| 1. |
- White, Harvey D, et al.
(författare)
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Darapladib for preventing ischemic events in stable coronary heart disease
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND:Elevated lipoprotein-associated phospholipase A2 activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A2.METHODS:In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization).RESULTS:During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02).CONCLUSIONS:In patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.).
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| 2. |
- White, Harvey D., et al.
(författare)
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Survival with Cardiac-Resynchronization Therapy in Mild Heart Failure
- 2014
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Ingår i: New England Journal of Medicine. - 0028-4793 .- 1533-4406. ; 370:18, s. 1702-1711
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Tidskriftsartikel (refereegranskat)abstract
- Background: Elevated lipoprotein-associated phospholipase A(2) activity promotes the development of vulnerable atherosclerotic plaques, and elevated plasma levels of this enzyme are associated with an increased risk of coronary events. Darapladib is a selective oral inhibitor of lipoprotein-associated phospholipase A(2). Methods: In a double-blind trial, we randomly assigned 15,828 patients with stable coronary heart disease to receive either once-daily darapladib (at a dose of 160 mg) or placebo. The primary end point was a composite of cardiovascular death, myocardial infarction, or stroke. Secondary end points included the components of the primary end point as well as major coronary events (death from coronary heart disease, myocardial infarction, or urgent coronary revascularization for myocardial ischemia) and total coronary events (death from coronary heart disease, myocardial infarction, hospitalization for unstable angina, or any coronary revascularization). Results: During a median follow-up period of 3.7 years, the primary end point occurred in 769 of 7924 patients (9.7%) in the darapladib group and 819 of 7904 patients (10.4%) in the placebo group (hazard ratio in the darapladib group, 0.94; 95% confidence interval [CI], 0.85 to 1.03; P=0.20). There were also no significant between-group differences in the rates of the individual components of the primary end point or in all-cause mortality. Darapladib, as compared with placebo, reduced the rate of major coronary events (9.3% vs. 10.3%; hazard ratio, 0.90; 95% CI, 0.82 to 1.00; P=0.045) and total coronary events (14.6% vs. 16.1%; hazard ratio, 0.91; 95% CI, 0.84 to 0.98; P=0.02). ConclusionsIn patients with stable coronary heart disease, darapladib did not significantly reduce the risk of the primary composite end point of cardiovascular death, myocardial infarction, or stroke. (Funded by GlaxoSmithKline; STABILITY ClinicalTrials.gov number, NCT00799903.)
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| 3. |
- Lindholm, Daniel, 1982-, et al.
(författare)
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Biomarker-Based Risk Model to Predict Cardiovascular Mortality in Patients With Stable Coronary Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : Elsevier. - 0735-1097 .- 1558-3597. ; 70:7, s. 813-826
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Tidskriftsartikel (refereegranskat)abstract
- Background Currently, there is no generally accepted model to predict outcomes in stable coronary heart disease (CHD).Objectives This study evaluated and compared the prognostic value of biomarkers and clinical variables to develop a biomarker-based prediction model in patients with stable CHD.Methods In a prospective, randomized trial cohort of 13,164 patients with stable CHD, we analyzed several candidate biomarkers and clinical variables and used multivariable Cox regression to develop a clinical prediction model based on the most important markers. The primary outcome was cardiovascular (CV) death, but model performance was also explored for other key outcomes. It was internally bootstrap validated, and externally validated in 1,547 patients in another study.Results During a median follow-up of 3.7 years, there were 591 cases of CV death. The 3 most important biomarkers were N-terminal pro–B-type natriuretic peptide (NT-proBNP), high-sensitivity cardiac troponin T (hs-cTnT), and low-density lipoprotein cholesterol, where NT-proBNP and hs-cTnT had greater prognostic value than any other biomarker or clinical variable. The final prediction model included age (A), biomarkers (B) (NT-proBNP, hs-cTnT, and low-density lipoprotein cholesterol), and clinical variables (C) (smoking, diabetes mellitus, and peripheral arterial disease). This “ABC-CHD” model had high discriminatory ability for CV death (c-index 0.81 in derivation cohort, 0.78 in validation cohort), with adequate calibration in both cohorts.Conclusions This model provided a robust tool for the prediction of CV death in patients with stable CHD. As it is based on a small number of readily available biomarkers and clinical factors, it can be widely employed to complement clinical assessment and guide management based on CV risk. (The Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy Trial [STABILITY]; NCT00799903)
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| 4. |
- Stewart, Ralph A. H., et al.
(författare)
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Physical Activity and Mortality in Patients With Stable Coronary Heart Disease
- 2017
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 70:14, s. 1689-1700
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND Recommendations for physical activity in patients with stable coronary heart disease (CHD) are based on modest evidence.OBJECTIVES The authors analyzed the association between self-reported exercise and mortality in patients with stable CHD.METHODS A total of 15,486 patients from 39 countries with stable CHD who participated in the STABILITY (Stabilization of Atherosclerotic Plaque by Initiation of Darapladib Therapy) study completed questions at baseline on hours spent each week taking mild, moderate, and vigorous exercise. Associations between the volume of habitual exercise in metabolic equivalents of task hours/week and adverse outcomes during a median follow-up of 3.7 years were evaluated.RESULTS A graded decrease in mortality occurred with increased habitual exercise that was steeper at lower compared with higher exercise levels. Doubling exercise volume was associated with lower all-cause mortality (unadjusted hazard ratio [HR]: 0.82; 95% confidence interval [CI]: 0.79 to 0.85; adjusting for covariates, HR: 0.90; 95% CI: 0.87 to 0.93). These associations were similar for cardiovascular mortality (unadjusted HR: 0.83; 95% CI: 0.80 to 0.87; adjusted HR: 0.92; 95% CI: 0.88 to 0.96), but myocardial infarction and stroke were not associated with exercise volume after adjusting for covariates. The association between decrease in mortality and greater physical activity was stronger in the subgroup of patients at higher risk estimated by the ABC-CHD (Age, Biomarkers, Clinical-Coronary Heart Disease) risk score (p for interaction = 0.0007).CONCLUSIONS In patients with stable CHD, more physical activity was associated with lower mortality. The largest benefits occurred between sedentary patient groups and between those with the highest mortality risk.
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| 5. |
- Wallentin, Lars, et al.
(författare)
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Lipoprotein-Associated Phospholipase A(2) Activity Is a Marker of Risk But Not a Useful Target for Treatment in Patients With Stable Coronary Heart Disease
- 2016
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Ingår i: Journal of the American Heart Association. - 2047-9980. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Background - We evaluated lipoprotein-associated phospholipase A(2) (Lp-PLA(2)) activity in patients with stable coronary heart disease before and during treatment with darapladib, a selective Lp-PLA(2) inhibitor, in relation to outcomes and the effects of darapladib in the STABILITY trial.Methods and Results - Plasma Lp-PLA(2) activity was determined at baseline (n=14 500); at 1 month (n=13 709); serially (n=100) at 3, 6, and 18 months; and at the end of treatment. Adjusted Cox regression models evaluated associations between Lp-PLA(2) activity levels and outcomes. At baseline, the median Lp-PLA(2) level was 172.4 mu mol/min per liter (interquartile range 143.1-204.2 mu mol/min per liter). Comparing the highest and lowest Lp-PLA(2) quartile groups, the hazard ratios were 1.50 (95% CI 1.23-1.82) for the primary composite end point (cardiovascular death, myocardial infarction, or stroke), 1.95 (95% CI 1.29-2.93) for hospitalization for heart failure, 1.42 (1.07-1.89) for cardiovascular death, and 1.37 (1.03-1.81) for myocardial infarction after adjustment for baseline characteristics, standard laboratory variables, and other prognostic biomarkers. Treatment with darapladib led to a approximate to 65% persistent reduction in median Lp-PLA(2) activity. There were no associations between on-treatment Lp-PLA(2) activity or changes of Lp-PLA(2) activity and outcomes, and there were no significant interactions between baseline and on-treatment Lp-PLA(2) activity or changes in Lp-PLA(2) activity levels and the effects of darapladib on outcomes.Conclusions - Although high Lp-PLA(2) activity was associated with increased risk of cardiovascular events, pharmacological lowering of Lp-PLA(2) activity by approximate to 65% did not significantly reduce cardiovascular events in patients with stable coronary heart disease, regardless of the baseline level or the magnitude of change of Lp-PLA(2) activity.
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| 6. |
- Giannitsis, Evangelos, et al.
(författare)
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Outcomes after planned invasive or conservative treatment strategy in patients with non-ST-elevation acute coronary syndrome and a normal value of high sensitivity troponin at randomisation : A Platelet Inhibition and Patient Outcomes (PLATO) trial biomarker substudy.
- 2017
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 2048-8726 .- 2048-8734. ; 6:6, s. 500-510
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: Current guidelines for patients with non-ST-elevation acute coronary syndrome (NSTE-ACS) recommend early invasive treatment in intermediate-to-high risk patients based on medical history, electrocardiogram (ECG) and elevated troponin. Patients with normal levels of cardiac troponin measured with a high-sensitivity method (cTnT-hs) might not benefit from early invasive procedures.METHODS AND RESULTS: In this Prospective Randomized Platelet Inhibition and Patient Outcomes (PLATO) blood-core substudy, 1232 patients presented with NSTE-ACS had a high sensitivity cardiac troponin T (cTnT-hs) level <99(th) percentile (<14 ng/l) at randomisation. The outcomes in relation to a planned invasive (n=473) vs planned conservative treatment (n=759), were evaluated by adjusted Cox proportional hazard analyses. In patients with a normal cTnT-hs at randomisation, regardless of randomised treatment, a planned invasive vs conservative treatment was associated with a 2.3-fold higher risk (7.3% vs 3.4%, p=0.0028) for cardiovascular (CV) death or myocardial infarction (MI), driven by higher rates of procedure-related MI (3.4% vs 0.1%), while there were no differences in rates of CV death (1.3% vs 1.3%, p=0.72) or spontaneous MI (3.0% vs 2.1%, p=0.28). There were significantly more major bleeds (hazard ratio (HR) 2.98, p<0.0001), mainly due to coronary artery bypass graft (CABG)-related (HR 4.05, p<0.0001) and non-CABG procedural-related major bleeding events (HR 5.31, p=0.0175), however there were no differences in non-procedure-related major bleeding (1.5% vs 1.9%, p=0.45). Findings were consistent for patients with a normal cTnI-hs at randomisation.CONCLUSIONS: In patients with NSTE-ACS and normal cTnT-hs, a planned early invasive treatment strategy was associated with increased rates of procedure-related MI and bleeding but no differences in long-term spontaneous MI, non-procedure-related bleeding or mortality.
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| 7. |
- Scirica, Benjamin M., et al.
(författare)
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Safety of ticagrelor in patients with baseline conduction abnormalities : A PLATO (Study of Platelet Inhibition and Patient Outcomes) analysis
- 2018
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Ingår i: American Heart Journal. - : Elsevier. - 0002-8703 .- 1097-6744. ; 202, s. 54-60
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Tidskriftsartikel (refereegranskat)abstract
- Background: Although bradyarrhythmias have been observed with ticagrelor and its use with advanced atrioventricular block is not recommended, questions arise regarding its use in patients with mild conduction abnormalities. The objectives were to compare rates of clinically relevant arrhythmias in relation to any mild baseline conduction abnormality in patients with acute coronary syndrome randomized to ticagrelor versus clopidogrel. Methods: We included all subjects in the electrocardiographic (ECG) substudy of the Platelet Inhibition and Patient Outcomes trial, excluding those with missing baseline ECG or with a pacemaker at baseline (N = 15,460). Conduction abnormality was defined as sinus bradycardia, first-degree atrioventricular block, hemiblock, or bundle-branch block. The primary arrhythmic outcome was the composite of any symptomatic brady-or tachyarrhythmia, permanent pacemaker placement, or cardiac arrest through 12 months. Results: Patients with baseline conduction abnormalities (n = 4,256, 27.5%) were older and more likely to experience the primary arrhythmic outcome. There were no differences by ticagrelor versus clopidogrel in the composite arrhythmic end point in those with baseline conduction disease (1-year cumulative incidence rate: 17% for both study arms; hazard ratio: 0.99 [0.86-1.15]) or without baseline conduction disease (1-year cumulative incidence rate: clopidogrel 12.8% vs ticagrelor 12.4%; hazard ratio: 0.98 (0.88-1.09). There were also no statistically significant differences between ticagrelor and clopidogrel in the rates of bradycardic (or any individual arrhythmic) events in patients with baseline conduction abnormalities. Conclusions: Ticagrelor compared to clopidogrel did not increase arrhythmic events even in subjects with acute coronary syndrome who present with mild conduction abnormalities on their baseline ECG. (C) 2018 Published by Elsevier Inc.
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| 8. |
- 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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