Prognosis in patients with prior myocardial infarction and PEGASUS-TIMI 54 criteria in the CLARIFY registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
S Biscaglia ◽  
G Campo ◽  
K Fox ◽  
J.C Tardif ◽  
M Tendera ◽  
...  
Keyword(s):  
High Risk ◽  
Major Bleeding ◽  
Artery Bypass ◽  
Real Life ◽  
Prolonged Treatment ◽  
Funding Source ◽  
Inclusion Criteria ◽  
Private Company ◽  
Exclusion Criteria ◽  
Coronary Syndrome

Abstract Background/Introduction The PEGASUS-TIMI 54 trial showed that prolonged treatment with ticagrelor reduces the cumulative occurrence of ischemic adverse events. CLARIFY is the biggest real life registry on chronic coronary syndrome. Purpose - To evaluate the percentage of patients eligible for long-term ticagrelor therapy in the CLARIFY registry. – To compare the outcome of this subgroup of patients with those with PEGASUS exclusion criteria or without PEGASUS inclusion criteria. Methods Within the CLARIFY population, we selected post MI patients and we excluded those with missing info (post MI evaluable population). Then, we divided patients into 3 groups: excluded (meeting PEGASUS exclusion criteria, namely use of P2Y12 receptor antagonists or chronic oral anticoagulant, any stroke, coronary-artery bypass grafting in the past 5 years); eligible (meeting PEGASUS high-risk inclusion criteria, namely age≥65 years; diabetes; multivessel disease; creatinine clearance <60 ml/min) and ineligible (not meeting PEGASUS high-risk inclusion criteria). We therefore compared the ischemic (CV death, MI and stroke) and bleeding (major bleeding) outcome of the 3 groups adjusting for age, sex, smoking and geographical region. Results Among the 11811 post-MI evaluable patients, 4706 (39.8%) were included in the eligible group, 5715 (48.4%) in the excluded group, and 1390 in the ineligible group (11.8%). Both the ischemic and bleeding endpoints were significantly different among the 3 groups with the excluded patients with the worst and ineligible patients with the best outcome (see table). The same trend was shown for CV death, while the occurrence of MI was not significantly different among the 3 groups. In the eligible group, the ratio between ischemic and bleeding events was 6:1, whereas between CV death and major bleeding was 3.5:1. Conclusions Around 40% of CLARIFY post-MI patients could benefit from prolonged ticagrelor therapy. In this group of patients, ischemic risk seems to be higher than the bleeding one. Ischemic & bleeding risk in the 3 groups Funding Acknowledgement Type of funding source: Private company. Main funding source(s): CLARIFY registry was funded by Servier

Applicability of the VOYAGER trial criteria: a cohort study on patients in the nationwide Danish Vascular Registry

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M Soegaard ◽  
P.B Nielsen ◽  
F Skjoeth ◽  
T.B Larsen ◽  
N Eldrup
Keyword(s):  
Myocardial Infarction ◽  
Lower Extremity ◽  
Major Adverse Cardiovascular Events ◽  
Funding Source ◽  
Inclusion Criteria ◽  
Private Company ◽  
Exclusion Criteria ◽  
Dual Pathway ◽  
Event Rates ◽  
Lower Extremity Revascularization

Abstract Introduction Peripheral artery disease (PAD) carries a high risk of debilitating stroke, myocardial infarction, and death. The VOYAGER PAD trial investigates whether rivaroxaban 2.5 mg plus aspirin vs aspirin alone leads to a reduction in major adverse cardiovascular events (MACE) in patients with symptomatic PAD undergoing revascularization. However, it is unclear whether patients enrolled in VOYAGER PAD reflect those undergoing lower extremity revascularization in daily clinical practice. Purpose To describe the proportion of patients eligible for the VOYAGER PAD trial within the nationwide Danish Vascular Registry (DVR), the reasons for ineligibility, and rates of cardiovascular outcomes in VOYAGER-eligible and VOYAGER-ineligible patients. Methods We identified and characterized all patients from 2000–2016 undergoing open surgical or endovascular revascularization for symptomatic PAD in the DVR and applied the VOYAGER inclusion and exclusion criteria. We computed one-year rates per 100 person-years of VOYAGER PAD trial endpoints of MACE, myocardial infarction, ischemic stroke, major amputation, major bleeding, cardiovascular (CV) death, and all cause death. Results In the DVR, 32,911 patients underwent lower extremity revascularization for symptomatic PAD and were evaluated for eligibility. Among these, 32.2% had at least one exclusion criteria and an additional 40.6% without exclusion criteria did not fulfil inclusion criteria. The “VOYAGER-eligible” population therefore comprised 27.2% of the identified patients (Figure 1A). Main reasons for exclusion were atrial fibrillation (30.7%), poorly regulated hypertension (19.6%), PCI or ACS within 12 months before (16.0%), treatment with strong inhibitors or inducers of cytochrome P450 (9.2%), active cancer (8.8%), and severe renal failure (8.3%). Main reasons for non-inclusion were aorto-iliac procedures (79.0%), non-successful revascularization (13.1%), and age<50 years (7.1%). Compared with “VOYAGER-eligible” patients, event rates were slightly lower among patients in the DVR not fulfilling inclusion criteria and markedly higher for “VOYAGER excluded” patients (Figure 1B). Conclusion In this nationwide cohort of symptomatic PAD patients undergoing lower extremity revascularization, 27.2% full filled the inclusion and exclusion criteria for dual pathway therapy in the VOYAGER PAD trial. Non-inclusion predominantly related to aorto-iliac procedures and were associated with lower event rates. Future studies are needed to clarify if these patients could also benefit from dual pathway therapy. Figure 1 Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer AG, Berlin, Germany

Edoxaban treatment of elderly patients with atrial fibrillation in routine clinical practice: 1-year results of the non-interventional Global ETNA-AF program

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Yamashita ◽  
C.C Wang ◽  
Y.-H Kim ◽  
R De Caterina ◽  
P Kirchhof ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Clinical Practice ◽  
Major Bleeding ◽  
Intracranial Haemorrhage ◽  
Clinical Care ◽  
Oral Anticoagulants ◽  
Clinical Event ◽  
Funding Source ◽  
Private Company ◽  
All Cause Mortality

Abstract Background The prevalence of atrial fibrillation (AF) and the need for appropriate anticoagulation increase with age. The benefit/risk profile of direct oral anticoagulants such as edoxaban in elderly population with AF in regular clinical practice is therefore of particular interest. Purpose Analyses of Global ETNA-AF data were performed to report patient characteristics, edoxaban treatment, and 1-year clinical events by age subgroups. Methods Global ETNA-AF is a multicentre, prospective, noninterventional program conducted in Europe, Japan, Korea, Taiwan, and other Asian countries. Demographics, baseline characteristics, and 1-year clinical event data were analysed in four age subgroups. Results Of 26,823 patients included in this analysis, 50.4% were ≥75 years old and 11.6% were ≥85 years. Increase in age was generally associated with lower body weight, lower creatinine clearance, higher CHA2DS2-VASc and HAS-BLED scores, and a higher percentage of patients receiving the reduced dose of 30 mg daily edoxaban. At 1-year, rates of ISTH major bleeding and ischaemic stroke were generally low across all age subgroups. The proportion of intracranial haemorrhage within major bleeding events was similar across age groups. All-cause mortality increased with age more than cardiovascular mortality. Conclusion Data from Global ETNA-AF support the safety and effectiveness of edoxaban in elderly AF patients (including ≥85 years) in routine clinical care with only a small increase in intracranial haemorrhage. The higher all-cause mortality with increasing age is not driven by cardiovascular causes. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Daiichi Sankyo

scholarly journals What is the potential cardiovascular risk reduction associated with achieving LDL-C levels recommended in the ESC/EAS guidelines for very high-risk patients? Data from 18 European countries

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
K.K Ray ◽  
S Bray ◽  
A.L Catapano ◽  
N Poulter ◽  
G Villa
Keyword(s):  
High Risk ◽  
Risk Reduction ◽  
Absolute Risk ◽  
European Countries ◽  
Lipid Lowering ◽  
Funding Source ◽  
Lipid Lowering Therapy ◽  
Cardiovascular Risk Reduction ◽  
Private Company ◽  
Very High

Abstract Background/Introduction For patients at very-high risk of cardiovascular (CV) events, the 2016 ESC/EAS dyslipidaemia guidelines recommended lipid-lowering therapy (LLT) to achieve an LDL-C level below 70 mg/dL. This was lowered to an LDL-C level below 55 mg/dL in the 2019 guidelines. Purpose To assess: 1) the risk profile of European patients with established atherosclerotic CV disease (ASCVD) receiving LLT; and 2) the treatment gap between the estimated risk and the population benefits if all patients were to achieve LDL-C levels of 70 mg/dL and 55 mg/dL. Methods We used data from Da Vinci, an observational cross-sectional study conducted across 18 European countries. Data were collected at a single visit between June 2017 and November 2018, for consented adults who had received any LLT in the prior 12 months and had an LDL-C measurement in the prior 14 months. LDL-C level was assessed at least 28 days after starting the most recent LLT (stabilised LLT). For each patient with established ASCVD receiving stabilised LLT, we: 1) calculated their absolute LDL-C reduction required to achieve LDL-C levels of 70 mg/dL and 55 mg/dL; 2) predicted their 10-year CV risk using the REACH score based on demographic and medical history; 3) simulated their relative risk reduction (RRR) by randomly sampling from the probability distribution of the rate ratio per 38.7 mg/dL (1 mmol/L) estimated by the Cholesterol Treatment Trialists Collaboration meta-analysis; and 4) calculated their absolute risk reduction (ARR) achieved by meeting LDL-C levels of 70 mg/dL and 55 mg/dL. Results A total of 2039 patients with established ASCVD were included in the analysis. Mean (SD) LDL-C was 83.1 (35.2) mg/dL. 40.4% and 19.3% of patients achieved LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. Mean (SD) 10-year CV risk calculated using the REACH score was 36.3% (15.4%). Mean absolute LDL-C reductions of 19.6 mg/dL and 30.4 mg/dL were needed to reach LDL-C levels of 70 mg/dL and 55 mg/dL, respectively. When adjusted for the LDL-C reduction required to achieve an LDL-C level of 70 mg/dL, mean ARR was 3.0%, leaving a mean (SD) residual 10-year CV risk of 33.3% (15.5%). When adjusted for the LDL-C reduction required to achieve an LDL-C level of 55 mg/dL, mean ARR was 4.6%, leaving a mean (SD) residual 10-year CV risk of 31.7% (15.2%). Conclusion(s) In a contemporary European cohort with ASCVD receiving LLT, the 10-year risk of CV events is high and many patients do not achieve LDL-C levels of 55 mg/dL or even of 70 mg/dL. Moreover, even if all patients were to achieve recommended LDL-C levels, they would still remain at a high residual risk of CV events. These data suggest these patients require even more intensive LLT. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Amgen

scholarly journals Outcomes associated with modern treatment paradigms in connective tissue disease (CTD)-associated pulmonary arterial hypertension (PAH): a meta-analysis of randomized controlled trials (RCTs)

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
V McLaughlin ◽  
C Zhao ◽  
J.G Coghlan ◽  
L.S Chung ◽  
S.C Mathai ◽  
...  
Keyword(s):  
Drug Treatment ◽  
Treatment Effect ◽  
Meta Analysis ◽  
Response To Treatment ◽  
Funding Source ◽  
Class Iii ◽  
Inclusion Criteria ◽  
Private Company ◽  
Mortality Event

Abstract Background CTD-PAH has historically represented a PAH subtype with poor prognosis. New therapies, as well as combination therapy approaches targeting multiple pathways have been approved for PAH based on RCTs. CTD-PAH patients comprise a subgroup of the RCT populations and efficacy analyses are based on subgroup analyses which can be less reliable than the overall analysis. We conducted a meta-analysis of RCTs of approved PAH therapies to evaluate outcomes of patients with CTD-PAH. Purpose To use meta-analysis to determine response to treatment in patients with CTD-PAH. Methods The PubMed and EMBASE databases were searched for English-only articles published between January 1, 2000 and November 25, 2019. Inclusion criteria were multicenter RCTs that enrolled adults with WHO group 1 pulmonary hypertension (PAH); enrollment in 2000 or later; long-term clinical morbidity and/or mortality event or 6-minute walk distance (6MWD) as an efficacy endpoint reported for ≥30 patients with CTD-PAH; and evaluation of a US Food and Drug Administration-approved PAH therapy. The primary outcomes were treatment effect as measured by the study time to first morbidity or morality event and change in 6MWD from baseline to between 3–6 months, per the data provided in each article. Results from individual studies were combined using a random-effects model for overall study population (PAH patients) and the subgroup of CTD-PAH patients. Results Ten RCTs (N=4329 PAH patients; n=1263 (29%) with CTD-PAH) met inclusion criteria and were included in the meta-analysis. At baseline, PAH patients had a mean age of 50 years, approximately 78% were female, and approximately 58% had functional class III or IV disease. These characteristics were balanced between treatment and control groups. Baseline 6MWD was 356 m for the overall population and 337 m for patients with CTD-PAH. Five RCTs (N=3172; n=941 with CTD-PAH [30%]) reported hazard ratios (HRs) for time to a morbidity or mortality event by drug treatment and PAH etiology: overall population HR=0.63 (95% confidence interval [CI], 0.56–0.72; P<0.001); CTD-PAH population HR=0.64 (95% CI, 0.51–0.80; P<0.001) (Figure). Nine RCTs reported mean change with drug treatment from baseline to 3 to 6 months in 6MWD for PAH and CTD patients: 33.9 m (95% CI, 21.9–45.9; P<0.001) in the overall population; 20.2 m (95% CI, 10.8–29.7; P<0.001) in CTD-PAH patients. Conclusions The improvement in 6MWD in patients with CTD-PAH is smaller than in those with other types of PAH, perhaps reflecting comorbidities and CTD-induced mobility constraints, independent of their cardiopulmonary capacity. Data from long term clinical morbidity/mortality endpoint studies in this large group of patients with CTD-PAH demonstrate that these patients derive significant benefit from currently available PAH therapies which, in many patients, comprised the addition of a drug targeting a second or third pathway involved in the pathophysiology of PAH. Treatment effect on morbidity/mortality Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Actelion Pharmaceuticals US, Inc.

Real-world use and accuracy of stress echocardiography: preliminary insights from the EVAREST study

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
W Woodward ◽  
A McCourt ◽  
C Dockerill ◽  
L Ayres ◽  
D Augustine ◽  
...  
Keyword(s):  
Clinical Practice ◽  
Real World ◽  
Stress Echocardiography ◽  
Significant Coronary Artery Disease ◽  
Phone Call ◽  
Funding Source ◽  
Private Company ◽  
Coronary Syndrome ◽  
Stress Echo ◽  
Cardiac Outcome

Abstract Background Stress echocardiography is a widely used, non-invasive imaging modality used to identify prognostically significant coronary artery disease. High levels of accuracy have been reported, however this is highly dependent on operator training and image quality. There are currently limited data available on the accuracy of stress echo in every day clinical practice. Purpose The EVAREST study links stress echo clinics in 30 NHS Hospital Trusts in England and therefore provides data to evaluate the performance and diagnostic accuracy of stress echo in “real-world” clinical practice. Methods Analysis was performed on the first 7415 patients recruited prospectively between 2015 and January 2020. Participants are included if they have undergone stress echo to investigate for ischaemic heart disease. Data is collected on medical history and stress echo performance. Participants are followed up for 12 months through health records and patient phone call, with all outcomes undergoing expert adjudication. A positive cardiac outcome is defined as initiation of anti-anginal medications, ≥70% stenosis on coronary angiography, revascularisation, confirmed acute coronary syndrome or cardiac-related death. Results Mean age of patients undergoing stress echo is 65±12.3 years and 56% are male. Average BMI is 28.9±5.6 kg/m2. 71.4% undergo dobutamine stress (DSE) and 28.4% exercise with <1% having a pacemaker-mediated stress. Contrast was used in 71.4% of studies. Stress echos were interpreted at time of clinic visit as positive for inducible ischaemia in 18.2% of patients. One-year outcome data is currently available for 1892 participants. Sensitivity and specificity for clinician prediction of a positive cardiac outcome was 88.7% and 94.4%, respectively. Positive and negative predictive value of stress echo was 76.4% and 97.6%, respectively. Conclusion EVAREST provides unprecedented, large-scale information on the “real world” use and accuracy of stress echo across different healthcare settings in the UK, demonstrating performance consistent with best practice. Ongoing data collection will be used to evaluate sources of heterogeneity in the predictive accuracy of stress echo and identify optimal approaches to further improve performance. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Ultromics Ltd., Lantheus Ltd.

Long-term outcomes of Japan-specific dosage of rivaroxaban in high-risk patients with non-valvular atrial fibrillation: analysis from the XAPASS

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
T Ikeda ◽  
S Ogawa ◽  
T Kitazono ◽  
J Nakagawara ◽  
K Minematsu ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
High Risk ◽  
Major Bleeding ◽  
Factor Xa ◽  
Incidence Rates ◽  
Funding Source ◽  
High Risk Patients ◽  
Reduced Dose ◽  
Risk Patients

Abstract Background XAPASS is a real-world, prospective, single-arm, observational study conducted as a post-marketing surveillance mandated by the health authority in Japan. Nowadays, direct oral anticoagulant therapy using factor Xa or thrombin inhibitor has been the standard of care for patients with non-valvular atrial fibrillation (NVAF) to prevent ischemic stroke. However, the clinical impact of reduced dosage (approved dose of 15 or 10 mg once daily in Japan is relatively reduced compared to global dosage) factor Xa inhibitor rivaroxaban in high-risk patients remains unclear. Purpose The present sub-analysis of XAPASS was carried out to assess long-term safety and effectiveness of reduced-dose rivaroxaban in high-risk NVAF patients for bleeding and thromboembolism. Methods All patients with NVAF who were newly started on rivaroxaban were eligible for surveillance. The principal safety outcome was a composite of major and non-major bleeding events, and the primary effectiveness outcome was a composite of ischaemic stroke, haemorrhagic stroke, non-central nervous system systemic embolism (non-CNS SE), and myocardial infarction (MI). In this present sub-analysis, high-risk patients were defined as those who had two of the following three risk factors: elderly (≥75 years old), low body weight (≤50 kg), and renal impairment (CrCl <50 mL/min). Results In total, 11,308 patients were enrolled between April 2012 and June 2014 from 1,419 hospitals, and overall data were analysed from 10,664 patients from whom data were collected. Among them, 3,694 patients matched the criteria for the high-risk patients defined in this sub-analysis, and 6,970 patients did not match the criteria (non-high-risk patients). The mean treatment duration was 791±673 days in the high-risk patients and 944±709 days in the non-high-risk patients. Mean patient age was 80.9±5.5 years and 69.0±9.0 years at baseline, respectively. Mean CHADS2 score was 2.8 and 1.8, and CHA2DS2-VASc score was 4.4 and 2.9, respectively. The rates of CHADS2 component comorbidities were lower in the non-high-risk patients except for diabetes mellitus. The incidence rates of any bleeding, major bleeding, and the primary effectiveness outcomes were 4.8, 1.6, and 2.1%/patient-year in the high-risk patients. The incidence rates of these clinical events in the non-high-risk patients were 3.3, 0.9, and 1.0%/patient-year, respectively. Conclusions Incidence rates of long-term bleeding and thromboembolism were higher in the high-risk patients than in the non-high-risk patients. However, the rates of these outcomes using the Japan-specific reduced dose were not so high. Furthermore, the balance between safety and effectiveness outcomes was within an acceptable range. The present study provides useful information for physicians to stratify high-risk patients using the reduced dose in daily clinical practice. Funding Acknowledgement Type of funding source: Private company. Main funding source(s): Bayer Yakuhin Ltd.

scholarly journals Efficacy and Safety of Long‐Term Antithrombotic Strategies in Patients With Chronic Coronary Syndrome: A Network Meta‐analysis of Randomized Controlled Trials

2021 ◽  
Author(s):  
Houyong Zhu ◽  
Xiaoqun Xu ◽  
Xiaojiang Fang ◽  
Fei Ying ◽  
Liuguang Song ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Major Bleeding ◽  
Meta Analysis ◽  
Efficacy And Safety ◽  
Bleeding Events ◽  
Coronary Syndrome ◽  
High Risk Factors ◽  
Cerebrovascular Events

Background Long‐term antithrombotic strategies for patients with chronic coronary syndrome with high‐risk factors represent an important treatment dilemma in clinical practice. Our aim was to conduct a network meta‐analysis to evaluate the efficacy and safety of long‐term antithrombotic strategies in patients with chronic coronary syndrome. Methods and Results Four randomized studies were included (n=75167; THEMIS [Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study], COMPASS [Cardiovascular Outcomes for People Using Anticoagulation Strategies], PEGASUS‐TIMI 54 [Prevention of Cardiovascular Events in Patients With Prior Heart Attack Using Ticagrelor Compared to Placebo on a Background of Aspirin–Thrombolysis in Myocardial Infarction 54], and DAPT [Dual Anti‐platelet Therapy]). The odds ratios (ORs) and 95% CIs) were calculated as the measure of effect size. The results of the network meta‐analysis showed that, compared with aspirin monotherapy, the ORs for trial‐defined major adverse cardiovascular and cerebrovascular events were 0.86; (95% CI, 0.80–0.93) for ticagrelor plus aspirin, 0.89 (95% CI, 0.78–1.02) for rivaroxaban monotherapy, 0.74 (95% CI, 0.64–0.85) for rivaroxaban plus aspirin, and 0.72 (95% CI, 0.60,–0.86) for thienopyridine plus aspirin. Compared with aspirin monotherapy, the ORs for trial‐defined major bleeding were 2.15 (95% CI, 1.78–2.59]) for ticagrelor plus aspirin, 1.51 (95% CI, 1.23–1.85) for rivaroxaban monotherapy, and 1.68 (95% CI, 1.37–2.05) for rivaroxaban plus aspirin. For death from any cause, the improvement effect of rivaroxaban plus aspirin was detected versus aspirin monotherapy (OR, 0.76; 95% CI, 0.65–0.90), ticagrelor plus aspirin (OR, 0.79; 95% CI, 0.66–0.95), rivaroxaban monotherapy (OR, 0.82; 95% CI, 0.69–0.97), and thienopyridine plus aspirin (OR, 0.58; 95% CI, 0.41–0.82) regimens. Conclusions All antithrombotic strategies combined with aspirin significantly reduced the incidence of major adverse cardiovascular and cerebrovascular events and increased the risk of major bleeding compared with aspirin monotherapy. Considering the outcomes of all ischemic and bleeding events and all‐cause mortality, rivaroxaban plus aspirin appears to be the preferred long‐term antithrombotic regimen for patients with chronic coronary syndrome and high‐risk factors.

3294Frequency, management and outcomes of patients with stable coronary artery disease eligible for COMPASS. An analysis of the CLARIFY registry

2019 ◽  
Vol 40 (Supplement_1) ◽  
Author(s):  
A Darmon ◽  
G Ducrocq ◽  
A Jasilek ◽  
J M Juliard ◽  
E Sorbets ◽  
...  
Keyword(s):  
Coronary Artery Disease ◽  
Coronary Artery ◽  
High Risk ◽  
Risk Score ◽  
Stable Coronary Artery Disease ◽  
Real Life ◽  
Bleeding Risk ◽  
Exclusion Criteria ◽  
Artery Disease ◽  
Stable Cad

Abstract Background The COMPASS trial demonstrated that a combination of rivaroxaban and aspirin improved cardiovascular (CV) outcomes in high-risk patients with either peripheral artery disease (PAD) or stable coronary artery disease (CAD) compared with aspirin alone, at the price of increased bleeding. A previous analysis of the REACH Registry reported an eligibility rate of 52.9% within a population with stable vascular disease. However, most of cardiologists actually treat patients with stable CAD, rather than PAD. Data regarding eligibility to COMPASS in CAD patients from real life practice are scarce. Purpose We aimed to describe the proportion of patients eligible to COMPASS within the CLARIFY Registry. Additionally, we aimed to describe their management and outcomes, comparing patients excluded from the trial (COMPASS Excluded), patients eligible for the trial (COMPASS Eligible), and patients who did not meet the “enrichment criteria” for enrolment (COMPASS Not Included). Methods We used the CLARIFY Registry, an international observational registry of more than 30.000 patients with stable CAD. In accordance with COMPASS exclusion criteria, patients with a REACH bleeding risk score >10, heart failure (HF), severe renal insufficiency, need for dual antiplatelet therapy (DAPT), or anticoagulant (AC) therapy were excluded. Then, COMPASS inclusion criteria were applied: CAD patients had to be 65 years or more, or, if younger, have documented atherosclerosis (PAD or revascularization involving at least two vascular beds) or at least two enrichment criteria (current smoker, diabetes mellitus, GFR <60 mL/min, or non lacunar ischemic stroke).The ischemic outcome was a composite of CV death, MI, or stroke and bleeding outcome was a composite of bleeding leading to either admission or transfusion, or haemorrhagic stroke. Results Among 15.185 patients with comprehensive data allowing precise assessment of eligibility, 43.1% (n=6.540) had at least one exclusion criteria (COMPASS-Excluded), 23.1% (n=3.503) did not have enrichment criteria (COMPASS-Not Included) and 33.9% (n=5.142) were eligible. The vast majority of excluded patients were excluded due to high bleeding risk (62.7% needing DAPT, and 52.7% for high REACH bleeding risk score). The rates (100 patients/year) of ischemic and bleeding outcome were 2.3 [2.1–2.5] and 0.5 [0.4–0.6] respectively for COMPASS-Eligible, 3.0 [2.8–3.2] and 0.6 [0.5–0.7] for COMPASS-Excluded and 1.2 [1.0–1.4] and 0.2 [0.2–0.3] for COMPASS-Not Included. Ischemic and bleeding events Conclusion In a large contemporary registry of stable CAD patients, approximately one of three patients was potentially eligible for adjunction of low-dose rivaroxaban to aspirin. This group is at particularly high risk of ischemic outcome. Patients with exclusion criteria for COMPASS had the worse ischemic and bleeding outcomes and represent a group in need of improved therapy. Acknowledgement/Funding None

Hematological Parameters As Exclusion Criteria in Clinical Trials of Acute Coronary Syndrome

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 3593-3593
Author(s):  
Ohad Oren ◽  
Douglas F. Beach
Keyword(s):  
Clinical Trials ◽  
Major Bleeding ◽  
Hematological Parameters ◽  
Active Bleeding ◽  
P Value ◽  
Exclusion Criteria ◽  
Coronary Syndrome ◽  
History Of ◽  
Risk For Bleeding ◽  
Or History

Abstract Background Non-cancerous medical conditions have a profound impact on the health of patients with malignancies. In individuals with lung cancer, the likelihood of death due to other causes is higher than that of the general population. It is therefore essential that patients with hematologic/oncologic diseases be effectively represented in non-oncologic clinical trials. Despite that truism, patients with cancer or with hematological impairments are typically excluded from clinical trials due to safety concerns. The frequency and degree to which hematological parameters or a diagnosis of cancer serve to exclude patients from practice-changing clinical studies in cardiology have yet to be determined. Whether studies that exclude patients based on such parameters have a lower incidence rate of major bleeding than those that do not is also unknown. Methods We focused on acute coronary syndrome (ACS). An investigation of the hematologic/oncologic exclusion profile of landmark studies of ACS was conducted. We searched The New England Journal of Medicine for all original research studies of ACS published between 2006 and 2016. Hematologic/oncologic exclusion criteria were reviewed. The nature of those parameters (laboratory value, disease state, medication use, clinical risk assessment) was analysed. The number of criteria per study as well as the percentage of participants excluded for meeting those criteria were recorded. The incidence of major bleeding (defined by TIMI bleeding criteria) among patients randomised into the interventional arms was compared between studies that excluded patients with particular derangements and those that did not. Results Thirty randomised clinical trials were found with a total number of patients of 235,981. Two thirds (20 out of 30) of the studies had at least one hematologic/oncologic exclusion criteria. The mean number of hematologic/oncologic exclusion criteria per study was 1.7. The most common exclusion parameter was laboratory-based. Ten studies (33.3%) specified cell count value as a cutoff for participation. Haemoglobin threshold (<10.0 mg/dl) was included in 4 studies (13.3%), while a platelet cutoff (<100k, >700k) was chosen in 9 publications (30%). Twelve studies (40%) issued active bleeding diathesis while six (20%) included "high-risk" for bleeding as exclusion criteria. Eight studies (26.6%) excluded patients who were chronically on oral anticoagulation. Six studies (20%) excluded patients with history of cancer. Seven studies (23.3%) had at least one subjective parameter in the list of exclusion criteria, such as "concerning lab abnormality", "high-risk" for bleeding, or "severe haematological disease". The aggregate incidence rate of major bleeding was significantly higher in studies that did not exclude for haemoglobin levels lower than 10 mg/dl compared with those that did (2.8% versus 1.6%, p value<0.05). Major bleeding rates were higher in studies that excluded patients on chronic anticoagulation than in studies that did not (3.6% versus 2.1%, p value<0.05). There was no significant difference in the incidence of major bleeding between studies that excluded patients with thrombocytopenia (platelets<100k), active bleeding or history of malignancy and studies that did not (Table 1). Not a single publication reported the fraction of patients excluded due to hematological impairments or history of cancer. Conclusions Hematological parameters as well as a medical history of a cancer commonly serve as exclusion criteria in studies of patients with ACS. Our analysis suggests that there may be a need for better standardization of exclusion criteria in studies in cardiovascular medicine, given that almost a quarter of high-quality studies of ACS include at least one inherently subjective parameter. The results provide support for uniformly setting severe anemia as exclusion criteria in studies of ACS until further data is available. Interestingly, enrolling patients with thrombocytopenia (platelets<100k), active bleeding or history of malignancy translated into similar rates of major bleeding, suggesting that some patient populations may be unnecessarily restricted from participating in clinical trials. Lastly, data pertaining to the subgroups of patients who were excluded based on those impairments is lacking and should be reported in future studies. Disclosures No relevant conflicts of interest to declare.

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