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- Anand, Sonia S, et al.
(författare)
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Rivaroxaban with or without aspirin in patients with stable peripheral or carotid artery disease: an international, randomised, double-blind, placebo-controlled trial.
- 2018
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Ingår i: Lancet (London, England). - 1474-547X. ; 391:10117, s. 219-229
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Tidskriftsartikel (refereegranskat)abstract
- Patients with peripheral artery disease have an increased risk of cardiovascular morbidity and mortality. Antiplatelet agents are widely used to reduce these complications.This was a multicentre, double-blind, randomised placebo-controlled trial for which patients were recruited at 602 hospitals, clinics, or community practices from 33 countries across six continents. Eligible patients had a history of peripheral artery disease of the lower extremities (previous peripheral bypass surgery or angioplasty, limb or foot amputation, intermittent claudication with objective evidence of peripheral artery disease), of the carotid arteries (previous carotid artery revascularisation or asymptomatic carotid artery stenosis of at least 50%), or coronary artery disease with an ankle-brachial index of less than 0·90. After a 30-day run-in period, patients were randomly assigned (1:1:1) to receive oral rivaroxaban (2·5 mg twice a day) plus aspirin (100 mg once a day), rivaroxaban twice a day (5 mg with aspirin placebo once a day), or to aspirin once a day (100 mg and rivaroxaban placebo twice a day). Randomisation was computer generated. Each treatment group was double dummy, and the patient, investigators, and central study staff were masked to treatment allocation. The primary outcome was cardiovascular death, myocardial infarction or stroke; the primary peripheral artery disease outcome was major adverse limb events including major amputation. This trial is registered with ClinicalTrials.gov, number NCT01776424, and is closed to new participants.Between March 12, 2013, and May 10, 2016, we enrolled 7470 patients with peripheral artery disease from 558 centres. The combination of rivaroxaban plus aspirin compared with aspirin alone reduced the composite endpoint of cardiovascular death, myocardial infarction, or stroke (126 [5%] of 2492 vs 174 [7%] of 2504; hazard ratio [HR] 0·72, 95% CI 0·57-0·90, p=0·0047), and major adverse limb events including major amputation (32 [1%] vs 60 [2%]; HR 0·54 95% CI 0·35-0·82, p=0·0037). Rivaroxaban 5 mg twice a day compared with aspirin alone did not significantly reduce the composite endpoint (149 [6%] of 2474 vs 174 [7%] of 2504; HR 0·86, 95% CI 0·69-1·08, p=0·19), but reduced major adverse limb events including major amputation (40 [2%] vs 60 [2%]; HR 0·67, 95% CI 0·45-1·00, p=0·05). The median duration of treatment was 21 months. The use of the rivaroxaban plus aspirin combination increased major bleeding compared with the aspirin alone group (77 [3%] of 2492 vs 48 [2%] of 2504; HR 1·61, 95% CI 1·12-2·31, p=0·0089), which was mainly gastrointestinal. Similarly, major bleeding occurred in 79 (3%) of 2474 patients with rivaroxaban 5 mg, and in 48 (2%) of 2504 in the aspirin alone group (HR 1·68, 95% CI 1·17-2·40; p=0·0043).Low-dose rivaroxaban taken twice a day plus aspirin once a day reduced major adverse cardiovascular and limb events when compared with aspirin alone. Although major bleeding was increased, fatal or critical organ bleeding was not. This combination therapy represents an important advance in the management of patients with peripheral artery disease. Rivaroxaban alone did not significantly reduce major adverse cardiovascular events compared with asprin alone, but reduced major adverse limb events and increased major bleeding.Bayer AG.
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- Cauwenberghs, Nicholas, et al.
(författare)
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The 2013 ACC/AHA risk score and subclinical cardiac remodeling and dysfunction: Complementary in cardiovascular disease prediction
- 2019
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Ingår i: International Journal of Cardiology. - : ELSEVIER IRELAND LTD. - 0167-5273 .- 1874-1754. ; 297, s. 67-74
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Tidskriftsartikel (refereegranskat)abstract
- Background: Echocardiography might enhance cardiovascular (CV) risk stratification beyond tools grading the risk for atherosclerotic CV diseases (ASCVD). We therefore studied the complementarity between the ASCVD risk score recommended by American cardiology societies and echocardiographic profiling in predicting adverse CV outcome in the community. Methods: 984 community-dwelling individuals between 40 and 79 years old (51.3% women) underwent CV risk profiling and echocardiography. We estimated their 10-year ASCVD risk from baseline risk factors using the Pooled Cohort Equations. Participants were categorized as at low (amp;lt;2.5%), borderline (2.5-amp;lt;7.5%) or intermediate-to-high (amp;gt;= 7.5%) ASCVD risk. Main outcome was the incidence of CV events collected on average 7.5 years later. Results: The probability for cardiac remodeling and/or dysfunction as assessed by echocardiography rose progressively with increasing 10-year ASCVD risk. During follow-up, 116 participants experienced at least one CV endpoint (15.8 events per 1000 person-years). With increasing 10-year ASCVD risk, the CV event rate increased stronger in participants with amp;gt;= 1 LV abnormality at baseline. Indeed, in individuals with an intermediate-to-high ASCVD risk and amp;gt;= 1 LV abnormality at baseline, the risk was significantly higher than the average population risk for a first CV event (HR: 3.00, P amp;lt; 0.001). Adding the presence of amp;gt;= 1 LV abnormality to a ASCVD risk score-based model yielded significant improvement in C-statistics (P = 0.024), integrated discrimination (P=0.0085) and net reclassification (P amp;lt; 0.001) for adverse CV events. Conclusions: Echocardiographic profiling enhanced CV risk stratification in individuals at intermediate-to-high ASCVD risk. Echocardiographic screening might supplement traditional ASCVD risk grading for CV disease prediction. (C) 2019 Elsevier B.V. All rights reserved.
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- McEvoy, John W., et al.
(författare)
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Isolated Diastolic Hypertension in the IDACO Study : An Age-Stratified Analysis Using 24-Hour Ambulatory Blood Pressure Measurements
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 78:5, s. 1222-1231
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Tidskriftsartikel (refereegranskat)abstract
- The prognostic implications of isolated diastolic hypertension (IDH), as defined by 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines, have not been tested using ambulatory blood pressure (BP) monitor thresholds (ie, 24-hour mean systolic BP <125 mm Hg and diastolic BP >= 75 mm Hg). We analyzed data from 11 135 participants in the IDACO (International Database on Ambulatory Blood Pressure in Relation to Cardiovascular Outcomes). Using 24-hour mean ambulatory BP monitor values, we performed Cox regression testing independent associations of IDH with death or cardiovascular events. Analyses were conducted in the cohort overall, as well as after age stratification (<50 years versus >= 50 years). The median age at baseline was 54.7 years and 49% were female. Over a median follow-up of 13.8 years, 2836 participants died, and 2049 experienced a cardiovascular event. Overall, irrespective of age, IDH on 24-hour ambulatory BP monitor defined by 2017 American College of Cardiology/American Heart Association criteria was not significantly associated with death (hazard ratio, 0.95 [95% CI, 0.79-1.13]) or cardiovascular events (hazard ratio, 1.14 [95% CI, 0.94-1.40]), compared with normotension. However, among the subgroup <50 years old, IDH was associated with excess risk for cardiovascular events (2.87 [95% CI, 1.72-4.80]), with evidence for effect modification based on age (P interaction <0.001). In conclusion, using ambulatory BP monitor data, this study suggests that IDH defined by 2017 American College of Cardiology/American Heart Association criteria is not a risk factor for cardiovascular disease in adults aged 50 years or older but is a risk factor among younger adults. Thus, age is an important consideration in the clinical management of adults with IDH.
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- Melgarejo, Jesus D., et al.
(författare)
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Association of Fatal and Nonfatal Cardiovascular Outcomes With 24-Hour Mean Arterial Pressure
- 2021
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Ingår i: Hypertension. - : Wolters Kluwer. - 0194-911X .- 1524-4563. ; 77:1, s. 39-48
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Tidskriftsartikel (refereegranskat)abstract
- Major adverse cardiovascular events are closely associated with 24-hour blood pressure (BP). We determined outcome-driven thresholds for 24-hour mean arterial pressure (MAP), a BP index estimated by oscillometric devices. We assessed the association of major adverse cardiovascular events with 24-hour MAP, systolic BP (SBP), and diastolic BP (DBP) in a population-based cohort (n=11 596). Statistics included multivariable Cox regression and the generalized R-2 statistic to test model fit. Baseline office and 24-hour MAP averaged 97.4 and 90.4 mm Hg. Over 13.6 years (median), 2034 major adverse cardiovascular events occurred. Twenty-four-hour MAP levels of <90 (normotension, n=6183), 90 to <92 (elevated MAP, n=909), 92 to <96 (stage-1 hypertension, n=1544), and >= 96 (stage-2 hypertension, n=2960) mm Hg yielded equivalent 10-year major adverse cardiovascular events risks as office MAP categorized using 2017 American thresholds for office SBP and DBP. Compared with 24-hour MAP normotension, hazard ratios were 0.96 (95% CI, 0.80-1.16), 1.32 (1.15-1.51), and 1.77 (1.59-1.97), for elevated and stage-1 and stage-2 hypertensive MAP. On top of 24-hour MAP, higher 24-hour SBP increased, whereas higher 24-hour DBP attenuated risk (P<0.001). Considering the 24-hour measurements, R-2 statistics were similar for SBP (1.34) and MAP (1.28), lower for DBP than for MAP (0.47), and reduced to null, if the base model included SBP and DBP; if the ambulatory BP indexes were dichotomized according to the 2017 American guideline and the proposed 92 mm Hg for MAP, the R-2 values were 0.71, 0.89, 0.32, and 0.10, respectively. In conclusion, the clinical application of 24-hour MAP thresholds in conjunction with SBP and DBP refines risk estimates.
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| 6. |
- Peetermans, Marijke, et al.
(författare)
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Plasminogen activation by staphylokinase enhances local spreading of S. aureus in skin infections.
- 2014
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Ingår i: BMC microbiology. - : Springer Science and Business Media LLC. - 1471-2180. ; 14:1
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Tidskriftsartikel (refereegranskat)abstract
- Background Staphylococcus aureus (S. aureus) is a frequent cause of skin and soft tissue infections. A unique feature of S. aureus is the combined presence of coagulases that trigger fibrin formation and of the plasminogen activator staphylokinase (SAK). Whereas the importance of fibrin generation for S. aureus virulence has been established, the role of SAK remains unclear.We studied the role of plasminogen activation by SAK in a skin infection model in mice and evaluated the impact of alpha-2-antiplasmin (¿2AP) deficiency on the spreading and proteolytic activity of S. aureus skin infections. The species-selectivity of SAK was overcome by adenoviral expression of human plasminogen. Bacterial spread and density was assessed non-invasively by imaging the bioluminescence of S. aureus Xen36.ResultsSAK-mediated plasmin activity increased the local invasiveness of S. aureus, leading to larger lesions with skin disruption as well as decreased bacterial clearance by the host. Even though fibrin and bacterial surfaces protected SAK-mediated plasmin activity from inhibition by ¿2AP, the deficiency of ¿2AP resulted in increased bacterial spreading. SAK-mediated plasmin also induced secondary activation of gelatinases, shown both in vitro and in lesions from the in vivo model.ConclusionSAK contributes to the phenotype of S. aureus skin infections by enhancing bacterial spreading as a result of fibrinolytic and proteolytic activation.
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