| 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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Apixaban Plus Mono Versus Dual Antiplatelet Therapy in Acute Coronary Syndromes Insights From the APPRAISE-2 Trial
- 2015
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 66:7, s. 777-787
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Bleeding limits anticoagulant treatment in patients with acute coronary syndromes (ACS). OBJECTIVES We investigated whether background concomitant antiplatelet therapy influences the effects of apixaban after ACS. METHODS This study examined high-risk ACS patients who were treated with aspirin or aspirin plus clopidogrel and who were randomized to apixaban 5 mg twice daily or placebo. In a post-hoc analysis, we assessed whether the effect of apixaban on efficacy and safety outcomes varied by the concomitant antiplatelet regimen by using simple Cox modeling and marginal structural models with propensity scores and antiplatelet therapy as a time-dependent covariate. RESULTS At baseline, of 7,364 patients, 16.3% (n = 1,202) were on aspirin alone, and 79.0% (n = 5,814) were on aspirin plus clopidogrel. A total of 19.2% (n = 1,415) switched antiplatelet therapy during follow-up. No differential effect of apixaban versus placebo was observed for the composite endpoint of cardiovascular death, myocardial infarction, and ischemic stroke in patients taking aspirin (12.21 per 100 patient-years vs. 13.21 per 100 patient-years; adjusted hazard ratio [HR]: 0.91; 95% confidence interval [CI]: 0.62 to 1.32) or aspirin plus clopidogrel (13.22 vs. 14.24; adjusted HR: 0.95; 95% CI: 0.78 to 1.14; p(interaction) = 0.84). Compared with placebo, apixaban increased Thrombolysis In Myocardial Infarction major bleeding in patients taking aspirin (1.48 vs. 0.25; adjusted HR: 6.62; 95% CI: 0.75 to 51.73) and in patients taking aspirin plus clopidogrel (2.58 vs. 1.02; adjusted HR: 2.44; 95% CI: 1.34 to 4.45; p(interaction) = 0.41). Similar results were obtained with marginal structural models and in patients treated with and without percutaneous coronary intervention. CONCLUSIONS Post-ACS treatment with apixaban versus placebo showed no efficacy, but it increased bleeding regardless of concomitant therapy with aspirin alone or aspirin plus clopidogrel. (Apixaban for Prevention of Acute Ischemic Events 2 [APPRAISE-2]; NCT00831441) (J Am Coll Cardiol 2015; 66: 777-87)
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| 3. |
- 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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| 4. |
- Lowenstern, Angela, et al.
(författare)
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Platelet-related biomarkers and their response to inhibition with aspirin and p2y12-receptor antagonists in patients with acute coronary syndrome
- 2017
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Ingår i: Journal of Thrombosis and Thrombolysis. - : Springer Science and Business Media LLC. - 0929-5305 .- 1573-742X. ; 44:2, s. 145-153
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Tidskriftsartikel (refereegranskat)abstract
- The PLATelet inhibition and patient Outcomes (PLATO) trial showed that treatment with ticagrelor reduced the rate of death due to vascular causes, myocardial infarction and stroke when compared to clopidogrel in patients with ST-elevation or non-ST-elevation acute coronary syndrome (ACS). While the comparative benefit of ticagrelor over clopidogrel increased over time, event rates accrued in both groups during the study period. The purpose of our biomarker-based exploratory analysis was to determine whether long-term platelet inhibition may be associated with platelet adaptation. A sample of 4000 participants from the PLATO trial also consented to participate in a prospectively designed biomarker substudy. Blood samples were procured at baseline, immediately prior to hospital discharge and at 1 and 6 months. Markers of platelet activity, including platelet count, serum CD40-ligand and soluble P-selectin were analyzed. Mean levels were compared at discharge, 1 and 6 months following study drug initiation-first for all patients and subsequently stratified by treatment group. A linear mixed model was used to estimate the short-term change rate (baseline to 1 month) and long-term change rate (1-6 months) for each biomarker. A Cox proportional hazards model was used to calculate hazard ratios for each change in biomarker over the two time periods examined: baseline to 1 month and 1 to 6 months. Prior to randomized treatment (baseline), sCD40 ligand and sP-selectin levels were elevated above the normal range of the assay (0.39 and 33.5 A μg/L, respectively). The mean level of each biomarker was significantly different at 1 month compared to baseline (p < 0.0001). When stratified by treatment group, at 1 month patients treated with ticagrelor had a larger increase in platelet count compared to those treated with clopidogrel (p < 0.0001). Similarly, when comparing biomarker levels for all patients at 6 months with those at 1 month, each differed significantly (p < 0.05). There was no significant difference between treatment groups during this time period. The rate of change for both platelet count and sP-selectin were significantly different between baseline and 1 month when compared to the 1 to 6-month time period (p < 0.0001). When comparing treatment groups, the rate of increase in platelets from baseline to 1 month was greater for patients treated with ticagrelor (p < 0.0001). This was no longer observed in the 1 to 6-month interval. Using a Cox proportional hazard model, the increase in platelet count from 1 to 6 months was associated with ischemic-thrombotic events, while sCD40 ligand decrease from 1 to 6 months was associated with hemorrhagic events. There were no differences between treatment groups for the associations with clinical endpoints. Dynamic changes in platelet count, sCD-40 ligand and sP-selectin occur over time among patients with ACS. Platelet-directed therapy with a P2Y12 receptor inhibitor in combination with aspirin modestly impacts the expression of these biomarkers. Platelet count and sCD40 ligand may offer modest overall predictive value for future ischemic-thrombotic or hemorrhagic clinical events, respectively. The existence of a platelet adaptome and its overall clinical significance among patients at risk for thrombotic events will require a more in-depth and platelet-biology specific investigation.
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