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| 10. |
- Olsson, Anders, 1940-, et al.
(författare)
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High-density lipoprotein, but not low-density lipoprotein cholesterol levels influence short-term prognosis after acute coronary syndrome : Results from the MIRACL trial
- 2005
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Ingår i: European Heart Journal. - : Oxford University Press (OUP). - 0195-668X .- 1522-9645. ; 26:9, s. 890-896
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Tidskriftsartikel (refereegranskat)abstract
- Aims: Patients with acute coronary syndrome (ACS) in the Myocardial lschaemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study had diminished cardiovascular events after 16 weeks of treatment of atorvastatin 80 mg daily. We determined whether plasma lipoproteins at baseline and then at 6 weeks after randomization predicted clinical outcome. Methods and results: Cox proportional hazards models were constructed to determine relations between lipoproteins and clinical endpoint events. Baseline LDL cholesterol (LDL-C) did not predict outcome. In contrast, baseline HDL-C predicted outcome with a hazard ratio of 0.986 per mg/dL increment in HDL-C, P < 0.001, indicating 1.4% reduction in risk for each 1 mg/dL increase in HDL-C. Atorvastatin treatment profoundly lowered LDL-C, but had minimal effect on HDL-C. Neither Week 6 LDL-C nor absolute change of LDL-C from baseline by Week 6 had any significant impact on clinical endpoints occurring between Week 6 and Week 16 after randomization. Conclusion Plasma HDL-C, but not LDL-C, measured in the initial stage of ACS predicts the risk of recurrent cardiovascular events over the ensuing 16 weeks. LDL-C reduction does not account for the clinical risk reduction with atorvastatin treatment after ACS. This finding may suggest that the clinical benefit of atorvastatin after ACS is mediated by qualitative changes in the LDL particle and/or by non-lipid (pleiotropic) effects of the drug.
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| 11. |
- Pitt, B, et al.
(författare)
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Correction
- 2023
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Ingår i: JACC. Heart failure. - 2213-1787. ; 11:9, s. 1288-
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)
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- Tikkanen, M.J., et al.
(författare)
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Comparison of Efficacy and Safety of Atorvastatin (80 mg) to Simvastatin (20 to 40 mg) in Patients Aged less than65 Versus =65 Years With Coronary Heart Disease (from the Incremental DEcrease through Aggressive Lipid Lowering [IDEAL] Study)
- 2009
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149. ; 103:5, s. 577-582
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Tidskriftsartikel (refereegranskat)abstract
- The efficacy and safety of atorvastatin (80 mg/day) versus simvastatin (20 to 40 mg/day) in older (age =65 years) versus younger (less than65 years) patients were assessed in a prespecified secondary analysis of the 8,888 patients with myocardial infarction in the IDEAL trial, a randomized open-label study. Several cardiovascular end points were evaluated, including the occurrence of a first major coronary event (MCE; nonfatal myocardial infarction, coronary heart disease death, or resuscitated cardiac arrest), the primary end point of the trial, and occurrence of any cardiovascular event (MCE, stroke, revascularization, unstable angina, congestive heart failure, and peripheral artery disease). Although there were no significant interactions between age and treatment, the magnitude of effect in favor of atorvastatin was higher in younger versus older patients (occurrence of first MCE, hazard ratio [HR] 0.80, 95% confidence interval [CI] 0.66 to 0.98; and HR 0.95, 95% CI 0.80 to 1.15, respectively; occurrence of any cardiovascular (CV) event, HR 0.80, 95% CI 0.71 to 0.89; and HR 0.88, 95% CI 0.79 to 0.99, respectively). These results were likely influenced by adherence, which was lower in older patients and those receiving atorvastatin compared with those receiving simvastatin. Rates of any reported serious adverse event were higher in older patients, but did not differ between the 2 statin groups. In conclusion, except for any CV events in the older group, significant reductions in primary and secondary end points were observed only in patients less than65 years of age. The safety of atorvastatin (80 mg) and simvastatin (20 to 40 mg) was similar in patients aged less than65 and greater than65 years with stable coronary disease.
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- Olsson, Andes G., et al.
(författare)
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Effects of High-Dose Atorvastatin in Patients =65 Years of Age With Acute Coronary Syndrome (from the Myocardial Ischemia Reduction With Aggressive Cholesterol Lowering [MIRACL] Study)
- 2007
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Ingår i: American Journal of Cardiology. - : Elsevier BV. - 0002-9149 .- 1879-1913. ; 99:5, s. 632-635
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Tidskriftsartikel (refereegranskat)abstract
- After acute coronary syndromes (ACSs), older patients are particularly susceptible to early complications, including death and recurrent ACS. Lipid management guidelines do not differentiate elderly from younger patients, and lack of evidence for statin benefits in older patients has led to underutilization of statins in the elderly. The MIRACL study randomized 3,086 patients to 16 weeks of 80 mg/day of atorvastatin or placebo 24 to 96 hours after ACS and demonstrated significant decreases in the combined primary end point (nonfatal acute myocardial infarction, resuscitated cardiac arrest, recurrent symptomatic myocardial ischemia). This post hoc analysis compared benefits of 80 mg of atorvastatin in older (=65 years) versus younger (<65 years) patients. Event rates were approximately two- to threefold higher in older than in younger patients. Treatment-by-age heterogeneity testing indicated no difference in treatment effect by age for any of the primary or secondary end points, and relative risk decreases in the primary end point with atorvastatin versus placebo were similar in younger and older patients (22% vs 14%, respectively). The safety profile of atorvastatin was similar between the 2 age groups. In conclusion, these results and a greater immediate cardiovascular risk in older patients argue for early, intensive atorvastatin therapy as routine practice after ACS. © 2007 Elsevier Inc. All rights reserved.
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- Damask, Amy, et al.
(författare)
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Patients with High Genome-Wide Polygenic Risk Scores for Coronary Artery Disease May Receive Greater Clinical Benefit from Alirocumab Treatment in the Odyssey Outcomes Trial
- 2020
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Ingår i: Circulation. - : Lippincott Williams & Wilkins. - 0009-7322 .- 1524-4539. ; 141:8, s. 624-636
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Tidskriftsartikel (refereegranskat)abstract
- Background: Alirocumab, an antibody that blocks proprotein convertase subtilisin/kexin type 9 (PCSK9), was associated with reduced major adverse cardiovascular events (MACE) and death in the ODYSSEY OUTCOMES trial. In this study, higher baseline LDL cholesterol (LDL-C) levels predicted greater benefit from alirocumab treatment. Recent studies indicate high polygenic risk scores (PRS) for coronary artery disease (CAD) identify individuals at higher risk who derive increased benefit from statins. Herein we perform post hoc analyses to determine whether high PRS for CAD identifies higher-risk individuals, independently from baseline LDLC and other known risk factors, who might derive greater benefit from alirocumab treatment. Methods: ODYSSEY OUTCOMES was a randomized, double-blind, placebo-controlled trial comparing alirocumab or placebo in 18,924 patients with acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin treatment. The primary endpoint (MACE) comprised death from CAD, nonfatal myocardial infarction, ischemic stroke, or unstable angina requiring hospitalization. A genome-wide PRS for CAD comprising 6,579,025 genetic variants was evaluated in 11,953 patients with available DNA samples. Analysis of MACE risk was performed in placebo treated patients while treatment benefit analysis was performed in all patients. Results: The incidence of MACE in the placebo group was related to PRS for CAD: 17.0% for high PRS patients (>90th percentile) and 11.4% for lower PRS patients (≤90th percentile) (p<0.001); this PRS relationship was not explained by baseline LDL-C or other established risk factors. Both the absolute and relative reduction of MACE by alirocumab compared to placebo was greater in high versus low PRS patients. There was an absolute reduction by alirocumab in high versus low PRS groups of 6.0% and 1.5%, respectively, and relative risk reduction by alirocumab of 37% in the high PRS group (hazard ratio [HR] 0.63; 95% confidence interval [CI] 0.46-0.86; p = 0.004) versus 13% reduction in the low PRS group (HR 0.87; 95% CI 0.78-0.98; p=0.022; interaction p = 0.04). Conclusions: A high PRS for CAD is associated with elevated risk for recurrent MACE after ACS, and larger absolute and relative risk reduction with alirocumab treatment, providing an independent tool for risk stratification and precision medicine.
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| 19. |
- Govsyeyev, Nicholas, et al.
(författare)
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Rivaroxaban in Patients with Symptomatic Peripheral Artery Disease after Lower Extremity Bypass Surgery with Venous and Prosthetic Conduits
- 2023
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Ingår i: Journal of Vascular Surgery. - : Elsevier. - 0741-5214 .- 1097-6809. ; 77:4, s. 1107-1118.e2
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Patients with peripheral artery disease (PAD) requiring lower extremity revascularization (LER) are at high risk of adverse limb and cardiovascular events. VOYAGER PAD demonstrated that rivaroxaban significantly reduced this risk with an overall favorable net benefit in patients undergoing surgical revascularization; however, the efficacy and safety in those treated by surgical bypass including stratified by bypass conduit (venous or prosthetic) has not been described.METHODS: In the VOYAGER PAD trial, patients with PAD after surgical and endovascular infrainguinal LER were randomized to rivaroxaban 2.5 mg twice daily or placebo and followed for a median of 28 months. The primary endpoint was a composite of acute limb ischemia (ALI), major amputation of vascular etiology, myocardial infarction, ischemic stroke, or cardiovascular death. The principal safety outcome was Thrombolysis in Myocardial Infarction (TIMI) major bleeding. Index procedure details including conduit type (venous or prosthetic) were collected at baseline.RESULTS: Among 6564 randomized, 2185 (33%) underwent surgical LER. Of these, surgical bypass was performed in 1448 (66%), using prosthetic conduit in 773 (53%) and venous in 646 (45%). Adjusting for baseline differences and anatomic factors, the risk for unplanned limb revascularization in the placebo arm was 2.5-fold higher for those receiving prosthetic versus venous conduits (adjHR 2.53, 95% CI 1.65-3.90; p<0.001) while the risk for ALI was 3 times greater (adjHR 3.07, 95% CI 1.84-5.11; p<0.001). Rivaroxaban reduced the primary outcome in patients treated with bypass surgery (HR 0.78, 95% CI 0.62-0.98) with consistent benefits in those receiving venous (HR 0.66, 95% CI 0.49-0.96) and prosthetic (HR 0.87, 95% CI 0.66-1.15) conduits (pinteraction 0.254). In the overall trial, TIMI major bleeding was increased with rivaroxaban; however, numbers in those treated with bypass surgery were low (5 with rivaroxaban, 9 with placebo, HR 0.55, 95% CI 0.18-1.65) and not powered to show statistical significance.CONCLUSIONS: Surgical bypass with prosthetic conduit is associated with significantly higher rates of major adverse limb events relative to venous conduits even after adjusting for patient and anatomic characteristics. Adding rivaroxaban 2.5 mg twice daily to aspirin or dual antiplatelet therapy significantly reduces this risk, increases bleeding, but has a favorable benefit risk in patients treated with bypass surgery and regardless of conduit type. Rivaroxaban should be considered after lower extremity bypass for symptomatic PAD to reduce ischemic complications of the heart, limb, and brain.
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| 20. |
- Hagström, Emil, et al.
(författare)
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Apolipoprotein B, Residual Cardiovascular Risk After Acute Coronary Syndrome, and Effects of Alirocumab
- 2022
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Ingår i: Circulation. - : Ovid Technologies (Wolters Kluwer Health). - 0009-7322 .- 1524-4539. ; 146:9, s. 657-672
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Apolipoprotein B (apoB) provides an integrated measure of atherogenic risk. Whether apoB levels and apoB lowering hold incremental predictive information on residual risk after acute coronary syndrome beyond that provided by low-density lipoprotein cholesterol is uncertain. METHODS: The ODYSSEY OUTCOMES trial (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) compared the proprotein convertase subtilisin/kexin type 9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome and elevated atherogenic lipoproteins despite optimized statin therapy. Primary outcome was major adverse cardiovascular events (MACE; coronary heart disease death, nonfatal myocardial infarction, fatal/nonfatal ischemic stroke, hospitalization for unstable angina). Associations between baseline apoB or apoB at 4 months and MACE were assessed in adjusted Cox proportional hazards and propensity score-matched models. RESULTS: Median follow-up was 2.8 years. In proportional hazards analysis in the placebo group, MACE incidence increased across increasing baseline apoB strata (3.2 [95% CI, 2.9-3.6], 4.0 [95% CI, 3.6-4.5], and 5.5 [95% CI, 5.0-6.1] events per 100 patient-years in strata <75, 75-<90, >= 90 mg/dL, respectively; P-trend<0.0001) and after adjustment for low-density lipoprotein cholesterol (P-trend=0.035). Higher baseline apoB stratum was associated with greater relative (P-trend<0.0001) and absolute reduction in MACE with alirocumab versus placebo. In the alirocumab group, the incidence of MACE after month 4 decreased monotonically across decreasing achieved apoB strata (4.26 [95% CI, 3.78-4.79], 3.09 [95% CI, 2.69-3.54], and 2.41 [95% CI, 2.11-2.76] events per 100 patient-years in strata >= 50, >35-<50, and <= 35 mg/dL, respectively). Compared with propensity score-matched patients from the placebo group, treatment hazard ratios for alirocumab also decreased monotonically across achieved apoB strata. Achieved apoB was predictive of MACE after adjustment for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol but not vice versa. CONCLUSIONS: In patients with recent acute coronary syndrome and elevated atherogenic lipoproteins, MACE increased across baseline apoB strata. Alirocumab reduced MACE across all strata of baseline apoB, with larger absolute reductions in patients with higher baseline levels. Lower achieved apoB was associated with lower risk of MACE, even after accounting for achieved low-density lipoprotein cholesterol or non-high-density lipoprotein cholesterol, indicating that apoB provides incremental information. Achievement of apoB levels as low as <= 35 mg/dL may reduce lipoprotein-attributable residual risk after acute coronary syndrome.
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- Kinlay, S, et al.
(författare)
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Effect of atorvastatin on risk of recurrent cardiovascular events after an acute coronary syndrome associated with high soluble CD40 ligand in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study
- 2004
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 110:4, s. 386-391
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Tidskriftsartikel (refereegranskat)abstract
- Background - Patients with acute coronary syndromes have elevated plasma levels of the proinflammatory, prothrombotic cytokine CD40 ligand (sCD40L). Statins inhibit CD40L signaling in vitro, but there are no prospective studies of statins and sCD40L in acute coronary syndromes. Methods and Results - We measured sCD40L in subjects with an acute coronary syndrome enrolled in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects were randomized in this double-blind trial to atorvastatin 80 mg/d or placebo for 16 weeks. Plasma CD40L was measured from 2908 (94%) of 3086 subjects at baseline and 2352 (76%) at 16 weeks. Odds ratios (Ors) and 95% Cis from logistic regression models assessed the risk of recurrent cardiovascular events over 16 weeks (death, nonfatal myocardial infarction, cardiac arrest, and worsening angina requiring rehospitalization) in the placebo group from baseline sCD40L and the effect of atorvastatin on the risk associated with CD40L in all subjects. The effects of atorvastatin on plasma concentrations of CD40L were assessed by Wilcoxon tests. There was a threshold effect, with only high sCD40L (>90th centile) being a risk factor for a recurrent cardiovascular event (OR 1.86, 95% CI 1.25 to 2.77). This risk was abolished by atorvastatin (OR 1.09, 95% CI 0.69 to 1.76), which reduced the risk by 48%. Atorvastatin had only a modest effect on sCD40L (P=0-08). Conclusions - In patients with acute coronary syndromes, atorvastatin abrogated the risk of recurrent cardiovascular events associated with high sCD40L. Early statin therapy after acute coronary syndromes counters the risk associated with elevated sCD40L.
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| 23. |
- Kinlay, S, et al.
(författare)
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High-dose atorvastatin enhances the decline in inflammatory markers in patients with acute coronary syndromes in the MIRACL study
- 2003
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 108:13, s. 1560-1566
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Tidskriftsartikel (refereegranskat)abstract
- Background - Inflammation promotes acute coronary syndromes and ensuing clinical complications. Although statins reduce inflammatory markers in asymptomatic adults or in patients with stable angina, the effect of statins on the markedly heightened inflammation in patients with acute coronary syndromes is unknown. Methods and Results - We measured C-reactive protein (CRP), serum amyloid A (SAA), and interleukin 6 (IL-6) in 2402 subjects enrolled the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) study. Subjects with unstable angina or non-Q-wave myocardial infarction were randomized to atorvastatin 80 mg/d or placebo within 24 to 96 hours of hospital admission and treated for 16 weeks. The effect of treatment on inflammatory markers was assessed by ANCOVA after adjustment for presenting syndrome, country, and initial level of marker. All 3 markers were markedly elevated at randomization and declined over the 16 weeks in both treatment groups. Compared with placebo, atorvastatin significantly reduced CRP, -83% (95% CI, -84%, -81%) versus -74% (95% CI, -75%, -71%) (P<0.0001) and SAA, -80% (95% CI, -82%, -78%) versus -77% (-79%, -75%) (P=0.0006) but not IL-6, -55% (95% CI, -57%, -53%) versus -53% (95% CI, -55%, -51%) (P=0.3). Reductions in CRP and SAA were observed in patients with unstable angina and non-Q-wave myocardial infarction, with initial LDL cholesterol <3.2 of =3.2 mmol/L (125 mg/dL), age =65 or <65 years, and in men and women. By 16 weeks, CRP was 34% lower with atorvastatin than with placebo. Conclusions - High-dose atorvastatin potentiated the decline in inflammation in patients with acute coronary syndromes. This supports the value of early statin therapy in these patients.
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| 24. |
- Kinlay, S., et al.
(författare)
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Inflammation, statin therapy, and risk of stroke after an acute coronary syndrome in the MIRACL study
- 2008
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Ingår i: Arteriosclerosis, Thrombosis and Vascular Biology. - 1079-5642 .- 1524-4636. ; 28:1, s. 142-147
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - Patients with acute coronary syndromes have an increased risk of stroke. We measured markers of inflammation in the MIRACL study, a randomized trial of atorvastatin versus placebo in acute coronary syndromes, to assess the relationship of inflammation to stroke. METHODS AND RESULTS - Baseline C-reactive protein (CRP), serum amyloid A (SAA), and interleukin-6 (IL-6) were collected in 2926 (95%) subjects. Baseline markers were related to stroke risk over the 16 weeks of the study. Subjects who subsequently experienced a stroke had higher CRP (27.5 versus 10.2 mg/L, P=0.0032), SAA (30.5 versus 16.0 mg/L, P=0.031), IL-6 (11 231 versus 6841 pg/L, P=0.004), and troponin (6.03 versus 3.19 ng/mL P=0.0032). The risk of stroke was related to greater CRP, SAA, and IL-6 in the placebo group only. Similarly, there was a graded increase in risk of stroke across quartiles of inflammatory markers in the placebo patients only. CONCLUSIONS - In acute coronary syndromes, the early risk of stroke relates to both heightened inflammation and size of myocardial necrosis. Treatment with atorvastatin abrogated the risk associated with elevated markers of inflammation in this study, a finding that provides a novel rationale for the use of statins in acute coronary syndromes. © 2008 American Heart Association, Inc.
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| 25. |
- Pedersen, T R, et al.
(författare)
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High-dose atorvastatin vs usual dose simvastatin for secondary prevention after myocardial infarction - The IDEAL study: A randomized controlled trial
- 2005
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Ingår i: Journal of the American Medical Association (JAMA). - : American Medical Association (AMA). - 0098-7484 .- 1538-3598. ; 294:19, s. 2437-2445
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Tidskriftsartikel (refereegranskat)abstract
- Context Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. Objective To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). Design, Setting, and Participants The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Interventions Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n=4439), or usual-dose simvastatin (20 mg/d; n=4449). Main Outcome Measure Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. Results During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% Cl, 0.78-1.01; P=.07). Nonfatal acute MI occurred in 321 (7.2%) and M7 (6.0%) in the 2 groups (HR, 0.83; 95% Cl, 0.71-0.98; P=.02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% Cl, 0.77-0.98; P=.02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% Cl, 0.76-0.91; Pless than.001). Non-cardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% Cl, 0.73-1.15; P=.47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% Cl, 0.85-1.13; P=.81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (Pless than.001). Serious myopathy and rhabdomyolysis were rare in both groups. Conclusions In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions.
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| 26. |
- Schwartz, G.G., et al.
(författare)
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Relation of characteristics of metabolic syndrome to short-term prognosis and effects of intensive statin therapy after acute coronary syndrome : An analysis of the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial
- 2005
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Ingår i: Diabetes Care. - : American Diabetes Association. - 0149-5992 .- 1935-5548. ; 28:10, s. 2508-2513
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE - We examined relations between characteristics of the metabolic syndrome, early cardiovascular risk, and effect of early, intensive statin therapy after acute coronary syndrome. RESEARCH DESIGN AND METHODS - A total of 3,038 patients in the Myocardial Ischemia Reduction with Aggressive Cholesterol Lowering (MIRACL) trial were characterized by the presence or absence of a history of diabetes, a history of hypertension and/or blood pressure =130/=85, BMI > 30 kg/m2, HDL cholesterol <40 mg/dl (men) or <50 mg/dl (women), and triglycerides =150 mg/dl. Patients with three or more of these characteristics were categorized as having metabolic syndrome. RESULTS - A total of 38% of patients (n = 1,161) met criteria for metabolic syndrome as defined in this study and had a 19% incidence of a primary end point event (death, nonfatal myocardial infarction, cardiac arrest, or recurrent unstable myocardial ischemia) during the 16-week trial. Patients with two or fewer characteristics (n = 1,877) were classified as not having metabolic syndrome and had a 14% incidence of a primary end point event. In univariate analysis, the individual characteristics that bore a significant relation to risk were diabetes and low HDL cholesterol. In a multivariable model including age, sex, and randomized treatment assignment, presence of metabolic syndrome was associated with a hazard ratio of 1.49 (95% Cl 1.24-1.79, P < 0.0001). Relative risk reduction with 80 mg atorvastatin daily compared with placebo was similar in patients with and without metabolic syndrome. CONCLUSIONS - Metabolic syndrome, as defined in the context of this clinical trial, is a strong predictor of early recurrent ischemic events after acute coronary syndrome. © 2005 by the American Diabetes Association.
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| 28. |
- Tsimikas, S, et al.
(författare)
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High-dose atorvastatin reduces total plasma levels of oxidized phospholipids and immune complexes present on apolipoprotein B-100 in patients with acute coronary syndromes in the MIRACL trial
- 2004
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Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 110:11, s. 1406-1412
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Tidskriftsartikel (refereegranskat)abstract
- Background-Oxidized phospholipids (OxPL) are present within atherosclerotic plaques and bound by lipoprotein (a) [Lp(a)] in plasma. This study evaluated the impact of atorvastatin on oxidized LDL (OxLDL) in patients with acute coronary syndromes (ACS). Methods and Results-OxLDL-E06 (OxPL content on apolipoprotein B-100 [apoB] detected by antibody E06), apoB-100 immune complexes (apoB-IC), OxLDL autoantibodies, and Lp(a) levels were measured in 2341 patients at baseline and after 16 weeks of treatment with atorvastatin 80 mg/d or placebo. The OxLDL-E06 and apoB-IC data are reported per apoB-100 particle (OxPL/apoB, IC/apoB) and as total levels on all apoB-100 particles (total apoB-OxPL and total apoB-IC [eg, OxPL/apoB or IC/apoBXapoB-100 levels]). Compared with baseline values, atorvastatin reduced apoB-100 (-33%), total apoB-OxPL (-29.7%), total apoB-IC IgG (-29.5%), and IgM (-25.7%) (P<0.0001 for all), whereas no change or an increase was observed with placebo. When normalized per apoB-100, compared with placebo, atorvastatin increased OxPL/apoB (9.5% versus -3.9%, P<0.0001) and Lp(a) (8.8% versus -0.7%, (P<0.0001). A strong correlation was noted between OxPL/apoB and Lp(a) (R=0.85, P<0.0001), consistent with previous data that Lp(a) binds OxPL. Conclusions-After atorvastatin treatment, total OxPL on all apoB-100 particles was decreased. However, there was enrichment of OxPL on a smaller pool of apoB-100 particles, in parallel with similar increases in Lp(a), suggesting binding by Lp(a). These data support the hypothesis that atorvastatin promotes mobilization and clearance of proinflammatory OxPL, which may contribute to a reduction in ischemic events after ACS.
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