Oral anticoagulants (OACs) and aspirin can trigger bleeding events when used alone or in combination. The purpose of this study was to compare the risk of any type of bleeding in individuals exposed to a combination of OAC and aspirin with the risk in those taking an OAC or aspirin alone.

MEDLINE and Web of Science were queried in January 2021 for eligible articles. Studies were included if they were either randomized controlled trials (RCTs) or observational studies and evaluated the number of any bleeding events in two groups, one with exposure to both OAC and aspirin and one with exposure to OAC alone or aspirin alone. Pooled odds ratios were calculated using a random-effects model.

Forty-two studies were included. In an analysis of 15 RCTs and 19 observational studies evaluating OAC plus aspirin versus OAC alone, a significant difference in the risk of bleeding was observed in the combination groups, with an odds ratio [OR] of, 1.36 (95% CI, 1.15-1.59) for RCTs and an OR of 1.42 (95% CI-, 1.09-1.87) for observational studies. When OAC plus aspirin was compared to aspirin alone, a higher rate of bleeding was found in the combination group (OR, 2.36; 95%CI, 1.91-2.92) in the analysis of 15 RCTs, but no significant difference was found among 10 observational studies (OR, 1.93; 95% Cl, 0.99-3.75).

The risk of any type of bleeding was significantly increased among patients taking aspirin plus OAC compared to those taking OAC alone in both RCTs and observational studies. Evaluation of RCTs comparing OAC plus aspirin to aspirin alone suggests increased bleeding risk as well.

A marked prolongation of the prothrombin time-international normalized ratio (PT-INR) is frequently observed during biliary obstruction in patients using warfarin. The objective of this study was to identify factors associated with PT-INR prolongation during biliary obstruction in patients using warfarin.

Among 44 patients using warfarin who had biliary obstruction, we retrospectively investigated warfarin doses and laboratory data before and during biliary obstruction. The primary outcome was the association between changes in PT-INR (ΔPT-INR) and changes in laboratory data before and during biliary obstruction.

Median PT-INR was 1.59 (IQR 1.38-1.95) before biliary obstruction and 2.27 (IQR 1.60-3.49) during biliary obstruction, indicating significant prolongation during the obstruction (P < 0.001). ΔPT-INR showed strong positive correlations with change in total bilirubin (ΔT-Bil; ρ = 0.692, P < 0.001) and change in conjugated bilirubin (ΔC-Bil; ρ = 0.731, P < 0.001). ΔPT-INR showed a weak negative correlation with the change in albumin (ΔAlb; ρ =  -0.371, P < 0.05). When ΔPT-INR was used as the dependent variable in multiple linear regression analysis, ΔT-Bil, ΔC-Bil, and ΔAlb were significantly associated with ΔPT-INR.

PT-INR was prolonged during biliary obstruction in patients using warfarin, and changes in bilirubin levels were associated with ΔPT-INR. If biliary obstruction with markedly elevated bilirubin levels occurs, measuring PT-INR could lead to safer warfarin therapy.

The choice of antithrombotic therapy, anticoagulants or antiplatelets, after prosthetic heart valve replacement or repair, remains a disputed topic in the literature. Antithrombotic therapies are used after heart valve intervention to reduce the rates of thromboembolic events, therefore improving patient outcomes. Different interventions may require different therapeutic regimens to achieve the most efficacious clinical outcome for patients.

This review aims to summarize and critique the available literature concerning therapeutic agents used for bioprosthetic and mechanical valves as well as for valve repair, so as to assist clinicians and researchers in making decisions with regard to their patients and research endeavors.

Anticoagulation control has been associated with risk of thromboembolism and hemorrhage. Herein, we explore the relationship between anticoagulation control achieved in left ventricular assist device (LVAD) patients and evaluate the association with risk of thromboembolism and hemorrhage. Patients (19 years old or older) with a continuous flow LVAD placed from 2006 to 2012. Percent time spent in target range (PTTR) for international normalized ratio (INR) was estimated with target range of 2.0-3.0. Proportion of time spent in target range was categorized into PTTR > 60%, PTTR ≥ 50 < 60%, and PTTR < 50%. The relationship between PTTR and thromboembolism and hemorrhage was assessed. One hundred fifteen participants contributed 624.5 months of follow-up time. Only 20% of patients achieved anticoagulation control (PTTR > 60% for INR range of 2-3). After adjusting for chronic kidney disease, history of diabetes, history of atrial fibrillation, and age at implant, compared with patients with PTTR < 50%, the relative risk of thromboembolism in patients with PTTR ≥ 60% (hazard ratio [HR]: 0.37; 95% confidence interval [CI]: 0.14-0.96; p = 0.042) was significantly lower, but not for patients with a PTTR of ≥ 50 < 60% (HR: 0.21; 95% CI: 0.02-1.82; p = 0.16). The relative risk for hemorrhage was also significantly lower among patients with a PTTR ≥ 60% (HR: 0.45; 95% CI: 0.21-0.98; p = 0.045), but not among those with PTTR of ≥ 50 < 60% (HR: 0.47; 95% CI: 0.14-1.56; p = 0.22). This current study demonstrates that LVAD patients remain in the INR target range an average of 42.9% of the time. To our knowledge, this is the first report with regard to anticoagulation control as assessed by PTTR and its association with thromboembolism, hemorrhage, or death among patients with ventricular assist devices (VADs).

Despite the frequent use of antiplatelet medication (AM) in the elderly patients, very few studies have investigated its prescription. We describe AM prescription through retrospective study in ambulatory elderly patients.

All subjects aged over 80 years with a medical prescription delivered in March 2015 and affiliated to the Mutualité Sociale Agricole de Bourgogne. Subjects with prescriptions for AM were compared with those without.

A total of 15 141 ambulatory elderly patients (83-89 years, 61.3% of women) were included and 4412 (29.14%) had a prescription for AM. The latter were more frequently men than those without AM (43% vs 36.93%, P < .0001) and more frequently had chronic comorbidities (77.24% vs 64.65%, P < .0001). Compared with ambulatory subjects without AM, those with AM more frequently had coronary heart disease (35.15% vs 14.49%), severe hypertension (30% vs 25.65%), diabetes (27.42% vs 20.64%), peripheral arterial diseases (16.28% vs 5.96%) and disabling stroke (9% vs 5.56% (all P < .0001). In addition, they had more prescriptions of beta-blockers (45.24% vs 36.90%), angiotensin conversion enzyme inhibitor (31.35% vs 25.44%), calcium channel blockers (33.34% vs 27.90%), nitrate derivatives (10.6% vs 6.03%) or hypolipidemic agents (HA; 49.81% vs 29.72%) (all P < .0001) than those without AM.

In this study, which is very interested for its size and the advanced age of the subjects, long-course AM was prescribed in one third of ambulatory elderly patients. Coronary heart disease, severe hypertension and diabetes were more frequent in AM subjects. However, the low percentage of declared strokes was surprising. We provide additional data to doctors following subjects with AM.

Cardiac and thoracic surgery are associated with an increased risk of venous thromboembolism (VTE). The safety and efficacy of primary thromboprophylaxis in patients undergoing these types of surgery is uncertain.

To assess the effects of primary thromboprophylaxis on the incidence of symptomatic VTE and major bleeding in patients undergoing cardiac or thoracic surgery.

The Cochrane Peripheral Vascular Diseases Group Trials Search Co-ordinator searched the Specialised Register (last searched May 2014) and CENTRAL (2014, Issue 4). The authors searched the reference lists of relevant studies, conference proceedings, and clinical trial registries.

Randomised controlled trials (RCTs) and quasi-RCTs comparing any oral or parenteral anticoagulant or mechanical intervention to no intervention or placebo, or comparing two different anticoagulants.

We extracted data on methodological quality, participant characteristics, interventions, and outcomes including symptomatic VTE and major bleeding as the primary effectiveness and safety outcomes, respectively.

We identified 12 RCTs and one quasi-RCT (6923 participants), six for cardiac surgery (3359 participants) and seven for thoracic surgery (3564 participants). No study evaluated fondaparinux, the new oral direct thrombin, direct factor Xa inhibitors, or caval filters. All studies had major study design flaws and most lacked a placebo or no treatment control group. We typically graded the quality of the overall body of evidence for the various outcomes and comparisons as low, due to imprecise estimates of effect and risk of bias. We could not pool data because of the different comparisons and the lack of data. In cardiac surgery, 71 symptomatic VTEs occurred in 3040 participants from four studies. In a study of 2551 participants, representing 85% of the review population in cardiac surgery, the combination of unfractionated heparin with pneumatic compression stockings was associated with a 61% reduction of symptomatic VTE compared to unfractionated heparin alone (1.5% versus 4.0%; risk ratio (RR) 0.39; 95% confidence interval (CI) 0.23 to 0.64). Major bleeding was only reported in one study, which found a higher incidence with vitamin K antagonists compared to platelet inhibitors (11.3% versus 1.6%, RR 7.06; 95% CI 1.64 to 30.40). In thoracic surgery, 15 symptomatic VTEs occurred in 2890 participants from six studies. In the largest study evaluating unfractionated heparin versus an inactive control the rates of symptomatic VTE were 0.7% versus 0%, respectively, giving a RR of 6.71 (95% CI 0.40 to 112.65). There was insufficient evidence to determine if there was a difference in the risk of major bleeding from two studies evaluating fixed-dose versus weight-adjusted low molecular weight heparin (2.7% versus 8.1%, RR 0.33; 95% CI 0.07 to 1.60) and unfractionated heparin versus low molecular weight heparin (6% and 4%, RR 1.50; 95% CI 0.26 to 8.60).

The evidence regarding the efficacy and safety of thromboprophylaxis in cardiac and thoracic surgery is limited. Data for important outcomes such as pulmonary embolism or major bleeding were often lacking. Given the uncertainties around the benefit-to-risk balance, no conclusions can be drawn and a case-by-case risk evaluation of VTE and bleeding remains preferable.

It is unclear whether participation in a randomized controlled trial (RCT), irrespective of assigned treatment, is harmful or beneficial to participants. We compared outcomes for patients with the same diagnoses who did ("insiders") and did not ("outsiders") enter RCTs, without regard to the specific therapies received for their respective diagnoses.

By searching the MEDLINE (1966-2010), Embase (1980-2010), CENTRAL (1960-2010) and PsycINFO (1880-2010) databases, we identified 147 studies that reported the health outcomes of "insiders" and a group of parallel or consecutive "outsiders" within the same time period. We prepared a narrative review and, as appropriate, meta-analyses of patients' outcomes.

We found no clinically or statistically significant differences in outcomes between "insiders" and "outsiders" in the 23 studies in which the experimental intervention was ineffective (standard mean difference in continuous outcomes -0.03, 95% confidence interval [CI] -0.1 to 0.04) or in the 7 studies in which the experimental intervention was effective and was received by both "insiders" and "outsiders" (mean difference 0.04, 95% CI -0.04 to 0.13). However, in 9 studies in which an effective intervention was received only by "insiders," the "outsiders" experienced significantly worse health outcomes (mean difference -0.36, 95% CI -0.61 to -0.12).

We found no evidence to support clinically important overall harm or benefit arising from participation in RCTs. This conclusion refutes earlier claims that trial participants are at increased risk of harm.

Patients with prosthetic heart valves are at increased risk for valve thrombosis and arterial thromboembolism. Oral anticoagulation alone, or the addition of antiplatelet drugs, has been used to minimise this risk. An important issue is the effectiveness and safety of the latter strategy.

This is an update of our previous review; the goal was to create a valid synthesis of all available, methodologically sound data to further assess the safety and efficacy of combined oral anticoagulant and antiplatelet therapy versus oral anticoagulant monotherapy in patients with prosthetic heart valves.

We updated the previous searches from 2003 and 2010 on 16 January 2013 and searched the Cochrane Central Register of Controlled Trials (CENTRAL) on The Cochrane Library (2012, Issue 12), MEDLINE (OVID, 1946 to January Week 1 2013), and EMBASE (OVID, 1980 to 2013 Week 02). We have also looked at reference lists of individual reports, review articles, meta-analyses, and consensus statements. We included reports published in any language or in abstract form.

All reports of randomised controlled trials comparing standard-dose oral anticoagulation to standard-dose oral anticoagulation and antiplatelet therapy in patients with one or more prosthetic heart valves.

Two review authors independently performed the search strategy, assessed trials for inclusion and study quality, and extracted data. We collected adverse effects information from the trials.

One new study has been identified and included in this update. In total, 13 studies involving 4122 participants were included in this review update. Years of publication ranged from 1971 to 2011. Compared with anticoagulation alone, the addition of an antiplatelet agent reduced the risk of thromboembolic events (odds ratio (OR) 0.43, 95% confidence interval (CI) 0.32 to 0.59; P < 0.00001) and total mortality (OR 0.57, 95% CI 0.42 to 0.78; P = 0.0004). Aspirin and dipyridamole reduced these events similarly. The risk of major bleeding was increased when antiplatelet agents were added to oral anticoagulants (OR 1.58, 95% CI 1.14 to 2.18; P = 0.006).For major bleeding, there was no evidence of heterogeneity between aspirin and dipyridamole and in the comparison of trials performed before and after 1990, around the time when anticoagulation standardisation with the international normalised ratio was being implemented. A lower daily dose of aspirin (< 100 mg) may be associated with a lower major bleeding risk than higher doses.

Adding antiplatelet therapy, either dipyridamole or low-dose aspirin, to oral anticoagulation decreases the risk of systemic embolism or death among patients with prosthetic heart valves. The risk of major bleeding is increased with antiplatelet therapy. These results apply to patients with mechanical prosthetic valves or those with biological valves and indicators of high risk such as atrial fibrillation or prior thromboembolic events. The effectiveness and safety of low-dose aspirin (100 mg daily) appears to be similar to higher-dose aspirin and dipyridamole. In general, the quality of the included trials tended to be low, possibly reflecting the era when the majority of the trials were conducted (1970s and 1980s when trial methodology was less advanced).

Appropriate acute treatment with plasminogen activators (PAs) can significantly increase the probability of minimal or no disability in selected ischemic stroke patients. There is a great deal of evidence showing that intravenous recombinant tissue PAs (rt-PA) infusion accomplishes this goal, recanalization with other PAs has also been demonstrated in the development of this treatment. Recanalization of symptomatic, documented carotid or vertebrobasilar arterial territory occlusions have also been achieved by local intra-arterial PA delivery, although only a single prospective double-blinded randomized placebo-controlled study has been reported. The increase in intracerebral hemorrhage with these agents by either delivery approach underscores the need for careful patient selection, dose-appropriate safety and efficacy, proper clinical trial design, and an understanding of the evolution of cerebral tissue injury due to focal ischemia. Principles underlying the evolution of focal ischemia have been expanded by experience with acute PA intervention. Several questions remain open that concern the manner in which PAs can be applied acutely in ischemic stroke and how injury development can be limited.

OPININION STATEMENT: All patients with ischemic stroke should undergo a comprehensive assessment of cardiovascular risk. Patients with carotid artery disease, symptoms of cerebral ischemia and high cardiovascular risk profiles should be considered for noninvasive testing for coronary artery disease (CAD). Routine testing for CAD before carotid endarterctomy is not recommended. Patients with coexisting coronary and carotid artery disease should be more aggressively treated for reducing their "very high" risk of cardiovascular events. In patients candidates to carotid revascularization, a preoperative coronary angiography and coronary revascularization are not recommended. Warfarin is recommended in all patients with moderate to high risk of stroke. Novel oral anticoagulants represent an attractive alternative to warfarin. However, their place in therapy in clinical practice is not yet established. Percutaneous closure of the left atrial appendage for stroke prophylaxis may be considered in selected patients with atrial fibrillation and contraindications for oral anticoagulant therapy. Warfarin is not indicated in patients with heart failure who are in sinus rhythm. Percutaneous closure of patent foramen does not seem to be superior to medical therapy for the prevention of recurrences in patients with cryptogenic stroke.

The article describes the mechanisms of action, pharmacokinetics, and pharmacodynamics of aspirin, dipyridamole, cilostazol, the thienopyridines, and the glycoprotein IIb/IIIa antagonists. The relationships among dose, efficacy, and safety are discussed along with a mechanistic overview of results of randomized clinical trials. The article does not provide specific management recommendations but highlights important practical aspects of antiplatelet therapy, including optimal dosing, the variable balance between benefits and risks when antiplatelet therapies are used alone or in combination with other antiplatelet drugs in different clinical settings, and the implications of persistently high platelet reactivity despite such treatment.

The objective of this article is to summarize the published literature concerning the pharmacokinetics and pharmacodynamics of oral anticoagulant drugs that are currently available for clinical use and other aspects related to their management.

We carried out a standard review of published articles focusing on the laboratory and clinical characteristics of the vitamin K antagonists; the direct thrombin inhibitor, dabigatran etexilate; and the direct factor Xa inhibitor, rivaroxaban

The antithrombotic effect of each oral anticoagulant drug, the interactions, and the monitoring of anticoagulation intensity are described in detail and discussed without providing specific recommendations. Moreover, we describe and discuss the clinical applications and optimal dosages of oral anticoagulant therapies, practical issues related to their initiation and monitoring, adverse events such as bleeding and other potential side effects, and available strategies for reversal.

There is a large amount of evidence on laboratory and clinical characteristics of vitamin K antagonists. A growing body of evidence is becoming available on the first new oral anticoagulant drugs available for clinical use, dabigatran and rivaroxaban.

The aim of this updated statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches to the implementation of guidelines and their use in high-risk populations.

To summarize evidence from clinical trials of heart valve disease and identify areas where further trials are needed.

Recent randomized studies suggest that statins do not influence progression of aortic stenosis. Other medical therapies with the potential to reduce progression of valve disease or decrease myocardial dysfunction include vasodilators in aortic regurgitation, angiotensin II receptor antagonists or beta-blockers in mitral regurgitation and angiotensin-converting enzyme inhibitors in aortic stenosis. However, these treatments have not been evaluated or have been evaluated only in small studies. Meta-analysis of randomized studies of antithrombotic strategies in patients with mechanical valves suggests overall risk is lower with the combination of warfarin with a lower target international normalized ratio and an antiplatelet drug. Novel anticoagulants have the potential to replace warfarin but have not yet been evaluated for this indication. Clinical trials are also needed to reliably evaluate different surgical strategies and novel percutaneous technology.

Clinical trials in heart valve disease have important limitations, including the small number of trials undertaken and the small size of most studies. Many trials were undertaken more than 10-20 years ago in patients with earlier generation valve prostheses. To improve outcomes for patients with heart valve disease more clinical trials of contemporary approaches are needed.

This article about currently available antiplatelet drugs is part of the Antithrombotic and Thrombolytic Therapy: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). It describes the mechanism of action, pharmacokinetics, and pharmacodynamics of aspirin, reversible cyclooxygenase inhibitors, thienopyridines, and integrin alphaIIbbeta3 receptor antagonists. The relationships among dose, efficacy, and safety are thoroughly discussed, with a mechanistic overview of randomized clinical trials. The article does not provide specific management recommendations; however, it does highlight important practical aspects related to antiplatelet therapy, including the optimal dose of aspirin, the variable balance of benefits and hazards in different clinical settings, and the issue of interindividual variability in response to antiplatelet drugs.

This article concerning the pharmacokinetics and pharmacodynamics of vitamin K antagonists (VKAs) is part of the American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). It describes the antithrombotic effect of the VKAs, the monitoring of anticoagulation intensity, and the clinical applications of VKA therapy and provides specific management recommendations. Grade 1 recommendations are strong and indicate that the benefits do or do not outweigh the risks, burdens, and costs. Grade 2 recommendations suggest that the individual patient's values may lead to different choices. (For a full understanding of the grading, see the "Grades of Recommendation" chapter by Guyatt et al, CHEST 2008; 133:123S-131S.) Among the key recommendations in this article are the following: for dosing of VKAs, we recommend the initiation of oral anticoagulation therapy, with doses between 5 mg and 10 mg for the first 1 or 2 days for most individuals, with subsequent dosing based on the international normalized ratio (INR) response (Grade 1B); we suggest against pharmacogenetic-based dosing until randomized data indicate that it is beneficial (Grade 2C); and in elderly and other patient subgroups who are debilitated or malnourished, we recommend a starting dose of < or = 5 mg (Grade 1C). The article also includes several specific recommendations for the management of patients with nontherapeutic INRs, with INRs above the therapeutic range, and with bleeding whether the INR is therapeutic or elevated. For the use of vitamin K to reverse a mildly elevated INR, we recommend oral rather than subcutaneous administration (Grade 1A). For patients with life-threatening bleeding or intracranial hemorrhage, we recommend the use of prothrombin complex concentrates or recombinant factor VIIa to immediately reverse the INR (Grade 1C). For most patients who have a lupus inhibitor, we recommend a therapeutic target INR of 2.5 (range, 2.0 to 3.0) [Grade 1A]. We recommend that physicians who manage oral anticoagulation therapy do so in a systematic and coordinated fashion, incorporating patient education, systematic INR testing, tracking, follow-up, and good patient communication of results and dose adjustments [Grade 1B]. In patients who are suitably selected and trained, patient self-testing or patient self-management of dosing are effective alternative treatment models that result in improved quality of anticoagulation management, with greater time in the therapeutic range and fewer adverse events. Patient self-monitoring or self-management, however, is a choice made by patients and physicians that depends on many factors. We suggest that such therapeutic management be implemented where suitable (Grade 2B).

Based on their mode of action, it is reasonable to expect that the combination therapy of aspirin and a vitamin K antagonist (VKA) may be more beneficial in preventing (athero) thrombotic complications in high-risk patients for cardiovascular events. However, there is no consensus about additional aspirin use in the most common indications for VKA or the use of VKAs to be added to the most common aspirin indications. The variation in clinical outcomes and bleeding complications suggests that extrapolating from one indication to another may not be appropriate. So far, decisions about the combined use of aspirin and VKA are individualized in the absence of adequate data. Only in patients with mechanical heart valves the benefits and safety of combining aspirin with VKA therapy seems obvious. In patients with peripheral artery disease no beneficial effect was noted for the combination therapy, perhaps with an exception of those with graft failure. For all other clinical situations, this is unclear and should be avoided.

Management of symptomatic, intracranial, large-arterial atherosclerosis is controversial. We assessed the safety and efficacy of combining warfarin and low-dose aspirin to prevent stroke from intracranial atherosclerotic stenosis failing prior treatment with either aspirin or warfarin. Patients with severe intracranial stenosis were prescribed combination therapy, warfarin (international normalized ratio [INR] 2 to 3) and aspirin 81 mg daily. Ten men and six women treated with combination therapy had one recurrent ischemic event during 382 months of therapy. No patient suffered a myocardial infarction or sudden vascular death. No serious hemorrhagic complication occurred. The combination of warfarin and low-dose aspirin seems safe and effective in preventing recurrent stroke from symptomatic, intracranial, large-arterial occlusive disease after failure with either aspirin or warfarin monotherapy.

Cancer patients receive numerous medications, including antineoplastic agents, drugs for supportive care, and medications for comorbid illnesses. Therefore, they are at risk for drug interactions and duplicate prescribing.

A questionnaire eliciting information on demographics and medications taken in the previous 4 weeks was given to adult outpatients receiving systemic anticancer therapy for solid tumors. The Drug Interaction Facts software, version 4.0, was used to identify potential drug interactions and to classify them by level of severity (major, moderate, or minor) and the strength of scientific evidence for them (using categories [1-5] of decreasing certainty). Summary statistics and logistic regression were used to analyze the data. All statistical tests were two-sided.

The survey was completed by 405 patients. We observed 276 potential drug interactions, and at least one potential interaction was identified in 109 patients (27%; 95% confidence interval [CI] = 23% to 31%). Of the potential interactions, 25 (9%) were classified as major and 211 (77%) as moderate. Nearly half (49%) of potential interactions were supported by level 1 or 2 scientific evidence. Most potential drug interactions (87%) involved non-anticancer agents such as warfarin, antihypertensive drugs, corticosteroids, and anticonvulsants, but some (n = 36, 13%) involved antineoplastic agents. In multivariable analysis, increased risk of receiving drug combinations in which there were potential drug interactions was associated with receipt of increasing numbers of drugs (odds ratio [OR] = 1.4 per additional drug, 95% CI = 1.26 to 1.58, P<.001 from the Wald chi-square test), type of medication (drugs to treat comorbid conditions versus supportive care medications only; OR = 8.6, 95% CI = 2.9 to 25, P<.001), and the presence of brain tumors. Thirty-two (8%) patients were exposed to duplicate medications, most often corticosteroids, proton pump inhibitors, or benzodiazepines.

Potential drug interactions were common among cancer patients and most often involved medications to treat comorbid conditions. Duplicate medications were infrequent.

The aim of this new statement is to provide comprehensive and timely evidence-based recommendations on the prevention of ischemic stroke among survivors of ischemic stroke or transient ischemic attack. Evidence-based recommendations are included for the control of risk factors, interventional approaches for atherosclerotic disease, antithrombotic treatments for cardioembolism, and the use of antiplatelet agents for noncardioembolic stroke. Further recommendations are provided for the prevention of recurrent stroke in a variety of other specific circumstances, including arterial dissections; patent foramen ovale; hyperhomocysteinemia; hypercoagulable states; sickle cell disease; cerebral venous sinus thrombosis; stroke among women, particularly with regard to pregnancy and the use of postmenopausal hormones; the use of anticoagulation after cerebral hemorrhage; and special approaches for the implementation of guidelines and their use in high-risk populations.

Approximately 50,000 valve replacement operations take place in Europe annually and almost as many valve repair procedures. Previous European guidelines on management of patients after valve surgery were last published in 1995 and were limited to recommendations about antithrombotic prophylaxis. American guidelines covering the broader topic of the investigation and treatment of patients with valve disease were published in 1998 but devoted relatively little space to post-surgical management. This document represents the consensus view of a committee drawn from three European Society of Cardiology (ESC) Working Groups (WG): the WG on Valvular Heart Disease, the WG on Thrombosis, and the WG on Rehabilitation and Exercise Physiology. In almost all areas of patient management after valve surgery, randomized trials and meta-analyses do not exist. Such randomized trials as do exist are very few in number, are narrowly focused with small numbers, have limited general applicability, and do not lend themselves to meta-analysis because of widely divergent methodologies and different patient characteristics. Recommendations are therefore almost entirely based on non-randomized studies and relevant basic science.