Nuisance Bleeding Research Articles

Improving the Effectiveness of Anticoagulant Therapy: The Promise of Factor XI Inhibition

This continuing medical education-accredited symposium, held at the 2023 International Society for Thrombosis and Haemostasis (ISTH) congress in Montréal, Canada, focused on current unmet needs in anticoagulation, especially in the atrial fibrillation (AF) population, and reflected on the promise of the emerging class of Factor XI inhibitors for stroke prevention (SPAF) in susceptible patients. The faculty agreed that, although direct oral anticoagulants (DOAC) have represented a major advance compared with vitamin K antagonists, their utilisation remains suboptimal, often due to the prevailing fear of bleeding in many types of patients. Older age alone can be a reason for withholding anticoagulation, due to the risk and implications of bleeding. Frailty and comorbidities, such as chronic kidney disease (CKD), which can adversely affect the bioavailability of DOACs, are also deterrents to optimal anticoagulant use. Clinicians may try to avoid or mitigate bleeding by inappropriately prescribing low doses of DOACs, an off-label practice that has been found to fail to protect patients from thrombotic risk, without attenuating the risk of bleeding. In addition, the potential for drug-drug interactions and poor adherence also limit the optimal use of DOACs in real-world clinical practice. A recent patient survey focusing on the topic of ‘minor bleeding’, often referred to by clinicians as ‘nuisance bleeding’, and typically not well captured in clinical trials, revealed the far-reaching impact of ongoing problems with bleeding on quality of life, and the possibility that these experiences may deter patients from adherence to their prescribed anticoagulant regimen. Factor XI represents a promising new target for anticoagulation, which may minimise the risk of bleeding by pharmacologically ‘uncoupling’ the clotting pathway, leading to pathological thrombosis from the cascade largely responsible for physiological haemostasis. Phase II research with investigational Factor XI inhibitors has established their antithrombotic and safety potential, and some of these agents may also avoid other practical drawbacks of DOACs. Phase III evaluation of Factor XI inhibition is ongoing in a number of clinical settings.

Ticagrelor is related to nuisance bleeding after flow diversion of unruptured intracranial aneurysms.

Nuisance bleeding (NB) without urgent medical attention is rarely characterized despite its frequent occurrence in patients with cerebral aneurysms undergoing flow diversion (FD) who are maintained on dual antiplatelet therapy (DAPT). This study explored the risk factors for NB. Patients with unruptured cerebral aneurysms who underwent intervention using FD (July 2018 to May 2022) and had follow-up data were enrolled. Patient demographics, clinical characteristics, aneurysm features and follow-up data were analysed. Bleeding complications were classified as NB, internal bleeding and alarming bleeding. NB was characterized by easy bruising, bleeding from small cuts and nonfatal petechiae and ecchymosis. Univariate and multivariate logistic regression analyses were performed to determine risk factors for NB. This study assessed 121 patients. Of these, 52 (43.0%) patients had NB. Compared with the non-bleeding group, the NB group had more females (82.7% vs. 56.5%; p = 0.003), lower smoking rate (7.7% vs. 23.2%; p = 0.027) and smaller aneurysms (6.65 mm [4.60-9.60 mm] vs. 8.82 mm [5.65-15.65 mm]; p = 0.007) and had more patients maintained on ticagrelor-containing DAPT regimen (90.4% vs. 66.7%; p = 0.002). Multivariate logistic regression revealed that ticagrelor-containing DAPT regimen (odds ratio, 3.91; 95% confidence interval, 1.29-11.87; p = 0.016) was associated with NB. These results suggest that NB is a common bleeding complaint in patients on DAPT. In patients undergoing FD, DAPT with ticagrelor was the only independent risk factor for NB.

Long-term dual antiplatelet therapy and nuisance bleeding: impact on quality of life.

Long term dual antiplatelet therapy (LTDAPT), with ticagrelor 60 mg and low-dose aspirin, is indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high-risk patients with a history of ACS of at least 1 year. LTDAPT had a good tolerability and safety profile, but the risk of TIMI major bleeding was increased. However, even non-significant bleeding may be important because it has an effect on the quality of life and therefore may lead to treatment discontinuation. We, therefore, evaluated patients' experiences with LTDAPT and the impact of nuisance bleeding on quality of life and treatment adherence. We retrospectively reviewed 225 patients in follow-up after ACS with at least one high-risk condition, treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The outpatient follow-up program after hospitalization provides a visit on day 30 after discharge, then after 3 months, continuing with six-monthly checks. We assessed the presence and intensity of bleeding, as well as health-related quality of life (HRQoL), at each visit. The TIMI score was used to determine the severity of the bleeding. Any overt bleeding event that did not meet the major and minor criteria was labeled "minimal" and could be framed as "nuisance bleeding." The HRQoL was assessed by the EuroQol-5 and Dimension (EQ-5D) visual analog scale (VAS) score. Minimal bleedings were present in 49 patients (21%), but only in one case (by decision of the patient) there was a cause for discontinuation of therapy. However, 39 (79%) subjects had asked for opinions on stopping the therapy during the telephone consultation. Factors influencing LTDAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from the hospital. All adverse events, judged to be "not serious" in trials, may have an effect on the quality of life and therefore may lead to treatment discontinuation. The authors underline the importance of careful outpatient follow-up and ongoing counselling, to check out compliance and possible adverse effect of LTDAPT.

Pandemic-proof recruitment and engagement in a fully decentralized trial in atrial fibrillation patients (DeTAP)

The Coronavirus Disease 2019 (COVID-19) pandemic curtailed clinical trial activity. Decentralized clinical trials (DCTs) can expand trial access and reduce exposure risk but their feasibility remains uncertain. We evaluated DCT feasibility for atrial fibrillation (AF) patients on oral anticoagulation (OAC). DeTAP (Decentralized Trial in Afib Patients, NCT04471623) was a 6-month, single-arm, 100% virtual study of 100 AF patients on OAC aged >55 years, recruited traditionally and through social media. Participants enrolled and participated virtually using a mobile application and remote blood pressure (BP) and six-lead electrocardiogram (ECG) sensors. Four engagement-based primary endpoints included changes in pre- versus end-of-study OAC adherence (OACA), and % completion of televisits, surveys, and ECG and BP measurements. Secondary endpoints included survey-based nuisance bleeding and patient feedback. 100 subjects (mean age 70 years, 44% women, 90% White) were recruited in 28 days (traditional: 6 pts; social media: 94 pts in 12 days with >300 waitlisted). Study engagement was high: 91% televisits, 85% surveys, and 99% ECG and 99% BP measurement completion. OACA was unchanged at 6 months (baseline: 97 ± 9%, 6 months: 96 ± 15%, p = 0.39). In patients with low baseline OACA (<90%), there was significant 6-month improvement (85 ± 16% to 96 ± 6%, p < 0.01). 86% of respondents (69/80) expressed willingness to continue in a longer trial. The DeTAP study demonstrated rapid recruitment, high engagement, and physiologic reporting via the integration of digital technologies and dedicated study coordination. These findings may inform DCT designs for future cardiovascular trials.

Incidence of Gum Bleeding in Patients Taking Antiplatelet Therapy

Introduction: Medical practitioners often advise patients on antiplatelet therapy to either stop or alter their medications prior to invasive surgical procedure because of fear of excessive and uncontrolled bleeding. Objectives: The main objective of the study is to analyse the incidence of gum bleeding in patients taking antiplatelet therapy among local population of Pakistan Material and methods: This descriptive study was conducted in Saddique Family Hospital Gujranwala during June 2020 to December 2020. After permission from hospital ethical committee, total 120 patients meeting the inclusion and exclusion criteria will be enrolled in the study from Saddique Family Hospital Gujranwala. Detailed history and physical examination will be done to meet the inclusion and exclusion criteria. Informed consent will be obtained. Internal bleeding included hematoma, epistaxis, vaginal bleeding, melena, hematemesis, eye bleeding, and haematuria. Results: The data was collected from 120 patients. The mean age was 35.67±2.56 years. The mean BT was 19.5 ± 5.2 min, ranging from 5 min to more than 20 min. The incidence of bleeding was 32%. Seventeen patients had a BT longer than 20.5 min and less than 26 min: 5 nuisance bleeding and 1 internal bleeding (mild hematuria) which stopped after discontinuation of platelet inhibitory agents. Conclusion: It is concluded that available evidence suggests that most dental interventions can be safely performed without the interruption of antithrombotic therapy. Keywords: Antithrombotic, Therapy, Patients, Health

P99 LONG TERM DUAL ANTIPLATELET THERAPY AFTER MYOCARDIAL INFARCTION IN CLINICAL PRACTICE: IMPACT OF NUISANCE BLEEDING ON MEDICATION ADHERENCE

Abstract Background Long term dual antiplatelet therapy (LTDAPT) with ticagrelor 60 mg and low–dose aspirin are indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high–risk patients with a history of ACS of at least 1 year. LTDAPT had a well tolerability and safety profile, but the risk of TIMI major bleeding was increased. However even non significant bleeding may be important because have an effect on quality of life and therefore may lead to treatment discontinuation. Objective To understand the experiences of patients with LTDAPT and nuisance bleeding, and their impact on medication adherence. Methods We retrospectively reviewed 225 patients in follow up after ACS with at least one high risk condition (Fig. 1), treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The outpatient follow–up program after hospitalization provides a visits at day 30 after discharge and subsequently after 3 months, then continuing with six–monthly checks. The intensity of bleeding was assessed according to the TIMI score. Any overt bleeding event that did not meet the criteria of major and minor was defined “minimal”. Results they are shown in Fig. 2. Minmal bleedings were present in 49 patients (21%), but were not a cause for discontinuation of therapy. However 39 (79%) subjects had asked opinion on stop the therapy at the telephone consultation. We found that: (1) participants adhered to treatment when they believed long term DAPT was important to health outcomes; (2) those who experienced nuisance bleeding reported symptoms to be mild and manageable; (3) participants’ and their family’s understanding of LTDAPT risks and benefits, and their ability to manage symptoms, influenced medication adherence. Factors influencing long term DAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from hospital. Conclusions All adverse events judged to be “not serious” in trials may have an effect on quality of life and therefore may lead to treatment discontinuation. The need to educate the patient in order to improve adherence should therefore be emphasized. The authors underline the importance of careful outpatient follow–up and constant counselling in order to check out compliance and possible adverse effect of long term DAPT risks treatment.

Adolescent/Young Adult Long-Acting Reversible Contraception: Experience from a Multisite Adolescent Medicine Collaborative

To report on long-acting reversible contraception (LARC) experience and continuation rates in the Adolescent Medicine LARC Collaborative. LARC insertion data (682 implants and 681 intrauterine devices [IUDs]) were prospectively collected from January 1, 2017, through December 31, 2019, across 3 Adolescent Medicine practices. Follow-up data through December 31, 2020, were included to ensure at least 1year of follow-up of this cohort. Continuation rates were calculated at 1, 2, and 3years, overall and by Adolescent Medicine site, as were descriptive statistics for LARC procedural complications and patient experience. Implant and IUD insertion complications were uncommon and largely self-limited, with no IUD-related uterine perforations. Uterine bleeding was the most frequently reported concern at follow-up (35% implant, 25% IUD), and a common reason for early device removal (45% of implant removals, 32% of IUD removals). IUD malposition or expulsion occurred following 6% of all insertions. The pooled implant continuation rate at 1year was 87% (range, 86%-91% across sites; P=.63), 66% at 2years (range, 62%-84%; P=.01), and 42% at 3years (range, 36%-60%; P=.004). The pooled IUD continuation rate at 1year was 88% (range, 87%-90% across sites; P=.82), 77% at 2years (range, 76%-78%; P=.94), and 60% at 3years (range, 57%-62%; P=.88). LARC is successfully provided in Adolescent Medicine clinical settings, with continuation rates analogous to those of well-resourced clinical trials. Uterine bleeding after LARC insertion is common, making counselling imperative. Future analyses will assess whether the medical management of LARC-related nuisance bleeding improves continuation rates in our Adolescent Medicine patient population.

95 Long-term dual antiplatelet therapy after myocardial infarction in clinical practice: impact of nuisance bleeding on medication adherence

Abstract Aims Long-term treatment with ticagrelor 60 mg and low-dose aspirin are indicated after acute coronary syndrome (ACS) for the secondary prevention of atherothrombotic events in high-risk patients with a history of myocardial infarction of at least 1 year. Long-term dual antiplatelet therapy (DAPT) had a well tolerability and safety profile, but the risk of TIMI major bleeding was significantly increased. However even nonsignificant bleeding may be important because have an effect on quality of life and therefore may lead to treatment discontinuation. To understand the experiences of patients with long-term DAPT with ticagrelor 60 mg and low-dose aspirin and nuisance bleeding, and their impact of nuisance bleeding on medication adherence. Methods and results We retrospectively reviewed aggregate data of 187 patients (155 M e 38 F) (mean age 63.8 ± 9 years) in follow-up after ACS with at least one high risk condition (multivessel disease, diabetes, GFR &amp;lt; 60 mL/min, history of prior myocardial infarction, age &amp;gt; 65 years) treated with ticagrelor 60 mg twice daily (after 90 mg twice daily for 12 months). The high risk groups were represented as follows: multivessel disease 105 pts (82%), diabetes 63 pts (33%), GFR&amp;lt; 60 mL/min 27 pts (14%), history of prior MI 33 pts (17%), and &amp;gt;65 year aged 85 pts (45%). The outpatient follow-up programme after hospitalization provides visits at day 30 after discharge and subsequently after 3 months, then continuing with 6-monthly checks. The intensity of bleeding was assessed according to the TIMI score.1 Any overt bleeding event that did not meet the criteria of major and minor was defined ‘minimal’. Treatment was withdrawn in seven patients: three cases showed atrial fibrillation and were placed on oral anticoagulant drugs, one developed intracranial bleeding. In three patients, a temporary withdrawal was due to surgery (one colon polyposis and two cases of bladder papilloma). Minimal bleedings (nasal, gingival, conjunctival, subcutaneous/dermal, rectal and urinary) were present in 31 patients, but were not a cause for discontinuation of therapy. However, 22 (70%) subjects had asked opinion on stop the therapy at the telephone consultation. We found that: (i) participants adhered to treatment when they believed long-term DAPT was important to health outcomes; (ii) those who experienced nuisance bleeding reported symptoms to be mild and manageable; (iii) participants’ and their family’s understanding of long-term DAPT risks and benefits, and their ability to manage symptoms, influenced medication adherence. Factors influencing long-term DAPT knowledge included access to medication counselling, engaging with information communicated during medication counselling, and access to timely, relevant and expert information and advice after discharge from hospital. Conclusions All adverse events judged to be ‘not serious’ in trials may have an effect on quality of life and therefore may lead to treatment discontinuation. The need to educate the patient in order to improve adherence should therefore be emphasized. The authors underline the importance of careful outpatient follow-up and constant counselling in order to check out compliance and possible adverse effect of long term DAPT risks treatment.

243 Mental health status and sexual habits in young patient after acute coronary syndrome

Abstract Aims Acute coronary syndrome (ACS) has a huge potential impact on patients’ life, and little is known on the long-term effect on mental health in young patients. Methods and results We included consecutive young patients (≤45 years at presentation) with ACS referred from October 2013 until March 2021 to our clinic. Physical and mental status was evaluated through the standardized SF12 scale for physical (PCS) and mental status (MCS). Depression and perceived stress were evaluated with the patient health questionnaire 9 (PHQ9) and perceived stress scale (PSS). A total of 91 patients have been included and followed for a median of 40 months. History of anxiety or depression at baseline was reported in 1.1% and 2.2%, respectively. Physical and mental health status was impaired in 65.8% and 42.1% of patients, respectively (Figure). Predictors of poorer physical health were lower LVEF, WMSI, and multivessel disease. Predictors of poorer mental health were age and nuisance bleeding during follow-up. Mild/moderate depression was reported in 47.3%. Moderate/high stress was reported in 78.1%. 37.1% patients affirmed that their career trajectory worsened after the event and 37.8% declared a reduction of income. 53.8% declared mild to significant changes in their sexual activity, while 83.8% declared to have received no advises on sexual activity from their Doctor. Conclusions In conclusion, ACS is a dramatic event with a significant impact on young patients’ life at a physical, mental, and social level. Measures of social/psychological support in the aftermath of the event merit consideration in future research.

Validation of a pandemic-proof, decentralized cardiovascular trial: scalable design produces rapid recruitment, high engagement and protocol adherence in DeTAP (Decentralized Trial in Afib Patients)

Abstract Background The COVID-19 pandemic has curtailed clinical trial activity significantly. Decentralized clinical trial (DCT) designs may lower cost, expand trial access, and reduce exposure risk for patients and staff. Whether such designs can be used for large, pivotal drug trials is not known. Purpose We performed a feasibility study to inform whether a large phase 3 Cardiovascular DCT can achieve high quality trial results and also withstand health crises such as the COVID-19 pandemic. The DeTAP (Decentralized Trial in Afib Patients) was a single-arm, observational study that integrated a suite of digital health technologies, including paired home sensor devices, into a 100% virtual trial experience for atrial fibrillation (AF) patients on anticoagulation. Methods We recruited 100 AF patients over age 55 on oral anticoagulation (OAC) by traditional methods or by social media ads placed California-wide. Subjects completed an online prescreening, uploaded their active OAC prescription, and completed an e-consent via SMS message link. Participants downloaded a customized study app to integrate surveys and data from study-supplied wireless blood pressure (BP) and 6 lead EKG sensors (Figure 1A). Participants completed pre- and post-study engagement surveys, weekly OAC adherence surveys, 4 study televisits, 4 ECG/BP readings, and 4 post-study surveys over a 6 month period. The primary endpoints were protocol engagement-based measurements that quantified percent completion of: 1) televisits 2) surveys, 3) ECG/BP readings requirements. Secondary endpoints were the % changes in: 1) OAC adherence (OACA), 2) nuisance bleeding (NB), 3) individual patient engagement surveys. Results 100 participants were recruited in 26 days (traditional: 6 in 2 weeks; social media: 94 in 12 days) with a dramatic surge in enrollment driven by social media ads (Figure 1B, Table). A recruitment overflow occurred with &amp;gt;200 eligible candidates on a waitlist. All key study completion metrics showed high compliance: televisit (91%); surveys (85%); ECG/BP completion (90%). Overall OACA was unchanged, but for subjects who reported low initial OACA, there was significant improvement at 6 months (85±16% to 98±6%; p=0.002). 47 participants (57%) reported NB, which did not correlate with OACA. Participant engagement measure scores (PAM-13) trended higher (baseline, 70%; 6 months, 74%, p=0.32). Lastly, study participants exhibited strong interest in participating in a larger experimental drug DCT study (90%) in the future. Conclusion The DeTAP study, conducted fully during the COVID-19 pandemic, demonstrates that a decentralized CV medical intervention trial is feasible and can achieve rapid recruitment, high study retention, physiologic and adverse event reporting, and high study engagement via the proper integration of digital technologies and a dedicated DCT study coordination effort. These findings could be informative for virtualizing large pivotal clinical trials at scale. Funding Acknowledgement Type of funding sources: Private company. Main funding source(s): Bayer AG Figure 1. DeTAP Study Design and Recruitment TimelineTable 1. DeTAP Results

Patient perspectives of nuisance bleeding and adherence to dual antiplatelet therapy: a qualitative study

ObjectiveTo understand the experiences of patients with dual antiplatelet therapy (DAPT) and nuisance bleeding, and their perspectives of the impact of nuisance bleeding on medication adherence and information seeking.MethodsWe conducted...

Nuisance bleeding complications in patients with cerebral aneurysm treated with Pipeline embolization device

BackgroundPatients with cerebral aneurysms treated with the Pipeline embolization device (PED) are maintained on dual antiplatelet therapy (DAPT) to prevent thromboembolic complications. Rates of minor, “nuisance” bleeding in these patients...

5197Correlates and prognostic significance of nuisance bleeding after acute myocardial infarction. The FAST-MI programme

Abstract Background Following acute myocardial infarction (AMI), most patients receive potent antithrombotic medications, which may promote nuisance bleedings (ecchymoses, minor nose or dental bleeds etc.). Little information is available on the factors related to nuisance bleedings, nor on their prognostic significance in post-AMI patients. Aims and methods A health status questionnaire was sent to all patients participating in the nationwide French FAST-MI cohorts (2010 and 2015) one year after the acute episode, with a specific question on the presence of nuisance bleedings. Overall, 3968 patients answered the question on the presence nuisance bleedings. In the 2010 cohorts, we also analysed whether the presence of nuisance bleedings at one year was an independent correlate of 5-year mortality. Results 54% of the patients reported the presence of nuisance bleedings (59% in 2010 and 51% in 2015). In univariate analyses, nuisance bleedings were more frequently found in younger patients, women, patients with STEMI, current smokers, patients treated with PCI, those receiving newer P2Y12 inhibitors or ACE-inhibitors but less frequent in patients with diabetes, hypertension, or those receiving ARBs or direct oral anticoagulants. Using logistic regression analysis, however, the only independent correlates of nuisance bleedings were: female gender (OR 1.45, 1.25–1.68), age ≤60 years (OR 1.22, 1.06–1.41), VKAs (OR 1.72, 1.28–2.31), clopidogrel (OR 1.62, 1.29–2.03), prasugrel (OR 3.16, 2.43–4.09), ticagrelor (OR 2.61, 2.04–3.35) at discharge, diabetes (OR 0.74, 0.63–0.88) and year 2015 vs 2010 (OR 0.62, 0.53–0.73). In the 2010 cohort, the presence of nuisance bleeding at one year was not a predictor of mortality at 5 years (90% survival in both patients with or without nuisance bleedings; adjusted HR 0.96, 95% CI 0.69–1.33) (Figure). Figure 1. 5-yr survival by nuisance bleed Conclusion Nuisance bleedings one year after AMI are extremely frequent. They are more common in women, younger patients, in patients receiving P2Y12 inhibitors, especially newer P2Y12-i, and in those receiving VKAs; in contrast, diabetic patients report less nuisance bleedings. The presence of nuisance bleeding at one year does not appear to impact 5-year mortality. Acknowledgement/Funding Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier

P5473Perceived well-being after acute myocardial infarction according to diabetic status and its impact long-term mortality. The FAST-MI programme

Abstract Background Little information is available regarding subjective well-being according to diabetic status in patients surviving an acute myocardial infarction (AMI). Aims and methods A health status questionnaire was sent to all patients participating in the nationwide French FAST-MI cohorts (2005, 2010 and 2015) one year after the acute episode of AMI, with a specific question on overall health condition (how do you feel: very well, well, fair, poor) (n=6082), and additional questions on the presence of any chest pain (n=4590), presence nuisance bleedings (n=3968), and reporting of perceived medication side-effects (n=2220). Answers were analysed according to diabetic status. We also analysed in the 2005 and 2010 cohorts whether subjective health status at one year was a correlate of 5-year mortality. Results Compared with non-diabetic patients (n=4692), those with diabetes (n=1390) had a poorer perceived health status (poor/fair health status: 40% vs 30%, P&lt;0.001), more presence of chest pain (31% vs 23%, P&lt;0.001), but less nuisance bleedings (47% vs 56%, P&lt;0.001) and similar reported medication side-effects (37% vs 41%, P=0.12). Using logistic regression analysis, diabetes was an independent correlate of poorer health status (any diabetes OR vs non-diabetic 1.29, 1.13–1.49, P&lt;0.001; non-insulin-treated: 1.17, 1.00–1.36, P=0.05, insulin-treated: 1.58, 1.29–1.94, P&lt;0.001). In diabetic patients, perceived health condition at one year was an independent correlate of 5-year death (Cox multivariate analysis): compared with patients reporting very good health, HR (95% CI) 2.16 (1.08–4.32) for good health, 3.06 (1.53–6.11) for fair health, and 3.63 (1.55–8.55) for poor health; in non-diabetic patients, 5-year survival was similar in those reporting good or very good health status, but lower in those reporting fair or poor health status (Figure). Figure 1. 5-year survival by health status Conclusion Compared with non-diabetic patients, patients with diabetes described a poorer general health and more residual chest pain after AMI, but had less nuisance bleedings. Health condition reported one year after AMI was an independent correlate of subsequent long-term mortality, particularly for diabetic patients. Acknowledgement/Funding Amgen, AstraZeneca, Bayer, Daiichi-Sankyo, Eli-Lilly, GSK, MSD, Novartis, Pfizer, Sanofi, Servier

Antithrombotic Medication and the Risk of Vitreous Hemorrhage in Atrial Fibrillation: Korean National Health Insurance Service National Cohort.

PurposeAntithrombotic therapy could be related with nuisance bleeding. This study investigated whether vitreous hemorrhage (VH) is associated with specific types of antithrombotic medication in patients with atrial fibrillation (AF).Materials and MethodsIn the Korean National Health Insurance Service National Sample Cohort, we identified 9352 antiplatelet/anticoagulant-treated AF patients. The occurrence of VH was compared between warfarin (n=1493) and a propensity score (PS)-matched antiplatelet group (n=1493) and between warfarin (n=1493) and a PS-matched warfarin+antiplatelet group (n=1493).ResultsThe outcomes of VH were lower in the warfarin than in the matched antiplatelet (1.45 vs. 3.72 events/1000 patient-years) and matched warfarin+antiplatelet groups (1.45 vs. 6.87 events/1000 patient-years). Compared with warfarin, the risk of VH increased with antiplatelet [adjusted hazard ratio (aHR) 3.90; 95% confidence interval (CI) 1.22–12.4, p=0.022] and warfarin+antiplatelet agents (aHR 4.39, 95% CI 1.74–11.2, p=0.002). Compared with warfarin only, warfarin+antiplatelet agents increased the risk of VH in patients ≥65 years, regardless of gender and hypertension. The risk of VH was significantly higher with dual antiplatelet therapy (aHR: 5.02, 95% CI: 1.56–16.2, p=0.007) or in dual (aHR: 5.02, 95% CI: 1.74–14.5, p=0.003) or triple therapy using warfarin and antiplatelet agents than with warfarin monotherapy (aHR: 6.12, 95% CI: 1.76–21.3, p=0.004).ConclusionDual antiplatelet or triple therapy increased the risk of VH significantly, compared to warfarin monotherapy. Considering the low efficacy of preventing ischemic stroke and high risk of bleeding, dual or triple therapy using warfarin and antiplatelet agents should be avoided to prevent VH in AF patients.

Prognostic Significance of Nuisance Bleeding in Anticoagulated Patients With Atrial Fibrillation.

Bleeding is commonly cited as a reason for stopping oral anticoagulants (OACs). Whether minor bleeding events (nuisance bleeding, NB) in patients with atrial fibrillation on OACs are associated with OAC discontinuation, major bleeding, and stroke/systemic embolism (SSE) is unknown. Within the ORBIT-AF prospective, outpatient registry (Outcomes Registry for Better Informed Treatment of Atrial Fibrillation), we identified 6771 patients ≥18 years of age at 172 sites with atrial fibrillation and eligible follow-up visits. NB was ascertained from the medical record and was defined as minor bleeding that did not require medical attention (eg, bruising, hemorrhoidal bleeding). We used multivariable pooled logistic regression modeling to evaluate the associations between NB and major bleeding and SSE in the 180 days after documentation of NB. Our unit of analysis was the patient visit, occurring at ≈6-month intervals for a median of 1.5 years following enrollment. Changes in anticoagulation treatment satisfaction after NB were examined descriptively in a subset of patients. The median age of the overall population was 75.0 (interquartile range, 67.0-81.0); 90.0% were white and 42.5% were female. Among 6771 patients (18 560 visits), n=1357 (20.0%) had documented NB, for an incidence rate of 14.8 events per 100 person-years. Over 96.4% of patients remained on OAC therapy after the NB event. Overall, 287 (4.3%) patients experienced major bleeding and 64 (0.96%) had a SSE event during follow-up. NB was not associated with a significant increased risk of major bleeding over 6 months in models adjusting for the ATRIA bleeding score (Anticoagulation and Risk Factors in Atrial Fibrillation) (odds ratio, 1.04; 95% confidence interval, 0.68-1.60; P=0.86). NB was also not associated with increased SSE risk over 6 months in models adjusting for the CHA2DS2-VASc risk score (odds ratio, 1.24; 95% confidence interval, 0.53-2.91; P=0.62). NB is common among patients with atrial fibrillation on OACs. However, NB was not associated with a higher risk of major bleeding or SSE over the next 6 months, suggesting its occurrence should not lead to changes in anticoagulation treatment strategies in OAC-treated patients. URL: https://www.clinicaltrials.gov . Unique identifier: NCT01165710.

A qualitative study of nuisance bleeding and medication-related beliefs with dual antiplatelet drug therapy

ObjectivesThe purpose of this qualitative study was to explore perceptions of nuisance bleeding and medication-related beliefs among adults taking dual antiplatelet drug therapy. MethodsWe conducted qualitative telephone interviews with 34 community-dwelling adults with cardiovascular disease. ResultsUsing qualitative content analysis, we identified 4 dominant themes: nuisance bruising, nuisance bleeding, importance of medication adherence, and duration of therapy. Participants' bruising was frequently more severe than expected given the force of the bump that caused it. Concerns focused on whether increased bleeding tendencies would lead to hemorrhage in the event of a major traumatic injury, confusion about the duration of therapy, and the rationale for when and why therapy should be discontinued. ConclusionExcessive bruising and medication-related concerns about hemorrhage and duration of treatment were salient issues for participants. Effective clinician-patient communication should be used to assist individuals in managing concerns to help assure positive health outcomes with antiplatelet drugs.

A counseling program on nuisance bleeding improves quality of life in patients on dual antiplatelet therapy: A randomized controlled trial.

BackgroundNuisance bleeding is a major determinant of quality of life and drug discontinuation in patients on dual antiplatelet therapy (DAPT). However, no randomized trial has been focused on the impact of nuisance bleeding on quality of life.MethodsBATMAN is an investigator-driven, randomized, controlled, single-center, open trial (NCT02554006). Four hundred and forty-eight consecutive patients with indication to at least 6 months of DAPT were randomized to: i) multimodal counseling program focused on nuisance bleedings (interventional arm); ii) usual discharge process (control arm). The primary endpoint was the one-month health-related quality of life assessed by the EuroQol-5 Dimension (EQ-5D) visual analog scale (VAS) score. Secondary endpoints were EQ-5D at 1 and 6 months, EQ-5D VAS at 6 months, DAPT withdrawal, need of information regarding DAPT and/or nuisance bleedings, 6-month ischemic and bleeding adverse events.ResultsThe EQ5D-VAS was significantly higher in the interventional arm compared to the control arm at 1 and 6 months (81[74–88] vs. 73[64–80], p < 0.001 at 1 month; 82[76–88] vs. 74[65–81], p < 0.001 at 6 months). Patients in the interventional arm had also significantly lower pain/discomfort and anxiety/depression at the EQ-5D both at 1 and 6 months. Patients in the control arm withdrew DAPT significantly more (7 (3%) vs. 1 (0.4%), p = 0.03) and looked for information regarding DAPT and/or about nuisance bleeding more frequently than those in the interventional arm (178 (79%) vs.19 (8%), p < 0.001).ConclusionsThe systematic utilization of a multimodal counseling program improved quality of life and reduced the DAPT withdrawal rate in patients on DAPT.

Factors Associated With Clopidogrel Adherence in Community-Dwelling Patients.

The purpose of this study was to characterize predictors of adherence to clopidogrel therapy focusing on patients' perceptions of clopidogrel and nuisance bleeding. This was a cross-sectional study of community-dwelling cardiovascular patients with a self-reported prescription for clopidogrel. Self-report questionnaires assessed depressive symptoms, social support, nuisance bleeding, perceptions of clopidogrel, and adherence to therapy. Low, moderate, and high adherence groups based on the Morisky Medication Adherence Scale were compared and hierarchical multiple linear regression analysis was used to predict adherence. A total of 102 subjects were enrolled, and 55%, 28%, and 16% were classified as having low, moderate, and high adherence, respectively. Greater perceptions of clopidogrel necessity, lower perception of clopidogrel concern, and increased severity of nuisance bleeding were predictors of better adherence. Data from this cross-sectional study suggest that concerns about clopidogrel and feelings about its necessity play an important role in clopidogrel adherence.

Bazedoxifene and Conjugated Equine Estrogen: A Combination Product for the Management of Vasomotor Symptoms and Osteoporosis Prevention Associated with Menopause.

Bazedoxifene (BZA), a third-generation selective estrogen receptor modulator (SERM), has been combined with conjugated equine estrogen (CE) to create a tissue selective estrogen complex (TSEC) for the management of vasomotor symptoms (VMS) and the prevention of osteoporosis (OP) associated with menopause. Both of these outcomes of menopause contribute to significant negative effects on quality of life and increases in utilization of health care resources and dollars. Current treatment modalities for VMS and OP include estrogen therapy that requires the use of progestin in women who have a uterus to reduce the risk of endometrial hyperplasia and resultant cancer. However, progestin use results in nuisance bleeding as well as a further increased risk of breast cancer when combined with estrogen. And while SERMs can be used to prevent OP, their use alone has been shown to increase hot flashes. The combination of BZA and CE does not require progestin treatment with CE as the BZA component acts as an antagonist on endometrial tissue. The U.S. Food and Drug Administration approval of BZA/CE in 2013 was based on a series of five phase 3 studies known as the Selective estrogens, Menopause And Response to Therapy (SMART) trials. These trials, in their entirety, evaluated the impact of BZA/CE on VMS frequency and severity, bone mineral density, bone turnover markers, vaginal symptoms, lipid profiles, sleep, quality of life, breast density, and endometrial safety. The approved dose of BZA/CE is 20 mg BZA and 0.45 mg CE. Although this TSEC manages VMS while opposing breast and endometrial proliferation, preventing bone resorption, and improving lipid profiles, long-term experience with BZA/CE is currently lacking.