| 1. |
- Harskamp, Ralf E., et al.
(författare)
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Use of thienopyridine prior to presentation with non-ST-segment elevation acute coronary syndrome and association with safety and efficacy of vorapaxar : insights from the TRACER trial
- 2017
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Ingår i: European Heart Journal. - : SAGE PUBLICATIONS LTD. - 2048-8726 .- 2048-8734. ; 6:2, s. 155-163
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Tidskriftsartikel (refereegranskat)abstract
- Background: Vorapaxar is effective in the prevention of secondary atherothrombotic events, although the efficacy/safety balance appears less favorable in the treatment of patients with non-ST-segment elevation (NSTE) acute coronary syndrome (ACS). We hypothesized that patients with NSTE ACS already receiving thienopyridine prior to the ACS event may show differential efficacy/safety effects with vorapaxar vs. placebo added to their standard care. Methods: We studied 12,944 patients from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial with respect to thienopyridine use before admission for the index NSTE ACS event. The primary endpoint was a composite of cardiovascular death, myocardial infarction, stroke, rehospitalization for ischemia, and urgent revascularization. The key secondary endpoint was a composite of cardiovascular death, myocardial infarction, and stroke. Safety endpoints were bleeding complications. Results: Only 1513 patients (11.7%) were receiving thienopyridine before admission for the index NSTE ACS event. In these patients, Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) moderate/severe bleeding occurred in 5.7% treated with vorapaxar and 5.3% treated with a placebo (hazards ratio (HR) 1.10, 95% confidence interval (CI) 0.70-1.71); in thienopyridine-naive patients, the rates were 5.7% and 4.1%, respectively (HR 1.32, 95% CI 1.11-1.57; P-int=0.45). GUSTO severe bleeding in the prior thienopyridine group occurred in 0.5% of patients treated with vorapaxar and 1.3% of patients treated with placebo (HR 0.34, 95% CI 0.09-1.30); in thienopyridine-naive patients, the rates were 2.0% and 1.0%, respectively (HR 1.89, 95% CI 1.36-2.62; P-int=0.01). No interaction was observed between vorapaxar efficacy and prior thienopyridine use on the primary (adjusted P-int=0.53) or key secondary endpoints (P-int=0.61). Conclusions: TRACER was largely conducted in thienopyridine-naive patients with unknown tolerance to multiple antiplatelet treatments. Patients receiving thienopyridine before the index event may have had an attenuated increase in bleeding when adding vorapaxar, whereas concomitantly adding vorapaxar and thienopyridine in naive patients may have uncovered a latent susceptibility to bleeding.
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| 2. |
- Hagström, Emil, et al.
(författare)
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Growth Differentiation Factor 15 Predicts All-Cause Morbidity and Mortality in Stable Coronary Heart Disease
- 2017
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 63:1, s. 325-333
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Higher growth differentiation factor 15 (GDF-15) concentrations are associated with cardiovascular (CV) and non-CV morbidity and mortality. However, information on associations between GDF-15 and the risk of specific CV and non-CV events in stable coronary heart disease (CHD) patients is limited.METHODS: In 14 577 patients with stable CHD participating in the Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial (STABILITY), GDF-15 and other prognostic biomarkers (N-terminal pro-B-type natriuretic peptide, high-sensitivity troponin T, cystatin C, and high-sensitivity C-reactive protein) were measured. In adjusted Cox regression models, the associations between GDF-15 and the composite CV end point [CV death, myocardial infarction (MI), and stroke], as well as other CV and non-CV events, were assessed.RESULTS: The median concentration (interquartile range) of GDF-15 at baseline was 1253 (915-1827) ng/L. The hazard ratio for the composite end point for the highest compared to the lowest quartile of GDF-15 was 1.8 (95% CI, 1.5-2.2); for CV death, 2.63 (1.9-3.6); for sudden death, 3.06 (1.9-4.8); for heart failure (HF) death, 4.3 (1.3-14); for cancer death, 2.5 (1.3-4.7); for hospitalization for HF, 5.8 (3.2-10); for MI 1.4 (95% CI, 1.1-1.9); and for stroke, 1.8 (95% CI, 1.1-2.8). After adjustment for other prognostic biomarkers, GDF-15 remained significantly associated with all outcomes except for MI.CONCLUSIONS: In stable CHD, GDF-15 was independently associated with CV, non-CV, and cancer mortality, as well as with MI and stroke. When also adjusting for other prognostic biomarkers, the associations to all fatal and nonfatal events were maintained except for MI. Information on GDF-15, therefore, might be helpful when assessing the risk of adverse outcomes in patients with stable CHD. ClinicalTrials.gov Identifier: NCT00799903.
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| 3. |
- Stewart, Ralph A H, et al.
(författare)
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Self-Reported Health and Outcomes in Patients With Stable Coronary Heart Disease
- 2017
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 6:8
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Tidskriftsartikel (refereegranskat)abstract
- Background-—The major determinants and prognostic importance of self-reported health in patients with stable coronary heartdisease are uncertain.Methods and Results-—The STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) trialrandomized 15 828 patients with stable coronary heart disease to treatment with darapladib or placebo. At baseline, 98% ofparticipants completed a questionnaire that included the question, “Overall, how do you feel your general health is now?”Possible responses were excellent, very good, good, average, and poor. Adjudicated major adverse cardiac events, whichincluded cardiovascular death, myocardial infarction, and stroke, were evaluated by Cox regression during 3.7 years of follow-upfor participants who reported excellent or very good health (n=2304), good health (n=6863), and average or poor health(n=6361), before and after adjusting for 38 covariates. Self-reported health was most strongly associated with geographicregion, depressive symptoms, and low physical activity (P<0.0001 for all). Poor/average compared with very good/excellentself-reported health was independently associated with major adverse cardiac events (hazard ratio [HR]: 2.30 [95% confidenceinterval (CI), 1.92–2.76]; adjusted HR: 1.83 [95% CI, 1.51–2.22]), cardiovascular mortality (HR: 4.36 [95% CI, 3.09–6.16];adjusted HR: 2.15 [95% CI, 1.45–3.19]), and myocardial infarction (HR: 1.87 [95% CI, 1.46–2.39]; adjusted HR: 1.68 [95% CI,1.25–2.27]; P<0.0002 for all).Conclusions-—Self-reported health is strongly associated with geographical region, mood, and physical activity. In a globalcoronary heart disease population, self-reported health was independently associated with major cardiovascular events andmortality beyond what is measurable by established risk indicators.
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| 4. |
- Valgimigli, Marco, et al.
(författare)
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Trade-off of myocardial infarction vs. bleeding types on mortality after acute coronary syndrome : lessons from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) randomized trial
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 38:11, s. 804-810
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Dual antiplatelet therapy reduces non-fatal ischaemic events after acute coronary syndrome (ACS) but increases bleeding to a similar extent. We sought to determine the prognostic impact of myocardial infarction (MI) vs. bleeding during an extended follow-up period to gain insight into the trade-off between efficacy and safety among patients after ACS.Methods and results: In 12 944 patients with non-ST-segment elevation ACS from the Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome (TRACER) trial, we investigated the relative impact of MI and bleeding occurring> 30 days post-ACS and subsequent all-cause mortality. Bleeding was graded according to Bleeding Academic Research Consortium (BARC) criteria. MI was associated with a five-fold increase in mortality. BARC type 2 and 3, but not type 1, bleeding had a significant impact on mortality. MI was associated with a greater risk of mortality compared with BARC 2 [relative risk (RR) 3.5; 95% confidence interval (CI) 2.08-4.77; P< 0.001] and BARC 3a bleeding (RR 2.23; 95% CI 1.36-3.64; P = 0.001), and a risk similar to BARC 3b bleeding (RR 1.37; 95% CI 0.81-2.30; P = 0.242). Risk of death after MI was significantly lower than after BARC 3c bleeding (RR 0.22; 95% CI 0.13-0.36; P< 0.001). MI and bleeding had similar time-associations with mortality, which remained significant for several months, still being higher early after the event.Conclusion: In patients treated with antiplatelet therapy after ACS, both MI and bleeding significantly impacted mortality with similar time-dependency. Although BARC 2 and 3a bleeding were less prognostic for death than MI, the risk of mortality was equivalent between BARC 3b bleeding and MI, and was higher following BARC 3c bleeding.
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| 5. |
- Vidal-Petiot, Emmanuelle, et al.
(författare)
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Visit-to-visit variability of blood pressure and cardiovascular outcomes in patients with stable coronary heart disease. Insights from the STABILITY trial
- 2017
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Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 38:37, s. 2813-2822
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Tidskriftsartikel (refereegranskat)abstract
- Aims To study the relation between visit-to-visit variability of blood pressure (BP) and cardiovascular risk in patients with stable coronary heart disease. Methods and results In 15 828 patients from the STABILITY trial (darapladib vs. placebo in patients with established coronary heart disease), BP variability was assessed by the standard deviation (SD) of systolic BP, the SD of diastolic BP, maximum BP, and minimum BP, from 5 measurements (baseline and months 1, 3, 6, and 12) during the first year after randomisation. Mean (SD) average BP during the first year of study was 131.0 (13.7) mmHg over 78.3 (8.3) mmHg. Mean (SD) of the visit-to-visit SD was 9.8 (4.8) mmHg for systolic and 6.3 (3.0) mmHg for diastolic BP. During the subsequent median follow-up of 2.6 years, 1010 patients met the primary endpoint, a composite of time to cardiovascular death, myocardial infarction, or stroke. In Cox regression models adjusted for average BP during first year of study, baseline vascular disease, treatment, renal function and cardiovascular risk factors, the primary endpoint was associated with SD of systolic BP (hazard ratio for highest vs. lowest tertile, 1.30, 95% CI 1.10-1.53, P = 0.007), and with SD of diastolic BP (hazard ratio for highest vs. lowest tertile, 1.38, 95% CI 1.18-1.62, P < 0.001). Peaks and troughs in BP were also independently associated with adverse events. Conclusion In patients with stable coronary heart disease, higher visit-to-visit variabilities of both systolic and diastolic BP are strong predictors of increased risk of cardiovascular events, independently of mean BP.
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