RESUMEN
BACKGROUND: Elevated serum aspartate and alanine aminotransferase (AST and ALT) are often observed in patients with acute ST-segment elevation myocardial infarction (STEMI) and the condition is ascribed to liver hypoperfusion. We evaluated the prevalence and prognostic implication of hypoxic liver injury (HLI) in STEMI. METHODS: Patients with STEMI and no preexisting liver disease who underwent primary percutaneous coronary intervention (PCI) were enrolled. A blood test was performed at the time of presentation and transthoracic echocardiography was performed after the index PCI. We reviewed medical records and contacted families of the patients by telephone to assess outcomes. RESULTS: Of 456 patients (age 60 ± 13 years, 370 males), 31 patients (7%) died during follow-up (duration: 754 ± 540 days). Those patients were older (72 ± 10 vs. 59 ± 13 years), had higher AST (179 ± 224 vs. 64 ± 103 U/L), ALT (56 ± 79 vs. 35 ± 33 U/L), blood urea nitrogen (25 ± 15 vs. 17 ± 7 mg/dL), uric acid (6.9 ± 2.9 vs. 5.8 ± 1.6 mg/dL), creatine kinase-myocardial band isoenzyme (76 ± 104 vs. 41 ± 79 ng/mL), troponin I (19.9 ± 23.0 vs. 10.8 ± 19.1 ng/mL), and lower albumin (4.0 ± 0.5 vs. 4.2 ± 0.4 g/dL) at the time of presentation (p<0.05 for all). Particularly, AST independently predicted all-cause mortality (per 10 U/L increase, hazard ratio: 1.06, 95% confidence interval: 1.02-1.10, p=0.007), whereas cardiac markers did not. HLI (>2-fold elevation of AST or ALT upper normal limits) showed close correlation with reduced left ventricular ejection fraction (ß=-0.12, p=0.03) and patients with the condition (n=100 [20%]) had poorer survival than the others (Log-Rank, p=0.005). CONCLUSION: The presence of HLI predicts mortality in patients with STEMI who undergo successful primary PCIs.
Asunto(s)
Alanina Transaminasa/sangre , Servicio de Urgencia en Hospital/tendencias , Infarto del Miocardio/sangre , Infarto del Miocardio/cirugía , Intervención Coronaria Percutánea/tendencias , Anciano , Anciano de 80 o más Años , Ácido Aspártico/sangre , Biomarcadores/sangre , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/mortalidad , Intervención Coronaria Percutánea/mortalidad , Valor Predictivo de las Pruebas , Estudios Retrospectivos , Tasa de Supervivencia/tendencias , Resultado del TratamientoRESUMEN
BACKGROUND: The everolimus-eluting stent (EES) is a newly developed drug-eluting stent using the MULTILINK VISION stent platform combined with the drug everolimus contained in a polymer coating. Recently reported randomized trials have shown the noninferiority and subsequent superiority of the EES compared with the paclitaxel-eluting stent regarding in-stent late loss (LL) at 180 days. However, there have been no studies comparing head to head the EES with the sirolimus-eluting stent (SES), which has shown the least amount of LL among the previously released drug-eluting stent (DES). In addition, adjunctive antiplatelet therapy is a critical factor in optimizing long-term DES safety. Despite the recommendation of the American Heart Association/American College of Cardiology to maintain 12 months of dual antiplatelet therapy, there have been no prospective randomized trials comparing the efficacy and safety of different durations. STUDY DESIGN: In the Efficacy of Xience/promus versus Cypher in rEducing Late Loss after stENTing (EXCELLENT) trial, approximately 1,400 patients are being prospectively and randomly assigned in a 2 x 2 factorial design according to the type of stent (EES vs SES) and the duration of dual antiplatelet therapy (6 vs 12 months). The primary end point is in-segment LL at 9 months for comparison of type of stent, and the coprimary end point is target vessel failure at 12 months for comparison of dual antiplatelet therapy duration. SUMMARY: The EXCELLENT trial is the largest study yet performed to directly compare the efficacy and safety of the EES versus the SES. In addition, this study will also address the issue of a 6- versus 12-month duration of dual antiplatelet therapy for post-percutaneous coronary intervention management.
Asunto(s)
Estenosis Coronaria/cirugía , Stents Liberadores de Fármacos/normas , Oclusión de Injerto Vascular/prevención & control , Inmunosupresores/farmacología , Revascularización Miocárdica/instrumentación , Sirolimus/análogos & derivados , Sirolimus/farmacología , Angiografía Coronaria , Reestenosis Coronaria/epidemiología , Reestenosis Coronaria/etiología , Reestenosis Coronaria/prevención & control , Estenosis Coronaria/diagnóstico por imagen , Everolimus , Femenino , Estudios de Seguimiento , Oclusión de Injerto Vascular/complicaciones , Oclusión de Injerto Vascular/epidemiología , Humanos , Incidencia , Corea (Geográfico)/epidemiología , Masculino , Estudios Prospectivos , Diseño de Prótesis , Factores de Tiempo , Resultado del TratamientoRESUMEN
BACKGROUND: Amlodipine besylate has been used in Korea for the treatment of hypertension for >17 years, with well-established efficacy and tolerability. Amlodipine camsylate is a newer formulation developed for generic use. It has been assessed in terms of physical stability and pharmacokinetic and pharmacodynamic properties and been found to be effective in lowering blood pressure in preclinical and Phase I and II trials. However, to date, no studies have compared the clinical effectiveness of amlodipine camsylate and amlodipine besylate in treating hypertension. OBJECTIVE: This study was designed to determine the effectiveness and tolerability of amlodipine camsylate compared with amlodipine besylate in Korean patients with mild to moderate hypertension. METHODS: This Phase III, 8-week, prospective, randomized, double-blind, parallel-group study was conducted in 13 cardiology centers across the Republic of Korea. Male and female Korean patients aged 18 to 75 years having uncomplicated, mild to moderate, essential hypertension (sitting diastolic blood pressure [SiDBP] 90-<110 mm Hg) and receiving no antihypertensives in the 2 weeks before randomization were eligible. Patients were randomly assigned to receive oral treatment with amlodipine camsylate or amlodipine besylate. For the first 4 weeks, patients received amlodipine 5 mg QD (morning). After 4 weeks, if either blood pressure was > or =140/ > or =90 mm Hg or SiDBP had not decreased by > or =10 mm Hg from baseline, the dose of amlodipine was increased to 10 mg QD for 4 weeks. Trough blood pressure and heart rate were measured in duplicate with the patient in the sitting position at each clinic visit (baseline [week 0] and weeks 4 and 8 of treatment); mean values were calculated and recorded. At weeks 4 and 8, tolerability was assessed using history taking and laboratory analysis, and compliance was assessed using pill counts. The primary end point was change from baseline in SiDBP at week 8. Secondary end points were change from baseline in sitting systolic blood pressure (SiSBP) at week 8 in the total population and in the subgroup of patients who had previously received antihypertensive treatment versus those who had not. RESULTS: A total of 189 patients were enrolled (mean age, 53 years; 105 women, 84 men; mean body weight, 65.8 kg). One patient in the amlodipine camsylate group dropped out of the study at week 0 of treatment (this patient did not use any study medication) and was excluded from the modified intent-to-treat (ITT) analysis. Thus, 188 patients were treated and included in the ITT analysis (94 patients per treatment group; ITT analysis); 161 patients were included in the perprotocol (PP) analysis (n = 80 for amlodipine camsylate, n = 81 for amlodipine besylate) (14 patients in the amlodipine camsylate group and 13 patients in the amlodipine besylate group were excluded from the PP analysis due to consistent withdrawal or protocol violation). Mean (SD) SiSBP and SiDBP were significantly decreased from baseline in both groups (amlodipine camsylate, from 146.7 [12.3]/96.6 [5.4] to 127.9 [14.8]/83.4 [7.7] mm Hg [both, P < 0.001]; amlodipine besylate, from 146.8 [12.8]/96.7 [5.1] to 128.0 [10.1]/83.8 [7.5] mm Hg [both, P < 0.001]). The differences in SiSBP/SiDBP between the 2 groups at week 8 were not significant. The SiDBP response rates in the subgroups that had and had not been previously treated with antihypertensives were statistically similar (56/69 [81.2%] and 83/92 [90.2%], respectively). The prevalences of clinical adverse events (AEs) were not significantly different between the 2 treatment groups (amlodipine camsylate, 27.3 %; amlodipine besylate, 28.7%). The most common AEs were dizziness and dyspnea (both in 3/94 [3.2%] and 1/94 [1.1%] patients who received amlodipine camsylate and amlodipine besylate, respectively). CONCLUSION: The effectiveness and tolerability of amlodipine camsylate were not significantly different from those of amlodipine besylate in these Korean adults with mild to moderate hypertension.
Asunto(s)
Amlodipino/administración & dosificación , Amlodipino/uso terapéutico , Antihipertensivos/administración & dosificación , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/administración & dosificación , Bloqueadores de los Canales de Calcio/uso terapéutico , Hipertensión/tratamiento farmacológico , Adolescente , Adulto , Anciano , Amlodipino/efectos adversos , Análisis de Varianza , Antihipertensivos/efectos adversos , Presión Sanguínea/efectos de los fármacos , Bloqueadores de los Canales de Calcio/efectos adversos , Método Doble Ciego , Esquema de Medicación , Femenino , Humanos , Corea (Geográfico) , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Equivalencia TerapéuticaRESUMEN
BACKGROUND: Amlodipine, a third-generation dihydropyridine calcium antagonist, is prescribed in the management of angina and hypertension. A newly developed amlodipine formulation (amlodipine camsylate) is associated with similar physical properties, melting point, and solubility-and improved stability against long-term stability test and accelerated temperature test-compared with the conventional formulation (amlodipine besylate). OBJECTIVE: This study was performed to compare the pharmacokinetic (PK) and pharmacodynamic (PD) properties and safety profiles of a newly developed amlodipine formulation with a conventional formulation in healthy male subjects. METHODS: This randomized, open-label, 2-period crossover comparative study was conducted at the Clinical Trial Center, Gil Medical Center, Gachon Medical School (Incheon, Korea). Eighteen healthy male Korean subjects aged 20 to 40 years were enrolled. All subjects received a single oral dose (5-mg tablet) of a conventional (reference) or newly developed (test) amlodipine formulation. Blood samples for PK analysis of amlodipine were obtained during the 144-hour period after dosing. Systolic and diastolic blood pressure (BP) (SBP and DBP, respectively) and pulse rate (PR) were measured just before each blood sampling. Assessment of safety profiles, including hematology and biochemistry, electrocardiography, urinalysis, and monitoring of adverse events (AEs), was performed. RESULTS: All participants completed both treatment periods. Their mean (SD) age was 22.3 (1.5) years (range, 20-25 years) and their mean (SD) body weight was 67.9 (5.6) kg (range, 57-77 kg). The plasma concentration-time profiles of amlodipine were similar after administration of the 2 formulations. The reference and test formulations were pharmacokinetically equivalent. The 90% CIs for the mean treatment ratios of the log-transformed peak plasma concentration and the area under the plasma concentration-time curve were within the predetermined equivalence range of 80% to 125%. Despite administration of a single dose, significant maximal changes in SBP, DBP, and PR were achieved after drug administration for both formulations compared with baseline values (all, P < 0.001). No significant differences in PD profiles were found between the 2 formulations. No clinically relevant changes were observed in physical, biochemical, hematologic, electrocardiographic, or urinalysis findings during the study. Neither formulation caused any AEs during the study. CONCLUSIONS: The 2 amlodipine formulations were pharmacokinetically equivalent and showed similar PD characteristics in these healthy male subjects.
Asunto(s)
Amlodipino/farmacología , Amlodipino/farmacocinética , Antihipertensivos/farmacología , Antihipertensivos/farmacocinética , Adulto , Amlodipino/administración & dosificación , Antihipertensivos/administración & dosificación , Área Bajo la Curva , Pueblo Asiatico , Disponibilidad Biológica , Estudios Cruzados , Semivida , Humanos , MasculinoRESUMEN
The purpose of this study was to analyze long-term follow-up information from patients treated with stenting for unprotected left main coronary artery (LMCA) stenosis. Stenting of unprotected LMCA stenosis is often performed in selected patients, but the long-term safety of this therapy is not yet established. Between January 1995 and September 2000, 270 consecutive patients with unprotected LMCA stenosis and normal left ventricular function who underwent treatment at 4 clinical centers were included in this study. Data were forwarded to the coordinating center using a standard case report form. The procedural success rate was 98.9%. There were no deaths, 3 stent thromboses, and 3 Q-wave myocardial infarctions during the hospitalization. Angiographic follow-up was performed in 237 patients (follow-up rate 87.8%), and the restenosis rate was 21.1%. The reference size was an independent predictor of binary restenosis (odds ratio 0.543, 95% confidence interval 0.308 to 0.957, p = 0.03). During the follow-up period (32.3 +/- 18.5 months), there were 20 deaths (8 cardiac, 12 noncardiac) and 5 nonfatal myocardial infarctions. Target and new lesion revascularizations were required in 45 (16.7%) and 31 (11.5%) patients, respectively. The cumulative probabilities free from major adverse cardiac events were 81.9 +/- 2.4%, 78.4 +/- 2.6%, and 77.7 +/- 2.7%, respectively, at 1, 2, and 3 years. Combined coronary artery disease and postprocedural minimal luminal diameter were the significant predictors of major adverse cardiac events. Thus, the long-term prognosis of patients after stenting of unprotected LMCA stenosis was favorable in selected patients with normal left ventricular function.