RESUMO
BACKGROUND: It has long been an accepted belief that serum cholesterol significantly falls after myocardial infarction and that a return to pre-event levels takes approximately 3 months. The magnitude and clinical significance of this fall has recently been challenged. METHODS: In the Secondary Prevention of Acute Coronary Events-Reduction Of Cholesterol to Key European Targets (SPACE ROCKET) trial, we measured serum lipids of individuals on day 1 and between days 2 and 4 after acute myocardial infarction (AMI). Second, we performed a thorough literature review and compared all studies reporting data on absolute changes in lipids immediately after AMI, using weighted means. RESULTS: Of 1263 SPACE ROCKET participants, 128 had paired lipid measurements where both samples had been measured using identical methods at baseline and on days 2-4 after AMI. The mean lowering in total cholesterol between day 1 and day 2-4 was 0.71 mmol/L (95% CI 0.58-0.84; P < 0.0001) and in triglycerides was 0.10 mmol/L (-0.14-0.33; P = 0.405). A total of 25 papers showing absolute lipid changes post-AMI were identified. The combined data demonstrated a mean fall in total cholesterol of 9% to 11% from baseline over days 3-14 post-AMI, whereas for triglycerides, there was a rise of 18% from baseline to between day 9 and 12 weeks. CONCLUSIONS: After a secondary analysis of SPACE ROCKET data and a comparison of previously published data, we report a 10% fall in total cholesterol after AMI-a difference that is of high clinical significance. Consequently, measurement of serum lipids in patients with AMI should be performed within the first hours after presentation.
Assuntos
Lipídeos/sangue , Infarto do Miocárdio/sangue , Colesterol/sangue , Fluorbenzenos/uso terapêutico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Estudos Multicêntricos como Assunto , Infarto do Miocárdio/tratamento farmacológico , Pirimidinas/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Rosuvastatina Cálcica , Sinvastatina/uso terapêutico , Sulfonamidas/uso terapêutico , Triglicerídeos/sangueRESUMO
AIMS: We sought to evaluate reports that rosuvastatin 10 mg is a more efficacious treatment of hyperlipidaemia than is simvastatin 40 mg, hoping to assess this issue in the previously unstudied context of acute myocardial infarction. METHODS AND RESULTS: The Secondary Prevention of Acute Coronary Events - Reduction of Cholesterol to Key European Targets (SPACE ROCKET) Trial was an investigator-led, open-label, blinded-endpoint, multicentre, randomized, controlled trial assessing the proportion of patients, at 3 months, achieving European Society of Cardiology 2003 (ESC-03) lipid targets of total cholesterol (TC) less than 4.5 mmol/l (174 mg/dl) or low-density lipoprotein cholesterol (LDLc) less than 2.5 mmol/l (97 mg/dl). Of 1263 patients randomized, 77.6% simvastatin versus 79.9% rosuvastatin achieved ESC-03 targets [odds ratio (OR): 1.16; 95% confidence interval (CI): 0.88-1.53; P = 0.29]. There were statistically significant differences for simvastatin versus rosuvastatin, respectively, for mean LDLc 2.03 mmol/l (78 mg/dl) versus 1.94 mmol/l (75 mg/dl; P = 0.009) and also mean TC 3.88 mmol/l (150 mg/dl) versus 3.75 mmol/l (145 mg/dl; P = 0.005). A post-hoc analysis showed higher achievement of the new ESC, American Heart Association and American College of Cardiology optimal lipid target of LDLc less than 1.81 mmol/l (70 mg/dl) with rosuvastatin (45.0%) compared with simvastatin (37.8%; OR: 1.37; 95% CI: 1.09-1.72; P = 0.007). The proportion of patients achieving the Fourth Joint Task Force European Guidelines (2007) of TC less than 4.0 mmol/l (155 mg/dl) and LDLc less than 2.0 mmol/l (77 mg/dl) was 38.7% for simvastatin 40 mg and 47.7% for rosuvastatin 10 mg (OR: 1.48; 95% CI: 1.18-1.86; P = 0.001). CONCLUSION: We observed no superiority of either treatment for the ESC-03 lipid targets. Rosuvastatin 10 mg lowered mean cholesterol more effectively than simvastatin and achieved better results for the latest, more stringent, ESC target.
Assuntos
Colesterol/sangue , Fluorbenzenos/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Infarto do Miocárdio/prevenção & controle , Pirimidinas/uso terapêutico , Prevenção Secundária/métodos , Sinvastatina/uso terapêutico , Sulfonamidas/uso terapêutico , Idoso , Biomarcadores/sangue , LDL-Colesterol/sangue , Feminino , Humanos , Hiperlipidemias/sangue , Hiperlipidemias/complicações , Masculino , Pessoa de Meia-Idade , Infarto do Miocárdio/sangue , Infarto do Miocárdio/etiologia , Razão de Chances , Guias de Prática Clínica como Assunto , Estudos Prospectivos , Rosuvastatina Cálcica , Fatores de Tempo , Resultado do Tratamento , Reino UnidoRESUMO
Risk assessment is central to the management of acute coronary syndromes. Often, however, assessment is not complete until the troponin concentration is available. Using 2 multicenter prospective observational studies (Evaluation of Methods and Management of Acute Coronary Events [EMMACE] 2, test cohort, 1,843 patients; and EMMACE-1, validation cohort, 550 patients) of unselected patients with acute coronary syndromes, a point-of-admission risk stratification tool using frontal QRS-T angle derived from automated measurements and age for the prediction of 30-day and 2-year mortality was evaluated. Two-year mortality was lowest in patients with frontal QRS-T angles <38° and highest in patients with frontal QRS-T angles >104° (44.7% vs 14.8%, p <0.001). Increasing frontal QRS-T angle-age risk (FAAR) scores were associated with increasing 30-day and 2-year mortality (for 2-year mortality, score 0 = 3.7%, score 4 = 57%; p <0.001). The FAAR score was a good discriminator of mortality (C statistics 0.74 [95% confidence interval 0.71 to 0.78] at 30 days and 0.77 [95% confidence interval 0.75 to 0.79] at 2 years), maintained its performance in the EMMACE-1 cohort at 30 days (C statistics 0.76 (95% confidence interval 0.71 to 0.8] at 30 days and 0.79 (95% confidence interval 0.75 to 0.83] at 2 years), in men and women, in ST-segment elevation myocardial infarction and non-ST-segment elevation myocardial infarction, and compared favorably with the Global Registry of Acute Coronary Events (GRACE) score. The integrated discrimination improvement (age to FAAR score at 30 days and at 2 years in EMMACE-1 and EMMACE-2) was p <0.001. In conclusion, the FAAR score is a point-of-admission risk tool that predicts 30-day and 2-year mortality from 2 variables across a spectrum of patients with acute coronary syndromes. It does not require the results of biomarker assays or rely on the subjective interpretation of electrocardiograms.
Assuntos
Síndrome Coronariana Aguda/fisiopatologia , Eletrocardiografia , Admissão do Paciente , Medição de Risco/métodos , Síndrome Coronariana Aguda/diagnóstico , Síndrome Coronariana Aguda/mortalidade , Fatores Etários , Idoso , Intervalos de Confiança , Diagnóstico Diferencial , Feminino , Seguimentos , Mortalidade Hospitalar/tendências , Humanos , Masculino , Razão de Chances , Prognóstico , Estudos Prospectivos , Fatores de Risco , Taxa de Sobrevida/tendências , Reino Unido/epidemiologiaRESUMO
BACKGROUND: Pharmacogenetics aims to maximize benefits and minimize risks of drug treatment. Our objectives were to examine the influence of common variants of hepatic metabolism and transporter genes on the lipid-lowering response to statin therapy. METHODS AND RESULTS: The Genetic Effects On STATins (GEOSTAT-1) Study was a genetic substudy of Secondary Prevention of Acute Coronary Events-Reduction of Cholesterol to Key European Targets (SPACE ROCKET) (a randomized, controlled trial comparing 40 mg of simvastatin and 10 mg of rosuvastatin) that recruited 601 patients after myocardial infarction. We genotyped the following functional single nucleotide polymorphisms in the genes coding for the cytochrome P450 (CYP) metabolic enzymes, CYP2C9*2 (430C>T), CYP2C9*3 (1075A>C), CYP2C19*2 (681G>A), CYP3A5*1 (6986A>G), and hepatic influx and efflux transporters SLCO1B1 (521T>C) and breast cancer resistance protein (BCRP; 421C>A). We assessed 3-month LDL cholesterol levels and the proportion of patients reaching the current LDL cholesterol target of <70 mg/dL (<1.81 mmol/L). An enhanced response to rosuvastatin was seen for patients with variant genotypes of either CYP3A5 (P=0.006) or BCRP (P=0.010). Furthermore, multivariate logistic-regression analysis revealed that patients with at least 1 variant CYP3A5 and/or BCRP allele (n=186) were more likely to achieve the LDL cholesterol target (odds ratio: 2.289; 95% CI: 1.157, 4.527; P=0.017; rosuvastatin 54.0% to target vs simvastatin 33.7%). There were no differences for patients with variants of CYP2C9, CYP2C19, or SLCO1B1 in comparison with their respective wild types, nor were differential effects on statin response seen for patients with the most common genotypes for CYP3A5 and BCRP (n=415; odds ratio: 1.207; 95% CI: 0.768, 1.899; P=0.415). CONCLUSION: The LDL cholesterol target was achieved more frequently for the 1 in 3 patients with CYP3A5 and/or BCRP variant genotypes when prescribed rosuvastatin 10 mg, compared with simvastatin 40 mg. Clinical Trial Registration- URL: http://isrctn.org. Unique identifier: ISRCTN 89508434.