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- Charytan, David M., et al.
(författare)
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Efficacy and Safety of Evolocumab in Chronic Kidney Disease in the FOURIER Trial
- 2019
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Ingår i: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 73:23, s. 2961-2970
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Tidskriftsartikel (refereegranskat)abstract
- BACK GROUND Data on PCSK9 inhibition in chronic kidney disease (CKD) is limited. OBJECTIVES The purpose of this study was to compare outcomes with evolocumab and placebo according to kidney function. METHODS The FOURIER (Further Cardiovascular Outcomes Research with PCSK9 Inhibition in Subjects with Elevated Risk) trial randomized individuals with clinically evident atherosclerosis and low-density lipoprotein cholesterol (LDL-C) amp;gt;= 70 mg/dl or non-high-density lipoprotein cholesterol amp;gt;= 100 mg/dl to evolocumab or placebo. The primary endpoint (cardiovascular death, myocardial infarction, stroke, hospitalization for unstable angina, or coronary revascularization), key secondary endpoint (cardiovascular death, myocardial infarction, or stroke), and safety were analyzed according to chronic kidney disease (CKD) stage estimated from CKD-epidemiology estimated glomerular filtration rate. RESULTS There were 8,077 patients with preserved kidney function, 15,034 with stage 2 CKD, and 4,443 with amp;gt;= stage 3 CKD. LDL-C reduction with evolocumab compared with placebo at 48 weeks was similar across CKD groups at 59%, 59%, and 58%, respectively. Relative risk reduction for the primary endpoint was similar for preserved function (hazard ratio [HR]: 0.82; 95% CI: 0.71 to 0.94), stage 2 (HR: 0.85; 95% CI: 0.77 to 0.94), and stage amp;gt;= 3 CKD (HR: 0.89; 95% CI: 0.76 to 1.05); p(int) = 0.77. Relative risk reduction for the secondary endpoint was similar across CKD stages (p(int) = 0.75)-preserved function (HR: 0.75; 95% CI: 0.62 to 0.90), stage 2 (HR: 0.82; 95% CI: 0.72 to 0.93), stage amp;gt;= 3 (HR: 0.79; 95% CI: 0.65 to 0.95). Absolute RRs at 30 months for the secondary endpoint were -2.5% (95% CI: -0.4% to -4.7%) for stage amp;gt;= 3 CKD compared with -1.7% (95% CI: 0.5% to -2.8%) with preserved kidney function. Adverse events, including estimated glomerular filtration rate decline, were infrequent and similar regardless of CKD stage. CONCLUSIONS LDL-C lowering and relative clinical efficacy and safety of evolocumab versus placebo were consistent across CKD groups. Absolute reduction in the composite of cardiovascular death, MI, or stroke with evolocumab was numerically greater with more advanced CKD. (C) 2019 by the American College of Cardiology Foundation.
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- Faergeman, Ole, et al.
(författare)
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Plasma Triglycerides and Cardiovascular Events in the Treating to New Targets and Incremental Decrease in End-Points Through Aggressive Lipid Lowering Trials of Statins in Patients With Coronary Artery Disease
- 2009
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Ingår i: AMERICAN JOURNAL OF CARDIOLOGY. - : Elsevier BV. - 0002-9149. ; 104:4, s. 459-463
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Tidskriftsartikel (refereegranskat)abstract
- We determined the ability of in-trial measurements of triglycerides (TGs) to predict new cardiovascular events (CVEs) using data from the Incremental Decrease in End Points through Aggressive Lipid Lowering (IDEAL) and Treating to New Targets (TNT) trials. The trials compared atorvastatin 80 mg/day with moderate-dose statin therapy (simvastatin 20 to 40 mg/day in IDEAL and atorvastatin 10 mg/day in TNT) in patients with clinically evident coronary heart disease or a history of myocardial infarction. The outcome measurement in the present research was CVE occurring after the first year of the trial. After adjusting for age, gender, and study, risk of CVEs increased with increasing TGs (p andlt;0.001 for trend across quintiles of TGs). Patients in the highest quintile had a 63% higher rate of CVEs than patients in the lowest quintile (hazard ratio 1.63, 95% confidence interval 1.46 to 1.81) and the relation of TGs to risk was apparent even within the normal range of TGs. The ability of TG measurements to predict risk decreased when high-density lipoprotein cholesterol and apolipoprotein B:apolipoprotein A-I were included in the statistical analysis, and it was abolished with inclusion of further variables (diabetes, body mass index, glucose, hypertension, and smoking; (p = 0.044 and 0.621, respectively, for trend across quintiles of TGs). Similar results were obtained in patients in whom low-density lipoprotein cholesterol had been lowered to guideline-recommended levels. In conclusion, even slightly increased TG levels are associated with higher risk of recurrence of CVEs in statin-treated patients and should be considered a useful marker of risk.
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- Fellström, Bengt, et al.
(författare)
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Effect of fluvastatin on renal end points in the Assessment of Lescol in Renal Transplant (ALERT) trial
- 2004
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Ingår i: Kidney International. - : Elsevier BV. - 0085-2538 .- 1523-1755. ; 66:4, s. 1549-1555
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Hyperlipidemia is a risk factor for long-term renal transplant dysfunction, but no prospective clinical trials have investigated the effects of statin treatment on graft function in renal transplant recipients. The aim of the present study was to evaluate the effect of fluvastatin on long-term renal transplant function and development of chronic allograft nephropathy in the ALERT (Assessment of Lescol in Renal Transplantation) study. METHODS: ALERT was a randomized, double-blind, placebo-controlled study of the effect of fluvastatin, 40 mg and 80 mg daily, in renal transplant recipients. Patients were randomized to receive either fluvastatin (N= 1050) or placebo (N= 1052) and followed for five to six years. Renal end points included graft loss or doubling of serum creatinine or death; glomerular filtration rate (GFR) was also measured during follow-up in a subset of patients (N= 439). RESULTS: There were 283 patients (13.5%) with graft loss, mainly due to chronic rejection (82%), yielding an annual rate of 2.4%. Fluvastatin treatment significantly lowered mean low-density lipoprotein (LDL)-cholesterol levels by 32% (95% CI -33 to -30) compared with placebo, but had no significant effect on the incidence of renal graft loss or doubling of serum creatinine, or decline in GFR throughout follow-up in the whole study population. Neither was any treatment effect by fluvastatin found in any of the subgroups analyzed. CONCLUSION: Fluvastatin treatment significantly improves lipid values in renal transplant recipients but has no effect on graft loss or doubling of serum creatinine.
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- Holme, Ingar, et al.
(författare)
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Adherence-adjusted efficacy with intensive versus standard statin therapy in patients with acute myocardial infarction in the IDEAL study
- 2009
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Ingår i: EUROPEAN JOURNAL OF CARDIOVASCULAR PREVENTION and REHABILITATION. - 1741-8267. ; 16:3, s. 315-320
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Tidskriftsartikel (refereegranskat)abstract
- Background The Incremental Decrease in End Points through Aggressive Lipid Lowering trial showed that the primary endpoint major coronary event was reduced by 11% (0.78-1.01) using atorvastatin 80 mg versus simvastatin 20-40 mg in patients with coronary heart disease (P=0.07). Adherence was high in both treatment groups but significantly higher in patients treated with simvastatin. Design The Incremental Decrease in End Points through Aggressive Lipid Lowering was a prescription trial with a prospective randomized open label endpoint evaluation. Methods and results Adherence was calculated as exposure time on prescribed drugs divided by total follow-up time until death or end of follow-up and was a potential confounder. Adjusting for categorical adherence below or above 80% by two methods revealed that the relative risk reduction of the primary endpoint was more in the region of 15% (P=0.02) than 11% as found unadjusted. Censoring at the first occurrence of a cardiovascular event rather than at death increased this estimate to 17% (P=0.02). Noncardiovascular mortality was reduced on atorvastatin treatment by 21% (1-37%) after adjustment for adherence, whereas such reduction was not observed for cardiovascular mortality. Conclusion This study found that the difference in adherence between treatment groups may have underestimated the true effect of the treatment differential. Usage of prospective randomized open label endpoint evaluation design should be carefully considered when well-known treatments are compared with rather new ones and especially in segments where patients could be more vulnerable, as in the elderly. Nonadherers in a clinical trial may be at especially high risk of fatal and nonfatal endpoints from various diseases and should be carefully monitored.
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| 8. |
- Holme, Ingar, et al.
(författare)
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Congestive heart failure is associated with lipoprotein components in statin-treated patients with coronary heart disease Insights from the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL)
- 2009
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Ingår i: ATHEROSCLEROSIS. - : Elsevier BV. - 0021-9150. ; 205:2, s. 522-527
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Tidskriftsartikel (refereegranskat)abstract
- Background: Very few, if any, studies have assessed the ability of apolipoproteins to predict new-onset of congestive heart failure (HF) in statin-treated patients with coronary heart disease (CHD). Aims: To employ the Incremental Decrease in End points Through Aggressive Lipid Lowering Trial (IDEAL) study database to assess the association of on-treatment lipoprotein components with prediction of HF events and to compare their predictive value with that of established risk factors such as hypertension and diabetes. Methods: We used Cox regression models to study the relationships between on-treatment levels of apolipoproteins A1 and B to subsequent HE Chi square information value from the log likelihood was used to compare the predictive value of lipoprotein components with established risk factors of HF. Findings: In the IDEAL study, on-treatment apolipoproteins proved to be associated with the occurrence of new-onset HE Variables related to low-density lipoprotein cholesterol (LDL-C) carried less predictive information than those related to high-density lipoprotein cholesterol (HDL-C), and apoA-1 was the single variable most strongly associated with HF. LDL-C was less predictive than both non-HDL-C (total cholesterol minus HDL-C) and apoB. The ratio of apoB to apoA-1 was most strongly related to HF after adjustment for potential confounders, among which diabetes had a stronger correlation with HF than did hypertension. ApoB/apoA-1 carried approximately 2.2 times more of the statistical information value than that of diabetes. Calculation of the net reclassification improvement index revealed that about 3.7% of the patients had to be reclassified into more correct categories of risk once apoB/apoA-1 was added to the adjustment factors. The reduction in risk by intensive lipid-lowering treatment as compared to usual-dose simvastatin was well predicted by the difference in apoB/apoA-1 on-treatment levels. Interpretation: The on-treatment ratio of apoB/apoA-1 was the strongest predictor of HF in CHD patients of both IDEAL treatment arms combined, mostly driven by the strong association with apoA-1, whereas LDL-C and non-HDL-C were less able to predict HF outcome. The predictive information value contained within apoB/apoA-1 was about 2.2 times more than that of diabetes. Between-treatment group differences in HF were to a significant extent explained by on-treatment differences in apoB/apoA-1, mostly through the changes in apoB. We argue therefore, on-treatment lipoprotein components contribute to the overall future risk of HF in statin-treated patients with CHD.
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| 9. |
- Jardine, Alan G., et al.
(författare)
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Fluvastatin prevents cardiac death and myocardial infarction in renal transplant recipients : post-hoc subgroup analyses of the ALERT Study
- 2004
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Ingår i: American Journal of Transplantation. - : Elsevier BV. - 1600-6135 .- 1600-6143. ; 4:6, s. 988-995
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Tidskriftsartikel (refereegranskat)abstract
- Renal transplant recipients have a greatly increased risk of premature cardiovascular disease. The ALERT study was a multicenter, randomized, double-blind, placebo-controlled trial of fluvastatin (40-80 mg/day) in 2102 renal transplant recipients followed for 5-6 years. The main study used a composite cardiac end-point including myocardial infarction, cardiac death and cardiac interventions. Although reduced by fluvastatin, this primary end-point failed to achieve statistical significance thus precluding analysis of predefined subgroups. Therefore, in the present survival analysis, we used an alternative primary end-point of cardiac death or definite nonfatal myocardial infarction (as used in other cardiac outcome trials) which was significantly reduced by Fluvastatin therapy and permits subgroup analysis. Fluvastatin reduced LDL-cholesterol by 1 mmol/L compared with placebo, and the incidence of cardiac death or definite myocardial infarction was reduced from 104 to 70 events (RR 0.65; 95% CI 0.48, 0.88; p = 0.005). Fluvastatin use was associated with reduction in cardiac death or nonfatal myocardial infarction, which achieved statistical significance in many subgroups. The subgroups included patients at lower cardiovascular risk, who were younger, nondiabetic, nonsmokers and without pre-existing CVD. These data support the early introduction of statins following renal transplantation.
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| 10. |
- Jönsson, Bengt, et al.
(författare)
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Cost-effectiveness of cholesterol lowering. Results from the Scandinavian Simvastatin Survival Study (4S)
- 1996
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Ingår i: European heart journal. - : Oxford University Press. - 1522-9645 .- 0195-668X. ; 17:7, s. 1001-1007
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Tidskriftsartikel (refereegranskat)abstract
- An analysis of the cost-effectiveness of simvastatin was conducted, based on the Scandinavian Simvastatin Survival Study (4S). The total cost of hospitalization in the placebo group was 52.8 million Swedish kronor (SEK) (5.15 million pounds), compared with SEK 36.0 million (3.51 million pounds) in the simvastatin group. This amounts to a 32% reduction, or a saving of SEK 16.8 million (1.6 million pounds) or SEK 7560 (738 pounds) per patient. The net cost per patient for the duration of the study (5.4 years) was SEK 13,540 (1324 pounds). Simvastatin treatment saved an estimated 0.377 undiscounted life years (0.240 life years discounted at 5% per annum). The cost of simvastatin therapy per discounted life-year saved was therefore SEK 56,400 (5502 pounds). Sensitivity analysis, examining the effect of different life expectancies, costs of initiation and monitoring of simvastatin therapy, and discount rates, showed the results to be stable. Conclusion. The cost per life-year saved of simvastatin in the treatment of post-myocardial infarction and angina patients, as determined from 4S data, is well within the range normally considered cost-effective.
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