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1.
Br J Clin Pharmacol ; 88(9): 4092-4099, 2022 09.
Article in English | MEDLINE | ID: mdl-35384015

ABSTRACT

AIMS: Antithrombotic management initiatives could prevent inappropriate prescribing and improve patient outcomes especially in patients on combined antithrombotic therapy. To investigate this, a multidisciplinary antithrombotic stewardship program (ASP) was implemented in our hospital. The primary aim of this study was to determine the efficacy of this ASP by assessing the number of patients on combined antithrombotic therapy for whom one or more interventions were needed. METHODS: A prospective cohort study in a large teaching hospital was conducted. Hospitalized patients were included who received combined antithrombotic therapy in which an oral anticoagulant was combined with one (double therapy) or two (triple therapy) platelet aggregation inhibitors. The ASP proactively evaluated the appropriateness of this combined antithrombotic therapy. If needed, ASP improved the concerned therapy. Each improvement measurement recommended by the ASP was counted as one intervention. RESULTS: A total of 460 patients were included over a period of 12 months. Of these, 251 (54.6%) patients required at least one intervention from the ASP. The most common interventions were: (1) to define and document the maximum duration of the combined antithrombotic therapy needed instead of lifetime use of the combination (65.5%), (2) to discontinue antithrombotic therapy as the proper indication was lacking (19.4%), and (3) to adjust the dosage (8.1%). CONCLUSION: An intervention was needed in more than half of the patients on combined antithrombotic therapy. Implementation of a dedicated ASP evaluating combined antithrombotic therapy improves the use and safety of antithrombotic medication.


Subject(s)
Fibrinolytic Agents , Platelet Aggregation Inhibitors , Anticoagulants , Humans , Inappropriate Prescribing/prevention & control , Platelet Aggregation Inhibitors/therapeutic use , Prospective Studies
2.
Eur Heart J Case Rep ; 5(4): ytab120, 2021 Apr.
Article in English | MEDLINE | ID: mdl-34109290

ABSTRACT

BACKGROUND: Non-bacterial thrombotic endocarditis (NBTE) is a rare form of endocarditis notably described in patients with advanced malignancy and auto-immune diseases. It is characterized by the formation of sterile, fibrin-containing vegetations on cardiac endothelium, in the absence of positive blood cultures. It is predominantly located on the mitral- and aortic valve (AV). Vegetations in NBTE are prone to embolize. Trousseau syndrome (TS) is defined as unexplained thrombotic events that precede the diagnosis of malignancy. CASE SUMMARY: A 49-year-old pre-menopausal woman with a history of visual disturbances, recurrent deep vein thrombosis (DVT) with concurrent pulmonary emboli (PE), and uterine myomas with dysfunctional uterine bleeding was resuscitated for ventricular fibrillation. While echocardiography revealed vegetations on the AV, blood cultures remained negative. Additional work-up for the aetiology of sterile vegetations revealed a low-grade ovarian carcinoma. Cardiac analysis showed evidence of myocardial infarction in the absence of coronary atherosclerosis as a cause for ventricular fibrillation. DISCUSSION: Unexplained thrombotic events (venous, arterial, or both) warrant further investigation, e.g., with regard to TS. NBTE is a potential source of thromboembolism in TS and a rare ante-mortem finding, which prompts additional investigation of the underlying cause. In our patient, a triad of (suspected) (i) arterial/systemic embolization (i.e. visual disturbances, splenic infarction, coronary embolism), (ii) peripheral thrombophlebitis/hypercoagulability (i.e. DVT and PE), and (iii) malignancy (i.e. gynaecological abnormalities) raised suspicion of NBTE in the setting of TS. Early diagnosis and treatment of NBTE is of importance due to the high incidence of embolization, with possible fatal outcome.

3.
Res Pract Thromb Haemost ; 5(1): 223-230, 2021 Jan.
Article in English | MEDLINE | ID: mdl-33537547

ABSTRACT

BACKGROUND: In premenopausal women, treatment with direct oral factor Xa inhibitors is associated with an increased risk of heavy menstrual bleeding (HMB) compared with vitamin K antagonists (VKA). Treatment with the direct oral thrombin inhibitor dabigatran appears to be associated with a reduced risk of HMB compared with VKA. These findings come from small observational studies or post hoc analyses of trials in which HMB was not a primary outcome. Use of tranexamic acid during the menstrual period may be effective in patients with HMB, but prospective data regarding efficacy and safety in patients on anticoagulant treatment are lacking. RATIONALE AND DESIGN: A direct comparison of a factor Xa inhibitor and a thrombin inhibitor with HMB as primary outcome, as well as an evaluation of the effects of adding tranexamic acid in women with anticoagulant-associated HMB is highly relevant for clinical practice. The MEDEA study is a randomized, open-label, pragmatic clinical trial to evaluate management strategies in premenopausal women with HMB associated with factor Xa inhibitor therapy. OUTCOMES: Women using factor Xa inhibitors with proven HMB, as assessed by a pictorial blood loss assessment chart (PBAC) score of >150, will be randomized to one of three study arms: (i) switch to dabigatran; (ii) continue factor Xa inhibitor with addition of tranexamic acid during the menstrual period; or (iii) continue factor Xa inhibitor without intervention. The primary outcome is the difference in PBAC score before and after randomization. Here, we present the rationale and highlight several unique features in the design of the study.

4.
Lancet Haematol ; 5(11): e512-e519, 2018 Nov.
Article in English | MEDLINE | ID: mdl-30314712

ABSTRACT

BACKGROUND: The IDEAL DVT study showed that it was safe to shorten the duration of elastic compression therapy on an individualised basis after deep vein thrombosis for prevention of post-thrombotic syndrome. In this study, we assessed the cost-effectiveness of this strategy. METHODS: IDEAL DVT was a multicentre, randomised, non-inferiority trial that included patients with acute proximal deep vein thrombosis of the leg. After 6 months of elastic compression therapy, patients were randomly assigned (1:1) to the standard 2 years of elastic stocking compression therapy or shortened duration of compression therapy based on the patient's Villalta score. For our cost-effectiveness analysis, we assessed quality-adjusted life-years (QALYs), measured with the three-level version of EQ-5D (EQ-5D-3L; Dutch and UK tariff) and the 36-item Short Form Health Survey (SF-36), and costs in € (health-care and societal perspective) according to the intention-to-treat approach. Data were collected at 3, 6, 12, and 24 months after diagnosis of thrombosis. We calculated incremental net monetary benefit using a QALY threshold of €30 000, and obtained bootstrapped means and 95% CIs. IDEAL DVT is registered with ClinicalTrials.gov, number NCT01429714. FINDINGS: Between March 22, 2011, and July 1, 2015, 865 patients were enrolled in IDEAL DVT. 437 were assigned to individualised duration of elastic compression therapy and 428 to standard duration of elastic compression therapy. Nine patients were eventually excluded because of recurrent venous thromboembolism within 6 months after the first event. From a societal perspective, for every QALY lost measured with the EQ-5D Dutch tariff, cost savings were €305·992 (incremental net monetary benefit €3205, 95% CI 502-5741), and for every QALY lost based on the Short-Form Six-Dimension (SF-6D) utility score (derived from SF-36), cost savings were €6030·941 (€3540, 95% CI 1174-5953). Using the UK tariff for EQ-5D, the individualised strategy was more effective and less costly (€4071, 1452-6647). The probability that the individualised strategy was cost-effective was 99% at a threshold of €30 000 per QALY (EQ-5D Dutch tariff). INTERPRETATION: Individually shortened duration of elastic compression therapy was cost-effective compared with standard duration elastic compression therapy. Use of an individualised approach to elastic stocking compression therapy for the prevention of post-thrombotic syndrome after deep vein thrombosis could lead to substantial costs savings without loss in health-related quality of life. FUNDING: Netherlands Organisation for Health Research and Development.


Subject(s)
Cost-Benefit Analysis , Postthrombotic Syndrome/prevention & control , Stockings, Compression/economics , Humans , Quality of Life , Time Factors
5.
Lancet Haematol ; 5(1): e25-e33, 2018 Jan.
Article in English | MEDLINE | ID: mdl-29217387

ABSTRACT

BACKGROUND: Therapy with elastic compression stockings has been the cornerstone for prevention of post-thrombotic syndrome for decades in patients after acute deep venous thrombosis. It is uncertain who benefits most from therapy, and what the optimum duration of therapy should be. We therefore aimed to assess the safety and efficacy of individualised duration of compression therapy versus the standard duration of 24 months following an initial treatment period of 6 months. METHODS: We did a multicentre, randomised, single-blind, allocation-concealed, non-inferiority trial at 12 hospitals in the Netherlands and two in Italy. We randomly assigned patients (1:1) with acute proximal deep vein thrombosis of the leg and without pre-existent venous insufficiency (Clinical Etiological Anatomical and Pathophysiological score

Subject(s)
Postthrombotic Syndrome/prevention & control , Stockings, Compression , Adult , Aged , Female , Humans , Male , Middle Aged , Reference Standards , Safety , Single-Blind Method , Stockings, Compression/adverse effects , Time Factors , Treatment Outcome
6.
Ann Intern Med ; 160(7): 451-7, 2014 Apr 01.
Article in English | MEDLINE | ID: mdl-24687068

ABSTRACT

BACKGROUND: Although well-established for suspected lower limb deep venous thrombosis, an algorithm combining a clinical decision score, d-dimer testing, and ultrasonography has not been evaluated for suspected upper extremity deep venous thrombosis (UEDVT). OBJECTIVE: To assess the safety and feasibility of a new diagnostic algorithm in patients with clinically suspected UEDVT. DESIGN: Diagnostic management study. (ClinicalTrials.gov: NCT01324037) SETTING: 16 hospitals in Europe and the United States. PATIENTS: 406 inpatients and outpatients with suspected UEDVT. MEASUREMENTS: The algorithm consisted of the sequential application of a clinical decision score, d-dimer testing, and ultrasonography. Patients were first categorized as likely or unlikely to have UEDVT; in those with an unlikely score and normal d-dimer levels, UEDVT was excluded. All other patients had (repeated) compression ultrasonography. The primary outcome was the 3-month incidence of symptomatic UEDVT and pulmonary embolism in patients with a normal diagnostic work-up. RESULTS: The algorithm was feasible and completed in 390 of the 406 patients (96%). In 87 patients (21%), an unlikely score combined with normal d-dimer levels excluded UEDVT. Superficial venous thrombosis and UEDVT were diagnosed in 54 (13%) and 103 (25%) patients, respectively. All 249 patients with a normal diagnostic work-up, including those with protocol violations (n = 16), were followed for 3 months. One patient developed UEDVT during follow-up, for an overall failure rate of 0.4% (95% CI, 0.0% to 2.2%). LIMITATIONS: This study was not powered to show the safety of the substrategies. d-Dimer testing was done locally. CONCLUSION: The combination of a clinical decision score, d-dimer testing, and ultrasonography can safely and effectively exclude UEDVT. If confirmed by other studies, this algorithm has potential as a standard approach to suspected UEDVT. PRIMARY FUNDING SOURCE: None.


Subject(s)
Algorithms , Decision Support Techniques , Fibrin Fibrinogen Degradation Products/analysis , Ultrasonography, Doppler, Color , Upper Extremity Deep Vein Thrombosis/diagnosis , Feasibility Studies , Humans , Probability , Prospective Studies , Upper Extremity Deep Vein Thrombosis/diagnostic imaging
7.
Atherosclerosis ; 197(2): 916-21, 2008 Apr.
Article in English | MEDLINE | ID: mdl-17875305

ABSTRACT

INTRODUCTION: Myeloperoxidase (MPO), an antimicrobial enzyme of the innate immune system, has been proposed to exert a wide array of pro-atherogenic effects throughout all stages of the atherosclerotic process. In view of the potent anti-inflammatory effects of statins in vitro, we evaluated the impact of statin therapy on plasma MPO levels in patients with heterozygous familial hypercholesterolemia (FH), treated with either intensive or conventional lipid-lowering therapy. Furthermore, we evaluated the relation between MPO levels and atherosclerosis progression, as determined by intima media thickness (IMT). METHODS: We measured plasma MPO levels, lipoprotein profiles, high sensitivity-C-reactive protein (hs-CRP) as well as IMT of carotid artery segments in 122 FH patients at baseline and after 2-year treatment with atorvastatin 80 mg or simvastatin 40 mg QD. RESULTS: Baseline median MPO values were 147pM (interquartile range (IQR) 122-217) and 144pM (IQR 118-216) and these increased significantly to 221pM (IQR 144-290) and 255pM (IQR 152-324) during 2-year follow-up in both the atorvastatin 80 mg and simvastatin 40 mg group, respectively. There was no correlation between MPO levels and IMT progression, change in lipoproteins or hs-CRP. CONCLUSION: In FH patients, statins do not prevent an increase in MPO levels during follow-up. Moreover, MPO levels are not associated with atherosclerosis progression in these patients.


Subject(s)
Carotid Artery Diseases/blood , Hyperlipoproteinemia Type II/blood , Peroxidase/blood , Adult , Carotid Artery Diseases/complications , Carotid Artery Diseases/pathology , Cohort Studies , Disease Progression , Female , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipoproteinemia Type II/complications , Hyperlipoproteinemia Type II/drug therapy , Male , Middle Aged , Peroxidase/drug effects , Tunica Intima/pathology , Tunica Media/pathology
8.
Am J Cardiol ; 95(2): 264-6, 2005 Jan 15.
Article in English | MEDLINE | ID: mdl-15642565

ABSTRACT

In the 2-year Atorvastatin versus Simvastatin on Atherosclerosis Progression extension study, patients with familial hypercholesterolemia who continued to take atorvastatin 80 mg for an additional 2 years had complete arrest of the progression of mean carotid intima-media thickness (0.89 mm at the start vs 0.90 mm at the end of the study, p = 0.58). In contrast, patients previously taking simvastatin 40 mg had significant regression of intima-media thickness (0.95 mm at the start vs 0.92 mm at the end of the study, p = 0.01). Therefore, both placebo- and statin-treated patients with familial hypercholesterolemia are best treated with high-dose atorvastatin, a therapeutic regimen that induces atherosclerosis regression and is safe and well tolerated over a 4-year period.


Subject(s)
Heptanoic Acids/administration & dosage , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hyperlipoproteinemia Type II/drug therapy , Pyrroles/administration & dosage , Adult , Aged , Atorvastatin , Cholesterol/blood , Cholesterol, HDL/blood , Cholesterol, LDL/blood , Coronary Artery Disease/blood , Coronary Artery Disease/drug therapy , Coronary Artery Disease/pathology , Drug Administration Schedule , Female , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/pathology , Longitudinal Studies , Male , Middle Aged , Randomized Controlled Trials as Topic , Treatment Outcome , Triglycerides/blood
9.
J Investig Med ; 52(3): 177-84, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15222407

ABSTRACT

BACKGROUND: Little is known about the effects of statins on the quality of circulating low-density lipoprotein (LDL) in relation to atherosclerosis progression. METHODS: In a double-blind, randomized trial of 325 patients with familial hypercholesterolemia (FH), we assessed the effects of high-dose atorvastatin (80 mg) and conventional-dose simvastatin (40 mg) on LDL subfraction profile (n = 289), LDL oxidizability (n = 121), and circulating autoantibodies to oxidized LDL (n = 220). Progression of atherosclerosis was measured by carotid intima media thickness (IMT) (n = 325). RESULTS: At baseline, the patients showed an intermediate LDL subfraction profile composed of three LDL subfractions (LDL1, LDL2, LDL3), with LDL2 as the predominant subfraction. A strong negative correlation was found between plasma triglycerides and the LDL subfraction profile (r = -.64, p = .000). Both plasma levels of triglycerides and small dense LDL3 correlated weakly with baseline IMT (r = .11, p = .04 and r = .15, p = .01, respectively; n = 289). No association was found between baseline IMT and oxidation parameters or circulating antibodies to oxidized LDL. Atorvastatin reduced triglycerides, LDL cholesterol, and all LDL subfractions to a greater extent than did simvastatin and led to regression of carotid IMT. However, LDL subfraction pattern and plasma levels of autoantibodies to oxidized LDL remained unchanged in both treatment groups, and LDL oxidizability increased minimally to a similar extent in both groups. Significant treatment differences were found for the rate of in vitro oxidation of LDL and the amount of dienes formed during in vitro oxidation of LDL, which both decreased more following atorvastatin than after simvastatin. CONCLUSION: Change of IMT after statin treatment was associated with baseline IMT (r = .41), LDL cholesterol (r = -.20), and the amount of dienes formed during in vitro oxidation of LOL (r = .28) but not with plasma levels of antibodies to oxidized LDL, in vitro LDL oxidizability, and LDL subfraction profile.


Subject(s)
Anticholesteremic Agents/therapeutic use , Carotid Arteries , Heptanoic Acids/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Lipoproteins, LDL/blood , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Atorvastatin , Carotid Arteries/diagnostic imaging , Carotid Arteries/drug effects , Female , Heptanoic Acids/pharmacology , Humans , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/diagnostic imaging , Lipid Peroxidation/immunology , Lipoproteins, LDL/immunology , Male , Middle Aged , Pyrroles/pharmacology , Simvastatin/pharmacology , Tunica Media/diagnostic imaging , Tunica Media/drug effects , Ultrasonography
10.
Atherosclerosis ; 173(2): 261-7, 2004 Apr.
Article in English | MEDLINE | ID: mdl-15064100

ABSTRACT

BACKGROUND: Cholesteryl ester transfer protein (CETP) mediates the transfer of neutral lipids between lipoproteins. The role of CETP in atherogenesis is controversial. To better understand the relationships between plasma CETP levels, lipoproteins and atherosclerosis, we assessed these parameters in patients with an enhanced risk for atherosclerosis. METHODS AND RESULTS: We investigated 281 patients with familial hypercholesterolemia (FH) in which the effects of two statins were compared in a 2-year, randomized, double-blinded study. Patients were stratified in quartiles according to their CETP baseline levels. In addition to correlations with decreased high-density lipoprotein cholesterol (HDL-c), increased low-density lipoprotein cholesterol (LDL-c) and enhanced triglyceride levels, higher CETP levels were also associated with reduced HDL particle size, and smaller and denser LDL. Statins reduced plasma CETP levels and atherogenic lipoproteins. Nevertheless, baseline CETP concentration was positively associated with IMT after 2 years of therapy. CONCLUSION: This study provides evidence that CETP levels are associated with a more atherogenic lipid profile and increased progression of atherosclerosis. Statin treatment improved the lipoprotein profile in FH patients, but to a lesser extent in those with high CETP levels. These findings might imply that statin treatment does not entirely counteract the lipoprotein abnormalities associated with high CETP levels.


Subject(s)
Arteriosclerosis/pathology , Carrier Proteins/metabolism , Glycoproteins/metabolism , Heptanoic Acids/administration & dosage , Hyperlipoproteinemia Type II/blood , Hyperlipoproteinemia Type II/drug therapy , Pyrroles/administration & dosage , Simvastatin/administration & dosage , Administration, Oral , Analysis of Variance , Arteriosclerosis/prevention & control , Atorvastatin , Carrier Proteins/blood , Cholesterol Ester Transfer Proteins , Dose-Response Relationship, Drug , Double-Blind Method , Drug Administration Schedule , Female , Follow-Up Studies , Glycoproteins/blood , Humans , Hyperlipoproteinemia Type II/diagnosis , Linear Models , Lipoproteins, HDL/blood , Lipoproteins, LDL/blood , Male , Middle Aged , Probability , Prognosis , Reference Values , Risk Assessment , Severity of Illness Index , Treatment Outcome , Tunica Media/drug effects , Tunica Media/pathology
11.
Eur J Cardiovasc Prev Rehabil ; 10(6): 451-5, 2003 Dec.
Article in English | MEDLINE | ID: mdl-14671468

ABSTRACT

BACKGROUND: Measurement of intima-media thickness (IMT) is a well established surrogate marker for cardiovascular endpoints. We studied the long-term effects of statins on femoral IMT and plaque scoring in the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) study. METHODS AND RESULTS: Three hundred and twenty-five patients with familial hypercholesterolaemia were randomized to either atorvastatin 80 mg/day or simvastatin 40 mg/day. IMT was measured at baseline and at 2 years. At baseline, femoral IMT was 1.69 mm in the atorvastatin group and 1.61 mm in the simvastatin group; at 2 years, IMT increased by 0.06 mm (P=0.24) and 0.15 mm (P=0.012), respectively. No significant differences were obvious between these two treatment arms (P=0.26). Femoral plaques were present in 64.7% in the atorvastatin group and 56.1% in the simvastatin group at baseline; after 2 years, these proportions rose to 66.0% (P=0.47) and 67.3% (P=0.02), respectively (P=0.87 between treatment arms). Carotid plaques were present in 6.3% versus 4.9%; after 2 years, these percentages were 5.0% (P=0.48) versus 5.5% (P=0.71), respectively (P=0.90 between treatment arms). CONCLUSION: Our study indicates increased efficacy of atorvastatin 80 mg in retarding progression of atherosclerosis in the femoral artery compared with simvastatin 40 mg. Interestingly, in the carotid arteries these statins influenced IMT to a greater extent, whereas in the femoral artery the effects were more pronounced on plaque frequency. These findings underscore the generalized effects of lipid lowering on atherosclerosis.


Subject(s)
Anticholesteremic Agents/therapeutic use , Femoral Artery/pathology , Heptanoic Acids/therapeutic use , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Tunica Intima/pathology , Tunica Media/pathology , Arteriosclerosis/pathology , Arteriosclerosis/prevention & control , Atorvastatin , Carotid Arteries/pathology , Double-Blind Method , Female , Humans , Hyperlipoproteinemia Type II/drug therapy , Male , Middle Aged
13.
J Am Coll Cardiol ; 41(2): 275-9, 2003 Jan 15.
Article in English | MEDLINE | ID: mdl-12535822

ABSTRACT

OBJECTIVES: In the present study, we investigated the effects of statins on serum levels of soluble CD40 ligand (sCD40L) in patients with familial hypercholesterolemia (FH). BACKGROUND: Atherosclerotic disease seems to involve inflammatory and immunologic mechanisms, and sCD40L has recently been identified as one of the key players in the atherosclerotic process. HMG-Co A reductase inhibitors, statins, have been recognized as immunomodulators and reduce cardiovascular events and mortality, but the effects of statins on sCD40L has not been clarified. METHODS: In a randomized, double-blind, clinical trial, as part of the Atorvastatin versus Simvastatin on Atherosclerosis Progression (ASAP) trial, 110 patients with FH were given atorvastatin 80 mg/daily (n = 57) or simvastatin 40 mg/daily (n = 53) for two years. RESULTS: Our main findings were: 1) at baseline patients with FH had significantly higher (approximately 27-fold) serum levels of sCD40L than healthy controls; 2) statin therapy markedly decreased serum levels of sCD40L (approximately 40% reduction); 3) this decrease in sCD40L was found during both "aggressive" (i.e., atorvastatin) and "conventional" (i.e., simvastatin) statin therapy and was not correlated with the degree of reduction in cholesterol levels. CONCLUSIONS: Our findings may suggest enhanced CD40L-CD40 interaction in FH and that this inflammatory response may be downregulated by statins.


Subject(s)
CD40 Ligand/blood , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Atorvastatin , Coronary Artery Disease/blood , Double-Blind Method , Down-Regulation/drug effects , Female , Heptanoic Acids/administration & dosage , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/administration & dosage , Hyperlipoproteinemia Type II/blood , Male , Middle Aged , Pyrroles/administration & dosage , Simvastatin/administration & dosage , Treatment Outcome
14.
Atherosclerosis ; 165(2): 361-6, 2002 Dec.
Article in English | MEDLINE | ID: mdl-12417288

ABSTRACT

BACKGROUND: High sensitivity C-reactive protein (hs-CRP) has emerged as the best studied and most promising marker of inflammation in atherosclerotic vascular disease. MATERIALS AND METHODS: The ASAP (effects of Atorvastatin vs. Simvastatin on Atherosclerosis Progression) study was a 2-year randomised, double-blind trial with 325 familial hypercholesterolemia patients, treated with torvastatin 80 mg or imvastatin 40 mg. Intima media thickness (IMT) of carotid artery segments and hs-CRP levels were determined at baseline, 1 and 2 years. RESULTS: Baseline median hs-CRP values were 2.1 mg/l (interquartile range (IQR) 0.9-5.2) and 2.0 mg/l (IQR 0.8-3.0) and after 2 years these levels decreased to 1.1 mg/l (IQR 0.6-2.4) and 1.5 mg/l (IQR 0.6-3.0) in the atorvastatin 80 mg and simvastatin 40 mg group, respectively. These changes were significant within as well as between the two groups. No correlations were observed between change in hs-CRP after 2 years and change in lipids. A significant correlation was found in univariate analysis between the decrease of hs-CRP and the reduction of IMT. CONCLUSIONS: Our results show that atorvastatin 80 mg reduces hs-CRP levels to a greater extent than simvastatin 40 mg. Furthermore, we show that the extent of hs-CRP reduction is associated with the progression rate of the atherosclerotic process as measured by IMT.


Subject(s)
C-Reactive Protein/drug effects , Heptanoic Acids/therapeutic use , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipoproteinemia Type II/drug therapy , Pyrroles/therapeutic use , Simvastatin/therapeutic use , Adult , Atorvastatin , C-Reactive Protein/metabolism , Double-Blind Method , Female , Heptanoic Acids/pharmacology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/pharmacology , Hyperlipoproteinemia Type II/blood , Male , Middle Aged , Prospective Studies , Pyrroles/pharmacology , Simvastatin/pharmacology , Treatment Outcome , Tunica Intima/diagnostic imaging , Tunica Media/diagnostic imaging , Ultrasonography
15.
J Cardiovasc Risk ; 9(2): 89-95, 2002 Apr.
Article in English | MEDLINE | ID: mdl-12006916

ABSTRACT

Few things are better understood within the medical community than the relationship between elevated total and low-density lipoprotein cholesterol (LDL-C) levels, cardiovascular disease and death. There is consensus in the treatment guidelines of numerous national and international bodies that cholesterol levels in at-risk patients should be reduced to target levels that have been shown in population studies to be associated with low rates of coronary heart disease (CHD). However, dyslipidaemia continues to be underdiagnosed and undertreated. The 'landmark' statin trials have demonstrated unequivocally that effective lipid-lowering therapy significantly decreases CHD morbidity and mortality. Furthermore, these benefits of lipid-lowering therapy are not limited to middle-aged men, but extend across a broad range of patient populations. Recent trial data suggest that lowering LDL-C to target levels is possible in a substantial proportion of patients when statins are administered aggressively and results in a greater reduction in the risk of major coronary events. This reduction in events is seen in patients with stable coronary disease as well as those treated immediately after an acute coronary syndrome. Although strong clinical and angiographic evidence shows that intensive treatment prevents morbidity and saves lives, indications are that clinicians are still waiting too long to treat dyslipidaemia and when treatment is initiated it is often at inadequate dosages. Undertreatment of dyslipidaemia is an issue that the healthcare community can no longer ignore.


Subject(s)
Drug Therapy/statistics & numerical data , Cholesterol/blood , Coronary Disease/blood , Coronary Disease/drug therapy , Coronary Disease/etiology , Humans , Hydroxymethylglutaryl-CoA Reductase Inhibitors/therapeutic use , Hyperlipidemias/blood , Hyperlipidemias/complications , Hyperlipidemias/drug therapy , Hypolipidemic Agents/therapeutic use
16.
Curr Opin Lipidol ; 13(2): 165-71, 2002 Apr.
Article in English | MEDLINE | ID: mdl-11891419

ABSTRACT

Heterozygous familial hypercholesterolaemia is among the most common inherited dominant disorders, and is characterized by severely elevated LDL-cholesterol levels and premature cardiovascular disease. Although the cause of familial hypercholesterolaemia is monogenic, there is a substantial variation in the onset and severity of atherosclerotic disease symptoms. Additional atherogenic risk factors of environmental, metabolic and genetic origin, in conjunction with the LDL receptor defect, are presumed to influence the clinical phenotype in familial hypercholesterolaemia. The present review discusses recent developments in this field.


Subject(s)
Hyperlipoproteinemia Type II/genetics , Receptors, LDL/physiology , Chromosome Deletion , Genetic Variation , Humans , Hyperlipoproteinemia Type II/therapy , Lipid Metabolism , Mutation , Phenotype
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