| 1. |
- 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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| 2. |
- Kastelein, John J. P., et al.
(författare)
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Lipids, apolipoproteins, and their ratios in relation to cardiovascular events with statin treatment
- 2008
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 117:23, s. 3002-3009
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Tidskriftsartikel (refereegranskat)abstract
- Background - Low-density lipoprotein (LDL)cholesterol is the principal target of lipid-lowering therapy, but recent evidence has suggested more appropriate targets. We compared the relationships of on-treatment levels of LDL cholesterol, non-high-density lipoprotein (HDL) cholesterol, and apolipoprotein B, as well as ratios of total/HDL cholesterol, LDL/HDL cholesterol, and apolipoprotein B/A-I, with the occurrence of cardiovascular events in patients receiving statin therapy. Methods and Results - A post hoc analysis was performed that combined data from 2 prospective, randomized clinical trials in which 10 001 ("Treating to New Targets") and 8888 ("Incremental Decrease in End Points through Aggressive Lipid Lowering") patients with established coronary heart disease were assigned to usual-dose or high-dose statin treatment. In models with LDL cholesterol, non-HDL cholesterol and apolipoprotein B were positively associated with cardiovascular outcome, whereas a positive relationship with LDL cholesterol was lost. In a model that contained non-HDL cholesterol and apolipoprotein B, neither was significant owing to collinearity. Total/HDL cholesterol ratio and the apolipoprotein B/A-I ratio in particular were each more closely associated with outcome than any of the individual proatherogenic lipoprotein parameters. Conclusions - In patients receiving statin therapy, on-treatment levels of non-HDL cholesterol and apolipoprotein B were more closely associated with cardiovascular outcome than levels of LDL cholesterol. Inclusion of measurements of the antiatherogenic lipoprotein fraction further strengthened the relationships. These data support the use of non-HDL cholesterol or apolipoprotein B as novel treatment targets for statin therapy. Given the absence of interventions that have been proven to consistently reduce cardiovascular disease risk through raising plasma levels of HDL cholesterol or apolipoprotein A-I, it seems premature to consider the ratio variables as clinically useful.
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| 3. |
- Pedersen, Terje R, et al.
(författare)
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Comparison of Atorvastatin 80 mg/day Versus Simvastatin 20 to 40 mg/day on Frequency of Cardiovascular Events Late (Five Years) After Acute Myocardial Infarction (from the Incremental Decrease in End Points Through Aggressive Lipid Lowering [IDEAL] Trial)
- 2010
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Ingår i: AMERICAN JOURNAL OF CARDIOLOGY. - : Elsevier Science B. V., Amsterdam. - 0002-9149. ; 106:3, s. 354-359
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies have demonstrated that benefits of intensive statin therapy compared to standard statin therapy begin shortly after an acute event and are continued up to 2 years of follow-up. However, whether efficacy and safety of intensive statin therapy in patients with a recent cardiac event are maintained in longer-term follow-up has not been evaluated. We conducted a post hoc analysis of a subgroup of 999 patients who had a first acute myocardial infarction (MI) andlt;2 months before randomization in a prospective, open-label, blinded end-point evaluation trial of 8,888 patients with a history of MI that compared intensive statin therapy (atorvastatin 80 mg) to standard statin therapy (simvastatin 20 to 40 mg) over approximately 5 years of follow-up. We analyzed the same composite end point used in the Pravastatin or Atorvastatin Evaluation and Infection Therapy (PROVE IT) trial (death, MI, hospitalization for unstable angina, revascularization, and stroke). Rates of the composite end point were 44.7% (n = 226) in the simvastatin group and 37.9% (n = 187) in the atorvastatin group (hazard ratio 0.82, 95% confidence interval 0.67 to 0.99, p = 0.04). Although statistical power was smaller than that of the PROVE IT trial, the relative risk decrease observed at 5 years is consistent with that in the 2-year follow-up in PROVE IT. The 2 treatment regimens were well tolerated. In conclusion, our analysis provides support for the strategy of placing patients with recent MI on intensive statin therapy and maintaining the high dose over the long term, beyond 2 years.
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| 4. |
- Tikkanen, Matti J, et al.
(författare)
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Total Cardiovascular Disease Burden: Comparing Intensive With Moderate Statin Therapy Insights From the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) Trial
- 2009
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Ingår i: Journal of the American College of Cardiology. - : Elsevier BV. - 0735-1097 .- 1558-3597. ; 54:25, s. 2353-2357
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Tidskriftsartikel (refereegranskat)abstract
- Objectives This post-hoc analysis of the IDEAL (Incremental Decrease in End Points Through Aggressive Lipid Lowering) trial was designed to assess the comparative treatment efficacy of high-dose atorvastatin and usual-dose simvastatin for the prevention of events subsequent to the first event, using the Wei, Lin, and Weissfeld method. Background Time-to-first-event analysis of data is frequently utilized to provide efficacy outcome information in coronary heart disease prevention trials. However, during the course of such long-term trials, a large number of events occur subsequent to the first event, the analysis of which will be precluded by this approach. Methods The Wei, Lin, and Weissfeld method allows the analysis of repeated occurrence of events of the same type or of entirely different natures. It regards the recurrence times as multivariate event (failure) times, and models the marginal (individual) distribution for each event with the Cox proportional hazards model. Results In the IDEAL trial, compared with patients taking simvastatin 20 to 40 mg daily, patients receiving atorvastatin 80 mg daily had their relative risk of a first cardiovascular event reduced by 17% (p less than 0.0001), of a second by 24% (p less than 0.0001), of a third by 19% (p = 0.035), of a fourth by 24% (p = 0.058), and of a fifth by 28% (p = 0.117). Conclusions Our results indicate that intensive statin therapy continues to be more effective than standard statin therapy, even beyond the first event, and suggest that clinicians should not hesitate to prescribe high-dose statin therapy for patients experiencing multiple recurrent cardiovascular events.
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