| 1. |
- Cornel, Jan H., et al.
(författare)
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Anticoagulant therapy and outcomes in patients with prior or acute heart failure and acute coronary syndromes : Insights from the APixaban for PRevention of Acute ISchemic Events 2 trial
- 2015
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Ingår i: American Heart Journal. - : Elsevier BV. - 0002-8703 .- 1097-6744. ; 169:4, s. 531-538
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Tidskriftsartikel (refereegranskat)abstract
- Background Clinical outcomes and the effects of oral anticoagulants among patients with acute coronary syndrome (ACS) and either a history of or acute heart failure (HF) are largely unknown. We aimed to assess the relationship between prior HF or acute HF complicating an index ACS event and subsequent clinical outcomes and the efficacy and safety of apixaban compared with placebo in these populations. Methods High-risk patients were randomly assigned post-ACS to apixaban 5.0 mg or placebo twice daily. Median follow-up was 8 (4-12) months. The primary outcome was cardiovascular death, myocardial infarction, or stroke. The main safety outcome was thrombolysis in myocardial infarction major bleeding. Results Heart failure was reported in 2,995 patients (41%), either as prior HF (2,076 [28%]) or acute HF (2,028 [27%]). Patients with HF had a very high baseline risk and were more often managed medically. Heart failure was associated with a higher rate of the primary outcome (prior HF: adjusted hazard ratio [HR] 1.73, 95% CI 1.42-2.10, P < .0001, acute HF: adjusted HR 1.65, 95% CI 1.35-2.01, P < .0001) and cardiovascular death (prior HF: HR 2.54, 95% CI 1.82-3.54, acute HF: adjusted HR 2.52, 95% CI 1.82-3.50). Patients with acute HF also had significantly higher rates of thrombolysis in myocardial infarction major bleeding (prior HF: adjusted HR 1.22, 95% CI 0.65-2.27, P = .54, acute HF: adjusted HR 1.78, 95% CI 1.03-3.08, P = .04). There was no statistical evidence of a differential effect of apixaban on clinical events or bleeding in patients with or without prior HF; however, among patients with acute HF, there were numerically fewer events with apixaban than placebo (14.8 vs 19.3, HR 0.76, 95% CI 0.57-1.01, interaction P = .13), a trend that was not seen in patients with prior HF or no HF. Conclusions In high-risk patients post-ACS, both prior and acute HFs are associated with an increased risk of subsequent clinical events. Apixaban did not significantly reduce clinical events and increased bleeding in patients with and without HF; however, there was a tendency toward fewer clinical events with apixaban in patients with acute HF.
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| 2. |
- Hess, Connie N., et al.
(författare)
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Differential occurrence, profile, and impact of first recurrent cardiovascular events after an acute coronary syndrome
- 2017
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 187, s. 194-203
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Tidskriftsartikel (refereegranskat)abstract
- Objective Acute coronary syndrome (ACS) trials typically use a composite primary outcome (myocardial infarction [MI], stroke, or cardiovascular death), but differential patient characteristics, timing, and consequences associated with individual component end points as first events have not been well studied. We compared patient characteristics and prognostic significance associated with first cardiovascular events in the post-ACS setting for initially stabilized patients. Methods We combined patient-level data from 4 trials of post-ACS antithrombotic therapies (PLATO, APPRAISE-2, TRACER, and TRILOGY ACS) to characterize the timing of and characteristics associated with first cardiovascular events (MI, stroke, or cardiovascular death). Landmark analysis at 7 days after index ACS presentation was used to focus on spontaneous, postdischarge events that were not confounded by in-hospital procedural complications. Using a competing risk framework, we tested for differential associations between prespecified covariates and the occurrence of nonfatal stroke vs MI as the first event, and we examined subsequent events after the first nonfatal event. Results Among 46,694 patients with a median follow-up of 358 (25th, 75th percentiles 262, 486) days, a first ischemic event occurred in 4,307 patients (9.2%) as follows: MI in 5.8% (n = 2,690), stroke in 1.0% (n = 477), and cardiovascular death in 2.4% (n = 1,140). Older age, prior stroke/transient ischemic attack, prior atrial fibrillation, and higher diastolic blood pressure were associated with a significantly greater risk of stroke vs MI, whereas prior percutaneous coronary intervention was associated with a greater risk of MI vs stroke. Second events occurred in 32% of those with a first nonfatal stroke at a median of 13 (3, 59) days after the first event and in 32% of those with a first nonfatal MI at a median of 35 (5, 137) days after the first event. The most common second event was a recurrent MI among those with MI as the first event and cardiovascular death among those with stroke as the first event. Conclusions Approximately 9% of patients experienced a first cardiovascular event in the post-ACS setting during a median follow-up of 1 year. Although the profile and prognostic implications of stroke vs MI as the first nonfatal event differ substantially, approximately one-third of these patients experienced a second event, typically soon after the first event. These findings have implications for improving post-ACS care and influencing the design of future cardiovascular trials.
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| 3. |
- Khan, Razi, et al.
(författare)
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Characterising and predicting bleeding in high-risk patients with an acute coronary syndrome
- 2015
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Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 101:18, s. 1475-1484
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Tidskriftsartikel (refereegranskat)abstract
- Objective In the Apixaban for Prevention of Acute Ischemic Events (APPRAISE-2) trial, the use of apixaban, when compared with placebo, in high-risk patients with a recent acute coronary syndrome (ACS) resulted in a significant increase in bleeding without a reduction in ischaemic events. The aim of this analysis was to provide further description of these bleeding events and to determine the baseline characteristics associated with bleeding in high-risk post-ACS patients. Methods APPRAISE-2 was a multinational clinical trial including 7392 high-risk patients with a recent ACS randomised to apixaban (5 mg twice daily) or placebo. Bleeding including Thrombolysis in Myocardial Infarction (TIMI) major or minor bleeding, International Society on Thrombosis and Haemostasis (ISTH) major or clinically relevant non-major (CRNM) bleeding, and any bleeding were analysed using an on-treatment analysis. Kaplan-Meier curves were plotted to describe the timing of bleeding, and a Cox proportional hazards model was used to identify predictors of ISTH major or CRNM bleeding and any bleeding. Median follow-up was 241 days. Results The proportion of patients who experienced TIMI major or minor, ISTH major or CRNM, and any bleeding was 1.5%, 2.2% and 13.3%, respectively. The incidence of bleeding was highest in the immediate post-ACS period (0.11 in the first 30 days vs 0.03 after 30 days events per 1 patient-year); however, > 60% of major bleeding events occurred > 30 days after the end of the index hospitalisation. Gastrointestinal bleeding was the most common cause of major bleeding, accounting for 45.9% of TIMI major or minor and 39.5% of ISTH major or CRNM bleeding events. Independent predictors of ISTH major or CRNM bleeding events included older age, renal dysfunction, dual oral antiplatelet therapy, smoking history, increased white cell count and coronary revascularisation. Conclusions When compared with placebo, the use of apixaban is associated with an important short-term and long-term risk of bleeding in high-risk post-ACS patients, with gastrointestinal bleeding being the most common source of major bleeding. The baseline predictors of major bleeding appear to be consistent with those identified in lower-risk ACS populations with shorter-term follow-up.
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| 4. |
- Sharma, Abhinav, et al.
(författare)
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Clinical consequences of bleeding among individuals with a recent acute coronary syndrome : Insights from the APPRAISE-2 trial
- 2019
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Ingår i: American Heart Journal. - : MOSBY-ELSEVIER. - 0002-8703 .- 1097-6744. ; 215, s. 106-113
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Tidskriftsartikel (refereegranskat)abstract
- Background Patients with a recent acute coronary syndrome (ACS) receiving oral antiplatelets and anticoagulants are at risk for bleeding and subsequent adverse non-bleeding-related events. Methods In this post hoc analysis, we evaluated 7,392 high-risk patients (median follow-up 241 days) with a recent ACS randomized to apixaban or placebo in APPRAISE-2. Clinical events during a 30-day period after Thrombolysis in Myocardial Infarction (TIMI) major/minor bleeding were analyzed using unadjusted and adjusted Cox proportional-hazards models. Results In total, 153 (2.1%) patients experienced TIMI major/minor bleeding during follow-up. Bleeding risk for patients on triple therapy (apixaban, thienopyridine, and aspirin) was increased compared with those on dual therapy (apixaban plus aspirin: hazard ratio [HR] 2.02, 95% CI 1.08-3.79; thienopyridine plus aspirin: HR 1.99, 95% CI 1.41-2.83). Those receiving apixaban/aspirin had similar bleeding risk compared with those receiving thienopyridine/aspirin (HR 1.01, 95% CI 0.53-1.95). Patients who experienced TIMI major/minor bleeding had an increased risk of 30-day all-cause mortality (HR 24.7, 95% CI 15.34-39.66) and ischemic events (HR 6.7, 95% CI 3.14-14.14). Conclusions In a contemporary cohort of high-risk patients after ACS, bleeding was associated with a significantly increased risk of subsequent ischemic events and mortality regardless of antithrombotic or anticoagulant strategy. Patients receiving apixaban plus aspirin had a similar bleeding risk compared with those receiving thienopyridine plus aspirin. Interventions to improve outcomes in patients after ACS should include strategies to optimize the reduction in ischemic events while minimizing the risk of bleeding.
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| 6. |
- Tricoci, Pierluigi, et al.
(författare)
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Effects of genetic variation in protease activated receptor 4 after an acute coronary syndrome : Analysis from the TRACER trial
- 2018
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Ingår i: Blood Cells, Molecules & Diseases. - : Elsevier BV. - 1079-9796 .- 1096-0961. ; 72, s. 37-43
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Tidskriftsartikel (refereegranskat)abstract
- Variation in platelet response to thrombin may affect the safety and efficacy of PAR antagonism. The Thr120 variant of the common single nucleotide polymorphism (SNP) rs773902 in the protease-activated receptor (PAR) 4 gene is associated with higher platelet aggregation compared to the Ala120 variant. We investigated the relationship between the rs773902 SNP with major bleeding and ischemic events, safety, and efficacy of PAR1 inhibition in 6177 NSTE ACS patients in the TRACER trial. There was a lower rate of GUSTO moderate/severe bleeding in patients with the Thr120 variant. The difference was driven by a lower rate in the smaller homozygous group (recessive model, HR 0.13 [0.02-0.92] P= 0.042). No significant differences were observed in the ischemic outcomes. The excess in bleeding observed with PAR1 inhibition was attenuated in patients with the Thr120 variant, but the interactions were not statistically significant. In summary, lower major bleeding rates were observed in the overall TRACER cohort with the hyperreactive PAR4 Thr120 variant. The increase in bleeding with vorapaxar was attenuated with the Thr120 variant, but we could not demonstrate an interaction with PAR1 inhibition. These findings warrant further exploration, including those of African ancestry where the A allele (Thr120) frequency is similar to 65%.
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