| 1. |
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| 2. |
- Cleland, J. G., et al.
(author)
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A description of the clinical characteristics at baseline of patients recruited into the Carvedilol or Metoprolol European Trial (COMET)
- 2004
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In: Cardiovascular drugs and therapy / sponsored by the International Society of Cardiovascular Pharmacotherapy. - 0920-3206. ; 18:2, s. 139-52
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Journal article (peer-reviewed)abstract
- BACKGROUND & AIMS: The COMET trial was a prospective, double-blind, randomised trial comparing carvedilol, a comprehensive adrenergic receptor antagonist, with metoprolol, a beta-1-selective agent in patients with heart failure and left ventricular systolic dysfunction. The trial showed a reduction in mortality with carvedilol that was consistent across subgroups. The purpose of this report is to describe in greater detail the heterogeneity of this population at baseline with particular reference to the impact of symptomatic severity, age and gender on patient characteristics. METHODS: A descriptive report using data entered in the COMET study data-base. RESULTS: The characteristics of the population studied were similar to those reported in previous trials of beta-blockers. Almost all patients were receiving diuretics and ACE inhibitors with few patients taking angiotensin receptor blockers. As expected, older patients had more co-morbidity. Older patients and women reported worse symptoms and poorer well-being despite similar ventricular dimensions and systolic dysfunction. NT-proBNP was higher in patients with more severe symptoms and older patients but not in women, although differences in NT-proBNP may have been confounded by differences in renal function. CONCLUSION: Age and gender, as well as the severity of cardiac dysfunction, appear to have an important effect on the severity of heart failure symptoms and patient 'well-being'. This could have important implications for the relationship between symptoms and prognosis and therefore the way in which patients are selected for clinical trials and the goals of treatment. This will be the subject of further analyses.
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| 7. |
- Dobre, Daniela, et al.
(author)
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Clinical effects of initial 6 months monotherapy with bisoprolol versus enalapril in the treatment of patients with mild to moderate chronic heart failure. Data from the CIBIS III trial
- 2008
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 22:5, s. 399-405
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Journal article (peer-reviewed)abstract
- Purpose To assess the clinical effects and safety profile of initial monotherapy with either bisoprolol or enalapril in elderly patients with heart failure (HF). Methods In CIBIS III, 1010 patients with mild to moderate HF and age >= 65 years were randomized to monotherapy with either bisoprolol or enalapril for 6 months. Results Bisoprolol had a similar effect as enalapril on the combined end-point of all-cause mortality or hospitalization (HR 1.02; p=0.90), as well as on each of the individual end-points. A trend towards fewer sudden deaths was observed with bisoprolol (NS). On the other hand, more cases of worsening HF requiring hospitalization or occurring while in hospital were observed in the bisoprolol group (HR 1.67; p=0.03). The two groups were similar with regard to treatment cessations and early introduction of the second drug. Conclusions Bisoprolol and enalapril had a similar effect on the combined end-point of mortality or hospitalization during 6 months monotherapy. However, more worsening HF events were observed in the bisoprolol group.
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| 8. |
- Du, Y., et al.
(author)
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Activation of T Lymphocytes as a Novel Mechanism in Beta1-Adrenergic Receptor Autoantibody-Induced Cardiac Remodeling
- 2019
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 33:2, s. 149-161
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Journal article (peer-reviewed)abstract
- Background: Numerous studies have reported significantly elevated titers of serum autoantibody against the second extracellular loop of β 1 -adrenoceptor (β 1 -AA), a catecholamine-like substance with β 1 -adrenergic activity, in patients with heart failure. Although evidence demonstrates that this autoantibody may alter T cell proliferation and secretion, the role of T lymphocytes in heart failure induced by β 1 -AA remains unclear. The current study was designed to determine whether T cell disorder contributes to heart failure induced by β 1 -AA. Methods and Results: β 1 -AA monoclonal antibodies (β 1 -AAmAb) produced using the hybridoma technique were administered in wild-type mice or T lymphocyte deficiency nudes for 12weeks. T lymphocytes from heart failure patients and neonatal cardiomyocytes were utilized in vitro. Mouse protein antibody array analysis was employed to detect the cytokines responsible for β 1 -AAmAb-induced heart failure. Compared to wild-type mice, T lymphocyte deficiency mice prevented cardiac function from getting worse, attenuated adverse remodeling, and ameliorated cardiomyocyte apoptosis and fibrosis. As shown by protein array, the serum level of interleukin (IL)-6 was significantly lower in the nude group as compared to wild-type after β 1 -AAmAb treatment. Mechanistic studies in vitro demonstrated that T lymphocyte culture supernatants stimulated by β 1 -AAmAb caused direct damage in the cardiomyocytes, and β 1 -AAmAb promoted proliferation of T lymphocytes isolated from patients with heart failure and increased IL-6 release. IL-6-specific siRNA virtually abolished cardiomyocyte apoptosis, suggesting that IL-6 may be a key cytokine released by T lymphocytes and responsible for β 1 -AAmAb-induced cardiac remodeling. Conclusions: Collectively, we demonstrate that β 1 -AAmAb-induced cardiac remodeling via mediating T lymphocyte disorder and releasing a variety of IL-6. © 2019, Springer Science+Business Media, LLC, part of Springer Nature.
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| 10. |
- Guimarães, Patrícia O, et al.
(author)
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Effect of Apixaban on All-Cause Death in Patients with Atrial Fibrillation : a Meta-Analysis Based on Imputed Placebo Effect
- 2017
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 31:3, s. 295-301
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Journal article (peer-reviewed)abstract
- PURPOSE: Vitamin K antagonists (VKAs) are the standard of care for stroke prevention in patients with atrial fibrillation (AF); therefore, there is not equipoise when comparing newer oral anticoagulants with placebo in this setting.METHODS: To explore the effect of apixaban on mortality in patients with AF, we performed a meta-analysis of apixaban versus placebo using a putative placebo analysis based on randomized controlled clinical trials that compared warfarin, aspirin, and no antithrombotic control. We used data from two prospective randomized controlled trials for our comparison of apixaban versus warfarin (Apixaban for Reduction in Stroke and Other Thromboembolic Events in Atrial Fibrillation) and apixaban versus aspirin (Apixaban Versus Acetylsalicylic Acid to Prevent Stroke in Atrial Fibrillation Patients Who Have Failed or Are Unsuitable for Vitamin K Antagonist Treatment). Using meta-analysis approaches, we indirectly compared apixaban with an imputed placebo with respect to the risk of death in patients with AF. We used results from meta-analyses of randomized trials as our reference for the comparison between warfarin and placebo/no treatment, and aspirin and placebo/no treatment.RESULTS: In these meta-analyses, a lower rate of death was seen both with warfarin (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.57-0.97) and aspirin (OR 0.86, 95% CI 0.69-1.07) versus placebo/no treatment. Using data from ARISTOTLE and AVERROES, apixaban reduced the risk of death by 34% (95% CI 12-50%; p = 0.004) and 33% (95% CI 6-52%; p = 0.02), respectively, when compared with an imputed placebo. The pooled reduction in all-cause death with apixaban compared with an imputed placebo was 34% (95% CI 18-47%; p = 0.0002).CONCLUSIONS: In patients with AF, indirect comparisons suggest that apixaban reduces all-cause death by approximately one third compared with an imputed placebo.
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| 11. |
- Herlitz, Johan, et al.
(author)
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Five-year mortality after acute myocardial infarction in relation to previous history, level of initial care, complications in hospital, and medication at discharge
- 1996
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In: Cardiovascular Drugs and Therapy. - : Springer New York LLC. - 0920-3206 .- 1573-7241. ; 10:4, s. 485-490
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Journal article (peer-reviewed)abstract
- The purpose of this study was to describe the prognosis during 5 years of follow-up in a consecutive population of patients discharged from hospital after acute myocardial infarction (AMI) in relation to clinical history, level of initial care, complications during hospitalization, and medication at discharge. All patients admitted to a single hospital from February 15, 1986 to November 9, 1987 due to AMI, regardless of age and whether or not they were treated in the coronary care unit, and who were discharged alive from hospital were included in the study. There were 862 patients with AMI, 740 of whom were discharged alive. Information on medication at discharge was available in 713 patients (96%). In a multivariate analysis taking into account age, sex, history of cardiovascular diseases, whether patients were admitted to coronary care unit or not, complications during hospitalization, and medication at discharge, the following factors appeared to be independent predictors of mortality: age (p < 0.001), history of AMI (p < 0.001), congestive heart failure in hospital (p < 0.001), whether beta-blockers had been prescribed at discharge (p < 0.01), and a history of diabetes (p < 0.01). This study indicates that in consecutive patients surviving the hospital phase of AMI, the development of complications while in hospital and the manner in which medication was prescribed at discharge independently influenced their long-term prognosis, but age was the most important factor in long-term prognosis.
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| 12. |
- Herlitz, Johan, et al.
(author)
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Long term mortality after acute myocardial infarction in relation to prescribed dosages of a beta-blocker at hospital discharge
- 2001
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In: Cardiovascular Drugs and Therapy. - : Springer New York LLC. - 0920-3206 .- 1573-7241. ; 14:6, s. 589-595
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Journal article (peer-reviewed)abstract
- his study was designed to describe the 5-year mortality rate in relation to the dose of metoprolol prescribed at hospital discharge after hospitalisation for acute myocardial infarction (AMI). All patients discharged alive after being hospitalized for AMI at Sahlgrenska Hospital (covering half of the community of Göteborg, with 500,000 inhabitants) during 1986–1987 (period I) and all patients discharged alive after hospitalization for AMI at Sahlgrenska Hospital and östra Hospital (covering the whole area of the community of Göteborg) in 1990–1991 (period II) were included. Overall mortality was retrospectively evaluated over 5 years of follow-up. In all there were 2161 patients who were discharged after AMI. Seventy-three percent of these patients were prescribed a beta-blocker and 59% were prescribed metoprolol. Of the patients prescribed metoprolol, 34% were on 200 mg, 46% on 100 mg, and 20% on 50 mg or less. Information on 5-year mortality was available for 2142 of the 2161 patients (99.1%). The 5-year mortality was 24% among patients prescribed 200 mg, 33% among patients prescribed 100 mg, and 43% among patients prescribed 50 mg (P < 0.0001).="" patients="" prescribed="" another="" beta-blocker="" had="" a="" 5-year="" mortality="" of="" 39%,="" and="" patients="" prescribed="" no="" beta-blocker="" at="" all="" had="" a="" 5-year="" mortality="" of="" 61%.="" when="" correcting="" for="" dissimilarities="" at="" baseline,="" patients="" who="" were="" prescribed="">le100 mg had an adjusted risk ratio for death of 0.79 (95% confidence limit 0.64–0.96; P = 0.021) as compared with patients not prescribed a beta blocker. The corresponding figure for patients prescribed >100 mg was 0.63 (95% confidence limit 0.48–0.84; P = 0.001). Both patients prescribed high and low doses of metoprolol after AMI appeared to benefit from treatment. There was a trend indicating more benefit when larger doses were prescribed.
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| 13. |
- Herlitz, Johan, et al.
(author)
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Similar risk reduction of death of extended-release metoprolol once daily and immediate release metoprolol twice daily during 5 years after myocardial infarction
- 1999
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In: Cardiovascular Drugs and Therapy. - : Springer New York LLC. - 0920-3206 .- 1573-7241. ; 13:2, s. 127-135
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Journal article (peer-reviewed)abstract
- The pooled results from five placebo-controlled postinfarction studies with metoprolol have shown a significant reduction in total mortality. All five studies used immediate-release metoprolol twice daily. An extended-release formulation of metoprolol for once-daily use has since been developed. The aim of the present study was to compare the two different forms of metoprolol with regard to the risk reduction of death for 5 years postinfarction and to analyze whether treatment with the beta-blocker metoprolol is associated with a reduced mortality after the introduction of modern therapies such as thrombolysis, aspirin, and ACE inhibitors. All patients discharged after an acute myocardial infarction (AMI) from Sahlgrenska University Hospital (SU) during 1986-1987 (n = 740, Period I) and during 1990-1991 (n = 1446, Period II) from both SU and Ostra Hospital, Göteborg, Sweden, were included in the study. During Period I, 56% were prescribed immediate-release metoprolol compared with 61% prescribed extended-release metoprolol during Period II. Immediate-release metoprolol was not available for outpatient use during Period II. In a multivariate analysis, all variables significantly associated with either increased or decreased postinfarction mortality during Periods I and II (univariate analysis of patient characteristics, medical history, complications during the AMI medication at discharge) studied were with Cox's proportional hazards model. Treatment with immediate-release metoprolol was significantly associated with reduced mortality over 5 years during Period I (relative risk reduction for total mortality, -34%, P = 0.003; 95% CI for RR, 0.51-0.87), and treatment with extended-release metoprolol was significantly associated with reduced mortality during Period II (-34%, P < 0.0001; 95% CI for RR, 0.53-0.82). Thrombolysis and the use of aspirin and ACE inhibitors were more frequently used during Period II. The results showed that postinfarction treatment with extended-release metoprolol given once daily was associated with a similar risk reduction of death over 5 years as immediate-release metoprolol given twice daily. The data, furthermore, indicate that the beta-blocker metoprolol is associated with a reduced risk of death after the introduction of modern therapy such as thrombolysis, aspirin, and ACE inhibitors.
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| 14. |
- Hill, JA, et al.
(author)
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Medical Misinformation: Vet the Message!
- 2019
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In: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206. ; 33:3, s. 275-276
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Journal article (other academic/artistic)
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| 15. |
- Hogenhuis, Jochem, et al.
(author)
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BNP and functional status in heart failure.
- 2004
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 18:6, s. 507; author reply 509-
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Journal article (peer-reviewed)
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| 16. |
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| 17. |
- Husser, D, et al.
(author)
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Analysis of the surface electrocardiogram for monitoring and predicting antiarrhythmic drug effects in atrial fibrillation
- 2004
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 18:5, s. 377-386
-
Research review (peer-reviewed)abstract
- Specific antiarrhythmic therapy with class I and III drugs for atrial fibrillation (AF) conversion and prevention of its recurrence is frequently utilized in clinical practice. Besides being only moderate effective, the utilization of antiarrhythmic drugs may be associated with serious side effects. In the clinical setting it is difficult to directly evaluate the effects of antiarrhythmic drugs on the individual patient's atrial electrophysiology, thereby predicting their efficacy in restoring and maintaining sinus rhythm. Analysis of the surface electrocardiogram in terms of P-wave signal averaged ECG during sinus rhythm and spectral characterization of fibrillatory waves during AF for evaluation of atrial antiarrhythmic drug effects is a new field of investigation. Both techniques provide reproducible parameters for characterizing atrial electrical abnormalities and seem to contain prognostic information regarding antiarrhythmic drug efficacy. Further research is needed which elucidates the most challenging clinical questions in AF management whom to place on antiarrhythmic drug treatment and what antiarrhythmic drug to prescribe. Analysis of the surface ECG might have the potential to answer these questions.
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| 20. |
- Krackhardt, F., et al.
(author)
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Results from the "Me & My Heart" (eMocial) Study: a Randomized Evaluation of a New Smartphone-Based Support Tool to Increase Therapy Adherence of Patients with Acute Coronary Syndrome
- 2023
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 37:4, s. 729-741
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Journal article (peer-reviewed)abstract
- Purpose This study evaluated whether patient support, administered via an electronic device-based app, increased adherence to treatment and lifestyle changes in patients with acute coronary syndrome (ACS) treated with ticagrelor in routine clinical practice. Methods Patients (aged >= 18 years) with diagnosed ACS treated with ticagrelor co-administered with low-dose acetylsalicylic acid were randomized into an active group (with support tool app for medication intake reminders and motivational messages) and a control group (without support tool app), and observed for 48 weeks (ClinicalTrials.gov Identifier: NCT02615704). Patients were asked to complete the 36-item Short-Form Health Survey (SF-36) and Lifestyle Changes Questionnaire (LSQ), and were assessed for blood pressure and body mass index (BMI) at baseline (visit 1) and at the end of the study (visit 2). Medication adherence was measured using the Brilique Adherence Questionnaire (BAQ). Results Patients (N = 676) were randomized to an active (n = 342) or a control (n = 334) group. BAQ data were available for 174 patients in the active group and 174 patients in the control group. Over the 48-week period, mean (standard deviation) adherence for the active and control groups was 96.4% (13.2%) and 91.5% (23.1%), respectively (effect of app intervention, p < 0.05). There were no significant differences in blood pressure and BMI between visits. General improvements in SF-36 and LSQ scores were observed for both groups. Conclusion The patient support tool app was associated with significant improvements in patient-reported treatment adherence compared with a data collection app alone in patients prescribed ticagrelor for ACS.
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| 21. |
- Kristensen, Søren L., et al.
(author)
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Prevalence of Prediabetes and Undiagnosed Diabetes in Patients with HFpEF and HFrEF and Associated Clinical Outcomes
- 2017
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 31:5/6, s. 545-549
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Journal article (peer-reviewed)abstract
- © 2017 The Author(s) Purpose: The prevalence and consequences of prediabetic dysglycemia and undiagnosed diabetes is unknown in patients with heart failure (HF) and preserved ejection fraction (HFpEF) and has not been compared to heart failure and reduced ejection fraction (HFrEF). Methods: We examined the prevalence and outcomes associated with normoglycemia, prediabetic dysglycemia and diabetes (diagnosed and undiagnosed) among individuals with a baseline glycated hemoglobin (hemoglobin A1c, HbA1c) measurement stratified by HFrEF or HFpEF in the Candesartan in Heart failure Assessment of Reduction in Mortality and morbidity programme (CHARM). We studied the primary outcome of HF hospitalization or cardiovascular (CV) death, and all-cause death, and estimated hazard ratios (HR) by use of multivariable Cox regression models. Results: HbA1c was measured at baseline in CHARM patients enrolled in the USA and Canada and was available in 1072/3023 (35%) of patients with HFpEF and 1578/4576 (34%) patients with HFrEF. 18 and 16% had normoglycemia (HbA1c < 6.0), 20 and 22% had prediabetes (HbA1c 6.0–6.4), respectively. Finally among patients with HFpEF 22% had undiagnosed diabetes (HbA1c > 6.4), and 40% had known diabetes (any HbA1c), with corresponding prevalence among HFrEF patients being 26 and 35%. The rates of both clinical outcomes of interest were higher in patients with undiagnosed diabetes and prediabetes, compared to normoglycemic patients, irrespective of HF subtype, and in general higher among HFrEF patients. For the primary composite outcome among HFpEF patients, the HRs were 1.02 (95% CI 0.63–1.65) for prediabetes, HR 1.18 (0.75–1.86) for undiagnosed diabetes and 2.75 (1.83–4.11) for known diabetes, respectively, p value for trend across groups < 0.001. Dysglycemia was also associated with worse outcomes in HFrEF. Conclusions: These findings confirm the remarkably high prevalence of dysglycemia in heart failure irrespective of ejection fraction phenotype, and demonstrate that dysglycemia is associated with a higher risk of adverse clinical outcomes, even before the diagnosis of diabetes and institution of glucose lowering therapy in patients with HFpEF as well as HFrEF.
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| 22. |
- Maret-Ouda, J., et al.
(author)
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Proton Pump Inhibitor and Clopidogrel Use After Percutaneous Coronary Intervention and Risk of Major Cardiovascular Events
- 2021
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 36:6, s. 1121-1128
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Journal article (peer-reviewed)abstract
- Purpose: Due to shared hepatic metabolism, concomitant medication with a proton pump inhibitor (PPI) and clopidogrel might reduce the effectiveness of clopidogrel in the prevention of cardiovascular events after percutaneous coronary intervention (PCI). We aimed to examine the risk of major cardiovascular events after PCI comparing patients who used clopidogrel together with PPI with those who used clopidogrel alone. Methods: This Swedish nationwide cohort study included patients who received clopidogrel after primary PCI in 2005–2019. Patients were followed for up to 12months after PCI. Data were retrieved from the Swedish Prescribed Drug Registry, Patient Registry, Cancer Registry, and Cause of Death Registry. Multivariable Cox regression provided hazard ratios (HRs) with 95% confidence intervals (CIs) for cardiovascular events comparing PPI users (exposed) with non-users of PPI (non-exposed). The HRs were adjusted for sex, age, comorbidity, calendar period, obesity, diabetes, anti-diabetic medication, tobacco-related diseases, hypertension, and congestive heart failure. Results: The cohort included 99,836 patients who received clopidogrel after primary PCI. Among these, 35,772 (35.8%) received concomitant PPI. Compared to non-users, PPI users had increased adjusted HRs of all study outcomes, i.e., the main outcome myocardial infarction (HR = 1.23, 95% CI 1.15–1.32) and the secondary outcomes coronary heart disease (HR = 1.28, 95% CI 1.24–1.33), stroke (HR = 1.21, 95% CI 1.05–1.40), and death due to coronary heart disease (HR = 1.52, 95% CI 1.37–1.69). The results were similar in analyses including both primary and secondary PCIs. Conclusions: In patients who receive clopidogrel after PCI, concomitant use of PPI seems to increase the risk of major cardiovascular events. © 2021, The Author(s).
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| 23. |
- Mochizuki, S., et al.
(author)
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JIKEI HEART Study--a morbi-mortality and remodeling study with valsartan in Japanese patients with hypertension and cardiovascular disease
- 2004
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In: Cardiovasc Drugs Ther. - 0920-3206. ; 18:4, s. 305-9
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Journal article (peer-reviewed)abstract
- BACKGROUND: Several recent clinical trials have demonstrated that angiotensin II receptor blockers (ARBs) have cardiovascular as well as renal protective effects. Asian patients including Japanese were under-represented in these trials, however, and no large-scale clinical trials of ARBs have yet been performed in Japan. It is therefore important to verify that the results of these studies are also valid for Japanese patients. The JIKEI HEART Study has been designed to investigate whether concomitant treatment with valsartan, an angiotensin II receptor blocker, in addition to conventional treatment, will improve the prognosis of Japanese patients with cardiovascular diseases (hypertension, ischemic heart disease, congestive heart failure). METHOD AND EVALUATION OF RESULTS: Around 3,000 patients with hypertension, ischemic heart disease and/or congestive heart failure will be randomized to receive either additional treatment with valsartan (80 mg/day) or conventional therapy. The follow-up period will be three years. The primary endpoint will be the onset of any cardiovascular event. Secondary endpoints will include death from any cause, changes in left ventricular size and function, renal function, changes in neuro-hormonal levels and quality-of-life assessments. Sub-studies will explore the effect in patients with diabetes mellitus, hyperlipidemia and the effects of combination of drugs. CONCLUSION: Improved prognosis would confirm the role of angiotensin II receptor blockers in the treatment of the cardiovascular disease in Japanese patients.
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| 24. |
- Morales-Rosado, Joel A, et al.
(author)
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Next-Generation Sequencing of CYP2C19 in Stent Thrombosis : Implications for Clopidogrel Pharmacogenomics.
- 2020
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 35:3 SI, s. 549-559
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Journal article (peer-reviewed)abstract
- PURPOSE: Describe CYP2C19 sequencing results in the largest series of clopidogrel-treated cases with stent thrombosis (ST), the closest clinical phenotype to clopidogrel resistance. Evaluate the impact of CYP2C19 genetic variation detected by next-generation sequencing (NGS) with comprehensive annotation and functional studies.METHODS: Seventy ST cases on clopidogrel identified from the PLATO trial (n = 58) and Mayo Clinic biorepository (n = 12) were matched 1:1 with controls for age, race, sex, diabetes mellitus, presentation, and stent type. NGS was performed to cover the entire CYP2C19 gene. Assessment of exonic variants involved measuring in vitro protein expression levels. Intronic variants were evaluated for potential splicing motif variations.RESULTS: Poor metabolizers (n = 4) and rare CYP2C19*8, CYP2C19*15, and CYP2C19*11 alleles were identified only in ST cases. CYP2C19*17 heterozygote carriers were observed more frequently in cases (n = 29) than controls (n = 18). Functional studies of CYP2C19 exonic variants (n = 11) revealed 3 cases and only 1 control carrying a deleterious variant as determined by in vitro protein expression studies. Greater intronic variation unique to ST cases (n = 169) compared with controls (n = 84) was observed with predictions revealing 13 allele candidates that may lead to a potential disruption of splicing and a loss-of-function effect of CYP2C19 in ST cases.CONCLUSION: NGS detected CYP2C19 poor metabolizers and paradoxically greater number of so-called rapid metabolizers in ST cases. Rare deleterious exonic variation occurs in 4%, and potentially disruptive intronic alleles occur in 16% of ST cases. Additional studies are required to evaluate the role of these variants in platelet aggregation and clopidogrel metabolism.
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| 26. |
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| 30. |
- S, Bouchez, et al.
(author)
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Levosimendan in Acute and Advanced Heart Failure: an Expert Perspective on Posology and Therapeutic Application.
- 2018
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In: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206. ; 32:6, s. 617-624
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Journal article (peer-reviewed)abstract
- Levosimendan, a calcium sensitizer and potassium channel-opener, is widely appreciated by many specialist heart failure practitioners for its effects on systemic and pulmonary hemodynamics and for the relief of symptoms of acute heart failure. The drug's impact on mortality in large randomized controlled trials has been inconsistent or inconclusive but, in contrast to conventional inotropes, there have been no indications of worsened survival and some signals of improved heart failure-related quality of life. For this reason, levosimendan has been proposed as a safer inodilator option than traditional agents in settings, such as advanced heart failure. Positive effects of levosimendan on renal function have also been described. At the HEART FAILURE 2018 congress of the Heart Failure Association of the European Society of Cardiology, safe and effective use levosimendan in acute and advanced heart failure was examined in a series of expert tutorials. The proceedings of those tutorials are summarized in this review, with special reference to advanced heart failure and heart failure with concomitant renal dysfunction. Meta-analysis of clinical trials data is supportive of a renal-protective effect of levosimendan, while physiological observations suggest that this effect is exerted at least in part via organ-specific effects that may include selective vasodilation of glomerular afferent arterioles and increased renal blood flow, with no compromise of renal oxygenation. These lines of evidence require further investigation and their clinical significance needs to be evaluated in specifically designed prospective trials.
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| 32. |
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| 33. |
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| 34. |
- Simpson, Joanne, et al.
(author)
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Real World : Eligibility for Sacubitril/Valsartan in Unselected Heart Failure Patients: Data from the Swedish Heart Failure Registry
- 2019
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In: Cardiovascular Drugs and Therapy. - : SPRINGER. - 0920-3206 .- 1573-7241. ; 33:3, s. 315-322
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Journal article (peer-reviewed)abstract
- PurposePARADIGM-HF demonstrated the superiority of sacubitril/valsartan over enalapril in patients with heart failure and reduced ejection fraction (HF-REF). How widely applicable sacubitril/valsartan treatment is in unselected patients with HF-REF is not known. We examined eligibility of patients with HF-REF for treatment with sacubitril/valsartan, according to the criteria used in PARADIGM-HF, in the Swedish Heart Failure Registry (SwedeHF).MethodsPatients were considered potentially eligible if they were not hospitalized, had symptoms (NYHA class II-IV) and a reduced LVEF (40%), and were prescribed an angiotensin-converting enzyme inhibitor (ACEI) or angiotensin receptor blocker (ARB) at a dose equivalent to enalapril 10mg daily. In these patients, we evaluated further eligibility according to the main additional PARADIGM-HF inclusion criteria.ResultsOf 12,866 outpatients in NYHA functional class II-IV with an LVEF 40%, 9577 were prescribed at least 10mg of enalapril (or equivalent) daily. Complete additional data were available for 3099 of these patients (32.4%) and of them 75.5% were potentially eligible for treatment with sacubitril/valsartan. The most common reason for ineligibility was a low natriuretic peptide level (n=462, 14.9%). Only a small proportion of patients were ineligible due to low eGFR or serum potassium level. Because only 78% of patients were taking 10mg enalapril or equivalent daily, only 58.9% of all patients (75.5% of 78%) were eligible for sacubitril/valsartan.ConclusionsBetween 34 and 76% of symptomatic patients with HF-REF in a real world population are eligible for treatment with sacubitril/valsartan, depending on background ACEI/ARB dose. The most common reason for ineligibility is a low natriuretic peptide level.
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| 35. |
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| 36. |
- Vallejo-Vaz, Antonio J, et al.
(author)
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Implications of ACC/AHA Versus ESC/EAS LDL-C Recommendations for Residual Risk Reduction in ASCVD: A Simulation Study FromDA VINCI.
- 2022
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In: Cardiovascular drugs and therapy. - : Springer Science and Business Media LLC. - 1573-7241 .- 0920-3206.
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Journal article (peer-reviewed)abstract
- Low-density lipoprotein cholesterol (LDL-C) recommendations differ between the 2018 American College of Cardiology/American Heart Association (ACC/AHA) and 2019 European Society of Cardiology/European Atherosclerosis Society (ESC/EAS) guidelines for patients with atherosclerotic cardiovascular disease (ASCVD) (<70 vs.<55mg/dl, respectively). In the DA VINCI study, residual cardiovascular risk was predicted in ASCVD patients. The extent to which relative and absolute risk might be lowered by achieving ACC/AHA versus ESC/EAS LDL-C recommended approaches was simulated.DA VINCI was a cross-sectional observational study of patients prescribed lipid-lowering therapy(LLT) across 18 European countries. Ten-year cardiovascular risk (CVR) was predicted among ASCVD patients receiving stabilized LLT. For patients with LDL-C≥70mg/dl, the absolute LDL-C reduction required to achieve an LDL-C of<70 or<55mg/dl (LDL-C of 69 or 54mg/dl, respectively) was calculated. Relative and absolute risk reductions (RRRs andARRs) were simulated.Of the 2039 patients, 61% did not achieve LDL-C<70mg/dl. For patients with LDL-C≥70mg/dl, median (interquartile range) baseline LDL-C and 10-year CVR were 93 (81-115) mg/dl and 32% (25-43%), respectively. Median LDL-C reductions of 24 (12-46) and 39 (27-91) mg/dl were needed to achieve an LDL-C of 69 and 54mg/dl, respectively. Attaining ACC/AHA or ESC/EAS goals resulted in simulated RRRs of 14% (7-25%) and 22% (15-32%), respectively, and ARRs of 4% (2-7%) and 6% (4-9%), respectively.In ASCVD patients, achieving ESC/EAS LDL-C goals could result in a 2% additional ARR over 10years versusthe ACC/AHA approach.
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- Yilmaz, Mehmet B., et al.
(author)
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Renal Effects of Levosimendan : A Consensus Report
- 2013
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In: Cardiovascular Drugs and Therapy. - : Springer Science and Business Media LLC. - 0920-3206 .- 1573-7241. ; 27:6, s. 581-590
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Research review (peer-reviewed)abstract
- Renal dysfunction is common in clinical settings in which cardiac function is compromised such as heart failure, cardiac surgery or sepsis, and is associated with high morbidity and mortality. Levosimendan is a calcium sensitizer and potassium channel opener used in the treatment of acute heart failure. This review describes the effects of the inodilator levosimendan on renal function. A panel of 25 scientists and clinicians from 15 European countries (Austria, Finland, France, Hungary, Germany, Greece, Italy, Portugal, the Netherlands, Slovenia, Spain, Sweden, Turkey, the United Kingdom, and Ukraine) convened and reached a consensus on the current interpretation of the renal effects of levosimendan described both in non-clinical research and in clinical study reports. Most reports on the effect of levosimendan indicate an improvement of renal function in heart failure, sepsis and cardiac surgery settings. However, caution should be applied as study designs differed from randomized, controlled studies to uncontrolled ones. Importantly, in the largest HF study (REVIVE I and II) no significant changes in the renal function were detected. As it regards the mechanism of action, the opening of mitochondrial K-ATP channels by levosimendan is involved through a preconditioning effect. There is a strong rationale for randomized controlled trials seeking beneficial renal effects of levosimendan. As an example, a study is shortly to commence to assess the role of levosimendan for the prevention of acute organ dysfunction in sepsis (LeoPARDS).
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