| 1. |
|
|
| 2. |
- Voight, Benjamin F, et al.
(författare)
-
Plasma HDL cholesterol and risk of myocardial infarction : a mendelian randomisation study
- 2012
-
Ingår i: The Lancet. - 0140-6736 .- 1474-547X. ; 380:9841, s. 572-580
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: High plasma HDL cholesterol is associated with reduced risk of myocardial infarction, but whether this association is causal is unclear. Exploiting the fact that genotypes are randomly assigned at meiosis, are independent of non-genetic confounding, and are unmodified by disease processes, mendelian randomisation can be used to test the hypothesis that the association of a plasma biomarker with disease is causal.METHODS: We performed two mendelian randomisation analyses. First, we used as an instrument a single nucleotide polymorphism (SNP) in the endothelial lipase gene (LIPG Asn396Ser) and tested this SNP in 20 studies (20,913 myocardial infarction cases, 95,407 controls). Second, we used as an instrument a genetic score consisting of 14 common SNPs that exclusively associate with HDL cholesterol and tested this score in up to 12,482 cases of myocardial infarction and 41,331 controls. As a positive control, we also tested a genetic score of 13 common SNPs exclusively associated with LDL cholesterol.FINDINGS: Carriers of the LIPG 396Ser allele (2·6% frequency) had higher HDL cholesterol (0·14 mmol/L higher, p=8×10(-13)) but similar levels of other lipid and non-lipid risk factors for myocardial infarction compared with non-carriers. This difference in HDL cholesterol is expected to decrease risk of myocardial infarction by 13% (odds ratio [OR] 0·87, 95% CI 0·84-0·91). However, we noted that the 396Ser allele was not associated with risk of myocardial infarction (OR 0·99, 95% CI 0·88-1·11, p=0·85). From observational epidemiology, an increase of 1 SD in HDL cholesterol was associated with reduced risk of myocardial infarction (OR 0·62, 95% CI 0·58-0·66). However, a 1 SD increase in HDL cholesterol due to genetic score was not associated with risk of myocardial infarction (OR 0·93, 95% CI 0·68-1·26, p=0·63). For LDL cholesterol, the estimate from observational epidemiology (a 1 SD increase in LDL cholesterol associated with OR 1·54, 95% CI 1·45-1·63) was concordant with that from genetic score (OR 2·13, 95% CI 1·69-2·69, p=2×10(-10)).INTERPRETATION: Some genetic mechanisms that raise plasma HDL cholesterol do not seem to lower risk of myocardial infarction. These data challenge the concept that raising of plasma HDL cholesterol will uniformly translate into reductions in risk of myocardial infarction.
|
|
| 3. |
- Komen, Joris J., et al.
(författare)
-
Association of Preceding Antithrombotic Therapy in Atrial Fibrillation Patients With Ischemic Stroke, Intracranial Hemorrhage, or Gastrointestinal Bleed and Mortality
- 2021
-
Ingår i: European Heart Journal - Cardiovascular Pharmacotherapy. - Oxford : Oxford University Press. - 2055-6837 .- 2055-6845. ; 7:1, s. 3-10
-
Tidskriftsartikel (refereegranskat)abstract
- AIMS: To analyze 90-day mortality in AF patients after a stroke or a severe bleed and assess associations with the type of antithrombotic treatment at the event.METHODS AND RESULTS: From the Stockholm Healthcare database, we selected 6 017 patients with a known history of AF who were diagnosed with ischemic stroke, 3 006 with intracranial hemorrhage, and 4 291 with a severe gastrointestinal bleed (GIB). The 90-day mortality rates were 25.1% after ischemic stroke, 31.6% after intracranial hemorrhage, and 16.2% after severe GIB. We used Cox regression and propensity score matched analyses to test the association between antithrombotic treatment at the event and 90-day mortality. After intracranial hemorrhage, there was a significantly higher mortality rate in warfarin compared to NOAC treated patients (adjusted hazard ratio (aHR): 1.36 CI: 1.04 - 1.78). After an ischemic stroke and a severe GIB, patients receiving antiplatelets or no antithrombotic treatment had significantly higher mortality rates compared to patients on NOACs, but there was no difference comparing warfarin to NOACs (aHR 0.84 CI: 0.63 - 1.12 after ischemic stroke, aHR 0.91 CI: 0.66 - 1.25 after severe GIB). Propensity score matched analysis yielded similar results.CONCLUSION: Mortality rates were high in AF patients suffering from an ischemic stroke, an intracranial hemorrhage, or a severe GIB. NOAC treatment was associated with a lower 90 day mortality after intracranial hemorrhage than warfarin.
|
|
| 4. |
- Komen, Joris J., et al.
(författare)
-
Oral anticoagulants in patients with atrial fibrillation at low stroke risk : a multicentre observational study
- 2022
-
Ingår i: European Heart Journal. - : OXFORD UNIV PRESS. - 0195-668X .- 1522-9645. ; 43:37, s. 3528-3538
-
Tidskriftsartikel (refereegranskat)abstract
- Aims There is currently no consensus on whether atrial fibrillation (AF) patients at low risk for stroke (one non-sex-related CHA(2)DS(2)-VASc point) should be treated with an oral anticoagulant. Methods and results We conducted a multi-country cohort study in Sweden, Denmark, Norway, and Scotland. In total, 59 076 patients diagnosed with AF at low stroke risk were included. We assessed the rates of stroke or major bleeding during treatment with a non-vitamin K antagonist oral anticoagulant (NOAC), a vitamin K antagonist (VKA), or no treatment, using inverse probability of treatment weighted (IPTW) Cox regression. In untreated patients, the rate for ischaemic stroke was 0.70 per 100 person-years and the rate for a bleed was also 0.70 per 100 person-years. Comparing NOAC with no treatment, the stroke rate was lower [hazard ratio (HR) 0.72; 95% confidence interval (CI) 0.56-0.94], and the rate for intracranial haemorrhage (ICH) was not increased (HR 0.84; 95% CI 0.54-1.30). Comparing VKA with no treatment, the rate for stroke tended to be lower (HR 0.81; 95% CI 0.59-1.09), and the rate for ICH tended to be higher during VKA treatment (HR 1.37; 95% CI 0.88-2.14). Comparing NOAC with VKA treatment, the rate for stroke was similar (HR 0.92; 95% CI 0.70-1.22), but the rate for ICH was lower during NOAC treatment (HR 0.63; 95% CI 0.42-0.94). Conclusion These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a question that can be tested through a randomized controlled trial. Key question What is the association between anticoagulant treatment and stroke and bleeding rate, in patients with one non-sex-related risk factor for stroke? Key findings Non-vitamin K antagonist oral anticoagulant (NOAC) treatment was associated with a lower stroke rate compared with no treatment. Non-vitamin K antagonist oral anticoagulant treatment was associated with a lower rate of intracranial haemorrhage compared with vitamin K antagonist (VKA) treatment. Take-home message These observational data suggest that NOAC treatment may be associated with a positive net clinical benefit compared with no treatment or VKA treatment in patients at low stroke risk, a hypothesis that can be tested through a randomized controlled trial.
|
|
| 5. |
- Komen, Joris J, et al.
(författare)
-
Persistence and adherence to non-vitamin K antagonist oral anticoagulant treatment in patients with atrial fibrillation across five Western European countries
- 2021
-
Ingår i: Europace. - : Oxford University Press. - 1099-5129 .- 1532-2092. ; 23:11, s. 1722-1730
-
Tidskriftsartikel (refereegranskat)abstract
- AimsTo assess persistence and adherence to non-vitamin K antagonist oral anticoagulant (NOAC) treatment in patients with atrial fibrillation (AF) in five Western European healthcare settings.Methods and resultsWe conducted a multi-country observational cohort study, including 559 445 AF patients initiating NOAC therapy from Stockholm (Sweden), Denmark, Scotland, Norway, and Germany between 2011 and 2018. Patients were followed from their first prescription until they switched to a vitamin K antagonist, emigrated, died, or the end of follow-up. We measured persistence and adherence over time and defined adequate adherence as medication possession rate ≥90% among persistent patients only.ResultsOverall, persistence declined to 82% after 1 year and to 63% after 5 years. When including restarters of NOAC treatment, 85% of the patients were treated with NOACs after 5 years. The proportion of patients with adequate adherence remained above 80% throughout follow-up. Persistence and adherence were similar between countries and was higher in patients starting treatment in later years. Both first year persistence and adherence were lower with dabigatran (persistence: 77%, adherence: 65%) compared with apixaban (86% and 75%) and rivaroxaban (83% and 75%) and were statistically lower after adjusting for patient characteristics. Adherence and persistence with dabigatran remained lower throughout follow-up.ConclusionPersistence and adherence were high among NOAC users in five Western European healthcare settings and increased in later years. Dabigatran use was associated with slightly lower persistence and adherence compared with apixaban and rivaroxaban.
|
|
