Risk of major bleeding by ethnicity and socioeconomic deprivation among 488,107 people in primary care: a cohort study

Abstract Background Antithrombotic medications (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. Methods Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Māori, the indigenous people of New Zealand) aged 30–79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n = 15,212), (2) CVD and no AF (n = 43,790), (3) no CVD or AF (n = 429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups. Results In all three subgroups (AF, CVD, no CVD/AF), Māori (adjHR 1.63 [1.39–1.91], 1.24 [1.09–1.42], 1.57 [95% CI 1.45–1.70], respectively), Pacific people (adjHR 1.90 [1.58–2.28], 1.30 [1.12–1.51], 1.62 [95% CI 1.49–1.75], respectively) and Chinese people (adjHR 1.53 [1.08–2.16], 1.15 [0.90–1.47], 1.13 [95% CI 1.01–1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Māori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [1.02–1.12], 1.07 [1.03–1.10], 1.10 [95% CI 1.08–1.12], respectively, for each increase in socioeconomic deprivation quintile). Conclusion Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD.

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Risk of Major Bleeding by Ethnicity and Socioeconomic Deprivation among 488,107 People in Primary Care: A Cohort Study

10.21203/rs.3.rs-144018/v1 ◽

2021 ◽

Author(s):

Wai Chung Tse ◽

Corina Grey ◽

Matire Harwood ◽

Rod Jackson ◽

Andrew Kerr ◽

...

Keyword(s):

Primary Care ◽

Cohort Study ◽

New Zealand ◽

Major Bleeding ◽

Statistical Significance ◽

Bleeding Risk ◽

Socioeconomic Deprivation ◽

Chinese People ◽

Major Bleed ◽

Increased Risk

Abstract Background: Antithrombotic medications (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. Methods: Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Māori, the indigenous people of New Zealand) aged 30-79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n=15,212), (2) CVD and no AF (n=43,790), (3) no CVD or AF (n=429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups. Results: In all three subgroups (AF, CVD, no CVD/AF), Māori (adjHR 1.63 [1.39-1.91], 1.24 [1.09-1.42], 1.57 [95% CI 1.45-1.70], respectively), Pacific people (adjHR 1.90 [1.58-2.28], 1.30 [1.12-1.51], 1.62 [95% CI 1.49-1.75], respectively) and Chinese people (adjHR 1.53 [1.08-2.16], 1.15 [0.90-1.47], 1.13 [95% CI 1.01-1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Māori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [95% CI 1.02-1.12, 1.07 [1.03-1.10], 1.10 [1.08-1.12], respectively, for each increase in socioeconomic deprivation quintile). Conclusion: Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD. Primary Funding Source: The Health Research Council of New Zealand

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Risk of Major Bleeding by Ethnicity and Socioeconomic Deprivation among 488,107 People in Primary Care: A Cohort Study

10.21203/rs.3.rs-98289/v1 ◽

2020 ◽

Author(s):

Wai Chung Tse ◽

Corina Grey ◽

Matire Harwood ◽

Rod Jackson ◽

Andrew Kerr ◽

...

Keyword(s):

Primary Care ◽

Cohort Study ◽

New Zealand ◽

Major Bleeding ◽

Bleeding Risk ◽

Socioeconomic Deprivation ◽

Chinese People ◽

Major Bleed ◽

Increased Risk ◽

Antithrombotic Medication

Abstract Background: Antithrombotic medication (antiplatelets and anticoagulants) reduce the risk of cardiovascular disease (CVD), but with the disadvantage of increasing bleeding risk. Ethnicity and socioeconomic deprivation are independent predictors of major bleeds among patients without CVD, but it is unclear whether they are also predictors of major bleeds among patients with CVD or atrial fibrillation (AF) after adjustment for clinical variables. Methods: Prospective cohort study of 488,107 people in New Zealand Primary Care (including 64,420 Māori, the indigenous people of New Zealand) aged 30-79 years who had their CVD risk assessed between 2007 and 2016. Participants were divided into three mutually exclusive subgroups: (1) AF with or without CVD (n=15,212), (2) CVD and no AF (n=43,790), (3) no CVD or AF (n=429,105). Adjusted hazards ratios (adjHRs) were estimated from Cox proportional hazards models predicting major bleeding risk for each of the three subgroups to determine whether ethnicity and socioeconomic deprivation are independent predictors of major bleeds in different cardiovascular risk groups . Results: In all three subgroups (AF, CVD, no CVD/AF), Māori (adjHR 1.63 [1.39-1.91], 1.24 [1.09-1.42], 1.57 [95% CI 1.45-1.70], respectively), Pacific people (adjHR 1.90 [1.58-2.28], 1.30 [1.12-1.51], 1.62 [95% CI 1.49-1.75], respectively) and Chinese people (adjHR 1.53 [1.08-2.16], 1.15 [0.90-1.47], 1.13 [95% CI 1.01-1.26], respectively) were at increased risk of a major bleed compared to Europeans, although for Chinese people the effect did not reach statistical significance in the CVD subgroup. Compared to Europeans, Māori and Pacific peoples were generally at increased risk of all bleed types (gastrointestinal, intracranial and other bleeds). An increased risk of intracranial bleeds was observed among Chinese and Other Asian people and, in the CVD and no CVD/AF subgroups, among Indian people. Increasing socioeconomic deprivation was also associated with increased risk of a major bleed in all three subgroups (adjHR 1.07 [95% CI 1.02-1.12, 1.07 [1.03-1.10], 1.10 [1.08-1.12], respectively, for each increase in socioeconomic deprivation quintile). Conclusion: Ethnicity and socioeconomic status should be considered in bleeding risk assessments to guide the use of antithrombotic medication for the management of AF and CVD. Primary Funding Source: The Health Research Council of New Zealand

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Bleeding Risk in a Cohort of Ambulatory Cancer Patients Receiving Outpatient Prophylactic Anticoagulation for Venous Thrombosis Prevention

Blood ◽

10.1182/blood-2019-128831 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 709-709

Author(s):

Andrew B Wilks ◽

Daniel Douce ◽

Steven Ades ◽

Mary Cushman ◽

Neil A. Zakai ◽

...

Keyword(s):

Lung Cancer ◽

High Risk ◽

Cancer Patients ◽

Major Bleeding ◽

Bleeding Risk ◽

Bleeding Events ◽

Major Bleed ◽

Prophylactic Dose ◽

Increased Risk ◽

Prophylactic Anticoagulation

Background: Recent clinical trials have evaluated the safety and efficacy of direct oral anticoagulant (DOAC) therapy for venous thromboembolism (VTE) prophylaxis in cancer outpatients at high risk for thrombosis. Bleeding risk in these trials were approximately 2% over the first 6 months of therapy. For individual patients, the utility of prophylactic anticoagulation (AC) depends on an acceptable safety profile between bleeding and thrombosis. We investigated whether ambulatory cancer patients on contemporary cancer-directed therapies and prophylactic AC had an increased risk of major bleeds over the first 6 months of therapy. Methods: As part of a single-center prospective cohort study, we assessed consecutive ambulatory patients initiating cancer-directed treatment, risk-stratified these patients for VTE using the Khorana score and educated them about VTE. High risk patients (Khorana score ≥3) were offered prophylactic AC. Major bleeding events and minor bleeding events (based on ISTH standard definitions) were prospectively captured via billing code screening and confirmed by physician review of the medical record. Logistic regression was used to compare the odds of developing a major bleed within 6 months in those who received prophylactic AC compared to those that did not. Results: A total of 1,210 patients were enrolled from October 2015 - June 2018, of which, 640 were women (52.9%). The most common cancers were gastrointestinal 270 (22%), lung 213 (18%), and breast 198 (16%). There were 393 patients (32%) with a Khorana score of 0, 706 (58%) with a Khorana score of 1-2, and 111 (9%) with a score of ≥3. A total of 421 patients received any AC (LMWH or DOAC). Of these, 282 received a prophylactic dose anticoagulant and 139 were receiving a full dose anticoagulant prior to enrolling for other medical reasons. Prophylactic dose anticoagulants prescribed included apixaban in 107 (41%), rivaroxaban in 6 (2.3%), enoxaparin in 119 (45.7%), and other heparin products in 50 (19.2%). A total of 27 (2.33%) major bleeds and 22 (1.81%) minor bleeds occurred within the first 6 months of starting therapy. Of these bleeding events, 8 (2.8%) occurred in those on prophylactic AC, and 6 (4.3%) occurred in those on full dose AC. The odds ratio (OR) of developing a major bleed on any type of AC was 1.78 [CI 0.817-3.88]. The OR of major bleeding on prophylactic AC was 1.49 [CI 0.64-3.479]. The OR of major bleed was highest in lung cancer patients on prophylactic AC (OR 2.81, CI 1.27-6.25). Men, when compared to women, were more likely to bleed on prophylactic AC in the first six month (OR 0.2; CI 0.07-0.52). The OR for major bleed with each 1 year increase in age was 1.02 (CI 0.99, 1.06). The OR of bleeding with a high risk Khorana score (≥3) compared to a lower score was 1.04 (CI 0.73-1.50). Conclusion: During the first six months of therapy, prophylactic AC was associated with an increased risk of major bleeding events in patients on cancer-directed therapy. In this study, the rate of major bleeding was similar as compared to published clinical trials. Neither age nor higher Khorana score were associated with an increased risk of major bleeds in patients on prophylactic AC. The finding that men, when compared to women, and patients with lung cancer may have an increased risk of major bleeding while on prophylactic AC and cancer-directed chemotherapy suggests these groups may warrant both increased education and monitoring to ensure safety while on prophylactic AC. Disclosures No relevant conflicts of interest to declare.

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High Soluble Thrombomodulin Is Associated with an Increased Risk of Major Bleeding during Treatment with Oral Anticoagulants: A Case–Cohort Study

Thrombosis and Haemostasis ◽

10.1055/s-0040-1715459 ◽

2020 ◽

Author(s):

Myrthe M. A. Toorop ◽

Nienke van Rein ◽

Suzanne C. Cannegieter ◽

Felix J. M. van der Meer ◽

Pieter H. Reitsma ◽

...

Keyword(s):

Cohort Study ◽

Vitamin K ◽

Major Bleeding ◽

Cox Regression ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

International Normalized Ratio ◽

Soluble Thrombomodulin ◽

Major Bleed ◽

Increased Risk

Abstract Background Major bleeding occurs in 1 to 3% of patients treated with oral anticoagulants per year. Biomarkers may help to identify high-risk patients. A proposed marker for major bleeding while using anticoagulants is soluble thrombomodulin (sTM). Methods Plasma was available from 16,570 patients of the BLEEDS cohort that consisted of patients who started treatment with vitamin K antagonists between 2012 and 2014. A case–cohort study was performed including all patients with a major bleed (n = 326) during follow-up and a random sample of individuals selected at baseline (n = 652). Plasma sTM levels were measured and stratified by percentiles. Patients were also categorized by international normalized ratio (INR). Adjusted hazard ratios (for age, sex, hypertension, and diabetes) with 95% confidence intervals (CIs) were estimated by means of Cox regression. Results Plasma sTM levels were available for 263 patients with a major bleed and 538 control subjects. sTM levels were dose-dependently associated with risk of major bleeding, with a 1.9-fold increased risk (95% CI: 1.1–3.1) for levels above the 85th percentile versus the <25th percentile. A high INR (≥4) in the presence of high (≥70th percentile) sTM levels was associated with a 7.1-fold (95% CI: 4.1–12.3) increased risk of major bleeding, corresponding with a bleeding rate of 14.1 per 100 patient-years. Conclusion High sTM levels at the start of treatment are associated with major bleeding during vitamin K antagonist treatment, particularly in the presence of a high INR.

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Complex antithrombotic therapy and bleeding risk in patients with peripheral arterial disease

European Heart Journal ◽

10.1093/ehjci/ehaa946.2396 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

A Tseng ◽

S Bhatt ◽

M Girardo ◽

D Liedl ◽

P Wennberg ◽

...

Keyword(s):

Peripheral Arterial Disease ◽

Triple Therapy ◽

Major Bleeding ◽

Antithrombotic Therapy ◽

Oral Anticoagulants ◽

Bleeding Risk ◽

Arterial Disease ◽

Risk Of Bleeding ◽

Increased Risk ◽

Peripheral Arterial

Abstract Introduction Antiplatelet therapy is the cornerstone of treatment for many atherosclerotic vascular pathologies including peripheral arterial disease (PAD). Patients with PAD often have comorbid conditions that require complex antithrombotic therapy, i.e. combined antiplatelet and anticoagulation. Methods All adult patients undergoing ankle brachial index (ABI) measurements were included in the study. ABI values between 1.00 and 1.40 were considered normal, and values below 1.00 or above 1.40 were considered PAD. Demographic, comorbidity and outcome data were obtained using diagnostic codes from the electronic health record. Three medication classes were analyzed: aspirin, non-aspirin oral antiplatelets (e.g. P2Y12 inhibitors) and oral anticoagulants (warfarin and the direct oral anticoagulants). Medication use was determined for patients who had been on a medication for at least one year. Cox proportional hazard analysis for the time to first bleeding event was analyzed. Bleeding was defined as any bleeding requiring medical evaluation (including clinically-relevant non-major bleeding and major bleeding). Results In all, 40,144 patients were included in the analysis (mean age 66±15, 43% female). Patients with PAD were more likely to be on double therapy (one antiplatelet with anticoagulation) (28% vs 19%) and triple therapy (dual antiplatelet with anticoagulation) (10% vs 4%). Unadjusted hazard ratios for bleeding risk showed increased risk of bleeding for patients with PAD (1.18, 95% confidence interval [CI]: 1.08–1.29), though the association is no longer present after adjustment for antithrombotic therapy. Adjusting for age, sex and PAD class, compared to no antithrombotic therapy, there was increased risk of bleeding for monotherapy (1.91, 95% CI: 1.61–2.26), double therapy (3.40, 95% CI: 2.89–4.00) and triple therapy (5.00, 95% CI: 4.21–5.96). Among medications, aspirin and anticoagulant use was independently associated with the greatest increase in risk of bleeding. Conclusion Patients in PAD are at increased risk of bleeding secondary to antithrombotic therapy. Complex antithrombotic therapy with double or triple therapy confer additional bleeding risk, particularly regimens containing aspirin and oral anticoagulants. Funding Acknowledgement Type of funding source: None

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Coeliac disease and invasive pneumococcal disease: a population-based cohort study

Epidemiology and Infection ◽

10.1017/s0950268816003204 ◽

2017 ◽

Vol 145 (6) ◽

pp. 1203-1209 ◽

Cited By ~ 9

Author(s):

A. RÖCKERT TJERNBERG ◽

J. BONNEDAHL ◽

M. INGHAMMAR ◽

A. EGESTEN ◽

G. KAHLMETER ◽

...

Keyword(s):

Cohort Study ◽

Coeliac Disease ◽

Invasive Pneumococcal Disease ◽

Pneumococcal Disease ◽

Cox Regression ◽

Statistical Significance ◽

Pneumococcal Vaccination ◽

Population Based ◽

Increased Risk ◽

Severe Infections

SUMMARYSevere infections are recognized complications of coeliac disease (CD). In the present study we aimed to examine whether individuals with CD are at increased risk of invasive pneumococcal disease (IPD). To do so, we performed a population-based cohort study including 29 012 individuals with biopsy-proven CD identified through biopsy reports from all pathology departments in Sweden. Each individual with CD was matched with up to five controls (n = 144 257). IPD events were identified through regional and national microbiological databases, including the National Surveillance System for Infectious Diseases. We used Cox regression analyses to estimate hazard ratios (HRs) for diagnosed IPD. A total of 207 individuals had a record of IPD whereas 45/29 012 had CD (0·15%) and 162/144 257 were controls (0·11%). This corresponded to a 46% increased risk for IPD [HR 1·46, 95% confidence interval (CI) 1·05–2·03]. The risk estimate was similar after adjustment for socioeconomic status, educational level and comorbidities, but then failed to attain statistical significance (adjusted HR 1·40, 95% CI 0·99–1·97). Nonetheless, our study shows a trend towards an increased risk for IPD in CD patients. The findings support results seen in earlier research and taking that into consideration individuals with CD may be considered for pneumococcal vaccination.

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Refugee-like migrants have similar health needs to refugees: a New Zealand post-settlement cohort study

BJGP Open ◽

10.3399/bjgpopen20x101013 ◽

2020 ◽

Vol 4 (1) ◽

pp. bjgpopen20X101013

Author(s):

Jonathan Donald Kennedy ◽

Serena Moran ◽

Sue Garrett ◽

James Stanley ◽

Jenny Visser ◽

...

Keyword(s):

Primary Care ◽

Cohort Study ◽

New Zealand ◽

Primary Care Practice ◽

Social Care ◽

Hospital Admissions ◽

Outpatient Service ◽

Care Practice ◽

Care Needs ◽

Health And Social Care

BackgroundRefugees and asylum seekers have specific health and social care needs on arrival in a resettlement country. A third group — migrants with a refugee-like background (refugee-like migrants) — are less well defined or understood.AimUsing routinely collected data, this study compared demographics, interpreter need, and healthcare utilisation for cohorts of refugee-like migrants and refugees.Design & settingA retrospective cohort study was undertaken in Wellington, New Zealand.MethodData were obtained for refugee-like migrants and refugees accepted under the national quota system (quota refugees), who enrolled in a New Zealand primary care practice between 2011 and 2015. Data from the primary care practice and nationally held hospital and outpatient service databases, were analysed. Age and sex standardisation adjusted for possible differences in cohort demographic profiles.ResultsThe cohorts were similar in age, sex, deprivation, and interpreter need. Refugee-like migrants were found to have similar, but not identical, health and social care utilisation to quota refugees. Primary care nurse utilisation was higher for refugee-like migrants. Clinical entries in the primary care patient record were similar in rate for the cohorts. Emergency department utilisation and hospital admissions were similar. Hospital outpatient utilisation was lower for refugee-like migrants.ConclusionThis research suggests that health, social care, and other resettlement services should be aligned for refugee-like migrants and quota refugees. This would mean that countries accepting quota refugees should plan for health and social care needs of subsequent refugee-like migrant family migration. Further research should investigate matched larger-scale national health and immigration datasets, and qualitatively explore factors influencing health-seeking behaviour of refugee-like migrants.

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Abstract 299: Association of Chronic Lung Disease with Treatments and Outcomes of Acute Coronary Syndromes: Results from the NCDR®

Circulation Cardiovascular Quality and Outcomes ◽

10.1161/circoutcomes.5.suppl_1.a299 ◽

2012 ◽

Vol 5 (suppl_1) ◽

Author(s):

Jonathan R Enriquez ◽

James A de Lemos ◽

Ramin Farzaneh-Far ◽

Anand Rohatgi ◽

S. A Peng ◽

...

Keyword(s):

Hospital Mortality ◽

Lung Disease ◽

Major Bleeding ◽

Chronic Lung Disease ◽

Beta Blockers ◽

Bleeding Risk ◽

Bleeding Complications ◽

Processes Of Care ◽

Increased Risk ◽

The Impact

Background: Previous reports are conflicting regarding outcomes, treatments, and processes of care after acute myocardial infarction (MI) for patients with chronic lung disease (CLD). Methods: Using the NCDR ACTION Registry ® -GWTG ™ (AR-G), demographics, clinical characteristics, treatments, processes of care, and in-hospital adverse events after NSTEMI and STEMI were compared between patients with (n= 22,624; 14.2%) and without (n= 136,266; 85.8%) CLD. CLD was defined by a history of COPD, chronic bronchitis, or emphysema. Multivariable adjustment using published AR-G in-hospital mortality and major bleeding risk adjustment models was performed to quantify the impact of CLD on treatments and outcomes. Results: CLD was present in 10.1% of STEMI patients and 17.0% of NSTEMI patients. In both STEMI and NSTEMI, CLD patients were older, more likely to be female, and had more comorbidities including diabetes, renal disease, prior MI and heart failure, compared to those without CLD. Although on admission CLD patients were more likely to be on cardiovascular medications, by discharge slightly fewer CLD patients received composite core measures (aspirin, beta-blockers, ACE-inhibitors, and statins) (table). In NSTEMI, CLD was also associated with less use of invasive procedures and with increased risk of both death and major bleeding. In STEMI, major bleeding but not mortality was increased. Conclusions: CLD is a common comorbidity and is independently associated with an increased risk for major bleeding after MI. In NSTEMI, CLD is also associated with receiving fewer evidence-based medications, less timely angiography and revascularization, and increased in-hospital mortality. Close attention should be given to this high-risk subgroup for the prevention and management of bleeding complications after MI, and further investigation is needed to determine the reasons for treatment and outcome disparities in NSTEMI.

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Abstract 13290: GDF-15 at One Month After an Acute Coronary Syndrome is Associated With Increased Risk of Major Bleeding - A PLATO Biomarker Substudy

Circulation ◽

10.1161/circ.132.suppl_3.13290 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Daniel Lindholm ◽

Emil Hagström ◽

Stefan K James ◽

Richard C Becker ◽

Christopher P Cannon ◽

...

Keyword(s):

Primary Endpoint ◽

Major Bleeding ◽

Proportional Hazards Model ◽

Bleeding Risk ◽

Cox Proportional Hazards Model ◽

Antiplatelet Treatment ◽

Additional Information ◽

Coronary Syndrome ◽

Increased Risk ◽

Dual Antiplatelet Treatment

Introduction: Levels of Growth Differentiation Factor-15 (GDF-15) are associated with major bleeding events in acute coronary syndromes (ACS), when measured at the time of initial presentation. We hypothesized that an additional measurement of GDF-15 at 1 month after ACS provides additional information regarding risk of major bleeding. Methods: In the PLATO trial, levels of GDF-15 were determined in 4049 ACS patients at both baseline and at 1 month, using an immunoassay (Roche). The primary endpoint was non-CABG related major bleeding. A 1-month landmark analysis was performed, in relation to GDF-15 elevation status at baseline and 1 month, using a cutoff of 1800 ng/L. The relation between GDF-15 at 1 month and the primary endpoint from 1 month onward was evaluated using a Cox proportional hazards model; adjusting for baseline GDF-15, age, anemia (hemoglobin <130 g/L in men, <120 g/L in women), impaired renal function (eGFR <50 mL/min/1.73m2), and history of gastrointestinal bleeding. Results: In the unadjusted analysis, patients with GDF-15 >1800 ng/L at 1 month had increased bleeding rates during follow-up, irrespective of the baseline value. Patients with GDF-15 ≤1800 ng/L at 1 month had lower bleeding risk regardless of initial level (see figure). In the adjusted analysis, GDF-15 >1800 ng/L at 1 month was independently associated with the outcome, hazard ratio 3.39 (95% CI 1.89-6.09). Conclusions: The level of GDF-15 at 1 month after ACS is related to the risk of bleeding during dual antiplatelet treatment. Assessment of GDF-15 level at 1 month provides additional information on the subsequent bleeding risk, regardless of the patient’s index GDF-15 level in the acute phase, and may therefore be helpful for decision-making on continued dual antiplatelet treatment.

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Effect of oral antiplatelet agents on major bleeding in users of coumarins

Thrombosis and Haemostasis ◽

10.1160/th08-05-0290 ◽

2008 ◽

Vol 100 (12) ◽

pp. 1076-1083 ◽

Cited By ~ 19

Author(s):

Olaf H. Klungel ◽

Patrick C. Souverein ◽

Anthonius de Boer ◽

Tom Schalekamp

Keyword(s):

Major Bleeding ◽

Conditional Logistic Regression ◽

Vitamin K Antagonists ◽

Antiplatelet Agents ◽

Bleeding Risk ◽

Primary Diagnosis ◽

Antiplatelet Drugs ◽

Antiplatelet Drug ◽

Concurrent Use ◽

Increased Risk

SummaryTreatment with vitamin K antagonists (coumarins) is associated with an increased risk of bleeding. In order to elucidate the bleeding risk of users of antiplatelet drugs among users of coumarins, we assessed the odds ratio of major bleeding associated with use of antiplatelet drugs in users of the coumarins acenocoumarol and phenprocoumon. We used data froma Dutch record linkage system, including pharmacy and linked hospitalization records for approximately two million subjects, to conduct a nested case control study in a cohort of new users of coumarins. Cases were patients who were hospitalized with a primary diagnosis of major bleeding while taking coumarin and were matched with up to four control subjects. Conditional logistic regression analysis was used to determine ORs and 95% confidence intervals (CI).We identified 1848 case patients who were matched to 5818 controls. Users of clopidogrel or aspirin showed a significantly increased risk of hospitalization because of major bleeding (OR 2.9, 95% CI 1.2–6.9 and OR 1.6, 95% CI 1.3–1.9, respectively), whereas users of dipyridamole and combinations of antiplatelet drugs showed a strong trend (OR 1.5, 95% CI 1.0–2.3 and OR 1.8, 95 % CI 1.0–3.3, respectively). In all cases, the risks were greater for upper gastrointestinal bleedings than for other bleedings. In conclusion, the use of any antiplatelet drug increases the risk of hospitalization for major bleeding among users of coumarins. Concurrent use of clopidogrel or dipyridamole and coumarins is probably not safer than concurrent use of aspirin and coumarins.

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