| 61. |
- Mahaffey, Kenneth W., et al.
(författare)
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Comparison of Clinical Trial Outcome Patterns in Patients Following Acute Coronary Syndromes and in Patients With Chronic Stable Atherosclerosis
- 2014
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Ingår i: Clinical Cardiology. - : Wiley. - 0160-9289 .- 1932-8737. ; 37:6, s. 337-342
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Tidskriftsartikel (refereegranskat)abstract
- Background: The transition of patients with atherosclerotic vascular disease from the acute phase of the disease to the chronic stable atherosclerosis (CSA) phase has not been well characterized. We sought to compare ischemic and bleeding outcomes in hospitalized patients enrolled in clinical trials of non-ST-elevation acute coronary syndrome (ACS) with patients enrolled in outpatient trials of CSA. Hypothesis: The risk for recurrent events will differ between the 2 populations. Methods: Patient-level outcome data were evaluated from 3 consecutive trials of patients with ACS with long-term follow-up and 2 trials of patients with CSA. Kaplan-Meier curves were generated for ischemic and bleeding outcomes. Results: In total, 37 370 patients were included in these analyses. Of these, 28 489 (76.2%) were from ACS trials and 8881 (23.8%) from chronic trials. During the first year of follow-up, 1353 deaths, 1081 cardiovascular (CV) deaths, 2113 myocardial infarctions (MIs), and 397 strokes occurred across the trials. Six-month Kaplan-Meier event rates for CV death, MI, or stroke were higher in the ACS trials compared with the CSA trials (8.6% vs 2.7%), as were the 1-year CV death rate (3.6% vs 1.7%) and 1-year rates for GUSTO moderate or severe bleeding (6.0% vs 1.3%). Qualitatively, the Kaplan-Meier curves appear to show an early increased risk as well as a continued increased risk over time. Conclusions: Patients with ACS enrolled while in the hospital appear to have different risk profiles for ischemic and bleeding outcomes compared with outpatients enrolled with CSA, including those patients with ACS after the acute phase.
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| 62. |
- Nelson, Adam J., et al.
(författare)
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Cardiovascular Effects of GnRH Antagonists Compared With Agonists in Prostate Cancer : A Systematic Review
- 2023
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Ingår i: JACC: CardioOncology. - 2666-0873. ; 5:5, s. 613-624
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Forskningsöversikt (refereegranskat)abstract
- Background: Androgen deprivation therapy is the cornerstone of treatment for patients with advanced prostate cancer. Meta-analysis of small, oncology-focused trials suggest gonadotropin-releasing hormone (GnRH) antagonists may be associated with fewer adverse cardiovascular outcomes compared with GnRH agonists. Objectives: This study sought to determine whether GnRH antagonists were associated with fewer major adverse cardiovascular events compared with GnRH agonists. Methods: Electronic databases were searched for all prospective, randomized trials comparing GnRH antagonists with agonists. The primary outcome was a major adverse cardiovascular event as defined by the following standardized Medical Dictionary for Regulatory Activities terms: “myocardial infarction,” “central nervous system hemorrhages and cerebrovascular conditions,” and all-cause mortality. Bayesian meta-analysis models with random effects were fitted. Results: A total of 11 eligible studies of a maximum duration of 3 to 36 months (median = 12 months) enrolling 4,248 participants were included. Only 1 trial used a blinded, adjudicated event process, whereas potential bias persisted in all trials given their open-label design. A total of 152 patients with primary outcome events were observed, 76 of 2,655 (2.9%) in GnRH antagonist-treated participants and 76 of 1,593 (4.8%) in agonist-treated individuals. Compared with GnRH agonists, the pooled OR of GnRH antagonists for the primary endpoint was 0.57 (95% credible interval: 0.37-0.86) and 0.58 (95% credible interval: 0.32-1.08) for all-cause death. Conclusions: Despite the addition of the largest, dedicated cardiovascular outcome trial, the volume and quality of available data to definitively answer this question remain suboptimal. Notwithstanding these limitations, the available data suggest that GnRH antagonists are associated with fewer cardiovascular events, and possibly mortality, compared with GnRH agonists.
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| 63. |
- Nicolau, Jose C., et al.
(författare)
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Dabigatran Dual Therapy vs Warfarin Triple Therapy Post-Percutaneous Coronary Intervention in Patients with Atrial Fibrillation With/Without a Proton Pump Inhibitor : A Pre-Specified Analysis of the RE-DUAL PCI Trial
- 2020
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Ingår i: Drugs. - : Springer Nature. - 0012-6667 .- 1179-1950. ; 80:10, s. 995-1005
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Tidskriftsartikel (refereegranskat)abstract
- Background and Objective In patients with atrial fibrillation following percutaneous coronary intervention, if a proton pump inhibitor is used, could that allow the use of warfarin triple therapy, or is there additional reduction in bleeding while using it with dual therapy? Methods The RE-DUAL PCI trial randomized 2725 patients with atrial fibrillation post-percutaneous coronary intervention to dabigatran dual therapy (110 or 150 mg twice daily, with clopidogrel or ticagrelor) or warfarin triple therapy (with clopidogrel or ticagrelor, and aspirin for 1-3 months). This prespecified subgroup analysis evaluated risks of a first major bleeding event or clinically relevant non-major bleeding event, all gastrointestinal bleeding, and a composite efficacy endpoint of all-cause mortality/thromboembolic event or unplanned revascularization according to baseline use of a proton pump inhibitor. Results Of 2678 analyzed patients, 1641 (61.3%) were receiving a proton pump inhibitor at baseline. Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy regardless of proton pump inhibitor use, with comparable risk of the composite efficacy endpoint (all interactionpvalues > 0.05). For gastrointestinal bleeding, no interaction was observed between study treatment and proton pump inhibitor use (interactionpvalues 0.84 and 0.62 for dabigatran 110 and 150 mg dual therapy, respectively, vs warfarin triple therapy). Conclusions Dabigatran 110 and 150 mg dual therapy reduced the risk of major bleeding events or clinically relevant non-major bleeding events vs warfarin triple therapy, regardless of proton pump inhibitor use at baseline, in patients with atrial fibrillation who underwent percutaneous coronary intervention. Risk of the composite efficacy endpoint appeared to be similar for dabigatran dual therapy vs warfarin triple therapy in patients receiving/not receiving a proton pump inhibitor.
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| 64. |
- Oldgren, Jonas, 1964-, et al.
(författare)
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Dabigatran dual therapy with ticagrelor or clopidogrel after percutaneous coronary intervention in atrial fibrillation patients with or without acute coronary syndrome : a subgroup analysis from the RE-DUAL PCI trial
- 2019
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 40:19, s. 1553-1562
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Tidskriftsartikel (refereegranskat)abstract
- AimsAfter percutaneous coronary intervention (PCI) in patients with atrial fibrillation, safety and efficacy with dabigatran dual therapy were evaluated in pre-specified subgroups of patients undergoing PCI due to acute coronary syndrome (ACS) or elective PCI, and those receiving ticagrelor or clopidogrel treatment.Methods and resultsIn the RE-DUAL PCI trial, 2725 patients were randomized to dabigatran 110 mg or 150 mg with P2Y12 inhibitor, or warfarin with P2Y12 inhibitor and aspirin. Mean follow-up was 14 months, 50.5% had ACS, and 12% received ticagrelor. The risk of the primary endpoint, major or clinically relevant non-major bleeding event, was reduced with both dabigatran dual therapies vs. warfarin triple therapy in patients with ACS [hazard ratio (95% confidence interval), 0.47 (0.35-0.63) for 110 mg and 0.67 (0.50-0.90) for 150 mg]; elective PCI [0.57 (0.43-0.76) for 110 mg and 0.76 (0.56-1.03) for 150 mg]; receiving ticagrelor [0.46 (0.28-0.76) for 110 mg and 0.59 (0.34-1.04) for 150 mg]; or clopidogrel [0.51 (0.41-0.64) for 110 mg and 0.73 (0.58-0.91) for 150 mg], all interaction P-values >0.10. Overall, dabigatran dual therapy was comparable to warfarin triple therapy for the composite endpoint of death, myocardial infarction, stroke, systemic embolism, or unplanned revascularization, with minor variations across the subgroups, all interaction P-values >0.10.ConclusionThe benefits of both dabigatran 110 mg and 150 mg dual therapy compared with warfarin triple therapy in reducing bleeding risks were consistent across subgroups of patients with or without ACS, and patients treated with ticagrelor or clopidogrel.
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| 65. |
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| 66. |
- Pareek, Manan, et al.
(författare)
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Single and multiple cardiovascular biomarkers in subjects without a previous cardiovascular event
- 2017
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Ingår i: European Journal of Preventive Cardiology. - : Oxford University Press (OUP). - 2047-4881 .- 2047-4873. ; , s. 1648-1659
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Tidskriftsartikel (refereegranskat)abstract
- Aims To assess the incremental value of biomarkers, including N-terminal prohormone of brain natriuretic peptide (NT-proBNP), high-sensitivity troponin T (hs-TnT), high-sensitivity C-reactive protein (hs-CRP), interleukin-6 (IL-6), growth differentiation factor 15 (GDF-15), and procollagen type 1 N-terminal propeptide (P1NP), in predicting incident cardiovascular events and mortality among asymptomatic individuals from the general population, beyond traditional risk factors, including fasting glucose and renal function (cystatin C), medication use, and echocardiographic measures. Methods and results Prospective population-based cohort study of 1324 subjects without a previous cardiovascular event, who underwent baseline echocardiography and biomarker assessment between 2002 and 2006. The clinical endpoint was the composite of myocardial infarction, invasively treated stable/unstable ischemic heart disease, heart failure, stroke, or all-cause mortality. Predictive capabilities were evaluated using Cox proportional-hazards regression, Harrell's concordance index (C-index), and net reclassification improvement. Median age was 66 (interquartile range: 60-70) years, and 413 (31%) were female. During median 8.6 (interquartile range: 8.1-9.2) follow-up years, 368 (28%) composite events occurred. NT-proBNP, hs-TnT, GDF-15, and IL-6 were significantly associated with outcome, independently of traditional risk factors, medications, and echocardiography ( p < 0.05 for all). Separate addition of NT-proBNP and GDF-15 to traditional risk factors, medications, and echocardiographic measurements provided significant improvements in discriminative ability (NT-proBNP: C-index 0.714 vs. 0.703, p = 0.03; GDF-15: C-index 0.721 vs. 0.703, p = 0.02). Both biomarkers remained significant predictors of outcome upon inclusion in the same model ( p < 0.05 for both). Conclusions NT-proBNP and GDF-15 each enhance prognostication beyond traditional risk factors, glucose levels, renal function, and echocardiography in individuals without known cardiovascular disease.
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| 67. |
- Pedersen, Line Reinholdt, et al.
(författare)
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Prognostic implications of left ventricular hypertrophy diagnosed on electrocardiogram vs echocardiography
- 2020
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Ingår i: Journal of Clinical Hypertension. - : Wiley. - 1524-6175 .- 1751-7176. ; 22:9, s. 1647-1658
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Tidskriftsartikel (refereegranskat)abstract
- It is unclear whether 12-lead ECG employing standard criteria for left ventricular hypertrophy (LVH) provides similar information with respect to long-term cardiovascular risk as echocardiography. The authors performed a retrospective cohort study of 1376 individuals without cardiovascular disease, who underwent ECG (LVH defined using the Sokolow-Lyon voltage combination (>35 mm) or the Cornell voltage-duration product (>2440 mm × ms)) and echocardiography (LVH defined as LV mass index (LVMI) >95 g/m2 for women and >115 g/m2 for men). The prognostic ability of LVH was assessed in Cox regression models adjusted for age, sex, smoking, systolic blood pressure, total cholesterol, antihypertensive medication, and fasting glucose. The primary end point was the composite of coronary events, heart failure, stroke, or death. The main secondary end point was heart failure or cardiovascular death. Median age was 67 (range 56-79) years, 68% were male. Eleven percent had ECG-defined LVH, 17% had echocardiographic LVH. Over median 8.5 years, 29% experienced a primary event. Event rates were 29%/35% for persons without/with ECG-defined LVH and 27%/39% for those without/with echocardiographic LVH. The Sokolow-Lyon combination, Cornell product, and ECG-defined LVH did not significantly predict the primary end point (P ≥.05), but ECG-defined LVH predicted heart failure or cardiovascular death (adjusted hazard ratio (HR), 1.86, 95% confidence interval (CI), 1.13-3.08); P =.02). Conversely, LVMI was a significant, independent predictor of the primary end point (adjusted HR, 1.87, 95% CI, 1.13-3.10; P =.01), as was echocardiographic LVH (adjusted HR, 1.27, 95% CI, 1.01-1.61; P =.04). Echocardiographic LVH may be a better predictor of long-term cardiovascular risk than ECG-defined LVH in middle-aged and older individuals.
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| 68. |
- Peterson, Benjamin E., et al.
(författare)
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Evaluation of Dual Versus Triple Therapy by Landmark Analysis in the RE-DUAL PCI Trial
- 2021
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Ingår i: JACC. - : American College of Cardiology. - 1936-8798 .- 1876-7605. ; 14:7, s. 768-780
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim of this study was to explore the early versus late benefits and risks of dabigatran dual therapy versus warfarin triple therapy in the RE-DUAL PCI (Randomized Evaluation of Dual Antithrombotic Therapy With Dabi-gatran Versus Triple Therapy With Warfarin in Patients With Nonvalvular Atrial Fibrillation Undergoing Percutaneous Coronary Intervention) trial.BACKGROUND: Patients with atrial fibrillation who undergo percutaneous coronary intervention are at increased risk for both bleeding and thrombotic events.METHODS: A total of 2,725 patients with atrial fibrillation underwent percutaneous coronary intervention and were randomized to receive dabigatran 110 mg, or dabigatran 150 mg plus a P2Y(12) inhibitor (and no aspirin), or warfarin plus a P2Y(12) inhibitor plus aspirin. Landmark analysis was performed at 30 and 90 days.RESULTS: There was a consistent and large reduction in major or clinically relevant nonmajor bleeding in patients randomized to dual therapy during the first 30 days (110 mg: hazard ratio [HR]: 0.45; 95% confidence interval [CI]: 0.31 to 0.66; p < 0.0001; 150 mg: HR: 0.46; 95% CI: 0.30 to 0.72; p = 0.0006) compared with warfarin triple therapy. There was early net clinical benefit in both dabigatran groups versus warfarin (110 mg: HR: 0.65; 95% CI: 0.47 to 0.88; p = 0.0062; 150 mg: HR: 0.54; 95% CI: 0.37 to 0.79; p = 0.0015), due to larger reductions in bleeding than increased thrombotic events for dabigatran 110 mg and bleeding reduction without increased thrombotic risk for dabigatran 150 mg dual therapy versus warfarin triple therapy. After the removal of aspirin in the warfarin group, bleeding remained lower with dabigatran 110 mg and was similar with dabigatran 150 mg versus warfarin.CONCLUSIONS: In RE-DUAL PCI, in which patients in the dual-therapy arms were treated with aspirin for an average of only 1.6 days, there was early net clinical benefit with both doses of dabigatran dual therapy, without an increase in thrombotic events with dabigatran 150 mg. This could be helpful in the subset of patients with elevated risk for both bleeding and thrombotic events.
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| 69. |
- Rao, Sunil, V, et al.
(författare)
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A Multicenter, Phase 2, Randomized, Placebo-Controlled, Double-Blind, Parallel-Group, Dose-Finding Trial of the Oral Factor XIa Inhibitor Asundexian to Prevent Adverse Cardiovascular Outcomes After Acute Myocardial Infarction
- 2022
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Ingår i: Circulation. - : American Heart Association. - 0009-7322 .- 1524-4539. ; 146:16, s. 1196-1206
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Oral activated factor XI (FXIa) inhibitors may modulate coagulation to prevent thromboembolic events without substantially increasing bleeding. We explored the pharmacodynamics, safety, and efficacy of the oral FXIa inhibitor asundexian for secondary prevention after acute myocardial infarction (MI).METHODS: We randomized 1601 patients with recent acute MI to oral asundexian 10, 20, or 50 mg or placebo once daily for 6 to 12 months in a double-blind, placebo-controlled, phase 2, dose-ranging trial. Patients were randomized within 5 days of their qualifying MI and received dual antiplatelet therapy with aspirin plus a P2Y12 inhibitor. The effect of asundexian on FXIa inhibition was assessed at 4 weeks. The prespecified main safety outcome was Bleeding Academic Research Consortium type 2, 3, or 5 bleeding comparing all pooled asundexian doses with placebo. The prespecified efficacy outcome was a composite of cardiovascular death, MI, stroke, or stent thrombosis comparing pooled asundexian 20 and 50 mg doses with placebo.RESULTS: The median age was 68 years, 23% of participants were women, 51% had ST-segment-elevation MI, 80% were treated with aspirin plus ticagrelor or prasugrel, and 99% underwent percutaneous coronary intervention before randomization. Asundexian caused dose-related inhibition of FXIa activity, with 50 mg resulting in >90% inhibition. Over a median follow-up of 368 days, the main safety outcome occurred in 30 (7.6%), 32 (8.1%), 42 (10.5%), and 36 (9.0%) patients receiving asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian versus placebo: hazard ratio, 0.98 [90% CI, 0.71-1.35]). The efficacy outcome occurred in 27 (6.8%), 24 (6.0%), 22 (5.5%), and 22 (5.5%) patients assigned asundexian 10 mg, 20 mg, or 50 mg, or placebo, respectively (pooled asundexian 20 and 50 mg versus placebo: hazard ratio, 1.05 [90% CI, 0.69-1.61]).CONCLUSIONS: In patients with recent acute MI, 3 doses of asundexian, when added to aspirin plus a P2Y12 inhibitor, resulted in dose-dependent, near-complete inhibition of FXIa activity without a significant increase in bleeding and a low rate of ischemic events. These data support the investigation of asundexian at a dose of 50 mg daily in an adequately powered clinical trial of patients who experienced acute MI.
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| 70. |
- Redfors, Björn, et al.
(författare)
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Outcomes According to Coronary Revascularization Modality in the ISCHEMIA Trial.
- 2024
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Ingår i: Journal of the American College of Cardiology. - 1558-3597. ; 83:5, s. 549-558
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Tidskriftsartikel (refereegranskat)abstract
- In the ISCHEMIA trial, the risk of ischemic events was similar in patients with stable coronary artery disease treated with an invasive (INV) strategy of angiography and percutaneous (PCI) or surgical (CABG) coronary revascularization and a conservative (CON) strategy of initial medical therapy.To analyze separately the outcomes of INV patients treated with PCI or CABG.Patients without preceding primary outcome events were categorized as INV-PCI or INV-CABG from the time of revascularization. The ISCHEMIA primary outcome (composite of cardiovascular death, protocol-defined myocardial infarction (MI) or hospitalization for unstable angina, heart failure or resuscitated cardiac arrest) was used.Among INV-CABG patients, primary outcome events occurred in 84/512 (16.4%) at median follow-up of 2.85 years; 48 events (57.1%) occurred within 30 days after CABG, including 40 procedural MIs; among INV-PCI patients, primary outcome events occurred in 147/1500 (9.8%) at median follow-up of 2.94 years; 31 of which (21.1%) within 30 days after PCI, including 23 procedural MIs. In comparison, 352/2591 (13.6%) CON patients had primary outcome events at median follow-up 3.2 years, 22 of which (6.3%) within 30 days of randomization. The adjusted primary outcome risks (HR [95%CI]) were higher after both CABG and PCI within 30 days (16.25 (11.44-23.07) and 2.99 (1.97-4.53)) and lower thereafter (0.63 (0.44-0.89) and 0.66(0.53-0.82)).In ISCHEMIA, early revascularization by PCI and CABG was associated with higher early risks and lower long-term risks of cardiovascular events compared with CON. The early risk was greatest after CABG, due to protocol-defined procedural MIs.
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