Long-term Antiplatelet Treatment Research Articles

Effect of antiplatelet treatment on aneurysmal subarachnoid hemorrhage patients after endovascular treatment: a systematic review with meta-analysis.

Antiplatelet treatment (APT) has been reported to be used in some patients with aneurysmal subarachnoid hemorrhage (aSAH) after endovascular treatment, but there is controversy among different studies regarding its clinical effects. This study intends to conduct a meta-analysis to evaluate the impact of APT on aSAH patients after endovascular treatment. The PubMed, EMBASE, and Cochrane Library databases were systematically searched up to January 2022 for eligible English publications. Quality assessment was conducted for the included studies. Publication bias and heterogeneity were assessed by Egger's test and the I2 statistic, respectively. Odds ratios (ORs) with 95% confidence intervals (CIs) were calculated by meta-analysis. Robustness was checked by subgroup and sensitivity analyses. In total, 597 and 522 patients with and without APT, respectively, in 5 retrospective studies were retained for the meta-analysis. Pooled analyses showed that the APT group had a lower mortality (41/499 [8%] versus 56/402 [14%]; OR = 0.533; 95% CI, 0.347-0.820; P = 0.004) and a higher proportion of favorable clinical outcomes (400/532 [75%] versus 266/421 [63%]; OR = 1.801; 95% CI, 1.359-2.414; P = 0.000) than the control group. There was no significant difference in the incidence of hemorrhagic complications (39/564 [7%] versus 26/503 [5%]; OR = 1.386; 95% CI, 0.825-2.329; P = 0.218) between groups. Although the incidence of delayed cerebral ischemia (DCI) was significantly lower in the APT group (65/512 [13%] versus 105/447 [23%]; OR = 0.325; 95% CI, 0.107-0.988; P = 0.048), it showed substantial heterogeneity (I2 = 64.7%). Subsequent sensitivity analysis suggested that the meta-analysis was robust. Subgroup analyses revealed that long-term (> 2weeks) APT (60/479 [13%] versus 103/428 [24%]; OR = 0.212; 95% CI, 0.056-0.806; P = 0.023) significantly reduced the DCI rate and that different grouping methods in the included studies may be a source of heterogeneity. In the absence of randomized controlled trials, a meta-analysis of retrospective studies suggested that APT was associated with reduced mortality and better functional outcomes in aSAH patients after endovascular treatment without an increased incidence of hemorrhagic complications. Long-term APT was also associated with a decrease in the incidence of DCI. Well-designed randomized controlled trials are warranted and updated meta-analyses are needed to verify our findings.

Increased Let-7e expression is associated with long-term all-cause mortality and antiplatelet treatment in patients with type 2 diabetes mellitus

Abstract Background In the light of growing prevalence of type 2 diabetes mellitus (T2DM), efforts are made to discover novel biomarkers. MicroRNAs (miRNAs-miR) are non-coding RNAs used in various processes involved in regulating gene expression which play a role in platelet function. Purpose To analyze the ability of platelet-derived miRNAs in prediction of mortality and response to antiplatelet treatment among T2DM-patients. Methods 252 diabetic subjects were enrolled and were receiving either acetylsalicylic acid (ASA) 75mg (65%) or 150 mg (15%) or clopidogrel (19%). Plasma miR-126, miR-223, miR-125a-3p and Let-7e expressions were assessed by qRT-PCR and compared between the patients who survived and those who died. Median observation time was 5.9 years. Adjusted Cox-regression analysis was used for prediction of mortality. Differential miRNAs expression due to different antiplatelet treatment was analyzed. Results ROC curve analysis revealed increasing concentrations of miR-126, Let-7e and miR-125a-3p levels had a diagnostic ability for prediction of long-term all-cause mortality (c-index=0.75, p<0.001; 0.72, p<0.001; 0.72, p=0.001, respectively). Multivariate Cox regression model revealed high miR-126 and Let-7e expressions which were strong and independent predictors of all-cause long-term mortality (HR=5.08, 95% CI: 1.92–13.43; p=0.001; HR=5.94, 95% CI: 1.98–17.79; p=0.001,respectively). After including all miRNAs into one multivariate Cox regression model, only Let-7e was predictive of future occurrence of long-term all-cause death (HR=7.83, 95% CI: 1.2–51.1; p=0.032). MiR-126, Let-7e and miR-223 expressions in the clopidogrel group were significantly higher than in the ASA group (p=0.014; p=0.013; p=0.028, respectively). Conclusions Let-7e expression is a strong and independent predictor of long-term all-cause mortality among patients with T2DM. MiR-223, miR-126 and Let-7e present significant interactions with antiplatelet treatment and clinical outcomes. Funding Acknowledgement Type of funding sources: None. Figure 1Table 1

Surgical treatment for antiplatelet intracerebral hemorrhage (SAP-ICH): protocol for a prospective cohort study of emergency surgery for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment

BackgroundDespite the capability of emergency surgery to reduce the mortality of severe spontaneous intracranial hemorrhage (SSICH) patients, the effect and safety of surgical treatment for severe spontaneous intracranial hemorrhage (SSICH) patients receiving long-term oral antiplatelet treatment (LOAPT) remains unclear. In consideration of this, the cohort study is aimed at figuring out the effect and safety of emergency surgery for SSICH patients on LOAPT.MethodsAs a multicenter and prospective cohort study, it will be conducted across 7 representative clinical centers. Starting in September 2019, the observation is scheduled to be completed by December 2022, with a total of 450 SSICH patients recruited. The information on clinical, radiological, and laboratory practices will be recorded objectively. All of the patients will be monitored until death or 6 months after the occurrence of primary hemorrhage.ResultsIn this study, two comparative cohorts and an observational cohort will be set up. The primary outcome is the effect of emergency surgery, which is subject to assessment using the total mortality and comparison in the survival rate of SSICH patients on LOAPT between surgical treatment and conservative treatment. The second outcome is the safety of surgery, with the postoperative hemorrhagic complication which is compared between the operated SSICH patients on and not on LOAPT. Based on the observation of the characteristics and outcome of SSICH patients on LOAPT, the ischemic events after discontinuing LOAPT will be further addressed, and the coagulation function assessment system for operated SSICH patients on LOAPT will be established.ConclusionsIn this study, we will investigate the effect and safety of emergency surgery for SSICH patients on LOAPT, which will provide an evidence for management in the future.Ethics and disseminationThe research protocol and informed consent in this study were approved by the Institutional Review Board of Beijing Tiantan Hospital (KY2019-096-02). The results of this study are expected to be disseminated in peer-reviewed journals in 2023.Trial registrationName: Effect and safety of surgical intervention for severe spontaneous intracerebral hemorrhage patients on long-term oral antiplatelet treatment.ChiCTR1900024406. Date of registration is July 10, 2019.

Evaluation of treatment adaptation for low response to ASA in vascular surgery

HintergrundEine verminderte antithrombozytäre Prophylaxe („Low-Response [LR]“/„high on-treatment platelet reactivity [HPR]“) mit Acetylsalicylsäure (ASS) ist mit einem erhöhten Risiko für thrombembolische Ereignisse assoziiert. Die Prävalenz einer Low-Response ist mit ca. 20 % häufig und ein Therapieregime wurde bisher noch nicht etabliert. Das Ziel dieser prospektiven Studie war es, die Effektivität eines Therapieschemas zur Therapieanpassung bei detektierter LR/HPR bei gefäßchirurgischen Patienten zu evaluieren.MethodikInsgesamt wurden 36 gefäßchirurgischen Patienten mit einer antithrombozytären Dauermedikation mit ASS 100 mg/Tag und einer nachgewiesenen ASS-Low-Response (ALR) in die Studie eingeschlossen. Entsprechend dem festgelegten Therapieplan wurde bei diesen Patienten eine Therapieanpassung durchgeführt und eine Kontrollaggregometrie zur Erfolgskontrolle durchgeführt. Das verwendete Therapieschema folgte dem Test-and-treat-Prinzip. Zur Beurteilung der Wirkung von ASS diente die Impedanzaggregometrie mittels Mehrelektrodenaggregometer (Multiplate).ErgebnisseInsgesamt konnten alle 36 Patienten erfolgreich in eine Response überführt werden. Bei 32 (88,89 %) Patienten erfolgte eine Dosiserhöhung auf 300 mg ASS, 2 (5,56 %) Patienten wurden von ASS auf Clopidogrel umgestellt. Bei weiteren 2 (5,56 %) Patienten wurde auf eine orale Antikoagulation mit Phenprocoumon aufgrund anderer Indikationen umgestellt. Blutungskomplikationen oder Nebenwirkungen traten nicht auf.SchlussfolgerungDas gewählte Therapieschema zur Behandlung einer Low-Response erwies sich als effektiv und sicher bei gefäßchirurgischen Patienten. Überwiegend führte eine leitliniengerechte Dosiserhöhung der Prophylaxe von 100 mg auf 300 mg ASS zu einer effektiven Thrombozytenaggregationshemmung in der Aggregometrie.

SEDAR-SEMICYUC consensus recommendations on the management of haemostasis disorders in severely ill patients with COVID-19 infection

The infection by the coronavirus SARS-CoV-2, which causes the disease called COVID-19, mainly causes alterations in the respiratory system. In severely ill patients, the disease often evolves into an acute respiratory distress syndrome that can predispose patients to a state of hypercoagulability, with thrombosis at both venous and arterial levels. This predisposition presents a multifactorial physiopathology, related to hypoxia as well as to the severe inflammatory process linked to this pathology, including the additional thrombotic factors present in many of the patients.In view of the need to optimise the management of hypercoagulability, the working groups of the Scientific Societies of Anaesthesiology-Resuscitation and Pain Therapy (SEDAR) and of Intensive, Critical Care Medicine and Coronary Units (SEMICYUC) have developed a consensus to establish guidelines for actions to be taken against alterations in haemostasis observed in severely ill patients with COVID-19. These recommendations include prophylaxis of venous thromboembolic disease in these patients, and in the peripartum, management of patients on long-term antiplatelet or anticoagulant treatment, bleeding complications in the course of the disease, and the interpretation of general alterations in haemostasis.

Evaluation of the use of anti-platelet therapy throughout the peri-operative period in patients with femoral neck fracture surgery. A retrospective cohort study.

Fracture neck of femur (hip fracture) is a very common problem among old age group. Such elderly patients usually have some comorbidities for which they may use anti-platelet therapy (such as clopidogrel, aspirin, or others) for long duration (chronic use). These anti-platelet medications might make the blood thin and increase bleeding tendency. So, if these elderly people present with fracture neck of femur requiring surgical intervention, they might be at increased risk of bleeding and other complications if the use of these anti-platelet agents was continued throughout the peri-operative period. This current study aims to find out whether it is safe or not to continue the use of anti-platelet drugs during the peri-operative period in patients with hip fracture surgery. If it is safe and there are no complications, then there is no harm to continue the use of these drugs peri-operatively without any surgical delay. But if it is unsafe and there is increased risk of bleeding or blood transfusion or other complications, then such medications must be stopped peri-operatively. Thus, the medical practice and care will be improved to achieve patient safety. It was a retrospective study which reviewed files and notes of patients who had hip fracture surgery. These patients were divided into 2 groups. First group was on long-term anti-platelet treatment (APTG), and the use of these medicines continued during the peri-operative phase. The second group was not on anti-platelet treatment at all (NAPTG). Then, a comparison was done between both groups in terms of the following parameters during the peri-operative (pre- and post-operative) period: (i) intra-operative blood loss, (ii) operative time in minutes (length of surgery), (iii) pre-operative haemoglobin level, (iv) the need for blood transfusion, (v) haematoma formation, (vi) re-operation for any reason, (vii) post-operative wound infection, and (viii) duration in days to achieve complete wound healing post-operatively. So these measures are good parameters to assess bleeding tendency and bleeding risk. Data was collected, and statistical analysis was done using Pearson's chi-squared test and independent sample t test as appropriate. 325 participants were enrolled in the study. There were 163 patients in the APTG (Anti-Platelet Treatment Group) and 162 patients in the NAPTG (Non-Anti-Platelet Treatment Group). It has been found that there was no statistically significant difference between the APTG and NAPTG in terms of these peri-operative parameters: (i) intra-operative blood loss, (ii) operative time in minutes (length of surgery), (iii) pre-operative haemoglobin level, (iv) the need for blood transfusion, (v) haematoma formation, (vi) re-operation for any reason, (vii) post-operative wound infection, and (viii) duration in days to achieve complete wound healing post-operatively (P > 0.650). It is safe to continue the use of anti-platelet therapy throughout the peri-operative phase in patients with hip fracture surgery. The continuation of such therapy is not associated with increased risk of bleeding or blood transfusion or other complications in patients who had surgical treatment for femoral neck fracture.

Antithrombotic Therapy for Peripheral Revascularisation.

Lower extremity artery disease (LEAD) represents a major public health burden, affecting hundreds of millions of people worldwide. Although risk-factor modification, exercise training and medical treatment are the mainstays of the management of LEAD, endovascular or surgical revascularisation is recommended when there is the risk of limb amputation and when drug-resistant claudication severely affects patient lifestyle. Over recent years, the number of peripheral vascular interventions (PVI) has soared worldwide, driven by the improvements in endovascular techniques and devices. This growth was accompanied by a large number of clinical trials aimed at assessing the safety and efficacy of the various revascularisation modalities, while very little evidence was collected regarding the best antithrombotic treatment in patients undergoing peripheral revascularisation. In particular, considering the extensive length of diseased vessels usually treated in PVI, an optimised approach to both platelet function and coagulation cascade is of paramount importance. However, the role of antiplatelet and anticoagulant drugs following lower extremity revascularisation is largely extrapolated from the coronary field. Current guidelines recommend long-term single antiplatelet treatment for the majority of both endovascular and surgical revascularisation procedures, preceded by an initial short-term dual antiplatelet treatment in case of PVI. We present an overview of the indications and techniques of both endovascular and surgical peripheral revascularisation, followed by an in-depth analysis of the available evidence regarding type and duration of antiplatelet and anticoagulant treatment following revascularisation.

Costs of bleeding on long-term antiplatelet treatment without routine co-prescription of proton-pump inhibitors.

Long-term antiplatelet treatment is associated with major bleeding. To determine the costs associated with major bleeding in patients treated with aspirin-based antiplatelet treatment for secondary prevention of vascular events without routine prescription of proton-pump inhibitors and to estimate the likely long-term savings from routine co-prescription. In a prospective population-based cohort study of TIA, ischemic stroke, and MI treated with antiplatelet drugs, we evaluated hospital care costs associated with bleed management during 10-year follow-up. Bleeding-associated costs were averaged across all patients. For upper GI-bleeds, mean costs were compared with the cost of routine co-prescription of proton-pump inhibitor. Among 3166 patients on antiplatelet therapy with 405 first bleeding events, the average cost of major bleeding was $13,093 (S.D. 20,501), with similar costs for upper GI bleeds and intracranial bleeds (p = 0.235). However, total costs among the 3166 patients were higher for upper GI bleeds ($1,158,385 vs. $740,123). Averaged across all patients, the 10-year cost of major bleeding was $838 (95%CI: 680-1007), $411 due to upper GI bleeding, the cost of which increased from $175 in those aged <75 years to $644 at age ≥75 years (p < 0.0001). The corresponding costs of routine life-long co-prescription of proton-pump inhibitor to those patients not on prior treatment were $85 (84-88) and $39 (38-42). In secondary prevention with aspirin-based antiplatelet treatment without routine proton-pump inhibitor use, the long-term costs of upper-GI bleeding at age ≥75 years are much higher than at younger age groups, and are at least 10-fold greater than the drug cost of routine co-prescription of proton-pump inhibitor.

Age-specific risks, severity, time course, and outcome of bleeding on long-term antiplatelet treatment after vascular events: a population-based cohort study

SummaryBackgroundLifelong antiplatelet treatment is recommended after ischaemic vascular events, on the basis of trials done mainly in patients younger than 75 years. Upper gastrointestinal bleeding is a serious complication, but had low case fatality in trials of aspirin and is not generally thought to cause long-term disability. Consequently, although co-prescription of proton-pump inhibitors (PPIs) reduces upper gastrointestinal bleeds by 70–90%, uptake is low and guidelines are conflicting. We aimed to assess the risk, time course, and outcomes of bleeding on antiplatelet treatment for secondary prevention in patients of all ages.MethodsWe did a prospective population-based cohort study in patients with a first transient ischaemic attack, ischaemic stroke, or myocardial infarction treated with antiplatelet drugs (mainly aspirin based, without routine PPI use) after the event in the Oxford Vascular Study from 2002 to 2012, with follow-up until 2013. We determined type, severity, outcome (disability or death), and time course of bleeding requiring medical attention by face-to-face follow-up for 10 years. We estimated age-specific numbers needed to treat (NNT) to prevent upper gastrointestinal bleeding with routine PPI co-prescription on the basis of Kaplan–Meier risk estimates and relative risk reduction estimates from previous trials.Findings3166 patients (1582 [50%] aged ≥75 years) had 405 first bleeding events (n=218 gastrointestinal, n=45 intracranial, and n=142 other) during 13 509 patient-years of follow-up. Of the 314 patients (78%) with bleeds admitted to hospital, 117 (37%) were missed by administrative coding. Risk of non-major bleeding was unrelated to age, but major bleeding increased steeply with age (≥75 years hazard ratio [HR] 3·10, 95% CI 2·27–4·24; p<0·0001), particularly for fatal bleeds (5·53, 2·65–11·54; p<0·0001), and was sustained during long-term follow-up. The same was true of major upper gastrointestinal bleeds (≥75 years HR 4·13, 2·60–6·57; p<0·0001), particularly if disabling or fatal (10·26, 4·37–24·13; p<0·0001). At age 75 years or older, major upper gastrointestinal bleeds were mostly disabling or fatal (45 [62%] of 73 patients vs 101 [47%] of 213 patients with recurrent ischaemic stroke), and outnumbered disabling or fatal intracerebral haemorrhage (n=45 vs n=18), with an absolute risk of 9·15 (95% CI 6·67–12·24) per 1000 patient-years. The estimated NNT for routine PPI use to prevent one disabling or fatal upper gastrointestinal bleed over 5 years fell from 338 for individuals younger than 65 years, to 25 for individuals aged 85 years or older.InterpretationIn patients receiving aspirin-based antiplatelet treatment without routine PPI use, the long-term risk of major bleeding is higher and more sustained in older patients in practice than in the younger patients in previous trials, with a substantial risk of disabling or fatal upper gastrointestinal bleeding. Given that half of the major bleeds in patients aged 75 years or older were upper gastrointestinal, the estimated NNT for routine PPI use to prevent such bleeds is low, and co-prescription should be encouraged.FundingWellcome Trust, Wolfson Foundation, British Heart Foundation, Dunhill Medical Trust, National Institute of Health Research (NIHR), and the NIHR Oxford Biomedical Research Centre.

Cerebral Arteriopathies, Venous Thrombosis, and Migraine.

AbstractIn this article, the authors review stroke preventive strategies in a diverse group of conditions, namely the nonatherosclerotic cerebral arteriopathies, migraine-associated or migraine-induced stroke, and cerebral venous sinus thrombosis. Although these conditions are less common causes of stroke in the aggregate, they are frequent causes of stroke in teenagers and young adults. Aside from posing unique diagnostic challenges, their management is limited by the absence of randomized clinical trials or high-level evidence that is specific to these conditions. Therapeutic decision-making is largely based on expert opinion, clinical experience, and retrospective studies; it is often empiric. It remains uncertain whether otherwise routine secondary stroke-preventive strategies, such as long-term antiplatelet treatment, lipid-lowering medications, and antihypertensive agents, are applicable to patients with stroke from a cerebral arteriopathy or migraine-associated stroke.

Bleeding in patients on long-term antiplatelet treatment

Bleeding in patients on long-term antiplatelet treatment

Antiplatelet Treatment in Stroke: New Insights.

Stroke is a feared vascular event among healthy people and those with cardiovascular disease, and holds a leading position as a cause of disability and death worldwide. Antiplatelet therapy is central in the management of patients with ischemic nonembolic stroke and transient ischemic attacks. In this narrative review, we provide an overview and update of evidence regarding antiplatelet treatment in the primary and secondary prevention of stroke. Aspirin, clopidogrel and aspirin plus dipyridamole are the mainstays of antiplatelet treatment post-stroke, while promising agents include triflusal, cilostazol and ticagrelor. Available data are in favor of dual antiplatelet treatment in the early treatment of atherosclerotic large vessel disease. Long-term dual antiplatelet treatment should be individualized keeping in mind the higher rates of bleeding complications. Treatment with an antiplatelet agent is recommended to reduce recurrent stroke and death in patients with a non-cardioembolic ischemic stroke or transient ischemic attack. Moreover, clinicians should carefully assess the pros and cons in each case and individualize the need for prolonged dual antiplatelet therapy.

Clopidogrel Treatment Is Associated with a Decrease in Cancer Incidence

Introduction: Multiple studies have shown an association between aspirin treatment and a reduced incidence of cancer. An antiplatelet effect is one of the hypotheses explaining these results. Whether the antiplatelet thienopyridine drug, clopidogrel, influences the incidence of cancer is unknown.Objective: To assess the effect of clopidogrel on the incidence of cancer.Methods: A population-based historical cohort study within the HMO-Clalit Health Services population was performed. Members living in the Sharon-Shomron district ≥ 50 years were included in this cohort between January 2000 and January 2012, and followed until December 2014. We excluded patients treated with prasugrel or ticagrelor, and those diagnosed with cancer prior to or within 1 year of study inclusion. The study population was divided into 4 groups based on antiplatelet treatment with aspirin, clopidogrel, both (defined as ≥ 1 monthly prescription at any stage) or neither.To determine whether long-term antiplatelet treatment (i.e. follow-up for ≥ 5 years since the first antiplatelet dose) is associated with decreased rates of cancer (defined by ICD-9 codes), we applied a logistic regression model. With this model, the Exp(ß) was used to calculate the odds ratio (OR) and the 95% confidence interval (CI) of each type of antiplatelet treatment compared to the reference group of patients who did not receive treatment. Cox proportional hazards regression models were fitted to assess the association between the duration of time until cancer developed and the different anti-platelet treatments.Results: The study cohort included 184,781 patients with a median age of 54.9 years (range: 50-100.1), 53.7% female, 19.6% past or current smokers, and mean BMI of 31±8.3 kg/m2. Patients receiving antiplatelet drugs were older, had higher BMI and were more likely to be men and smokers, compared to patients receiving no treatment (p<0.001 for all). Long-term (≥5 years) follow up from antiplatelet treatment with clopidogrel, aspirin or both was associated with a lower risk of cancer, compared to no antiplatelet treatment (median follow up: 155 months (range, 12-179)), before and after adjustment for baseline variables (Table 1).Any duration of treatment with clopidogrel (HR 0.42, 95% CI: 0.33-0.53), aspirin (HR 0.76, 95% CI: 0.74-0.78) or both (HR 0.49, 95% CI: 0.47-0.52) was also associated with a lower risk of incident cancer (p<0.001), compared to patients who received no treatment, in multivariate analysis. The reduction in cancer incidence with clopidogrel alone was maintained in a subgroup analysis of solid cancers (OR 0.53, p=0.001) as well as gastrointestinal (GI; OR 0.45, p=0.02) and non-GI malignancies (OR 0.43, p<0.01). In an exploratory secondary analysis after adjustment for baseline variables and duration of antiplatelet treatment, patients receiving clopidogrel only, had a lower risk of cancer than the aspirin only group (HR 0.57, 95% CI: 0.36-0.91, p=0.018), on long term follow-up.Conclusions: Clopidogrel treatment, with or without aspirin, was associated with a lower risk of cancer when compared to no antiplatelet treatment. The risk of cancer was reduced with aspirin only, similar to prior studies. The effect of clopidogrel alone was at least comparable to that of aspirin, despite shorter median exposure to clopidogrel (Table 1). Our results supports the antiplatelet role in reducing the risk of cancer.Table 1The long-term risk of cancer* in subjects treated with aspirin, clopidogrel or both, compared with no antiplatelet treatmentLong-term follow-up Study Groups (N)No anti-platelet (75,624)Clopidogrel only(271)Aspirin only (64,362)Combined anti-platelet (15,103)Incidence of cancer, % (n)11.7 (8816)6.6 (18)8.8 (5692)8.5 (1286)No. of cancer cases / 1000 patient years12.85.67.67.0Median duration of follow up (range), months119 (12-179)179 (24-179)179 (12-179)179 (12-179)Median duration of antiplatelet treatment (range), monthsNA43 (1-168)87 (1-172)Aspirin: 117 (1-170); Clopidogrel 13 (1-170)Risk of cancer, HR (95% CI)Unadjusted1 (ref.)0.32 (0.20-0.51)**0.48 (0.46-0.49)**0.40 (0.37-0.42)**adjusted for: age, gender, BMI, smoking status1 (ref.)0.37 (0.23-0.58)**0.54 (0.52-0.56)**0.46 (0.44-0.49)***More than 5 years follow up from first anti platelet prescription.**p<0.001NA, not applicable DisclosuresLeader:Novartis: Research Funding.

Dual antiplatelet therapy in acute ischemic stroke.

Stroke recurrence is common in the early period after a cerebral ischemic event. Treatment with an antiplatelet agent is recommended to reduce recurrent stroke and death in patients with a non-cardioembolic ischemic stroke and transient ischemic attack. Compared to monotherapy, dual antiplatelet therapy has more robust inhibition of platelet activation but a higher risk of systemic bleeding and intracranial hemorrhage. Randomized controlled trials and meta-analyses suggest that short-term use of dual antiplatelet treatment initiated early after ischemic stroke and TIA reduces the risk of recurrent stroke and major vascular events without significantly increasing the hemorrhagic complication rates, particularly in those with large-vessel disease, while long-term dual antiplatelet treatment increases the risk of systemic and intracranial hemorrhage over time, offsetting any potential benefit. Until further data becomes available, clinicians should carefully assess this risk and benefit in each case and continually reevaluate the need for prolonged dual antiplatelet therapy.

Prevention and treatment of atherosclerosis in haemophilia - how to balance risk of bleeding with risk of ischaemic events.

Life expectancy for patients with haemophilia (PWH) has significantly increased in the last decades, due to improvement of clotting factor replacement therapy. However, despite a lower cardiovascular mortality rate and contrasting prevalence for non-fatal ischaemic heart disease (IHD), cardiovascular diseases are increasing in PWH. The prevalence of cardiovascular risk factors in PWH is as prevalent as in the general population, whereas an increased risk of hypertension has been observed in some studies. Furthermore, PWH are not protected against atherosclerosis. Coronary artery disease treatment is extremely challenging in PWH. Two 'institutional' guidelines for the management of IHD in PWH have been published. Since these recommendations, the use of new drugs such as prasugrel, ticagrelor, bivalirudin, new oral anticoagulants and new drug-eluting stents have been recommended in the general population but should be evaluated in PWH. Some questions arise: which trough level during long-term single or dual antiplatelet treatment (DAT) is really needed? The clinical role of platelet testing remains ill defined but may be considered in selected patients. A multidisciplinary approach is necessary for the management of IHD in PWH in order to treat the patient as any patient according to the cardiological guidelines during the acute phase, and long-term management should be discussed.

Effects of long-term blood pressure lowering and dual antiplatelet treatment on cognitive function in patients with recent lacunar stroke: a secondary analysis from the SPS3 randomised trial

The primary outcome results for the SPS3 trial suggested that a lower systolic target blood pressure (<130 mm Hg) might be beneficial for reducing the risk of recurrent stroke compared with a higher target (130-149 mm Hg), but that the addition of clopidogrel to aspirin was not beneficial compared with aspirin plus placebo. In this prespecified secondary outcome analysis of the SPS3 trial, we aimed to assess whether blood pressure reduction and dual antiplatelet treatment affect changes in cognitive function over time in patients with cerebral small vessel disease. In the SPS3 trial, patients with recent (within 6 months) symptomatic lacunar infarcts from 81 centres in North America, Latin America, and Spain were randomly assigned, in a two-by-two factorial design, to target levels of systolic blood pressure (1:1; 130-149 mm Hg vs <130 mm Hg; open-label) and to a once-daily antiplatelet treatment (1:1; aspirin 325 mg plus clopidogrel 75 mg vs aspirin 325 mg plus placebo; double-blind). For this analysis, the main cognitive outcome was change in Cognitive Abilities Screening Instrument (CASI) during follow-up. Patients were tested annually for up to 5 years, during which time the mean difference in systolic blood pressure was 11 mm Hg (SD 16) between the two targets (138 mm Hg vs 127 mm Hg at 1 year). We used linear mixed models to compare changes in CASI Z scores over time. The SPS3 trial is registered with ClinicalTrials.gov, number NCT00059306. The study took place between March 23, 2003, and April 30, 2012. 2916 of 3020 SPS3 participants (mean age 63 years [SD 11]) with CASI scores at study entry were included in the analysis, with a median follow-up of 3·0 years (IQR 1·0-4·9). Mean changes in CASI Z scores from study entry to assessment at years 1 (n=2472), 2 (n=1968), 3 (n=1521), 4 (n=1135), and 5 (n=803) were 0·12 (SD 0·83), 0·15 (0·84), 0·16 (0·95), 0·19 (0·99), and 0·14 (1·09), respectively. Changes in CASI Z scores over time did not differ between assigned antiplatelet groups (p=0·858) or between assigned blood pressure target groups (p=0·520). There was no interaction between assigned antiplatelet groups and assigned blood pressure target groups and change over time (p=0·196). Cognitive function is not affected by short-term dual antiplatelet treatment or blood pressure reduction in fairly young patients with recent lacunar stroke. Future studies of cognitive function after stroke should be of longer duration or focus on patients with higher rates of cognitive decline. US National Institute of Neurological Disorders and Stroke.

Long-term dual antiplatelet treatment and bleeding complications in diabetic patients treated with drug eluting stent implantation

BackgroundDual antiplatelet treatment (DAPLT) for at least 12months is recommended after drug eluting stent (DES) implantation, but concerns regarding the extended use of this treatment persist due to increased risk of bleeding. In this study are assessed the incidence, correlates, and clinical significance of bleeding complications in diabetic patients after long-term DAPLT post DES implantation. MethodsWe studied 610 consecutive diabetic patients after DES implantation. The primary end point was the occurrence of any bleeding according to the BARC and TIMI definitions. ResultsThe incidence of overall bleeding was higher in patients on DAPLT (21.1% vs. 4.4%, p<0.001); minor/minimal according to the TIMI definition, and type 1 or 2 according to the BARC definition, were more frequently observed in patients on DAPLT (20.3% vs. 3.0%, p<0.001, 15.6% vs. 2.0%, p<0.001 and 4.4% vs. 0.5%, p=0.034, respectively), whereas there was no effect on type 3 (3.5% vs. 2.0%, p=ns). DAPLT was an independent predictor for overall (HR 5.35, 95% CI: 2.69–10.67, p<0.001), minor (HR 7.45, 95% CI: 3.25–17.12, p<0.001, for TIMI classification) and type 1 or 2 bleeding (HR 8.17, 95% CI 3.29–20.25, p<0.001); furthermore smoking was also predictor for overall bleeding (HR 1.65, 95% CI: 1.05–2.61, p=0.030). Cardiovascular adverse events were not more frequent in patients with bleeding as compared with those without bleeding. ConclusionsLong-term DAPLT in diabetic patients after DES implantation is associated with higher risk of overall and minor but not major bleeding; smoking may have a significant role in the occurrence of bleeding complications.

030: Incidence and predictors of bleeding complications in diabetic patients during long-term follow-up after DES implantation

We investigate the frequency, correlates, and clinical significance of bleeding complications in diabetic patients (pts) with long-term dual antiplatelet treatment (DAPLT) after drug-eluting stent (DES) implantation. We assessed 610 consecutive diabetic pts (male 80%, mean age 65±9 years) after DES implantation. Five years clinical follow-up (FU), obtained in 587/610 (96%) of them. At the end of FU, 211 (36%) pts were on single APLT (SAPLT) and 376 (64%) on DAPLT. Bleeding complications were defined according to PLATO and TIMI definitions The incidence of bleeding was higher in DAPLT pts (14.6% vs 3.8%, p<0.0001). Minor bleeding according to PLATO occurred in 1.9% of pts on SAPLT and 11.7% on DAPLT (p<0.0001) and according to TIMI in 2.4% vs 13.6% respectively (p< 0.0001). Major bleeding according to PLATO presented the 1.9% of pts on SAPLT and 2.9% on DAPLT; according to TIMI the incidence of major bleeding was 1.4% and 1.1% respectively (p:NS for both PLATO and TIMI definitions). The incidence of cardiovascular adverse events was similar between pts with bleeding as compared with those without bleeding. In a multivariable analysis, smoking was an independent predictor for overall as well as major bleeding according to PLATO (HR 6.2, 95% CI 1.2-30.4, p=0.024), whereas DAPLT was an independent predictor for overall and minor bleeding (HR 6.2, 95% CI 2.2–17.3, p<0.0001) Long-term DAPLT in diabetic patients treated with DES is associated with higher risk of overall and minor but not major bleeding. Smoking was an independent predictor for overall bleeding and major bleeding according to PLATO definitions

Abstract 9755: Bleeding Complications During Long-term Dual Antiplatelet Treatment In Diabetic Patients Treated With 1 St Generation Drug Eluting Stent Implantation

Background: Dual antiplatelet treatment (DAPLT) for at least 12 months is recommended after drug-eluting stent (DES) implantation. We investigate the frequency, correlates, and clinical significance of bleeding complications in diabetic patients (pts) on long-term DAPLT (5 years) after 1 st generation DES implantation. Methods: We assessed 610 consecutive diabetes mellitus (DM) pts (male 80%, mean age 65±9 years) after 1 st generation DES implantation (sirolimus 80%, paclitaxel 10%, combination 10%). Five years clinical follow-up (FU), obtained in 587/610 (96%) of them; at the end of FU, 211(36%) pts were on single APLT (SAPLT) and 376 (64%) on DAPLT. Bleeding complications were defined according to PLATO and TIMI definitions. Hard end-point (HEP) was considered the combination of death, non-fatal myocardial infarction, and cerebrovascular accident; stent thrombosis (ST) is assessed according to ARC definition. Results: There was no difference in the incidence of ST and HEP in pts treated with DAPLT vs. SAPLT. The incidence of bleeding was higher on DAPLT pts (14.6% vs 3.8%, p &lt; 0.0001). Minor bleeding according to PLATO occurred in 1.9% of pts on SAPLT and 11.7% on DAPLT (p&lt;0.0001) and according to TIMI in 2.4% vs. 13.6% respectively (p&lt; 0.0001). Major bleeding according to PLATO presented the 1.9% of pts on SAPLT and 2.9% on DAPLT (p: NS); according to TIMI the incidence of major bleeding was 1.4% and 1.1% respectively (p: NS). The incidence of cardiovascular adverse events was similar between pts with bleeding as compared with those without bleeding. In a multivariable analysis, smoking was an independent predictor for overall as well as major bleeding according to PLATO (HR 6.2, 95% CI 1.2-30.4, p=0.024), whereas DAPLT was an independent predictor for overall and minor bleeding (HR 6.2, 95% CI 2.2-17.3, p&lt;0.0001) Conclusions: Long-term DAPLT in DM pts treated with 1 st generation DES is associated with higher risk of overall and minor but not major bleeding. Smoking was an independent predictor for overall and major bleeding according to PLATO definitions.

Markers of hypercoagulability in CAD patients. Effects of single aspirin and clopidogrel treatment.

BackgroundCardiovascular disease with disturbances in the haemostatic system, might lead to thrombotic complications with clinical manifestations like acute myocardial infarction (AMI) and stroke. Activation of the coagulation cascade with subsequent increased thrombin generation, characterizes a prothrombotic phenotype. In the present study we investigated whether prothrombotic markers were associated with risk factors and clinical subgroups in a cohort of patients with angiographically verified coronary artery disease (CAD). The patients were randomized to long-term treatment with the antiplatelet drugs aspirin or clopidogrel, and we further investigated the effect on hypercoagulability of such treatment for 1 year, of which limited data exists.MethodsVenous blood samples were collected in fasting condition between 08:00 and 10:30 am, at baseline when all patients were on aspirin therapy (n = 1001) and in 276 patients after 1 year follow-up on aspirin or clopidogrel. In vivo thrombin generation was assessed by prothrombin fragment 1 + 2 (F1+2) and D-dimer, and the endogenous thrombin potentiale (ETP) in the calibrated automated thrombogram (CAT) assay, representing ex vivo thrombin generation. In addition soluble tissue factor (sTF) and free- and total tissue factor pathway inhibitor (TFPI) were measured.ResultsWe found age to be significantly associated with F1+2 and D-dimer (β = 0.229 and β =0.417 respectively, p <0.001, both). Otherwise, only weak associations were found. F1+2 and D-dimer were higher in women compared to men (p <0.001 and p = 0.033, respectively). Smokers had elevated levels of ETP compared to non-smokers (p = 0.014). Additionally, patients on renin-angiotensin system (RAS) inhibition showed significantly higher levels of F1+2, compared to non-users (p = 0.013). Both aspirin and clopidogrel reduced levels of ETP after 12 months intervention (p = 0.003 and p <0.001, respectively) and the levels of F1+2 were significantly more reduced on aspirin compared to clopidogrel (p = 0.023).ConclusionsIn the present population of stable CAD, we could demonstrate a more hypercoagulable profile among women, smokers and patients on RAS medication, assessed by the prothrombotic markers F1+2, D-dimer and ETP. Long-term antiplatelet treatment with aspirin alone seems to attenuate thrombin generation to a greater extent than with clopidogrel alone. The study is registered at http://www.clinicaltrials.gov: NCT00222261.