assessed patients' functional status before and after aspirin therapy, focusing on the level of dependence. Pre-test results indicated that 80.97% of patients fell within the mild dependence category, while 19.03% were classified as moderately dependent. After undergoing aspirin therapy, post-test results revealed a substantial improvement in patients’ functional status. Only 4.76% of patients remained in the moderate dependence category, while a remarkable 95.24% transitioned to the independent range. These findings suggest that aspirin therapy may play a crucial role in enhancing the functional recovery of stroke patients, potentially promoting a higher level of independence and improved quality of life.

S1160 Role of Aspirin in the Prevention of Hepatocellular Carcinoma: A Systematic Review and Meta-Analysis

Introduction: Hepatocellular carcinoma is the sixth most prevalent cancer worldwide. Vaccination for hepatitis B and treatment of viral hepatitis are the most important preventive therapies against hepatocellular carcinoma. Recent studies have suggested that regular use of aspirin may play a role in the prevention of hepatocellular carcinoma, but its use remains controversial because of the paucity of studies. Methods: We conducted a systematic review and meta-analysis of studies that described the association between aspirin use and the incidence of hepatocellular carcinoma. We performed a comprehensive search in the databases of PubMed/MEDLINE, Embase, and the Cochrane Central Register of Controlled Trials through Nov 16, 2020. We considered randomized controlled trials, cohort studies, and case-control studies. We excluded abstracts, animal studies, case reports, reviews, editorials, and letters to editors. Our outcomes were the incidence of hepatocellular carcinoma and major gastrointestinal bleeding during the follow-up period. The random-effects model was used to calculate the hazard ratios (HR), risk ratio (RR), and confidence intervals (CI). A P-value < 0.05 was considered statistically significant. Heterogeneity was assessed using the Higgins I2 index. Results: Twelve studies involving 2,666,799 subjects were included in the meta-analysis. Subjects were either healthy individuals or diagnosed with hepatitis (alcoholic or viral). Pooled results of the included studies showed a significant decrease in hepatocellular carcinoma in patients who received aspirin therapy compared to those who did not (HR 0.56, 95% CI 0.46-0.67, P <0.01, I2 90.92%). Three studies assessed the risk of major gastrointestinal bleeding while on aspirin therapy. Pooled results of these studies showed no significant difference in the rates of major gastrointestinal bleeding between patients who consumed aspirin and controls (RR 1.1, 95% CI 0.97-1.27, P 0.14, I2 49.47%). Conclusion: Our meta-analysis demonstrated a significant reduction in the risk of hepatocellular carcinoma in individuals who consumed aspirin. Moreover, aspirin use did not increase the risk of developing major gastrointestinal bleeding. This suggests that the daily use of aspirin can be utilized as a primary preventive strategy for hepatocellular carcinoma. However, further randomized clinical trials with a large sample size are needed before implementing any strategies.Figure 1.: Aspirin usage and risk of liver cancer.

Aspirin May be Inadequate Thromboprophylaxis in Multiple Myeloma

BackgroundMultiple myeloma (MM) is associated with a 9-fold increased risk of venous thromboembolism (VTE). Current guidelines support routine thromboprophylaxis in select patients (ASCO, IMWG). The 2015 ASCO guidelines recommend low-molecular-weight heparin or low-dose aspirin in patients receiving immunomodulatory drugs (IMIDs) in combination with chemotherapy and/or dexamethasone. The IMWG guidelines recommend low-dose aspirin for MM patients with one or no VTE risk factors including those on lenalidomide in combination with low-dose dexamethasone, melphalan, or doxorubicin. Two randomized trials support thromboprophylaxis in patients receiving lenalidomide and thalidomide; however, patients with a prior history of VTE were excluded from participation (Palumbo 2011, Larocca 2012). We assessed the association between aspirin use and VTE in a large cohort of patients with MM.MethodsPatients diagnosed with MM within the Veterans Health Administration between September 1, 1999 and December 31, 2013 were identified in the Veterans Administration Central Cancer Registry (VACCR) using International Classification of Diseases (ICD)-O3 codes 9732/3. We retrospectively followed the cohort through December 2014. We excluded patients who did not receive MM-directed therapy within 6-months of diagnosis. We collected baseline information on demographics, comorbidities, laboratory data, MM-directed therapy, and use of aspirin, warfarin, and statins. All drug therapy was analyzed as time-varying. Using a previously validated algorithm, (Sanfilippo, 2015), we identified patients diagnosed with VTE after MM diagnosis by a combination of ICD-9 code for VTE plus pharmacologic treatment for VTE or IVC filter placement. We used competing risk analysis to assess the association between aspirin use and incident VTE while adjusting for known VTE risk factors and for death as a competing event.ResultsWe identified a cohort of 4,892 patients of whom 586 developed VTE. A total of 1,888 patients received aspirin therapy after MM diagnosis while 862 received warfarin therapy. After adjusting for known potential VTE risk factors, including history of VTE and use of IMIDs, aspirin was not associated with a decreased risk of VTE (adjusted Hazard Ratio (aHR) 1.18; 95% Confidence Interval (CI) 0.92-1.52). Warfarin use was associated with a trend towards reduction in risk of VTE (aHR 0.77; 95% CI 0.53-1.12). Risk factors for VTE after MM diagnosis included: history of prior VTE (aHR 3.83; 95% CI: 2.68-5.48), lenalidomide (aHR 2.36; 95% CI 1.82-3.05), and thalidomide (aHR 2.60; 95% CI: 2.09-3.24). The figure shows the high probability of developing VTE after MM diagnosis, especially among patients with a history of VTE.ConclusionsLenalidomide, thalidomide, and a prior VTE increased the risk of VTE after MM diagnosis. Patients with such history should be considered high risk for VTE. In this high-risk population, aspirin may not provide adequate thromboprophylaxis. [Display omitted] DisclosuresSanfilippo:Bristol Myers Squibb: Speakers Bureau. Carson:Seattle Genetics: Honoraria.

A Pathophysiologic Primary Prevention Review of Aspirin Administration to Prevent Cardiovascular Thrombosis

Cardiovascular disease is the leading metabolic cause of mortality in the United States. Among current therapies, low-dose aspirin has been shown to reduce cardiovascular thrombosis. However, aspirin also causes major complications (hemorrhagic stroke and gastrointestinal bleeding). The American Heart Association recommends that aspirin only be prescribed for "high-risk" individuals. No guidelines are available as to the duration of aspirin therapy. A reasonable approach to aspirin administration is to determine the appropriateness of aspirin therapy based on the pathophysiology of coronary artery thrombosis. It suggests that the coronary artery calcium (CAC) score be used as the basis for determining "high risk." This score was shown to accurately predict future cardiovascular events. The greater the CAC score, the greater the extent of coronary artery atherosclerotic plaque and future cardiovascular risk. A CAC score >400 places an individual at very-high 10-year risk for an atherosclerotic event. Since aggressive medical therapy initiates stabilization of unstable atherosclerotic plaques within 1 month and reversal within 2 years, this treatment significantly reduces the risk of the individual for a cardiovascular event. Thus, most individuals aged <75 years with a CAC score of >400 should receive aspirin therapy for a maximum of 2 years. Utilization of a CAC score greatly simplifies the decision of whom to treat with aspirin and for what duration. Importantly, focusing on two factors (hemorrhage and plaque stabilization) is easily understood by both the physician and the patient. CAC = coronary artery calcium; CVD = cardiovascular disease; LDL = low-density lipoprotein; OCT = optical coherence tomography.

Antepartum Aspirin Administration Reduces Activin A and Cardiac Global Longitudinal Strain in Preeclamptic Women.

BackgroundApproximately 60% of women have Stage B heart failure 1 year after a preeclamptic delivery. Emerging evidence suggests that the profibrotic growth factor activin A, which has been shown to induce cardiac fibrosis and hypertrophy, is elevated in preeclampsia and may be inhibited by aspirin therapy. We hypothesized that preeclamptic women receiving aspirin would have lower activin A levels and reduced global longitudinal strain (GLS), a sensitive measure of cardiac dysfunction, than women who do not receive aspirin. To test our hypothesis, we performed a cohort study of women with preeclampsia or superimposed preeclampsia and compared activin A levels and GLS in parturients who did or did not receive aspirin.Methods and ResultsNinety‐two parturients were enrolled, of whom 25 (27%) received aspirin (81 mg/day) therapy. GLS, plasma activin A, and follistatin, which inactivates activin A, were measured. Women receiving aspirin therapy had lower median (interquartile range) levels of activin A (8.17 [3.70, 10.36] versus 12.77 [8.37, 31.25] ng/mL; P=0.001) and lower activin/follistatin ratio (0.59 [0.31, 0.93] versus 1.01 [0.64, 2.60] P=0.002) than women who did not receive aspirin, which also remained significant after multivariable analysis. Furthermore, GLS was worse in patients who did not receive aspirin (−19.84±2.50 versus −17.77±2.60%; P=0.03) despite no differences in blood pressure between groups.ConclusionsOur study suggests that antepartum aspirin therapy reduced serum activin A levels and improved GLS in preeclamptic patients, suggesting that aspirin may mitigate the postpartum cardiac dysfunction seen in women with preeclampsia.

Association of aspirin resistance with 4-hydroxynonenal and its impact on recurrent cerebral infarction in patients with acute cerebral infarction.

ObjectivesTo investigate the association of aspirin resistance (AR) with the plasma 4‐hydroxynonenal (4‐HNE) level and its impact on recurrent cerebral infarction (CI) in patients with acute cerebral infarction (ACI) who were receiving aspirin therapy.MethodsOne hundred and fifty‐four ACI patients who previously received aspirin therapy (100 mg/day) were enrolled. Whole urine (for measuring 11dhTXB2 and creatinine) along with blood (for measuring the plasma 4‐HNE level) were collected at least 7 days after the patients received aspirin. A cutoff of 1500 pg/mg of 11dhTXB2/ creatinine was used to determine AR. A follow‐up period to monitor recurrence CI events was 1 year. In addition, blood testing was performed when the patients were first admitted to hospital.ResultsForty‐six of the 154 enrolled patients (29.9%) were found to be AR. No statistical difference in age, sex, hypertension, diabetes mellitus, coronary disease, smoking status, NIHSS score, TOAST classification, platelet count, thrombocytocrit, LDL‐C, HDL‐C, TG, and TC was found between the AR and aspirin‐sensitive (AS) patients, but the plasma 4‐HNE level was found to be higher in the AR patients than AS patients (p < .05). Multiple logistic regression analysis showed that the 4‐HNE level was associated with a higher risk of AR (OR = 1.034; 95% CI = 1.011–1.058; p < .05). Moreover, 1‐year follow‐up showed that AR was more prevalent in patients with recurrent CI (26 (56.6%)) than those without (20/(43.5%)) (p < .001).ConclusionsThe plasma 4‐HNE level is strongly associated with AR and thus may be a factor contributing to AR. Patients with AR have a greater risk of recurrence CI.

Secondary prevention among uninsured stroke patients: A free clinic study

Objectives:Free clinics manage a diversity of diseases among the uninsured. We sought to assess the medical management of stroke in a population of uninsured patients.Methods:A retrospective chart review was conducted to collect chronic disease statistics from 6558 electronic medical records and paper charts at nine free clinics in Tampa, Florida, from January 2016 to December 2017. Demographics and risk factors were compared between stroke patients and non-stroke patients. Medication rates for several comorbidities were also assessed.Results:Two percent (107) of patients had been diagnosed with a stroke. Stroke patients were older (mean (M) = 56.0, standard deviation (SD) = 11.2) than the rest of the sample (M = 43.3, SD = 15.4), p < 0.001 and a majority were men (n = 62, 58%). Of the stroke patients with hypertension (n = 79), 81% (n = 64) were receiving anti-hypertensive medications. Of the stroke patients with diabetes (n = 43), 72% (n = 31) were receiving diabetes medications. Among all stroke patients, 44% were receiving aspirin therapy (n = 47). Similarly, 39% of all stroke patients (n = 42) were taking statins.Conclusions:Uninsured patients with a history of stroke may not be receiving adequate secondary prevention highlighting the risk and vulnerability of uninsured patients. This finding identifies an area for improvement in secondary stroke prevention in free clinics.

Tiglilo double antiplatelet therapy for patients with acute coronary syndrome after PCI

Objective To evaluate the effect of tiglilo double antiplatelet therapy after percutaneous coronary intervention (PCI) for patients with acute coronary syndrome (ACS). Methods 110 patients with ACS who were admitted to our hospital from January, 2017 to October, 2018 for PCI were divided into two a control group and a study group, 55 cases for each group. The control group received aspirin plus clopidogrel antiplatelet therapy after operation, and the study group was treated with aspirin and tegrillo. The platelet function, inflammatory indicators, and platelet inhibition were observed. Results After the treatment, the levels of sCD40L, MPAR, and PRU, as well as the levels of hs-CRP, ET-1, and MMP-9, were significantly lower and the level of NO was significantly higher in the study group than in the control group (all P 0.05). Conclusion Tiglilo double antiplatelet therapy after PCI for patients with ACS can effectively improve the platelet aggregation and platelet inhibition rate and significantly reduce the inflammatory reaction in blood vessels, which is helpful to reduce the risk of adverse cardiac events after operation. Key words: Acute coronary syndrome; Percutaneous coronary intervention; Aspirin; Tigrillo; Antiplatelet

Low-Dose Aspirin Reduces the Rate of Renal Allograft Thrombosis in Pediatric Renal Transplant Recipients.

Renal allograft thrombosis is an important cause of early renal allograft loss. A previous study from our unit showed thrombosis rates in patients who received heparin that were similar to those who did not receive any thromboprophylaxis. This study evaluated the impact of aspirin prophylaxis on renal allograft thrombosis rates in pediatric renal transplant recipients. We conducted a retrospective study of 456 consecutive pediatric allografts from deceased and living related donors over age 22 years in a single center. Routine perioperative heparin was introduced in 1994 and was subsequently changed to aspirin prophylaxis in 2000. Group 1 comprised 126 patients who did not receive any thromboprophylaxis, group 2 comprised 128 patients who received heparin, and group 3 comprised 202 patients who received aspirin therapy. Variables associated with increased risk of renal allograft loss were examined using multivariable logistic regression. Thrombosis occurred in 11% (14/126) of grafts in group 1, 9% (11/128) of grafts in group 2, and 1% (2/202) of grafts in group 3 (odds ratio for aspirin group = 0.38, 95% confidence interval, 0.22-0.64; P = .02). In patients who received aspirin (group 3), there was only one renal allograft loss secondary to hemorrhage, and no grafts were lost in patients younger than 5 years of age. After our center introduced a change from heparin to aspirin prophylaxis, the thrombosis rate in pediatric renal allografts fell from 9% to 1%. Although there are a number of possible confounding variables, the introduction of aspirin has led to a reduced rate of renal allograft thrombosis.

Randomized Comparison of Clinical Effectiveness of Pharmacologic SPECT and PET MPI in Symptomatic CAD Patients

ObjectivesThis study compared the clinical effectiveness of pharmacologic stress myocardial perfusion imaging (MPI) plus positron emission tomography (PET) with single-photon emission computed tomography (SPECT) in patients with known coronary artery disease (CAD) presenting with symptoms suggestive of ischemia. BackgroundAlthough PET MPI has been shown to have higher diagnostic accuracy in detecting hemodynamically significant CAD than SPECT MPI, whether this impacts downstream management has not been formally evaluated in randomized trials. MethodsThis study consisted of a single-center trial in which patients with known CAD and suspected ischemia were randomized to undergo PET or attenuation-corrected SPECT MPI between June 2009 and September 2013. Post-test management was at the discretion of the referring physician, and patients were followed for 12 months. The primary endpoint was diagnostic failure, defined as unnecessary angiography (absence of ≥50% stenosis in ≥1 vessel) or additional noninvasive testing within 60 days of the MPI. Secondary endpoints were post-test escalation of antianginal therapy, referral for angiography, coronary revascularization, and health status at 3, 6, and 12 months. ResultsA total of 322 patients with an evaluable MPI were randomized (n = 161 in each group). At baseline, 88.8% of patients were receiving aspirin therapy, 76.7% were taking beta-blockers, and 77.3% were taking statin therapy. Diagnostic failure within 60 days occurred in only 7 patients (2.2%) (3 [1.9%] in the PET group and 4 [2.5%] in the SPECT group; p = 0.70). There were no significant differences between the 2 groups in subsequent rates of coronary angiography, coronary revascularization, or health status at 3, 6, and 12 months of follow-up (all p values ≥0.20); however, when subjects were stratified by findings on MPI in a post hoc analysis, those with high-risk MPI on PET testing had higher rates of angiography and revascularization on follow-up than those who had SPECT MPI, whereas those undergoing low-risk PET studies had lower rates of both procedures than those undergoing SPECT (interaction between randomized modality ∗high-risk MPI for 12-month catheterization [p = 0.001] and 12-month revascularization [p = 0.09]). ConclusionsIn this contemporary cohort of symptomatic CAD patients who were optimally medically managed, there were no discernible differences in rates of diagnostic failure at 60 days, subsequent coronary angiography, revascularization, or patient health status at 1 year between patients evaluated by pharmacologic PET compared with those evaluated by SPECT MPI. Downstream invasive testing rates with PET MPI were more consistent with high-risk features than those with SPECT MPI. (Effectiveness Study of Single Photon Emission Computed Tomography [SPECT] Versus Positron Emission Tomography [PET] Myocardial Perfusion Imaging; NCT00976053)

Advances in the Management of Peripheral Artery Disease.

This paper provides a concise update on the management of peripheral artery disease (PAD). PAD continues to denote a population at high risk for mortality but represents a threat for limb loss only when associated with foot ulcers, gangrene, or infections. Performing either angiogram or non-invasive testing for all patients with foot ulcers, gangrene, or foot infections will help increase the detection of PAD, and refined revascularization strategies may help optimize wound healing in this patient group. Structured exercise programs are becoming available to more patients with claudication as methods to improve adherence to community-based exercise programs will improve. Finally, ensuring more patients with PAD receive aspirin therapy and statins may improve long-term survival, while further research will help determine if adding newer antiplatelet or anticoagulant medications may reduce leg amputations in selected patients. Clinicians should have a low threshold to obtain an angiogram and to pursue revascularization in patients with foot ulcers, gangrene, or foot infections. In patients with claudication, clinicians should maximize the benefits derived from exercise therapy and medical management before offering percutaneous or surgical revascularization.

Increased Platelet Aggregation in Heart Transplant Recipients with Cardiac Allograft Vasculopathy

Purpose Cardiac allograft vasculopathy (CAV) remains a leading challenge to long-term survival after heart transplantation (HTx). Imaging of the coronary artery wall with optical coherence tomography has revealed layered fibrotic plaques resembling organized clots. Thus, thrombosis is suggested as a potential mechanism contributing to development and progression of CAV. We aimed to clarify whether HTx-patients with CAV have increased platelet aggregation compared with HTx-patients without CAV and healthy individuals. Methods In a cross sectional study, platelet aggregation was measured in whole blood from 59 HTx-patients (median 8.6 years from HTx) employing Multiplate® Analyzer using adenosine diphosphate (ADP) and arachidonic acid (AA). Results were reported as area under the curve (aggregation units (AU)*min). If patients received aspirin therapy and it was considered safe to interrupt treatment for 7 days, patients were included in the study. Healthy individuals (n=116) served as controls. CAV burden was determined by echocardiography and coronary angiography based on ISHLT classification. HTx-patients were divided into two groups; no CAV (CAV 0, n=39) and CAV (CAV 1-3, n=20). Results We found a significant increase in ADP-induced platelet aggregation in HTx-patients with CAV vs. no CAV (902 (95% CI 807-998) vs. 790 (95% CI 733-847) AU*min, P=0.03) and also when comparing with healthy individuals (810 (95 % CI 779-841) AU*min, P=0.03). AA-induced aggregation was higher in HTx-patients with CAV vs. no CAV, though non-significant (998 (95 % CI 908-1089) vs. 905 (95 % CI 840-970) AU*min, P=0.09). Conclusion HTx-patients with CAV have significantly increased ADP-induced platelet aggregation compared with HTx-patients without CAV and healthy individuals, suggesting that patients with CAV could potentially benefit from treatment with ADP receptor inhibitors. Overall, our results indicate that increased platelet aggregation may contribute to CAV development and progression.

Low-Dose Aspirin for Primary Prevention of Cardiovascular Events in Elderly Japanese Patients with Atherosclerotic Risk Factors: Subanalysis of a Randomized Clinical Trial (JPPP-70).

This post hoc subanalysis of the randomized Japanese Primary Prevention Project investigated whether once-daily low-dose aspirin versus no aspirin reduced the risk of cardiovascular events (CVEs) in patients aged ≥ 70years with atherosclerotic risk factors. Patients aged < 70years (young-old) or ≥ 70years (old) with hypertension, dyslipidemia, or diabetes participated between 2005 and 2007. Patients were randomized 1:1 to receive 100mg enteric-coated aspirin once daily or no aspirin plus standard of care. The primary outcome was a composite of death from cardiovascular causes plus nonfatal stroke and nonfatal myocardial infarction. The secondary outcome was a composite of the primary outcome plus transient ischemic attack, angina pectoris, and arteriosclerotic disease requiring medical or surgical intervention. Old (n = 7971) and young-old (n = 6493) patients were followed up for a median 5.02years. Aspirin did not reduce the risk of primary (hazard ratio [HR] 0.92 [95% confidence interval {CI} 0.74-1.16]; P = 0.50) or secondary (0.85 [0.70-1.04]; P = 0.11) outcomes in patients aged ≥ 70years. In old men with high-density lipoprotein < 40mg/dL, treatment with low-dose aspirin was associated with a reduction in the incidence of the primary endpoint compared with the group not receiving aspirin (10/260 vs 22/250; HR 0.44 [95% CI 0.20-0.93]; P = 0.03). This subgroup was also found to contain significant larger proportions of patients with elevated body mass index, patients with diabetes mellitus, and smokers (P < 0.001). Old patients also showed differences in bleeding outcomes. Serious extracranial hemorrhage requiring transfusion or hospitalization occurred significantly more frequently in the aspirin-treated group than in the non-aspirin-treated group (35 [0.88%] vs 18 [0.45%]; HR 1.96 [1.11-3.46]; P = 0.020). Gastrointestinal hemorrhage occurred significantly more frequently in the aspirin-treated group than the non-aspirin-treated group (63 [1.58%] vs 18 [0.45%]; relative risk [RR] 3.5 [2.08-5.90]; P < 0.0001). Cerebral hemorrhage (intracranial hemorrhage) tended to occur more frequently in the aspirin-treated group than the non-aspirin-treated group (22 [0.55%] vs 11 [0.28%]; RR 2.01 [0.97-4.14]; P = 0.058). Cerebral hemorrhage occurred significantly more frequently in old patients than in young-old patients (33 [0.41%] vs 10 [0.15%]; HR 2.7 [1.34-5.53]; P = 0.0055). Gastrointestinal hemorrhage occurred in a slightly higher proportion of old patients compared with young-old patients (81 [1.02%] vs 53 [0.82%]; RR 1.2 [0.88-1.76]; P = 0.21). Aspirin did not reduce the risk of the primary or secondary outcomes in old patients. Aspirin treatment may have reduced CVEs within a high CVE risk elderly population subgroup. Aspirin treatment in such a group requires caution, because of the increased risk of intracranial hemorrhage, severe extracranial hemorrhage requiring hospitalization or transfusion, and gastrointestinal bleeding in old patients receiving aspirin therapy. The study is registered at ClinicalTrials.gov [NCT00225849].

Aspirin resistance predicts unfavorable functional outcome in acute ischemic stroke patients

ObjectiveTo investigate the prognostic value of aspirin reaction units (ARU) in a 3-month follow-up study in a cohort of Chinese patients with first-ever ischemic stroke. MethodsProspective single-center survey of acute ischemic stroke patients receiving aspirin therapy. Two hundred and seventy-five Chinese patients with first-ever ischemic stroke who previously received aspirin therapy were enrolled. ARU was measured using the VerifyNow system. A cutoff of 550 ARU was used to determine the presence of aspirin resistance (AR). ResultsMedian age at study entry was 67 years (IQR: 59–75) and 142(51.6%) were male. A total of 52 of 275 enrolled patients (18.9%) were AR. Median regression estimated a statistically significant increase in NIHSS score of 0.033 point for every 1-point increase in ARU (95% CI, 0.024 to 0.068; P < 0.001). The unfavorable outcomes distribution across the ARU quartiles ranged between 11.8% (first quartile) to 64.8% (fourth quartile). After adjusting for other established risk factors, in multivariate models comparing the third and fourth quartiles against the first quartile of the ARU, levels of ARU were associated with unfavorable outcome, and the adjusted risk of unfavorable outcome increased by 145% (OR = 2.45 [95% CI 1.46–3.87], P = 0.011) and 317% (4.17[2.76–6.15], P < 0.001), respectively. Similarly, the adjusted risk of mortality increased by 215% (OR = 3.15 [95% CI 1.98–4.73], P = 0.008) and 429% (5.29[4.02–8.17], P < 0.001), respectively. ConclusionsThe results suggest that AR is a meaningful and independent marker to predict short-term functional outcome in patients with ischemic stroke.