Antiplatelet therapy for postdischarge medical management of acute coronary syndrome

Postdischarge management of patients with acute coronary syndrome is often suboptimal, despite their high risk of a subsequent event. Updated American College of Cardiology/American Heart Association guidelines emphasize the need for aggressive modification of risk factors and treatment with antiplatelet, antihypertensive, and lipid-lowering agents commenced in-hospital and continued long-term. Antiplatelet therapy involving aspirin and clopidogrel is the mainstay of secondary risk reduction. Increased adherence to medication and risk factor modification at discharge has been demonstrated with acute care quality improvement initiatives. Extension of these initiatives to postdischarge care will provide data on medication adherence post acute coronary syndrome and functional outcomes in the community setting. Successful secondary prevention of cardiovascular events requires implementation of evidence-based guidelines by physicians, and adherence to pharmacotherapy and lifestyle modifications by patients. Primary care physicians are well placed to influence adherence through their ongoing relationships with patients and can save lives by implementing secondary risk reduction measures after discharge.     

Decreased turnover aspirin resistance by bidaily aspirin intake and efficient cytoreduction in myeloproliferative neoplasms

Essential thrombocythemia (ET) and polycythemia vera (PV) are myeloproliferative neoplasms (MPN) with an increased risk of arterial and venous thrombosis. Aspirin is recommended to reduce this risk, but resistance to antiplatelet therapy seems to hamper its efficacy in some patients. We have previously shown that multiple electrode aggregometry (MEA) was a valuable tool to assess aspirin resistance in MPN. In this study, MEA was used to assess the reduction in aspirin resistance after bi-daily (BID) aspirin intake or cytoreduction.

Fifty one MPN patients (31 ET and 20 PV) receiving 75 mg aspirin once daily (OD) or BID, with or without cytoreductive treatment, were analyzed. Aspirin resistance was assessed using whole blood MEA (Multiplate®, Roche Diagnostics, Meylan, France).

In all patients, global aspirin resistance consisted mainly of turnover resistance (TOR). 94% of patients with OD aspirin intake and without cytoreduction displayed biological aspirin resistance. By switching to a BID aspirin regimen, the proportion of resistant patients reduced to 47%. Cytoreduction also contributed to reduce aspirin resistance in a similar way (50% of aspirin resistant patients). Combining cytoreduction and BID aspirin regimen was the most efficient way to reduce aspirin resistance yielding to 12% resistant patients. Moreover, a nonlinear correlation was observed between TOR and naive platelet counts regardless of aspirin regimen. Last, mutational status did not seem to affect TOR.

This study confirmed that BID aspirin is biologically more effective than OD aspirin in reduction of aspirin resistance. The latter was achieved through a reduction in TOR which was also decreased by cytoreductive therapy.     

Low-dose aspirin in patients with stable cardiovascular disease: a meta-analysis

Objective

Many recommendations for aspirin in stable cardiovascular disease are based on analyses of all antiplatelet therapies at all dosages and in both stable and unstable patients. Our objective was to evaluate the benefit and risk of low-dose aspirin (50-325 mg/d) in patients with stable cardiovascular disease.

Methods

Secondary prevention trials of low-dose aspirin in patients with stable cardiovascular disease were identified by searches of the MEDLINE database from 1966 to 2006. Six randomized trials were identified that enrolled patients with a prior myocardial infarction (MI) (n = 1), stable angina (n = 1), or stroke/transient ischemic attack (n = 4). A random effects model was used to combine results from individual trials.

Results

Six studies randomized 9853 patients. Aspirin therapy was associated with a significant 21% reduction in the risk of cardiovascular events (nonfatal MI, nonfatal stroke, and cardiovascular death) (95% confidence interval [CI], 0.72-0.88), 26% reduction in the risk of nonfatal MI (95% CI, 0.60-0.91), 25% reduction in the risk of stroke (95% CI, 0.65-0.87), and 13% reduction in the risk of all-cause mortality (95% CI, 0.76-0.98). Patients treated with aspirin were significantly more likely to experience severe bleeding (odds ratio 2.2, 95% CI, 1.4-3.4). Treatment of 1000 patients for an average of 33 months would prevent 33 cardiovascular events, 12 nonfatal MIs, 25 nonfatal strokes, and 14 deaths, and cause 9 major bleeding events. Among those with ischemic heart disease, aspirin was most effective at reducing the risk of nonfatal MI and all-cause mortality; however, among those with cerebrovascular disease, aspirin was most effective at reducing the risk of stroke.

Conclusion

In patients with stable cardiovascular disease, low-dose aspirin therapy reduces the incidence of adverse cardiovascular events and all-cause mortality, and increases the risk of severe bleeding.     

阿司匹林对CKD3期患者肾功能影响的探讨

目的:阿司匹林属非甾体类抗炎药,常期以来被认为具有肾毒性。本文选取肾脏疾病中数量较多的慢性肾脏病(CKD)3期患者为观察对象,探讨阿司匹林对肾功能的影响。方法:选取2012年3月~2013年3月于我科门诊随访且资料完整的CKD3期患者。服用阿司匹林的指征为轻度头晕及胸闷(包括心电图ST-T改变),且无反指征(如上消化出血和严重溃疡病)。患者随机进入阿司匹林组(100 mg/d)和空白对照组,随访6个月。主要观查血小板聚集功能(ADP诱导法)、血肌酐(Scr)水平和肾小球滤过率(e GFR)(EPI及MDRD公式计算)以及尿蛋白量的变化。结果:最终进入统计的患者为36例(每组各为18例),其中男22例,女14例,平均年龄(56.6±9.8)岁,Scr(121.8±26.1)μmol/L,e GFR(53.4±12.3)ml·min-1·1.73 m-2(EPI公式),e GFR(50.5±10.3)ml·min-1·1.73 m-2(MDRD简化公式),24 h尿蛋白(0.748±0.27)g。(1)治疗前两组患者年龄、身体质量指数(BMI)、血压、血小板计数、血尿素(BUN)、Scr、e GFR(EPI及MDRD公式计算)、24 h尿蛋白和尿白蛋白/尿肌酐比(ACR)差异均无统计学意义。(2)治疗前与治疗后3月、6月两组e GFR(EPI及MDRD公式计算)比较均差异无统计学意义(P0.05);两组治疗前后EPI和MDRD自身比较也差异无统计学意义(P0.05)。(3)治疗前、治疗后3月和6月两组24 h尿蛋白比较差异无统计学意义(P0.05),两组治疗前后24 h尿蛋白自身比较也差异无统计学意义(P0.05)。治疗后3月和6月两组ACR和尿红细胞比较也差异无统计学意义(P0.05)。(4)治疗后3月和6月,阿司匹林组血小板聚集功能较对照组明显下降(3月64.6∶74.9,6月61.9∶75.1),P=0.000。(5)阿司匹林组:血小板聚集功能治疗后3月和6月较治疗前明显下降(3月64.6∶74.4,6月61.9∶74.4),P=0.000,而对照组没有明显变化。(6)两组治疗后粪隐血均为阴性,两组治疗后3月和6月腹痛差异无统计学意义。结论:阿司匹林对CKD3期患者肾功能没有明显影响,可安全使用。     

Aspirin in the primary prophylaxis of venous thromboembolism in surgical patients

IntroductionVenous thromboembolism (VTE) is a common complication in surgical patients, especially those undergoing lower limb orthopaedic procedures as well as oncological resectional surgery. Numerous studies have evaluated the role of acetylsalicylic acid (ASA, aspirin) in primary VTE prevention, with contradictory results reflected in divergent guidelines. We reviewed current evidence for ASA as primary VTE prophylaxis.MethodsEnglish language studies meeting our inclusion criteria were retrieved from PubMed, EMBASE and Cochrane databases. Six studies (3 meta-analyses and 3 randomized trials) comparing ASA with placebo and 7 studies (1 meta-analysis, 5 randomized trials, and 1 prospective) comparing ASA with other anticoagulants were included in the final analysis. Retrospective studies and case reports were excluded.ResultsASA is more effective than placebo in primary VTE prevention. Although there is clinical equipoise when ASA is compared with other anticoagulants, studies specific to orthopaedic surgery suggest that ASA appears as effective as low molecular weight heparin (LMWH) and may reduce bleeding risk. Extended prophylaxis up to 4 weeks post surgery reduces VTE episodes.ConclusionsASA may be considered as a potential strategy in primary VTE prophylaxis in orthopaedic patients at high-risk of bleeding complications. Further studies comparing ASA with LMWH/oral anticoagulants in primary thromboprophylaxis following non-orthopaedic surgery are warranted.     

COXIBs and non-selective NSAIDs in the gastroenterological setting: What should patients and physicians do?

Although adverse effects of nonsteroidal anti-inflammatory drugs occur in only a small proportion of users, the widespread use of these drugs has resulted in a substantial overall number of affected persons who experience serious gastrointestinal complications. Dyspeptic symptoms are estimated to occur in 10-60% of nonsteroidal anti-inflammatory drug users and lead to discontinuation of treatment in 5-15% of rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs. It is now well established that the point prevalence of peptic ulcer disease in patients receiving conventional nonsteroidal anti-inflammatory drug therapy ranges between 10 and 30%, representing a 10- to 30-fold increase over that found in the general population. One out of 175 users of conventional nonsteroidal anti-inflammatory drugs in the USA will be hospitalized each year for nonsteroidal anti-inflammatory drug-induced gastrointestinal damage. The mortality of hospitalized patients remains about 5-10%, with an expected annual death rate of 0.08%. The selective COX-2 inhibitors consistently show comparable efficacy to that of conventional nonsteroidal anti-inflammatory drugs in patients with rheumatoid arthritis and osteoarthritis, but have a reduced propensity to cause gastrointestinal toxicity. In many cases, the gastric effects of therapeutically active doses of COX-2 inhibitors are indistinguishable from placebo. The safety benefits of COX-2 inhibitors given alone appear similar to those of combined therapy with conventional nonsteroidal anti-inflammatory drugs and gastroprotective agents. These findings warrant the consideration of COX-2 inhibitors as first-line therapy in patients requiring long-term pain control.     

Severity of Gastrointestinal Bleeding in Patients Treated with Direct-Acting Oral Anticoagulants

Background

Direct-acting oral anticoagulants (DOACs), which have gained approval for stroke prevention in nonvalvular atrial fibrillation and treatment of venous thromboembolism, have become increasingly preferred over warfarin given their predictable pharmacodynamics, lack of required monitoring, and superior outcomes. Direct-acting oral anticoagulants have been shown to be associated with an increased frequency of gastrointestinal bleeding compared with warfarin, but the severity and characteristics of gastrointestinal bleeding in these patients is poorly understood.

酪酸梭菌抗阿司匹林致小鼠胃溃 疡作用的初步研究

目的 观测酪酸梭菌是否对阿司匹林导致的胃溃疡具有预防效应,并对其机制进行初步探讨。方法 取30只健康 雄性ICR 小鼠,随机分成3 组,每组各10 只,即模型组、酪酸梭菌组、奥美拉唑组。酪酸梭菌组以6×108cfu/ 只的菌量,模型组和奥美拉唑组均予以相同体积的无菌培养基,灌胃4d 后再饥饿处理48h,然后以250mg/kg 剂量的阿司匹林灌胃造模,奥美拉唑组小鼠于造模前30min,腹腔注射奥美拉唑（13mg/kg）。造模4h 后,取胃组织分别测定SOD、CAT 活力、MDA 含量;进行常规HE 染色观察胃黏膜组织结构变化,PAS染色判断黏液量的变化,免疫组化法测定Bcl-2、Bax 表达水平。结果 模型组的SOD、CAT 活性明显降低,MDA 含量显著增加,而酪酸梭菌预处理后逆转了该趋势（P＜0.01）,与奥美拉唑组比较无统计学差异。HE染色观察,酪酸梭菌能减轻胃黏膜的病理损伤,与奥美拉唑组无统计学差异。PAS 结果提示酪酸梭菌能够增加黏液量。酪酸梭菌组的Bcl-2 表达较模型组显著增多,同时Bax 表达显著减少。结论 酪酸梭菌预处理通过抗氧化应激、增加胃黏液量、上调Bcl-2/Bax 表达比例,减轻阿司匹 林造成的胃溃疡损伤。     

丁苯酞氯化钠注射液联合双重抗血小板治疗 进展性脑梗死的临床疗效观察

目的 观察丁苯酞氯化钠注射液联合双重抗血小板治疗进展性脑梗死的临床疗效及不良反应。方法 86例急性进展性脑梗死患者随机分成治疗组和对照组。治疗组给予丁苯酞氯化钠注射液联合阿司匹林、氯吡格雷双重抗血小板治疗;对照组给予双重抗血小板治疗。在治疗前和治疗后第8及第15天行NIHSS评分和Barthel指数评分,观察并监测两组的不良反应。结果 与治疗前比较,两组患者治疗后第15天NIHSS评分显著降低,Barthel评分显著升高（P <0.05）。与治疗前比较,治疗后第8天,治疗组NIHSS评分显著下降,Barthel评分显著升高（P <0.05）。治疗组于治疗后第8及第15天比较同期对照组,NIHSS评分显著下降,Barthel评分显著升高（P <0.05）。两组患者均无严重不良反应。结论 丁苯酞氯化钠注射液联合阿司匹林、氯吡格雷双重抗血小板治疗进展性脑梗死安全有效。