| 1. |
- Henriksson, Catrin, 1961-, et al.
(författare)
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Patients’ experiences of clinical trial participation involving a product remotely assessing study drug adherence
- 2024
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Ingår i: Contemporary Clinical Trials Communications. - : Elsevier. - 2451-8654. ; 40
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Tidskriftsartikel (refereegranskat)abstract
- Background: The participation of patients in clinical trials is crucial for the development of healthcare. There are several challenges in the recruitment of trial participants with acute medical conditions. The registry-based randomized DAPA-MI clinical trial recruited patients during hospitalization for myocardial infarction and provided study drugs in bottles with smart caps that used wireless technology to transmit monitoring data. This interview study aimed to investigate patients’ experience of participation in a clinical trial and their attitude to the new bottle cap technology. Methods: A subset of patients participating in the DAPA-MI trial were recruited from four hospitals in Sweden. Semi-structured interviews were conducted and analysed using manifest content analysis. Results: Video interviews were performed including 21 patients (four women and 17 men). The median age was 59 years (range 44–80). Four categories of patients' experiences were identified. A willingness to contribute consisted of patients’ positive attitudes to participation and to be a part of development and research. The perception of information emphasized the value of the oral information as well as the importance of time for reflection. Be in a vulnerable condition highlighted the impaired ability to perceive and remember in the acute medical condition. Adaptation to a new technology described the overall positive experiences of the smart bottle cap to evaluate adherence. Conclusions: Patients’ experiences of trial participation were in general positive but some challenges in the acute setting of a myocardial infarction were revealed. The smart bottle cap was well accepted, despite some handling difficulties.
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| 2. |
- Ridderstråle, Wilhelm, 1971
(författare)
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Blood Pressure Elevation - Impact on Cardiovascular Structure and Endogenous Fibrinolysis
- 2008
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Blood pressure elevation is a major risk factor for cardiovascular events and the risk increases in a dose-dependant manner. It is of importance to identify subjects prone to develop hypertension and adverse cardiovascular remodeling in order to start treatment timely. The increased risk of myocardial infarction and ischemic stroke in hypertension suggests that the condition is associated with prothrombotic mechanisms. Our research group recently discovered that the capacity for activation of the endogenous fibrinolytic system by acute release of tissue plasminogen activator (t-PA) is markedly impaired in subjects with hypertension. This impairment could contribute to the increased risk for atherothrombotic events. The predictive value of blood pressure elevation (SBP 140-160 and/or DBP 85-95 mmHg; BPE group) or normal blood pressure (SBP 110-130 and DBP 60-80 mmHg; NC group) was studied in a cohort of 20-year old men investigated in 1987. The prevalence of hypertension was 74.5% and 5.9% in the BPE and NC group, respectively, at 20 year follow-up. The difference in blood pressure level at baseline between the groups contrasted even more at follow-up. Further, the BPE group had significantly increased left ventricular mass index and intima-media thickness compared to the NC group. We investigated if the impaired fibrinolytic capacity in untreated hypertension could be restored by chronic and acute blood pressure lowering. T-PA release was stimulated by infusion of substance P in the perfused-forearm model before and during chronic and acute blood pressure lowering. Chronic antihypertensive treatment with either the calcium antagonist felodipine or the ACE-inhibitor lisinopril, increased the amount of t-PA released and improved the rapidity of the t-PA response. Changes were similar in the two treatment groups, suggesting the improvement to be related to the blood pressure lowering per se. However, acute blood pressure lowering with intravenous sodium nitroprusside did not affect the stimulated t-PA release. The results of the two studies indicate that high blood pressure decreases the cellular content of t-PA, rather than interfering with the release mechanisms of the protein. Further, we explored the impact of the tensile force component of blood pressure on the regulation of fibrinolytic proteins by studying cultured endothelial cells in an in vitro biomechanical experimental model. Prolonged cyclic strain, mimicking the hypertensive state, was found to suppress t-PA gene expression and protein secretion. In contrast, the main inhibitor of t-PA, plasminogen activator inhibitor-1 was induced, adding to the negative effects of elevated blood pressure on fibrinolysis. In conclusion, blood pressure elevation in young age predicts adverse cardiovascular remodeling and hypertension twenty years later. Hypertension increases the risk of atherothrombotic events by impaired fibrinolysis, possibly through a direct inhibitory effect on t-PA expression by enhanced tensile stress. Chronic blood pressure lowering restores the endogenous fibrinolytic capacity, and this could contribute to the beneficial effect of anti-hypertensive therapy.
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| 3. |
- Ridderstråle, Wilhelm, 1971, et al.
(författare)
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Consistency of blood pressure and impact on cardiovascular structure over 20 years in young men
- 2010
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Ingår i: Journal of Internal Medicine. - 0954-6820. ; 267:3, s. 295-304
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To identify, in a prospective study, how blood pressure levels at the age of twenty predict hypertension and cardiovascular remodelling 20 years later. METHODS: Twenty-year-old men with blood pressure (BP) elevation [systolic blood pressure (SBP) 140-160 and/or diastolic blood pressure (DBP) 85-95 mmHg; blood pressure elevation (BPE) group] or normal BP [SBP 110-130 and DBP 60-80 mmHg; normal controls (NC) group] entered the study in 1987. In 2007, follow-up was conducted including ambulatory BP, echocardiography, anthropometric and intima media thickness (IMT) measurements. RESULTS: Assessed with 24-h ambulatory BP, the prevalence of hypertension was 35/47 (74.5%) and 1/17 (5.9%) in the BPE and NC group at follow-up respectively. Twenty-four hour mean arterial pressure (MAP) increased from 86.6 (0.8) to 97.2 (1.2) (P < 0.0001), and from 83.1 (1.5) to 88.1 (1.2) mmHg (P < 0.01) from baseline to follow-up in the BPE and NC group respectively. At follow-up, left ventricular mass index (LVMI) was 122 (4) and 106 (4) g m(-1) in the BPE and NC group (unpaired t-test; P < 0.01) respectively, whilst IMT was 0.61 (0.01) and 0.57 (0.01) mm in the BPE and NC group (P < 0.05) respectively. In a logistic regression model, prevalence of hypertension was best explained by office MAP and 24-h DBP at baseline (R(2) 0.333; P < 0.05). A combined model of office MAP, body mass index and insulin levels at baseline explained 56% of LVMI at follow-up. CONCLUSIONS: BP elevation in young age predicts hypertension and adverse cardiovascular remodelling at the age of 40 years. Baseline office MAP is the best predictor of hypertension, 24-h MAP and LVMI.
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| 4. |
- Ridderstråle, Wilhelm, 1971, et al.
(författare)
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Impaired capacity for stimulated fibrinolysis in primary hypertension is restored by antihypertensive therapy
- 2006
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Ingår i: Hypertension. - 1524-4563. ; 47:4, s. 686-91
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Tidskriftsartikel (refereegranskat)abstract
- The increased risk for myocardial infarction and ischemic stroke in primary hypertension suggests that the condition is associated with prothrombotic mechanisms. We have shown that patients with hypertension have an impaired capacity for acute endothelial tissue-type plasminogen activator (t-PA) release, an important local protective response to prevent formation of intravascular thrombi. The aim of the present study was to investigate whether this impairment could be restored by the lowering of blood pressure. The capacity for acute t-PA release in response to intraarterial infusion of substance P at 8 pmol/min was investigated in a perfused-forearm study in 20 hypertensive patients (12 men and 8 women). Studies were performed when patients were untreated and after 8 weeks of randomized treatment with lisinopril or felodipine that lowered blood pressure by 26/10 and 24/12 mm Hg, respectively. The t-PA release response increased significantly with treatment (ANOVA, P=0.0001), with a similar effect in the 2 treatment groups. The peak release of t-PA increased from 257 (58) to 445 (77) ng/min x L/tissue(-1) (t test, P=0.02). Also, treatment shortened the average time to peak secretion from 6.7 (1.4) to 2.7 (0.3) min (t test, P=0.01). In 6 patients with a delayed secretory peak (9 minutes or later), treatment normalized the response (chi2 test, P=0.008). Antihypertensive therapy restores the capacity for acute t-PA release and improves the rapidity of the response in patients with primary hypertension. Similar responses with the 2 regimens suggest that the improvement is related to the blood pressure reduction as such. This effect may contribute to the thromboprotective effect of antihypertensive treatment.
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| 5. |
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| 6. |
- Ridderstråle, Wilhelm, 1971, et al.
(författare)
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The impaired fibrinolytic capacity in hypertension is unaffected by acute blood pressure lowering
- 2011
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Ingår i: Journal of thrombosis and thrombolysis. - : Springer Science and Business Media LLC. - 1573-742X .- 0929-5305. ; 32:4, s. 399-404
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Tidskriftsartikel (refereegranskat)abstract
- The endogenous fibrinolytic system and the ability of the endothelium to release tissue-plasminogen activator (t-PA) play a pivotal role to protect humans from atherothrombotic events. We have recently reported that the decreased capacity for t-PA release in hypertension is restored with chronic blood pressure lowering. Thus, we explored if acute blood pressure lowering has the same effect. The capacity for acute t-PA release was investigated in the perfused-forearm model during stimulation by intra-arterial substance P 8 pmol/min in hypertensive subjects. The procedure was then repeated during acute blood pressure lowering (n = 9) induced by sodium nitroprusside (SNP) infusion or during placebo infusion (n = 3). SNP lowered mean arterial pressure from 108.6 (2.6) to 83.0 (2.6) (mean and SEM) mmHg (P < 0.001). Substance P induced significant increase in t-PA release during both high- and low-pressure conditions (P < 0.01, ANOVA). Peak t-PA release rate was 199 (77) and 167 (41) (mean and SEM) ng/min/l tissue, and accumulated t-PA release was 2,395 (750) and 2,394 (473) ng, during high- and low-pressure conditions, respectively. t-PA release and hemodynamic responses were almost identical during high- and low-pressure conditions (P = ns, for all). Acute blood pressure lowering does not restore stimulated t-PA release from the endothelium in hypertensive subjects. These findings are in contrast to previously described effects of chronic blood pressure treatment. Although data need to be confirmed in a larger study, they suggest that high blood pressure decreases the cellular t-PA pool rather than interferes with release mechanisms of the protein.
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| 7. |
- Saluveer, Ott, 1974, et al.
(författare)
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Profibrinolytic effect of the epigenetic modifier valproic Acid in man.
- 2014
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Ingår i: PloS one. - : Public Library of Science (PLoS). - 1932-6203. ; 9:10
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Tidskriftsartikel (refereegranskat)abstract
- The aim of the study was to test if pharmacological intervention by valproic acid (VPA) treatment can modulate the fibrinolytic system in man, by means of increased acute release capacity of tissue plasminogen activator (t-PA) as well as an altered t-PA/Plasminogen activator inhibitor -1 (PAI-1) balance. Recent data from in vitro research demonstrate that the fibrinolytic system is epigenetically regulated mainly by histone deacetylase (HDAC) inhibitors. HDAC inhibitors, including VPA markedly upregulate t-PA gene expression in vitro.
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| 8. |
- Steg, Philippe Gabriel, et al.
(författare)
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Cost-effectiveness of ticagrelor in patients with type 2 diabetes and coronary artery disease : a European economic evaluation of the THEMIS trial.
- 2022
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Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - : Oxford University Press. - 2055-6837 .- 2055-6845. ; 8:8, s. 777-785
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Tidskriftsartikel (refereegranskat)abstract
- AIMS: To conduct a health economic evaluation of ticagrelor in patients with type 2 diabetes and coronary artery disease (CAD) from a multinational payer perspective. Cost-effectiveness and cost-utility of ticagrelor were evaluated in the overall effect of Ticagrelor on Health Outcomes in Diabetes Mellitus Patients Intervention Study (THEMIS) trial population and in the predefined patient group with prior percutaneous coronary intervention.METHODS AND RESULTS: A Markov model was developed to extrapolate patient outcomes over a lifetime horizon. The primary outcome was incremental cost-effectiveness ratios (ICERs), which were compared with conventional willingness-to-pay thresholds [€47 000/quality-adjusted life-year (QALY) in Sweden and €30 000/QALY in other countries].Treatment with ticagrelor resulted in QALY gains of up to 0.045 in the overall population and 0.099 in patients with percutaneous coronary intervention (PCI). Increased costs and benefits translated to ICERs ranged between €27 894 and €42 252/QALY across Sweden, Germany, Italy, and Spain in the overall population. In patients with prior PCI, estimated ICERs improved to €18 449, €20 632, €20 233, and €13 228/QALY in Sweden, Germany, Italy, and Spain, respectively, driven by higher event rates and treatment benefit.CONCLUSION: Based on THEMIS results, ticagrelor plus aspirin compared with aspirin alone may be cost-effective in some European countries in patients with T2DM and CAD and no prior myocardial infarction (MI) or stroke. Additionally, ticagrelor is likely to be cost-effective across European countries in patients with a history of PCI.
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| 9. |
- Steg, P. Gabriel, et al.
(författare)
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Ticagrelor in Patients with Stable Coronary Disease and Diabetes
- 2019
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Ingår i: New England Journal of Medicine. - : MASSACHUSETTS MEDICAL SOC. - 0028-4793 .- 1533-4406. ; 381:14, s. 1309-1320
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Tidskriftsartikel (refereegranskat)abstract
- Patients with stable coronary artery disease and diabetes were randomly assigned to receive either ticagrelor plus aspirin or placebo plus aspirin. At 40 months, the incidence of the composite efficacy outcome of cardiovascular death, myocardial infarction, or stroke was lower with ticagrelor than with placebo; the frequency of major bleeding was higher with ticagrelor. Background Patients with stable coronary artery disease and diabetes mellitus who have not had a myocardial infarction or stroke are at high risk for cardiovascular events. Whether adding ticagrelor to aspirin improves outcomes in this population is unclear. Methods In this randomized, double-blind trial, we assigned patients who were 50 years of age or older and who had stable coronary artery disease and type 2 diabetes mellitus to receive either ticagrelor plus aspirin or placebo plus aspirin. Patients with previous myocardial infarction or stroke were excluded. The primary efficacy outcome was a composite of cardiovascular death, myocardial infarction, or stroke. The primary safety outcome was major bleeding as defined by the Thrombolysis in Myocardial Infarction (TIMI) criteria. Results A total of 19,220 patients underwent randomization. The median follow-up was 39.9 months. Permanent treatment discontinuation was more frequent with ticagrelor than placebo (34.5% vs. 25.4%). The incidence of ischemic cardiovascular events (the primary efficacy outcome) was lower in the ticagrelor group than in the placebo group (7.7% vs. 8.5%; hazard ratio, 0.90; 95% confidence interval [CI], 0.81 to 0.99; P=0.04), whereas the incidence of TIMI major bleeding was higher (2.2% vs. 1.0%; hazard ratio, 2.32; 95% CI, 1.82 to 2.94; P<0.001), as was the incidence of intracranial hemorrhage (0.7% vs. 0.5%; hazard ratio, 1.71; 95% CI, 1.18 to 2.48; P=0.005). There was no significant difference in the incidence of fatal bleeding (0.2% vs. 0.1%; hazard ratio, 1.90; 95% CI, 0.87 to 4.15; P=0.11). The incidence of an exploratory composite outcome of irreversible harm (death from any cause, myocardial infarction, stroke, fatal bleeding, or intracranial hemorrhage) was similar in the ticagrelor group and the placebo group (10.1% vs. 10.8%; hazard ratio, 0.93; 95% CI, 0.86 to 1.02). Conclusions In patients with stable coronary artery disease and diabetes without a history of myocardial infarction or stroke, those who received ticagrelor plus aspirin had a lower incidence of ischemic cardiovascular events but a higher incidence of major bleeding than those who received placebo plus aspirin. (Funded by AstraZeneca; THEMIS ClinicalTrials.gov number, NCT01991795.).
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| 10. |
- Ulfhammer, Erik, 1974, et al.
(författare)
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Prolonged cyclic strain impairs the fibrinolytic system in cultured vascular endothelial cells
- 2005
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Ingår i: J Hypertens. - 0263-6352. ; 23:8, s. 1551-7
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: We previously reported that patients with primary hypertension have an impaired ability to release tissue-type plasminogen activator acutely from the vascular endothelium, and recently found that lowering blood pressure can restore this capacity. We hypothesized that the suppression of the fibrinolytic system is caused by the chronic pressure-induced increased haemodynamic load on the endothelium. DESIGN AND METHODS: This study investigated the effect of the tensile force component of blood pressure by exposing cultured human aortic endothelial cells to 10% cyclic strain for 6-72 h. Messenger RNA levels of tissue-type plasminogen activator, urokinase-type plasminogen activator, and plasminogen activator inhibitor 1 were analysed using Taqman real-time reverse transcriptase-polymerase chain reaction and protein release by enzyme-linked immunosorbent assay. RESULTS: Tensile stimulation resulted in a transient initial upregulation of tissue-type plasminogen activator mRNA at 6 h (53%), which declined with time, and at 48 h had switched to a 28% downregulation. The reduction was sustained after 72 h. Tissue-type plasminogen activator protein secretion showed a similar but somewhat delayed response, with a transient increase in release at 6 h (60%), declining to a final 12% reduction at 72 h. A similar pattern was observed for urokinase-type plasminogen activator mRNA. By contrast, plasminogen activator inhibitor 1 mRNA expression and protein secretion increased at all timepoints (16-47%). CONCLUSION: Prolonged tensile stimulation impairs fibrinolytic activity in human aortic endothelial cells by a dual action, with suppression of plasminogen activator expression and increased inhibitor production. This effect of tensile stress may contribute to the reduced fibrinolytic capacity observed in patients with hypertension.
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