Use Of Clopidogrel Research Articles

Risk of Free Flap Failure in Head and Neck Reconstruction: Analysis of 21,548 Cases From A Nationwide Database.

Head and neck reconstruction is complicated and is made even more challenging by free flap failure. We identified risk factors associated with free flap failure in records extracted from a nationwide database of a 23 million populations. We used International Classification of Diseases, Ninth Version, codes 140 to 149 and 161 to identify patients in Taiwan's National Health Insurance Research Database with head and neck cancer between 2000 and 2013. Patient's age, sex, neoadjuvant treatment, comorbidities, and anticoagulation use were also retrieved. Free flap reconstruction twice, or free flap and pedicle flap reconstructions during the same hospitalization were recorded as free flap failure. Logistic regression was used to identify factors that increased risk of free flap failure. A total of 21,548 patients with head and neck cancer were identified; 883 (4.1%) experienced free flap failure. Use of aspirin, clopidogrel, urokinase, prostaglandin (PGE1), low-molecular-weight heparin, and operation time were associated with free flap failure. However, some potential confounders could not be identified from the database. Several statistically significant findings were prone to influence by potential confounders. The clinically applicable result was that longer operation time and preoperative chemotherapy could increase the likelihood of free flap failure. On the other hand, several factors were proved to be irrelevant to free flap failure.

Expanding the possibilities of antithrombotic therapy of cerebrovascular pathology

The paper provides an overview of the current state of the problem of antithrombotic therapy in angioneurology. Given the importance and prevalence of cerebral atherosclerosis as one of the leading etiological factors of acute and chronic cerebrovascular disorders (CCD), the paper focuses mainly on antiplatelet therapy. The most recent recommendations for the use of acetylsalicylic acid and clopidogrel, the main antiplatelet drugs, are highlighted. The clinical failure of primary or secondary prevention of cerebrovascular diseases, one of the reasons for which is resistance to the therapy, is considered separately. The authors discuss the causes of aspirin resistance and ways to overcome it, one of which may be a switch to another drug. The well-known medication dipyridamole is proposed as a possible alternative and/or addition to the treatment regimen. The most modern ideas about the mechanisms of its action are described, the pleiotropy of its effects is emphasized. The results of own studies on assessment of the effectiveness and safety of dipyridamole (curantil) in patients with various forms of CCD are presented. The results of the CCD pilot project to study the antiplatelet profile of dipyridamole in patients with such a cause of ischemic NMC as Ph-negative myeloproliferative diseases are discussed separately. It is noted that when prescribing both dipyridamole and acetylsalicylic acid preparations, comparable platelet aggregation levels are determined. In conclusion, the need to follow the paradigm of personalized therapy is emphasized, in which individually selected therapy is prescribed (including) taking into account resistance to a particular drug.

SECONDARY SPONTANEOUS INTRAMURAL ESOPHAGEAL HEMATOMA (IEH) FOR CLOPIDOGREL TREATMENT: A CASE REPORT

Giriş: Spontan İntramural Özofagus Hematomu (SIEH), yemek borusunun mukozasının kas tabakalarından ayrılması sonucu ortaya çıkan, nadir görülen bir özofagus hasarı şeklidir. En sık klinik prezentasyon şekilleri ani başlayan göğüs ağrısı, disfaji ve hematemez şeklindedir. Biz burda klopidogrel kullanımına sekonder gelişen, hematemez ile prezente olan SIEH vakası sunmaktayız.Olgu sunumu: 73 yaşında bayan hasta, yoğun bakım ünitesinde serebrovasküler hastalık (SVH) nedeni ile klopidogrel kullanmakta iken hematemezi olması nedeni yapılan endoskopisinde submukozal hematom izlendi. Klopidogrel tedavisi kesilerek takip edildi. Hastanın 1 hafta sonra yapılan kontrol endoskopisinde lineer mukozal düzensizlik dışında patoloji izlenmedi. Tartışma: IEH’ler, özefagus apopleksisi, intramural kanama ve intramural diseksiyon olarak tanımlanmıştır. Kadın cinsiyet, ileri yaş, kanama diyatezi varlığı, antikoagülan antitrombolitik ve antiplatelet ilaçların kullanımı predispozan faktörler arasındadır. Tanıda baryumlu özofagus grafisi, bilgisayarlı tomografi, MRI ve endoskopi kullanılabilmektedir. Endoskopide intramural hipoekoik submukozal lezyon görülebilir. Tedavi konservatif ve destek tedavisi şeklindedir.

Status of the clopidogrel use in ACS patients and related factors among county hospitals in China

Objective: To observe the use of clopidogrel and related factors for patients with acute coronary syndrome (ACS) in terms of early use, loading dose, dual antiplatelet therapy (DAPT) and maintenance dose hospitalized in non-PCI country hospitals in China. Methods: Patients hospitalized for ACS from 101 non-PCI country hospitals across China were recruited prospectively from October 2011 to November 2014. In-hospital clopidogrel use rate, the proportions of early use (within 24 hours), loading dose use (≥300 mg), DAPT (early use combined with aspirin) and maintenance dose use (following dose≥75 mg/d) were analyzed. Generalized estimated equation (GEE) model was used to explore factors associated to in-hospital clopidogrel use and loading dose use in both univariate and multivariate analyses, adjusting for cluster effect. Results: A total of 14 809 ACS patients were included, with an average age of (64.1±11.6) years and 60% (8 888/14 809) were male. The in-hospital clopidogrel use rate was 66.4% (9 828/14 809), which varied across different regions, years and sub-types of ACS (all P<0.05). Among users, the proportions of patients with early use, DAPT and maintenance dose use were 91.3% (8 734/9 562), 89.2% (8 526/9 562) and 95.1% (9 094/9 562), respectively, but the proportion of patients received loading dose was only 41.8% (3 995/9 562). Multivariate analyses showed that patients who admitted to hospital in earlier years and with non-ST elevation ACS, ≥75 years old, female, non-smoking, illiterate, heart rate≥100 beats per minute, atrial fibrillation, not on ECG monitoring, and not using other anti-ACS drugs were less likely to receive clopidogrel (all P<0.05). And those clopidogrel users who with non-ST elevation ACS, ≥75 years old, non-smoking, illiterate, not using other anti-ACS drugs were less likely to receive loading dose (all P<0.05). Conclusion: The use rate of clopidogrel and the loading dose among in-hospital ACS patients are both low and remain to be improved in non-PCI county hospitals in China. Special attention should be paid on non-ST elevation ACS, ≥75 years old, female, and illiterate patients to increase the rational use of clopidogrel and the loading dose.

Cost-effectiveness of CYP2C19 LOF-guided antiplatelet therapy in Chinese patients with acute coronary syndrome.

Aim: This study aimed to evaluate the cost-effectiveness of CYP2C19 loss-of-function(LOF)allele-guided antiplatelet therapy compared with the universal use of clopidogrel or ticagrelor among Chinese patients with acute coronary syndrome undergoing percutaneous coronary intervention. Methods: A two-part cost-effectiveness model comprising of a 1-year decision tree and a long-term Markov model was utilized to simulate outcomes of three treatment strategies: universal use of clopidogrel (75mg daily) or universal use of ticagrelor 90mg twice daily for all patients and CYP2C19 LOF-guided therapy (LOF allele carriers receiving ticagrelor, LOF allele noncarriers receiving clopidogrel). Model outcomes included quality-adjusted life years (QALYs) gained, direct medical costs and incremental cost-effectiveness ratios (ICERs). ICERs less than one-time gross domestic product per capita in China 59,660yuan/QALY were considered cost-effective. Results: Base-case analysis showed 'universal ticagrelor use' was cost-effective for an ICER of 33,875yuan per QALY gained compared with 'universal clopidogrel use' of which gained a 1.6932QALYs at lowest life-long cost of 2450yuan. CYP2C19 LOF-guided therapy had an effectiveness of 1.6975QALYs at a cost of 2812yuan, for an ICER of 84,118yuan per QALY gained relative to 'universal clopidogrel use'. Sensitivity analysis demonstrated that base-case results were significantly affected by five factors: the risk ratio of 'non-fatal myocardial infarction', 'non-fatal stroke' and 'cardiovascular death' in ticagrelor versus clopidogrel and the annual costs of clopidogrel and ticagrelor. According to the results of Monte Carlo simulation, when willing to pay is about 32,000yuan, patients willing to receive clopidogrel or ticagrelor are approximately equal. Conclusion: Optimal antiplatelet treatment is affected by lots of factors. The results of our study demonstrated that 'universal ticagrelor use' was cost-effective compared with 'universal clopidogrel use' for Chinese acute coronary syndrome patients with percutaneous coronary intervention.

Searching for the Optimal Predictors’ Model for Occlusion of the Femoral-popliteal and Femoral-tibial bypasses

Risk factors affecting the patency of shunts after infrainguinal reconstructions have been known for a long time. But so far, no effective model has been proposed, that allows to predict in a particular patient at what time and with what combination of risk factors bypass occlusion will occur. A statistical analysis of the risk factors for occlusion of such bypasses was made and developed a reliable prognostic model based on the regression function. A retrospective analysis of 136 cases of femoral-popliteal bypasses and femoral-tibial bypasses was carried out at the Department of Vascular Surgery of the Orel Regional Clinical Hospital from 2008 till 2018. Statistical data analysis was performed using Spearman’s rank correlation, binary logistic regression, ROC-curve and Kaplan-Meier survival graphs using IBM SPSS Statistics 22. A correlation was found between almost all analyzed factors and primary permeability. Based on the logistic regression, a reliable model of a combination of ischemia, superficial femoral artery patency, diabetes history, pre-operative INR data and hemoglobin level, with high prognostic significance, specificity, sensitivity and informativeness, was compiled. The constructed Kaplan-Meier survival graphs showed the dependence of the degree of ischemia and trophic disorders, history of diabetes, and the use of clopidogrel, atorvastatin / rozuvastatin, pentoxifylline, actovegin in the postoperative period from the primary patency over the time. To the patients, who have occlusion risk factors proposed in the developed model, should prolonged atorvastatin/rosuvastatin, clopidogrel, pentoxifylline, actovegin intake (more than 1 year, ideally for life) first be advised, and also they should appoint a periodic preventive examination of a vascular surgeon after 1 month, 3 months, 6 months, 1 year and 2 years after surgery with an ultrasound scan of the lower limb arteries and a bypass, as well as a complete blood count analysis (leukocytes and platelets).

Clopidogrel plus Aspirin Use is Associated with Worse Long-Term Outcomes, but Aspirin Use Alone is Safe in Patients with Vasospastic Angina: Results from the VA-Korea Registry, A Prospective Multi-Center Cohort

Anti-platelet agents are commonly used in vasospastic angina (VA) patients with comorbidity like coronary artery disease. However, long-term clinical outcomes in the use of aspirin, clopidogrel or the two agents together have rarely been investigated in VA patients. In a prospective study, we enrolled 2960 patients who received coronary angiography and ergonovine provocation test at 11 university hospitals in Korea. Among them, 1838 patients were diagnosed either with definite (n = 680) or intermediate (n = 1212) VA, using the criteria of chest pain, ECG changes and ergonovine provocation test results. They were analyzed according to their use of aspirin, clopidogrel or both, or no anti-platelet agent at all. The primary outcome was time to composite events of death from any cause, acute coronary syndrome (ACS) and symptomatic arrhythmia during a 3-year follow-up. A primary composite outcome was significantly more common in the aspirin plus clopidogrel group, at 10.8% (14/130), as compared with the non-antiplatelet group, at 4.4% (44/1011), (hazard ratio [HR] 2.41, 95% confidence interval [CI], 1.32–4.40, p = 0.004). With regard to the person-time event rate, similar results were shown, with the highest rate in the aspirin plus clopidogrel user at 4.72/1000 person months (95% CI, 2.79–7.96, log-rank test for primary outcome p = 0.016). The person-time event of the ACS rate was also highest in that group, at 2.81 (95% CI, 1.46–5.40, log-rank test for ACS p = 0.116). Kaplan-Meier survival analysis demonstrated poor prognosis in primary outcomes and ACS in aspirin plus clopidogrel users (log-rank test, p = 0.005 and p = 0.0392, respectively). Cox-proportional hazard regression analysis, adjusting for age, sex, history of coronary heart disease, hypertension, diabetes, presence or not of definite spasm, use of calcium channel blocker, demonstrated that the use of aspirin plus clopidogrel is an independent risk for the primary outcome (HR 2.01, CI: 1.07–3.81, p = 0.031). The aspirin-alone group had a similar primary and individual event rate compared to the no-antiplatelet agent group (HR 0.96, CI, 0.59–1.55, p = 0.872). Smokers using aspirin plus clopidogrel had poorer outcomes than non-smokers, with HR 6.36 (CI 2.31–17.54, p = 0.045 for interaction). In conclusion, among VA patients, aspirin plus clopidogrel use is associated with a poor clinical outcome at 3 years, especially in ACS. Aspirin alone appears to be safe for use in those patients.

PCV69 COST EFFECTIVENESS ANALYSIS OF TICAGRELOR VERSUS CLOPIDOGREL IN STEMI PATIENTS FROM NATIONAL HEART INSTITUTE PERSPECTIVE IN EGYPT

Acute coronary syndromes (ACS) are a major cause of morbidity and mortality in Egypt. Early diagnosis and prompt, effective therapy are essential to reverse ischemia, restore normal coronary blood flow, and limit myocardial damage .The main objective is to compare costs and outcomes associated with the use of Ticagrelor versus Clopidogrel in patients with STEMI following PCI from NHI perspective in Egypt. A cost utility study is adopted, The model design adopted was a combination of one-year decision tree followed by a long-term Markov model to ensure that all major clinical and resource generating events that a patient may experience throughout the course of their remaining life are captured . The clinical evidence was taken from PLATO-STEMI sub study , acquisition cost of drugs, monitoring cost and cost associated with each health state is collected from NHI and MOH hospitals in financial fiscal year 2019. Utilities were captured from published studies for the same target population . A discount rate of 3.5% is used for both cost &QALY, DSA and PSA were conducted. Ticagrelor over 25 year time horizon provides an incremental health gain of 16.87 QALYs compared with Clopidogrel, at an incremental cost of 243,499 EGP resulting in an ICER of 14,433 EGP/QALY. The result was below the accepted willingness to pay threshold of Egypt which is equal 86000 EGP/QALY. The costs associated with the MI health state in the first year of clopidogrel arm had the great impact on the results of the study based on the results of DSA, the results of PSA revealed from the cost-effectiveness acceptability curve that at a willingness to pay of 86000EGP per QALY, the probability of Ticagrelor being cost-effective is 100%. Ticagrelor revealed to be a cost effective treatment option for STEMI patients following PCI compared to Clopidogrel intervention from NHI perspective in Egypt.

Study design of Endoscopic Polypectomy On Clopidogrel (EPOC): a randomised controlled trial

Concurrent cardiovascular disease and antiplatelet use (clopidogrel, prasugrel and ticagrelor) use poses a significant peri-endoscopic management challenge with a paucity of high-quality evidence available. Antiplatelet temporary interruption places patients at risk of serious cardiovascular thrombotic events. Continuing these agents potentially increases the risk of procedure related bleeding however this risk could be sufficiently mitigated by cold snare polypectomy and endoscopic clipping to manage intraprocedural bleeding, making routine colonoscopy on continued antiplatelet agents safe.The EPOC trial will examine whether continuation of antiplatelet therapy (clopidogrel, prasugrel or ticagrelor) as single or dual therapy with aspirin, is inferior or superior to temporary interruption of antiplatelet therapy, current standard of care, with regard to the use of endoscopic rescue clips or clinically significant post-polypectomy bleeding after cold snare polypectomy of polyps ≤10mm. EPOC is a parallel group, proceduralist-blinded randomized controlled trial comparing recruiting patients on antiplatelet therapy undergoing elective colonoscopy.This trial is underway throughout Australia and New Zealand with a view to expanding to additional sites. 496 subjects in each arm are required for this study. EPOC is the first randomised controlled trial comparing temporary interruption with continuation of antiplatelet therapy in patients undergoing elective colonoscopy.

Exposure and response analysis of aleglitazar on cardiovascular risk markers and safety outcomes: An analysis of the AleCardio trial.

AimsThe AleCardio trial aimed to characterize the efficacy and safety of peroxisome proliferator‐activated receptor‐αγ agonist aleglitazar in patients with type 2 diabetes mellitus and acute coronary syndrome. The trial terminated early because of futility and safety signals. We evaluated whether the safety signals could be attributed to increased exposure to aleglitazar.Materials and MethodsThe AleCardio trial enrolled 7226 patients to receive aleglitazar 150 μg or matching placebo on top of standard care. A population pharmacokinetic analysis was conducted in a pharmacokinetic substudy to identify covariates that explained interindividual variability in exposure. Subsequently, the effect of these covariates on surrogate and clinical outcomes was assessed in the full patient population.ResultsConcomitant administration of clopidogrel was identified as a covariate that influenced the apparent clearance of aleglitazar. Patients using clopidogrel had a mean predicted area under the plasma‐concentration‐time curve (AUC0–24) of 174.7 ng h/mL (SD: ±112.9 ng h/mL) versus 142.2 ng h/mL (SD: ±92.6 ng h/mL) in patients without clopidogrel. The effect of aleglitazar compared with placebo on HbA1c, haemoglobin, serum creatinine and adiponectin was modified by concomitant clopidogrel use (P for interaction 0.007, 0.002, <0.001 and < 0.001, respectively).ConclusionsConcomitant use of clopidogrel was identified as a covariate that explained interindividual variability in exposure to aleglitazar. Patients using clopidogrel showed an additional lowering of HbA1c, at the expense of an additional decrease in haemoglobin, and an increase in serum creatinine and adiponectin. Clopidogrel is a moderate inhibitor of CYP2C8. Because aleglitazar is metabolized by CYP2C8, a pharmacokinetic interaction could explain differences in exposure and response to aleglitazar.

P3840Impact of potent P2Y12 inhibitors in adverse events reduction in diabetic patients with Acute Coronary Syndromes. An analysis from ACHILLES Registry

Abstract Background Diabetic patients (DM) with an acute coronary syndrome (ACS) have a worse prognosis than non-diabetic patients. The new P2Y12 inhibitors, both ticagrelor and prasugrel, have shown efficacy in cardiovascular event reduction in patients with DM and ACS. Purpose The main objective of this study was to analyze the use of antiplatelet agents, prognosis and adverse events during the follow-up in diabetic patients admitted after an acute coronary syndrome. Methods These patients belong to ACHILLES registry. All patients with type 1 ACS were included prospectively in a national, prospective and multicenter registry. We analyzed baseline characteristics and comorbidities focusing on the presence of DM and the use of potent antiplatelet agents (ticagrelor and prasugrel) in those patients. After 1 year of follow-up, adverse events in diabetic patients were analyzed according to the type of antiplatelet used [clopidogrel vs new antiplatelet drugs (NAD)]. Results Of 1,717 patients, 1,294 patients [mean age 65.0±13.3 years, 952 (73.6%) male] were finally analyzed (excluding patients discharged with oral anticoagulation). Diabetic patients had high prevalence of cardiovascular risk factors such as hypertension (54.9% vs 81.1%; p&lt;0.001), dyslipidemia (50.7% vs 72.8%; p&lt;0.001) or chronic kidney disease (22.1% vs 31.9%; p&lt;0.001). Diabetic patients had also higher rate of non-invasive management of ACS compared to non-diabetic patients (4.5% vs 9.1%; p=0.002). At discharge, the use of NAD in patients with DM was 40.4% compared to 50.8% in non-diabetic patients (p&lt;0.001). After 1 year of follow-up, 64 (5.0%/year) patients had a new ACS, 46 (3.6%/year) patients died due to cardiovascular causes, 76 (6.1%/year) died for any cause and 28 (2.2%/year) patients had a major bleeding events. The use of clopidogrel in diabetic patients was associated with an increase in all-cause mortality [HR 2.90; 95% CI (1.27–6.629), p=0.011] and in MACE [HR 2.14; 95% CI (1.22–3.77), p=0.008.] Diabetic patients treated with NAD had no differences in terms of major bleeding but those patients presented a significant reduction in cardiovascular mortality and MACE with NAD use. Event Free Survival according NAD Use Conclusions Patients with DM and ACS had high prevalence of concomitant cardiovascular risk factors but lower use of NAD compared with non-diabetic patients, despite DM patients had greater baseline risk. The use of NAD therapy was associated with a significant reduction in all-cause mortality, cardiovascular mortality and MACE without differences in major bleeding events.

45 External Validation of a Subdural Hematoma Risk Decision Instrument in Emergency Department Patients

Anticoagulation, hematoma size, and midline shift are significant prognostic factors for poor outcomes in the acute phase of subdural hematomas (SDH). They were used by Pruitt et al in 2017 to develop a decision instrument identifying low risk patients with traumatic SDH. We wished to externally validate this decision instrument in our emergency department (ED), an academic, Level 1 trauma center. We conducted a retrospective chart review study of patients ≥18 years old in the ED with CT-documented SDH from 2014-2016. Patients were considered high risk per the decision instrument if they had hematoma thickness >5mm, warfarin or clopidogrel use, initial Glasgow Coma Scale <14, midline shift, or ≥1 hematoma. Primary composite outcome included in-hospital death or transition to hospice, need for neurosurgery, neurologic decline, and/or worsening hematoma on CT. Five hundred twenty-three charts were reviewed, and 222 met inclusion criteria. Forty-one (18.5%) patients were low risk per the decision instrument. Of these, 13 (31.7%) experienced the composite outcome. The sensitivity for this instrument was 89.4% (95% CI 82.6% - 94.3%), and the specificity was 28.3% (95% CI 19.7% - 38.2%). Patients on novel oral anticoagulant (NOAC) agents had a 55.6% (5/9) composite outcome. Including all patients on NOACs as high risk did not affect sensitivity (89.4%, 95% CI 82.6% - 94.3%) and marginally worsened specificity (24.2%, 95% CI 16.2% - 33.9%). The current decision instrument resulted in a 31.7% adverse outcome rate for low risk patients. This could be due to differences in our patient population including higher rate of NOAC use, inclusion of patients with spontaneous SDH, and higher overall mortality in our population. We recommend further study before implementing reduced level of care for patients with SDH.

Clopidogrel Adherence to AHA/ACC Guideline in Patients with Open Heart Surgery in a Tertiary Heart Center

Background: Clopidogrel is an antiplatelet drug that is widely prescribed for cardiovascular disease. In cardiac surgery, it is used in patients after coronary artery bypass grafting (CABG) to prevent coagulation disorders. The irrational use of this drug can lead to bleeding and require surgical exploration along with increased therapeutic cost. Therefore, it is essential to study the pattern of clopidogrel use in hospitals. Methods: This study was conducted for a 6-month period to evaluate clopidogrel adherence to American Heart Association/American College of Cardiology (AHA / ACC) Guidelines in patients after coronary artery bypass grafting (CABG) surgery. Patients’ data were recorded in the pre-designed questionnaire, which included demographic data, past medical history, drug history along with the indications of clopidogrel use. Data analysis was performed by SPSS 16 software. Results: A total of 120 patients with a mean age of 61.3 ± 8.9 years old were recruited in to this study. Male to female ratio was 3 times. The main risk factors in patients with ischemic heart disease were male gender (74.2%), hypertension (80%), and smoking (47.5%). In addition to clopidogrel, most of the patients received aspirin (95.8%), followed by heparin (31.7%), and warfarin (5%) or enoxaparin (2.5%). The clopidogrel indications were non ST-elevation myocardial infarction / unstable angina (33.3%), acute ST-elevation myocardial infarction (20.8%), recent myocardial infarction or stroke (3.3%), and CABG off-pump (30%). In 70.8% of cases, the administration of clopidogrel was consistent with AHA / ACC standard guidelines and most of the irrational cases belonged to the usage of the drug after on-pump CABG surgery. Conclusion: The results showed that the rates of adherence to clopidogrel use with the AHA/ACC guidelines for patients who underwent CABG surgery was relatively good, but required further improvement.

The relationship between the combined use of various proton pump inhibitors with antiplatelet drugs and the risk of cardiovascular complications

In the article the problem of the combined use of clopidogrel and various proton pump inhibitors (PPIs) in terms of cardiovascular complications risk and stent thrombosis is considered. The results of meta - analyses and a systematic reviews affecting this issue are represented in detail. The inter - drug interactions mechanisms of various PPIs with clopidogrel based on the characteristics of the metabolism in the liver cytochromes system are discussed. The authors conducted a search, systematization and analysis of studies regarding the association between cardiovascular risk and combined use of individual medications from PPI class with clopidogrel, and these results are presented in the review. Currently available data do not allow to answer the question about the differences between individual PPIs in their impact on the risk of adverse cardiovascular events due to the small number of such studies, design heterogeneity, differences in the inclusion criteria and end points as well as in the rate of administration of individual PPIs.

Real-World Relationship Between Proton Pump Inhibitors and Cerebro-Cardiovascular Outcomes Independent of Clopidogrel

Previous studies have provided established evidence on adverse outcomes of the coadministration of proton pump inhibitors (PPIs) and clopidogrel, whereas cerebro-cardiovascular outcomes of PPI use in the absence of clopidogrel therapy remain controversial.In this study, we aimed to assess the association between PPIs and cerebro-cardiovascular outcomes independent of clopidogrel.Systematic searches were conducted in the Cochrane Library, PubMed, and Embase databases for all relevant studies up to August 2018. Odds ratios (ORs) with its 95% confidence intervals (CIs) were abstracted and pooled using the random-effects model.A total of 14 observational studies (13 cohort studies and 1 case-control study) were identified. Compared with non-PPI users, PPI users experienced higher risks of stroke (OR: 1.22, 95% CI: 1.08-1.36), myocardial infarction (MI; OR: 1.23, 95% CI: 1.14-1.32), cardiovascular death (OR: 1.83, 95% CI: 1.69-1.98), and major adverse cardiovascular events (MACEs; OR: 1.22, 95% CI: 1.05-1.40) independent of clopidogrel use, but not all-cause death (OR: 1.50, 95% CI: 0.99-2.25). In the subgroup analysis, PPI alone was associated with significant risks of new-onset MI (OR: 1.23, 95% CI: 1.13-1.35) and stroke (OR: 1.17, 95% CI: 1.05-1.30) in patients without previous MI or stoke and recurrent MI (OR: 1.24, 95% CI: 1.02-1.51) and stroke (OR: 1.36, 95% CI: 1.19-1.55) risks in patients with a previous MI.Based on current publications, PPI use seems to be associated with increased risks of stroke, MI, cardiovascular death, and MACEs independent of clopidogrel. Greater caution should be therefore exercised while considering its clinical benefits and further investigate any causal relationships.

Risk of Hypoglycemia and Concomitant Use of Repaglinide and Clopidogrel: A Population-Based Nested Case-Control Study.

This nested case-control study evaluated the potential interaction between repaglinide and clopidogrel. Cases were defined by inpatient admissions or emergency department visits due to hypoglycemia. Concomitant use of repaglinide and clopidogrel within 3days before the hypoglycemic event was the exposure of interest. For each case, up to four controls were randomly selected and matched by age, sex, type of glinide used (repaglinide or nateglinide), and time since cohort entry to the index date. Hypoglycemic risk was estimated by conditional logistic regressions. Concomitant use of repaglinide and clopidogrel was associated with an increased risk of hypoglycemia compared with repaglinide alone (adjusted odds ratio: 2.42; 95% confidence interval: 1.75-3.35). No significant associations were found with the two negative control object drug concomitants: nateglinide and clopidogrel and repaglinide and aspirin (without clopidogrel use). Our study suggests drug interaction between clopidogrel and repaglinide is clinically relevant and could increase the risk for hypoglycemia.

Abstract 3344: Effect of anticoagulation on the cancer stage at time of diagnosis of endometroid adenocarcinoma in a cohort of postmenopausal patients

Abstract Objectives: We sought to determine whether postmenopausal women on chronic anticoagulation were diagnosed with endometrial cancer at an earlier stage. Methods: A retrospective case-control study of women at a tertiary care medical center with a diagnosis of Endometrioid Adenocarcinoma on chronic anticoagulation at time of diagnosis in comparison with patients not on anticoagulation was performed. Patients with personal history of cancer, including breast cancer, non-postmenopausal bleeding, and non-Endometrioid Adenocarcinoma histopathology were excluded. Anticoagulation was defined as use of Enoxaparin, Warfarin, Apixaban, Rivaroxaban or Clopidogrel. Indications for anticoagulation included atrial fibrillation, deep vein thrombosis/pulmonary embolism, or stroke. The primary outcome was Endometrioid Cancer stage (I, II, III/IV and X). The secondary outcomes were duration of bleeding to presentation and presentation to diagnosis. Statistical analysis was performed using Wilcoxan-Rank Sum Test and Cochran-Armitage Trend Test. Results: 25 postmenopausal patients met the inclusion criteria for being treated in the last 10 years. 100 controls not on anticoagulation (non-AC) were identified for a 4:1 comparison to obtain a 2-sided alpha level of 0.05. Results were divided into 3 groups: 1) All patients, 2) Non-white patients, 3) White patients. Subjects were controlled for age (P&amp;lt;0.001) and BMI (P&amp;lt;0.049). The results indicated that non-AC patients were more likely to be diagnosed at Stage 1 when compared to the AC patients in all 3 categories. The trend was not statistically significant for the non-white patients (p=0.133), but was statistically significant in the overall population (p&amp;lt;0.001) and White patients (p&amp;lt;0.001). No statistical significance was detected for duration from bleeding to presentation and presentation to diagnosis between the AC and non-AC groups. However, median days from bleeding to presentation are considerably larger for the non-AC than AC (Group 1: 42 vs 14 days, Group 2: 75 vs 33 days Group 3: 30 vs 14 days, respectively). Conclusion: Non-anticoagulated patients had an earlier cancer stage at diagnosis. Although anticoagulated patients may present earlier, they have advanced cancer stage. These findings should prompt immediate evaluation of patients on chronic anticoagulation to optimize oncologic management and prognosis. Citation Format: Ghadear Shukr, Tra Pham, Thomas Buekers. Effect of anticoagulation on the cancer stage at time of diagnosis of endometroid adenocarcinoma in a cohort of postmenopausal patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3344.

Insomnia and Alcohol Use in Assisted Living

Insomnia and Alcohol Use in Assisted Living

Real-world use of ticagrelor versus clopidogrel in percutaneous coronary intervention-treated ST-elevation myocardial infarction patients: A single-center registry study

ObjectivesThe primary aim was to investigate the efficacy and safety of dual antiplatelet therapy (DAPT) using ticagrelor (T-DAPT) versus clopidogrel (C-DAPT) in a real-world ST-elevation myocardial infarction (STEMI) population. MethodsWe retrospectively analyzed 655 consecutive patients having primary percutaneous coronary intervention (PCI) for STEMI at Liverpool Hospital, Sydney, Australia (from January 2013 to April 2016). Medical and procedural therapies were at clinician discretion. Patient data were retrieved from hospital records and primary clinicians. ResultsT-DAPT (65%) was used more frequently, and in patients with lower mean CRUSADE (Can Rapid Risk Stratification of Unstable Angina Patients Suppress Adverse Outcomes with Early Implementation of the American College of Cardiology/American Heart Association Guidelines) score, than C-DAPT (24.6 vs. 32.2; p < 0.0001, respectively). All-cause mortality was 9.0% at 2.7 years follow-up, with fewer deaths for T-DAPT (4.5% vs. 17.2%; p < 0.0001). T-DAPT incurred less BARC (Bleeding Academic Research Consortium) 3–5 major bleeding (5.0% vs. 12.4%; p < 0.0001). Multivariate regression showed that C-DAPT, GRACE (Global Registry of Acute Cardiac Events) score, and renal insufficiency were independently associated with mortality. Intra-aortic balloon pump (IABP) and GRACE score independently predicted BARC 3–5 bleeding. Early DAPT discontinuation (1.7%) and ticagrelor intolerance (7.6%) was rare. Switching DAPT regimen was infrequent (21.7%) and mostly attributed to clinician preference (73.2%). Independent determinants of C-DAPT selection were older age, diabetes, prior PCI, IABP, and higher CRUSADE score. ConclusionTicagrelor was preferred in low bleeding risk patients, which may have contributed to less BARC 3–5 bleeding and lower mortality for T-DAPT. Thus, bleeding mitigation is a clinical priority when selecting DAPT for PCI-treated STEMI patients. Continuation of initial DAPT regimen was typical, but early switching from clopidogrel to ticagrelor shows willingness to optimize DAPT. Patients with very low CRUSADE scores (<21.5) may be appropriate for switching to a potent P2Y12 inhibitor.

The Use of Dual Antiplatelet Therapy in Acute Coronary Syndrome and Percutaneous Coronary Intervention

Currently, cardiovascular diseases play a leading role in the structure of morbidity. It is expected that by 2020 in developing countries cardiovascular diseases will take the leading position in the structure of mortality. Among the diseases of the cardiovascular system the leading position is occupied by coronary heart disease. One of the manifestations of coronary heart disease is acute coronary syndrome. In addition to endovascular treatment, dual antiplatelet therapy plays a key role in the treatment and prevention of acute coronary syndrome. Double antiplatelet therapy is a combination of acetylsalicylic acid and platelet P2Y 12 receptor inhibitors. One of the first drugs from the group of P2Y 12 receptor inhibitors is clopidogrel. It has been proven that the use of clopidogrel to date not always reduces the risk of development of thrombotic complications, of particular interest are the representatives of the new platelet P2Y 12 receptor inhibitors. Such platelet P2Y 12 -receptor inhibitors include ticagrelor and prasugrel. The article considers in detail the issue of efficiency and safety of prasugrel use. The results of the studies allow to distinguish this drug as an effective inhibitor of P2Y 12 platelet receptors in patients with acute coronary syndrome who have undergone percutaneous coronary intervention. Considering the pronounced antiplatelet effect of the drug, it should not be prescribed to patients with stroke and a history of transient ischemic attack. Prasugrel also should not be prescribed in a full dose to patients over 75 years old and patients weighing up to 60 kg. These studies showed that when the recommendations are followed, prasugrel demonstrates good results in reducing the frequency of cardiovascular events in patients with acute coronary syndrome and percutaneous coronary intervention. Separately, we can distinguish the effect of prasugrel on the development of stent thrombosis. So, in patients that underwent stenting, the use of prasugrel significantly reduced the frequency of confirmed stent thrombosis, which can also affect the development of undesirable cardiovascular events.