RESUMO
The Post-CABG trial was designed to assess the effects of 2 different lipid lowering strategies and low dose warfarin vs placebo (2 x 2 factorial) design on the progression of atherosclerosis in saphenous vein grafts. Atherosclerotic progression was determined by comparing baseline and follow-up angiograms (mean interval: 4.3 years) using quantitative angiography. Significant progression of disease in SVG's was reduced with the aggressive lipid lowering strategy compared to the moderate strategy; significant progression in SVG's was not altered by low dose warfarin. The beneficial effects on angiographic changes were demonstrated in multiple subgroups of participants in the trial. The composite clinical end point of death, MI, stroke, PTCA or repeat CABG was analyzed at the end of the trial and 3 years (extended follow-up) after closure of the angiographic trial. At the time of the extended follow-up the aggressive lipid strategy was associated with reduced clinical events; low dose warfarin was also associated with reduced clinical events.
Assuntos
Ponte de Artéria Coronária , Doença das Coronárias/prevenção & controle , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
The highest risk of a recurrent event in patients with acute coronary syndromes (ACS) occurs in the first month, with the rates of reported events ranging from 10% to 25%. Statins are the cornerstone of lipid-lowering therapy for the long-term care of patients with stable atherosclerotic disease. More recent accumulated data from several trials now show that statin therapy can also help reduce cardiovascular risk in unstable disease. These studies evaluated the effects of statin therapy begun before discharge, with the Myocardial Ischemia with Aggressive Cholesterol Lowering (MIRACL) trial showing that therapy could be started as early as 24 hours after onset with measurable clinical benefit. Registry data also suggest that long-term compliance may be improved in patients with a predischarge statin prescription compared with a postdischarge statin prescription. This is because many patients discharged without a statin prescription are either lost to further medical follow-up or do not receive a statin prescription from their primary care provider. The Third Report of the Expert Panel on Detection, Evaluation, and Treatment of High Blood Cholesterol in Adults (ATP III), which constitutes the updated clinical guidelines of the National Cholesterol Education Program (NCEP), recommends that lipid-lowering drug therapy be initiated at hospital discharge. ATP III also provides important information on the goals of lipid-lowering therapy in patients after ACS. The challenge for the specialist is to establish a predischarge plan that includes maximal dosing to achieve aggressive target goals and to work with the patient's primary care provider to maintain these goals long-term.
Assuntos
Doença das Coronárias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , LDL-Colesterol/sangue , Ponte de Artéria Coronária , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Fidelidade a Diretrizes , Hospitalização , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Alta do Paciente , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of two lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol levels to a mean yearly cholesterol level from 93 to 97 mg/dL compared with a moderate reduction to a level of 132 to 136 mg/dL decreased the progression of atherosclerosis in saphenous vein grafts. Low-dose anticoagulation did not affect progression. This secondary analysis tested the hypothesis that a similar decrease in progression of atherosclerosis would also be present in native coronary arteries as measured in the left main coronary artery (LMCA). METHODS AND RESULTS: A sample of 402 patients was randomly selected from 1102 patients who had baseline and follow-up views of the LMCA suitable for analysis. Patients treated with the aggressive lipid-lowering strategy had less progression of atherosclerosis in the LMCA as measured by changes in minimum (P=0.0003) lumen diameter or the maximum percent stenosis (P=0.001), or the presence of substantial progression (P=0.008), or vascular occlusion (P=0.005) when compared with the moderate strategy. CONCLUSIONS: A strategy of aggressive lipid lowering results in significantly less atherosclerosis progression than a moderate approach in LMCAs.
Assuntos
Anticolesterolemiantes/uso terapêutico , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico , Doença da Artéria Coronariana/terapia , Vasos Coronários/efeitos dos fármacos , Anticoagulantes/uso terapêutico , LDL-Colesterol/sangue , Resina de Colestiramina/uso terapêutico , Angiografia Coronária , Doença da Artéria Coronariana/sangue , Vasos Coronários/cirurgia , Progressão da Doença , Feminino , Seguimentos , Humanos , Lipídeos/sangue , Lovastatina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Período Pós-Operatório , Veia Safena/transplante , Resultado do TratamentoRESUMO
BACKGROUND: Animal and observational epidemiologic studies have reported that estrogens may increase the risk for gallstones. No major clinical trials have examined the effect of estrogen plus progestin therapy in postmenopausal women on the risk for biliary tract surgery. OBJECTIVE: To determine the effect of estrogen plus progestin on the risk for biliary tract surgery in postmenopausal women with known coronary artery disease. DESIGN: Randomized, double-blind placebo-controlled trial of postmenopausal hormone therapy for coronary heart disease. SETTING: 20 U.S. clinical centers. PARTICIPANTS: 2253 postmenopausal women with a gallbladder, 44 to 79 years of age at baseline, in the Heart and Estrogen/progestin Replacement Study (HERS). INTERVENTION: Conjugated equine estrogens, 0.625 mg, plus medroxyprogesterone acetate, 2.5 mg, daily in one tablet or identical placebo. MEASUREMENTS: Documented biliary tract surgery. RESULTS: A total of 147 women (7%) were hospitalized for biliary tract surgery in HERS. Treatment with estrogen plus progestin resulted in a marginally significant 38% increase in the relative risk for biliary tract surgery (P = 0.05). A small absolute difference in risk suggested that for every 185 women treated with estrogen plus progestin, one additional woman had biliary tract surgery per year. After adjustment for baseline and in-study statin use, the association was attenuated further (P = 0.09). After adjustment for treatment assignment and other variables, increased body mass index, fibric acid use, and a history of nonsurgical gallbladder disease were associated with an increased risk for biliary tract surgery, whereas statin use was associated with a decreased risk (for each comparison, P < 0.05). CONCLUSION: Estrogen plus progestin therapy among postmenopausal women with known coronary disease resulted in a marginally significant increase in the risk for biliary tract surgery.
Assuntos
Colelitíase/etiologia , Colelitíase/cirurgia , Doença das Coronárias/complicações , Estrogênios/efeitos adversos , Terapia de Reposição Hormonal/efeitos adversos , Pós-Menopausa , Progestinas/efeitos adversos , Adulto , Idoso , Doença das Coronárias/prevenção & controle , Terapia de Reposição de Estrogênios/efeitos adversos , Feminino , Humanos , Pessoa de Meia-Idade , Fatores de RiscoRESUMO
The Minnesota Regional Peripheral Arterial Disease Screening Program was designed to define the efficacy of community PAD detection efforts, to assess the disease-specific and health-related morbidity, to assess PAD awareness rates, and to determine the magnitude of atherosclerosis disease risk factors and the intensity of their management. The target population was recruited via mass media efforts directed at individuals over 50 years of age and those with leg pain with ambulation. Screening sessions included assessments of the ankle-brachial index, blood pressure, fasting lipid profile, and use of validated tools to detect symptomatic claudication (by the Modified WHO-Edinburgh Claudication Questionnaire), walking impairment (Walking Impairment Questionnaire - WIQ), quality of life (MOS SF-36), PAD awareness, and the intensity of PAD medical therapeutic interventions. PAD was defined as any ankle-brachial index < or =0.85 or a history of lower extremity revascularization. The program evaluated 347 individuals and identified 92 subjects with PAD and 255 subjects without PAD, yielding a detection rate of 26.5%. Individuals with PAD were older, tended to have higher blood pressures, and had a significant walking impairment and an impaired health-related quality of life compared with the non-PAD subjects. Current rates of tobacco use were low. Lipid-lowering, estrogen replacement, anti-platelet, and antihypertensive medications and exercise therapies were underutilized in the PAD cohort. Peripheral arterial disease awareness was low in these community-identified patients. This Program demonstrated that individuals with PAD can be efficiently identified within the community, but that current standards of medical care are low. These data can assist in the future development of PAD awareness, education, and treatment programs.
Assuntos
Arteriosclerose/diagnóstico , Doenças Vasculares Periféricas/diagnóstico , Idoso , Arteriosclerose/epidemiologia , Arteriosclerose/terapia , Pressão Sanguínea/fisiologia , Estudos de Coortes , Serviços de Saúde Comunitária/normas , Comorbidade , Terapia por Exercício , Extremidades/irrigação sanguínea , Extremidades/diagnóstico por imagem , Feminino , Seguimentos , Humanos , Claudicação Intermitente/complicações , Lipídeos/sangue , Masculino , Programas de Rastreamento , Minnesota/epidemiologia , Doenças Vasculares Periféricas/epidemiologia , Doenças Vasculares Periféricas/terapia , Prevalência , Qualidade de Vida , Radiografia , Fatores de Risco , Índice de Gravidade de Doença , CaminhadaRESUMO
CONTEXT: Peripheral arterial disease (PAD) is a manifestation of systemic atherosclerosis that is common and is associated with an increased risk of death and ischemic events, yet may be underdiagnosed in primary care practice. OBJECTIVE: To assess the feasibility of detecting PAD in primary care clinics, patient and physician awareness of PAD, and intensity of risk factor treatment and use of antiplatelet therapies in primary care clinics. DESIGN AND SETTING: The PAD Awareness, Risk, and Treatment: New Resources for Survival (PARTNERS) program, a multicenter, cross-sectional study conducted at 27 sites in 25 cities and 350 primary care practices throughout the United States in June-October 1999. PATIENTS: A total of 6979 patients aged 70 years or older or aged 50 through 69 years with history of cigarette smoking or diabetes were evaluated by history and by measurement of the ankle-brachial index (ABI). PAD was considered present if the ABI was 0.90 or less, if it was documented in the medical record, or if there was a history of limb revascularization. Cardiovascular disease (CVD) was defined as a history of atherosclerotic coronary, cerebral, or abdominal aortic aneurysmal disease. MAIN OUTCOME MEASURES: Frequency of detection of PAD; physician and patient awareness of PAD diagnosis; treatment intensity in PAD patients compared with treatment of other forms of CVD and with patients without clinical evidence of atherosclerosis. RESULTS: PAD was detected in 1865 patients (29%); 825 of these (44%) had PAD only, without evidence of CVD. Overall, 13% had PAD only, 16% had PAD and CVD, 24% had CVD only, and 47% had neither PAD nor CVD (the reference group). There were 457 patients (55%) with newly diagnosed PAD only and 366 (35%) with PAD and CVD who were newly diagnosed during the survey. Eighty-three percent of patients with prior PAD were aware of their diagnosis, but only 49% of physicians were aware of this diagnosis. Among patients with PAD, classic claudication was distinctly uncommon (11%). Patients with PAD had similar atherosclerosis risk factor profiles compared with those who had CVD. Smoking behavior was more frequently treated in patients with new (53%) and prior PAD (51%) only than in those with CVD only (35%; P <.001). Hypertension was treated less frequently in new (84%) and prior PAD (88%) only vs CVD only (95%; P <.001) and hyperlipidemia was treated less frequently in new (44%) and prior PAD (56%) only vs CVD only (73%, P<.001). Antiplatelet medications were prescribed less often in patients with new (33%) and prior PAD (54%) only vs CVD only (71%, P<.001). Treatment intensity for diabetes and use of hormone replacement therapy in women were similar across all groups. CONCLUSIONS: Prevalence of PAD in primary care practices is high, yet physician awareness of the PAD diagnosis is relatively low. A simple ABI measurement identified a large number of patients with previously unrecognized PAD. Atherosclerosis risk factors were very prevalent in PAD patients, but these patients received less intensive treatment for lipid disorders and hypertension and were prescribed antiplatelet therapy less frequently than were patients with CVD. These results demonstrate that underdiagnosis of PAD in primary care practice may be a barrier to effective secondary prevention of the high ischemic cardiovascular risk associated with PAD.
Assuntos
Arteriosclerose/prevenção & controle , Medicina de Família e Comunidade , Conhecimentos, Atitudes e Prática em Saúde , Idoso , Arteriosclerose/diagnóstico , Arteriosclerose/epidemiologia , Arteriosclerose/terapia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/prevenção & controle , Estudos Transversais , Feminino , Humanos , Claudicação Intermitente/diagnóstico , Claudicação Intermitente/terapia , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/uso terapêutico , Fatores de Risco , Ultrassonografia DopplerRESUMO
OBJECTIVE: At higher doses, simvastatin has been shown to produce significantly greater increases in high-density lipoprotein (HDL) cholesterol and apolipoprotein (apo) A-I than atorvastatin. To extend and confirm these findings, a 36-week, randomized, double-blind, dose-titration study was performed in 826 hypercholesterolemic patients to compare the effects of simvastatin and atorvastatin on HDL cholesterol, apo A-I, and clinical and laboratory safety. PRIMARY HYPOTHESIS: Simvastatin, across a range of doses, will be more effective than atorvastatin at raising HDL cholesterol and apo A-I levels. METHODS: A total of 826 hypercholesterolemic patients were enrolled in this double-blind, randomized, parallel, 36-week, dose-escalation study. Patients randomized to simvastatin received 40 mg/day for the first 6 weeks, 80 mg/day for the next 6 weeks, and remained on 80 mg/day for the final 24 weeks. Patients randomized to atorvastatin received 20 mg/day for the first 6 weeks, 40 mg/day for the next 6 weeks, and 80 mg/day for the remaining 24 weeks. RESULTS: During the first 12 weeks of the study, simvastatin increased HDL cholesterol and apo A-I more than the comparative doses of atorvastatin, while producing slightly lower reductions in low-density lipoprotein (LDL) cholesterol and triglycerides. At the maximal dose comparison, simvastatin 80 mg and atorvastatin 80 mg, the HDL cholesterol and apo A-I differences favoring simvastatin were larger than at the lower doses. In addition, at the maximal dose comparison, the incidence of drug-related clinical adverse experiences was approximately two-fold higher with atorvastatin 80 mg than with simvastatin 80 mg (23 versus 12%, p < 0.001), due predominantly to a greater incidence of gastrointestinal symptoms with atorvastatin (10 versus 3%, p < 0.001). The incidence of clinically significant alanine aminotransferase elevations was also higher with atorvastatin 80 mg than with simvastatin 80 mg (3.8 versus 0.5%, p < 0.010), especially in women (6.0 versus 0.6%). CONCLUSIONS: At the doses compared in this study, simvastatin led to greater increases in HDL cholesterol and apo A-I levels than atorvastatin. At the maximum dose comparison, there were fewer drug-related gastrointestinal symptoms and clinically significant aminotransferase elevations with simvastatin.
Assuntos
Anticolesterolemiantes/uso terapêutico , Ácidos Heptanoicos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hipercolesterolemia/tratamento farmacológico , Lipídeos/sangue , Pirróis/uso terapêutico , Sinvastatina/uso terapêutico , Adulto , Idoso , Anticolesterolemiantes/administração & dosagem , Anticolesterolemiantes/efeitos adversos , Apolipoproteína A-I/sangue , Atorvastatina , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Método Duplo-Cego , Feminino , Ácidos Heptanoicos/administração & dosagem , Ácidos Heptanoicos/efeitos adversos , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Hipercolesterolemia/sangue , Masculino , Pessoa de Meia-Idade , Pirróis/administração & dosagem , Pirróis/efeitos adversos , Sinvastatina/administração & dosagem , Sinvastatina/efeitos adversos , Resultado do Tratamento , Estados UnidosRESUMO
BACKGROUND: Since coronary artery bypass graft patients remain at risk of coronary artery and bypass graft occlusion after successful surgery, adjunct treatment regimens are under investigation. In a study of the patients of the multicenter Post Coronary Artery Bypass Graft (Post CABG) Trial, 1 mg warfarin was found to have no important effect on coagulation parameters. STUDY DESIGN: The effects of 1, 2 and 3 mg warfarin were evaluated at six-week intervals in 20 Post CABG Trial patients receiving titrated dose increases in comparison to 20 patients of similar age, gender and time from CABG treated with placebo. RESULTS: International normalized ratio (INR) values increased with warfarin dose increments for 1, 2, and 3 mg, respectively (0.95+/-0.16, 1.08+/-0.19, and 1.34+/-0.39) and in comparison to placebo treated patients (dosextreatment p<0.001). Factor VII coagulant activity decreased with warfarin titration (1 mg, 119.0+/-18.3 %; 2 mg, 100.6+/-32.8 %; 3 mg, 95.0+/-27.8 %) and in comparison to placebo (dosextreatment p=0.008). Levels of prothrombin fragment F1.2, tissue plasminogen activator, fibrinogen and von Willebrand factor were unchanged with warfarin dose increments and in comparison to placebo. CONCLUSIONS: At doses up to 3 mg, warfarin acts on the INR through a reduction of factor VII with no effect on the fibrinolytic system, fibrinogen or von Willebrand factor. At these doses F1.2 did not document reduced coagulation activity. The observations of this study were consistent with the decision in the Post CABG Trial to increase the warfarin dose above 1 mg to achieve a distinct effect of warfarin that was less than full anticoagulation.
Assuntos
Anticoagulantes/uso terapêutico , Ponte de Artéria Coronária , Doença das Coronárias/prevenção & controle , Oclusão de Enxerto Vascular/prevenção & controle , Complicações Pós-Operatórias/prevenção & controle , Trombose/prevenção & controle , Varfarina/uso terapêutico , Adulto , Idoso , Anticoagulantes/administração & dosagem , Anticoagulantes/efeitos adversos , Aspirina/administração & dosagem , Aspirina/uso terapêutico , Doença das Coronárias/sangue , Doença das Coronárias/cirurgia , Relação Dose-Resposta a Droga , Quimioterapia Combinada , Fator VII/análise , Feminino , Fibrinogênio/análise , Humanos , Coeficiente Internacional Normatizado , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/análise , Hemorragia Pós-Operatória/induzido quimicamente , Protrombina/análise , Recidiva , Veia Safena/patologia , Veia Safena/transplante , Ativador de Plasminogênio Tecidual/análise , Resultado do Tratamento , Varfarina/administração & dosagem , Varfarina/efeitos adversos , Fator de von Willebrand/análiseRESUMO
BACKGROUND: An increased prevalence of hyperhomocysteinemia with an increased incidence of cardiovascular disease events has been reported among stable renal transplant recipients (RTRs). Preliminary studies in a small number of these individuals have shown that serum creatinine and cystatin C, both markers of kidney function and glomerular filtration rate, are independent determinants of fasting tHcy concentrations; however, determinants of tHcy concentrations after a methionine load have not been studied. METHODS: We determined the prevalence of both fasting and 4-h post-methionine load (PML) tHcy concentrations in 78 stable RTRs and compared the role of cystatin C with the role of serum creatinine as determinants of fasting and PML tHcy. RESULTS: Of the 78 RTRs, 21 (26.9%) had fasting and PML tHcy within the respective reference intervals, and 57 (73.1%) had increased plasma tHcy. Of these 57 RTRs, 22 had fasting hyperhomocysteinemia, 9 had PML hyperhomocysteinemia, and 26 had combined hyperhomocysteinemia (both fasting and PML). Unadjusted Pearson correlations showed that fasting plasma tHcy correlated with both cystatin C (r = 0.564; P <0.001) and creatinine (r = 0.519; P <0.001) and that increases in PML tHcy modestly correlated with cystatin (r = 0.205; P = 0.072), but not creatinine (r = 0.057; P = 0.624). General linear regression modeling with stepwise analysis of covariance showed that both cystatin C (partial R = 0.554; P <0.001) and creatinine (partial R = 0.535; P <0.001) were independent predictors of fasting tHcy, but of the two, only cystatin C (partial R = 0.242; P = 0.035) was an independent predictor of increased PML tHcy. CONCLUSIONS: Clinically stable RTRs have an excess prevalence of moderate hyperhomocysteinemia, and additional cases can be detected by methionine loading. Both creatinine and cystatin C are independent predictors of fasting tHcy in these individuals; however, only cystatin C is a determinant of tHcy concentration after a methionine load, probably because cystatin C is a more sensitive marker of glomerular filtration rate than serum creatinine.
Assuntos
Cistatinas/sangue , Homocisteína/sangue , Hiper-Homocisteinemia/diagnóstico , Transplante de Rim/efeitos adversos , Metionina , Adulto , Idoso , Biomarcadores/sangue , Cistatina C , Jejum , Feminino , Humanos , Hiper-Homocisteinemia/etiologia , Masculino , Pessoa de Meia-Idade , Análise de RegressãoRESUMO
Although many investigators have evaluated the technical variability of quantitative angiographic techniques used to study atherosclerosis regression in native coronary arteries, few have studied the variability inherent in repeated studies of atherosclerotic saphenous vein grafts. This study describes 2 studies performed during the course of the Post Coronary Artery Bypass Graft (CABG) Clinical Trial that were designed to assess the reproducibility of: (1) repeated angiographic views within a short time period; and (2) reproducibility of the total process of quantitative analysis of saphenous vein graft angiograms. Statistical methods are described that provide a more meaningful assessment of the impact of measurement variability in the analytic process versus the variability related to changes induced by pharmacologic interventions. One such method, the increase in standard deviation (SD) among patients (ISDP), showed that repeated angiographic views increased the variability of calculation of lesion minimal diameter by 1.5%, whereas the ISDP for repetition of the entire process of quantitative angiographic readings increased variability 6.4%. These data from the Post CABG trial reveal that technical variability is small and has negligible impact on the conclusions of the study.
Assuntos
Angiografia Coronária/normas , Ponte de Artéria Coronária , Doença da Artéria Coronariana/diagnóstico por imagem , Doença da Artéria Coronariana/cirurgia , Progressão da Doença , Seguimentos , Humanos , Reprodutibilidade dos Testes , Veia Safena/diagnóstico por imagem , Veia Safena/transplanteRESUMO
SCH 48461, an inhibitor of gastrointestinal absorption of cholesterol, was evaluated for its effects on lipid parameters in patients with primary hypercholesterolemia in a multicenter, double-blind, randomized, parallel-group study. Following the baseline phase, which consisted of a 2- to 10-week drug washout and dietary stabilization phase and a 4-week placebo lead-in (placebo baseline phase), 190 patients were randomized to an 8-week double-blind active drug (SCH 48461 1, 6.25, 25, 100, 200, or 400 mg) or 40 mg lovastatin once daily each morning or placebo treatment phase. By week 2, patients who received SCH 48461 6.25 to 400 mg or lovastatin demonstrated greater reduction from baseline in directly measured low-density lipoprotein cholesterol (LDL-C) levels than patients in the placebo group (p < or = 0.03). Overall, the percent reductions in LDL-C from baseline increased as the dose of SCH 48461 increased, with 0.6% to 15.5% reductions from the minimum dose of 1 mg to the maximum dose of 400 mg. Lovastatin 40 mg/day reduced LDL-C by 30.7% (p < 0.01). Statistically significant decreases were also seen for total cholesterol and apolipoprotein B (apo B) with doses of 25 mg to 400 mg of SCH 48461 and lovastatin. SCH 48461 was well tolerated. There was a similar incidence of adverse events in each SCH 48461- or lovastatin-treated group compared to placebo. This study demonstrated a clinically and statistically significant cholesterol-lowering effect of SCH 48461 in patients with primary hypercholesterolemia.
Assuntos
Anticolesterolemiantes/uso terapêutico , Azetidinas/uso terapêutico , LDL-Colesterol/sangue , Hipercolesterolemia/tratamento farmacológico , Anticolesterolemiantes/efeitos adversos , Apolipoproteína A-I/sangue , Azetidinas/efeitos adversos , HDL-Colesterol/sangue , Relação Dose-Resposta a Droga , Método Duplo-Cego , Feminino , Humanos , Hipercolesterolemia/sangue , Lovastatina/uso terapêutico , Masculino , Pessoa de Meia-Idade , Placebos , Triglicerídeos/sangueRESUMO
BACKGROUND: A fairly immediate reduction in angina pectoris symptoms after cholesterol lowering has been described. Our previous findings in rabbits and in a four-patient human pilot study indicated the existence of an RBC membrane barrier to oxygen (O2) transport in the presence of hypercholesterolemia. Our current objective was to determine whether, and to what extent, the plasma cholesterol concentration is an influencing factor in RBC O2 release and cellular O2 availability. STUDY DESIGN: In an unique O2 diffusion analysis system, blood samples from 100 patients referred for lipid modification were analyzed. After 1 to 2 minutes of mixing in our diffusion analysis system, the next 1 to 2 minutes of circulation is comparable with 1 to 2 seconds of myocardial capillary flow. RBC O2 diffusion was defined by the depletion rate of total O2 content in blood from full O2 saturation (98%) to desaturation (approximately 60%). Relative tissue O2 availability was defined as the percentage decrease in O2 availability between the high-cholesterol group and the low-cholesterol group. RESULTS: The 100 patients were divided almost equally into two groups on the basis of plasma cholesterol ranges of 175 to 229 mg/dL (n=49) and 230 to 299 mg/dL (n = 51). The mean cholesterol concentrations and percentage increases in the high-cholesterol group over the low-cholesterol group were: for plasma, 206 +/- 0.3 and 256 +/- 0.4 mg/dL, 24.3% (p < 0.001); for RBCs, 93 +/- 0.2 and 106 +/- 0.2mg/dL, 14.0% (p < 0.001); and for RBC membranes, 41 +/- 0.1 and 54 +/- 0.2mg/dL, 31.7% (p < 0.001). The blood O2 diffusion curves were distinctly different between the high- and the low-cholesterol groups (p < 0.05). Blood O2 diffusion, defined by the blood O2 diffusion curves, was inversely proportional to the plasma, RBC, and RBC-membrane cholesterol concentrations. The relative tissue O2 availability, after a circulation period of more than 3 minutes in the diffusion system, showed a decrease of 17.5% (p < 0.05) between the plasma cholesterol groups. In comparing the two plasma cholesterol concentration extremes of less than 200mg/dL (n= 14) and greater than 275 mg/dL (n= 11) after a circulation period of more than 3 minutes in the diffusion system, we found a decrease in relative tissue O2 availability of 35.8% (p < 0.05). CONCLUSIONS: The plasma cholesterol concentration may be an influencing factor in RBC-membrane cholesterol content, which, in turn, may regulate RBC-membrane O2 transport, RBC O2 release, and cellular O2 availability. The implications of this work include the addition of angina pectoris control to the indications for appropriate lipid modification and the development of an in vitro blood stress test to replace patient cardiac stress testing.
Assuntos
Colesterol/sangue , Eritrócitos/metabolismo , Oxigênio/metabolismo , Difusão , Membrana Eritrocítica/metabolismo , Hematócrito , Humanos , Técnicas In VitroRESUMO
BACKGROUND: Patients with peripheral arterial disease (PAD) are at an increased risk of cardiovascular mortality and morbidity and thus are an excellent group in whom to evaluate the feasibility and the effect of an aggressive multifactorial intervention on atherosclerotic vascular disease risk factors. The Arterial Disease Multiple Intervention Trial (ADMIT) was designed to determine the efficacy, safety, and compliance of an multifactorial therapy on selected atherosclerotic disease risk factors in patients with PAD. METHODS: By a 2 x 2 x 2 factorial design, eligible participants (N = 468) were randomly assigned to low-dose warfarin, antioxidant vitamins, and niacin or its corresponding placebo, and followed up for 1 year. All participants were encouraged to use aspirin. Pravastatin was added to the drug regimen for those who needed to reduce LDL cholesterol to recommended levels. RESULTS: Niacin increased HDL cholesterol levels by 30%, with the majority of effect achieved at a dosage of 500 mg twice daily. Warfarin had an anticoagulant effect. The antioxidant vitamins resulted in a significant increase in vitamin E, C, and beta-carotene plasma levels. Overall, compliance was high and few adverse effects were reported. CONCLUSIONS: ADMIT demonstrates that it is both feasible and safe to modify multiple atherosclerotic disease risk factors effectively with intensive combination therapy in patients with PAD.
Assuntos
Anticoagulantes/uso terapêutico , Antioxidantes/uso terapêutico , Arteriosclerose/etiologia , Arteriosclerose/prevenção & controle , Niacina/uso terapêutico , Vitaminas/uso terapêutico , Varfarina/uso terapêutico , Idoso , Anticolesterolemiantes/uso terapêutico , Arteriosclerose/sangue , Aspirina/administração & dosagem , LDL-Colesterol/sangue , Estudos de Viabilidade , Feminino , Fibrinolíticos/administração & dosagem , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/administração & dosagem , Pravastatina/uso terapêutico , Fatores de Risco , Automedicação , Fatores de Tempo , Resultado do Tratamento , Triglicerídeos/sangueRESUMO
BACKGROUND: The results of angiographic studies have suggested that calcium channel-blocking agents may prevent new coronary lesion formation, the progression of minimal lesions, or both. METHODS AND RESULTS: The Prospective Randomized Evaluation of the Vascular Effects of Norvasc Trial (PREVENT) was a multicenter, randomized, placebo-controlled, double-masked clinical trial designed to test whether amlodipine would slow the progression of early coronary atherosclerosis in 825 patients with angiographically documented coronary artery disease. The primary outcome was the average 36-month angiographic change in mean minimal diameters of segments with a baseline diameter stenosis of 30%. A secondary hypothesis was whether amlodipine would reduce the rate of atherosclerosis in the carotid arteries as assessed with B-mode ultrasonography, which measured intimal-medial thicknesses (IMT). The rates of clinical events were also monitored. The placebo and amlodipine groups had nearly identical average 36-month reductions in the minimal diameter: 0.084 versus 0.095 mm, respectively (P:=0.38). In contrast, amlodipine had a significant effect in slowing the 36-month progression of carotid artery atherosclerosis: the placebo group experienced a 0.033-mm increase in IMT, whereas there was a 0. 0126-mm decrease in the amlodipine group (P:=0.007). There was no treatment difference in the rates of all-cause mortality or major cardiovascular events, although amlodipine use was associated with fewer cases of unstable angina and coronary revascularization. CONCLUSIONS: Amlodipine has no demonstrable effect on angiographic progression of coronary atherosclerosis or the risk of major cardiovascular events but is associated with fewer hospitalizations for unstable angina and revascularization.
Assuntos
Anlodipino/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Doença da Artéria Coronariana/fisiopatologia , Idoso , Doença da Artéria Coronariana/diagnóstico por imagem , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RadiografiaRESUMO
CONTEXT: Although niacin increases low levels of high-density lipoprotein cholesterol (HDL-C), which frequently accompany diabetes, current guidelines do not recommend use of niacin in patients with diabetes because of concerns about adverse effects on glycemic control; however, this is based on limited clinical data. OBJECTIVE: To determine the efficacy and safety of lipid-modifying dosages of niacin in patients with diabetes. DESIGN AND SETTING: Prospective, randomized placebo-controlled clinical trial conducted in 6 clinical centers from August 1993 to December 1995. PARTICIPANTS: A total of 468 participants, including 125 with diabetes, who had diagnosed peripheral arterial disease. INTERVENTIONS: After an active run-in period, participants were randomly assigned to receive niacin (crystalline nicotinic acid), 3000 mg/d or maximum tolerated dosage (n = 64 with diabetes; n = 173 without diabetes), or placebo (n = 61 with diabetes; n = 170 without diabetes) for up to 60 weeks (12-week active run-in and 48-week double-blind). MAIN OUTCOME MEASURES: Plasma lipoprotein, glucose, hemoglobin A(1c) (HbA(1c)), alanine aminotransferase, and uric acid levels; hypoglycemic drug use; compliance; and adverse events, in patients with diabetes vs without who were receiving niacin vs placebo. RESULTS: Niacin use significantly increased HDL-C by 29% and 29% and decreased triglycerides by 23% and 28% and low-density lipoprotein cholesterol (LDL-C) by 8% and 9%, respectively, in participants with and without diabetes (P<.001 for niacin vs placebo for all). Corresponding changes in participants receiving placebo were increases of 0% and 2% in HDL-C and increases of 7% and 0% in triglycerides, and increases of 1% and 1% in LDL-C. Glucose levels were modestly increased by niacin (8.7 and 6.3 mg/dL [0.4 and 0.3 mmol/L]; P =.04 and P<.001) in participants with and without diabetes, respectively. Levels of HbA(1c) were unchanged from baseline to follow-up in participants with diabetes treated with niacin. In participants with diabetes treated with placebo, HbA(1c) decreased by 0.3% (P =.04 for difference). There were no significant differences in niacin discontinuation, niacin dosage, or hypoglycemic therapy in participants with diabetes assigned to niacin vs placebo. CONCLUSIONS: Our study suggests that lipid-modifying dosages of niacin can be safely used in patients with diabetes and that niacin therapy may be considered as an alternative to statin drugs or fibrates for patients with diabetes in whom these agents are not tolerated or fail to sufficiently correct hypertriglyceridemia or low HDL-C levels. JAMA. 2000;284:1263-1270
Assuntos
Glicemia , Diabetes Mellitus/tratamento farmacológico , Angiopatias Diabéticas/tratamento farmacológico , Hipolipemiantes/uso terapêutico , Lipídeos/sangue , Lipoproteínas/sangue , Niacina/uso terapêutico , Doenças Vasculares Periféricas/tratamento farmacológico , Vasodilatadores/uso terapêutico , Idoso , Complicações do Diabetes , Diabetes Mellitus/sangue , Angiopatias Diabéticas/sangue , Angiopatias Diabéticas/complicações , Método Duplo-Cego , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Doenças Vasculares Periféricas/sangue , Doenças Vasculares Periféricas/complicações , Estudos ProspectivosRESUMO
BACKGROUND: The Post Coronary Artery Bypass Graft Trial, designed to compare the effects of 2 lipid-lowering regimens and low-dose anticoagulation versus placebo on progression of atherosclerosis in saphenous vein grafts of patients who had had CABG surgery, demonstrated that aggressive lowering of LDL cholesterol (LDL-C) levels to <100 mg/dL compared with a moderate reduction to 132 to 136 mg/dL decreased the progression of atherosclerosis in grafts. Low-dose anticoagulation did not significantly affect progression. METHODS AND RESULTS: Approximately 3 years after the last trial visit, Clinical Center Coordinators contacted each patient by telephone to ascertain the occurrence of cardiovascular events and procedures. The National Death Index was used to ascertain vital status for patients who could not be contacted. Vital status was established for all but 3 of 1351 patients. Information on nonfatal events was available for 95% of surviving patients. A 30% reduction in revascularization procedures and 24% reduction in a composite clinical end point were observed in patients assigned to aggressive strategy compared with patients assigned to moderate strategy during 7.5 years of follow-up, P=0. 0006 and 0.001, respectively. Reductions of 35% in deaths and 31% in deaths or myocardial infarctions with low-dose anticoagulation compared with placebo were also observed, P=0.008 and 0.003, respectively. CONCLUSIONS: -The long-term clinical benefit observed during extended follow-up in patients assigned to the aggressive strategy is consistent with the angiographic findings of delayed atherosclerosis progression in grafts observed during the trial. The apparent long-term benefit of low-dose warfarin remains unexplained.
Assuntos
Anticolesterolemiantes/administração & dosagem , Anticoagulantes/administração & dosagem , Ponte de Artéria Coronária , Doença das Coronárias/tratamento farmacológico , Doença das Coronárias/cirurgia , Varfarina/administração & dosagem , Adulto , Idoso , LDL-Colesterol/sangue , Doença das Coronárias/mortalidade , Método Duplo-Cego , Seguimentos , Humanos , Tábuas de Vida , Pessoa de Meia-Idade , Infarto do Miocárdio/tratamento farmacológico , Infarto do Miocárdio/mortalidade , Infarto do Miocárdio/cirurgia , Resultado do TratamentoRESUMO
OBJECTIVE: Clinicians often recommend that intake of all meat, particularly red meat, be reduced in conjunction with a low-fat, low-cholesterol diet to reduce low-density lipoprotein (LDL) cholesterol. This study was designed to determine the long-term effects of lean red meat (beef, veal and pork) compared to lean white meat (poultry and fish) consumption on lipoprotein concentrations in free-living hypercholesterolemic subjects consuming a National Cholesterol Education Program (NCEP) Step I diet. METHODS: A randomized, crossover design was utilized. Hypercholesterolemic men and women (LDL cholesterol between 3.37 and 4.92 mmol/L) (triglycerides <3.96 mmol/L) (n = 145) were counseled to consume > or =80% of their 170 g/d meat intake as either lean red meat or lean white meat for two 36-week phases, separated by a four-week washout period of free meat selection. Subjects were instructed to follow an NCEP Step I diet throughout the study. RESULTS: There were no significant differences in lipid concentrations between the lean red meat and lean white meat phases. LDL cholesterol was 4.02+/-0.04 (SEM) and 4.01+/-0.04 mmol/L in the white and red phases, respectively; this represented a decrease of approximately 2% from baseline concentrations (p < 0.01). Total cholesterol also declined by 1% from baseline (p < 0.05), and high-density lipoprotein (HDL) cholesterol rose over the study period by approximately 2% to approximately 3% from baseline to reach concentrations of 1.37+/-0.03 mmol/L and 1.38+/-0.03 mmol/L in the white and red phases, respectively (p < 0.001). Triglycerides were not altered by treatment. CONCLUSIONS: Consumption of lean red meat or lean white meat, as part of an NCEP Step I diet, is similarly effective for reducing LDL cholesterol and elevating HDL cholesterol concentrations in free-living persons with hypercholesterolemia.
Assuntos
Colesterol/sangue , Hipercolesterolemia/dietoterapia , Lipoproteínas/sangue , Carne , Adolescente , Adulto , Idoso , Estudos Cross-Over , Feminino , Produtos Pesqueiros , Humanos , Hipercolesterolemia/sangue , Hipercolesterolemia/prevenção & controle , Masculino , Pessoa de Meia-Idade , Cooperação do Paciente , Produtos Avícolas , Características de ResidênciaRESUMO
BACKGROUND: Elevated levels of low-density lipoprotein (LDL) cholesterol promote the development of atherosclerosis and coronary heart disease. HYPOTHESIS: Simvastatin 80 mg/day will be more effective than simvastatin 40 mg/day at reducing LDL cholesterol and will be well tolerated. METHODS: Two similar, randomized, multicenter, controlled, double-blind, parallel-group, 48-week studies were performed to evaluate the long-term lipid-altering efficacy and safety of simvastatin 80 mg/day in patients with hypercholesterolemia. One study conducted in the US enrolled patients meeting the National Cholesterol Education Program (NCEP) LDL cholesterol criteria for pharmacologic treatment. In the other multinational study, patients with LDL cholesterol levels > or = 4.2 mmol/l were enrolled. At 20 centers in the US and 19 countries world-wide, 1,105 hypercholesterolemic patients, while on a lipid-lowering diet, were randomly assigned at a ratio of 2:3 to receive simvastatin 40 mg (n = 436) or 80 mg (n = 669) once daily for 24 weeks. Those patients completing an initial 24-week base study were enrolled in a 24-week blinded extension. Patients who had started on the 80 mg dose in the base study continued on the same dose in the extension, while those who had started on the 40 mg dose were rerandomized at a 1:1 ratio to simvastatin 40 or 80 mg in the extension. RESULTS: There was a significant advantage in the LDL cholesterol-lowering effect of the 80 mg dose compared with that of the 40 mg dose, which was maintained over the 48 weeks of treatment. The mean percentage reductions (95% confidence intervals) from baseline in LDL cholesterol for the 40 and 80 mg groups were 41% (42, 39) and 47% (48, 46), respectively, for the 24-week base study, and 41% (43, 39) and 46% (47, 45), respectively, after 48 weeks of treatment (p < 0.001 between groups). Larger reductions in total cholesterol and triglycerides were also observed with the 80 mg dose compared with the 40 mg dose at Weeks 24 and 48. Both doses were well tolerated, with close to 95% of patients enrolled completing the entire 48 weeks of treatment. Myopathy (muscle symptoms plus creatine kinase increase > 10 fold upper limit of normal) and clinically significant hepatic transaminase increases (> 3 times the upper limit of normal) occurred infrequently with both doses. There was no significant difference between the groups in the number of patients with such increases, although there were more cases for both with the 80 mg dose. CONCLUSIONS: Compared with the 40 mg dose, simvastatin 80 mg produced greater reductions in LDL cholesterol, total cholesterol, and triglycerides. Both doses were well tolerated.