cerivastatin and Myocardial-Infarction

The aim of our study was to evaluate whether a single dose of cerivastatin at the time of admission of patients with unstable angina pectoris (UAP) or non-Q-wave myocardial infarction (NQMI) can influence the serum level of C-reactive protein (CRP), interleukin-6 (IL-6) and interleukin-8 (IL-8) 24 h later. Forty-four patients with rest chest pain and subendocardial ischemia on ECG were randomized to receive cerivastatin 0.3 mg at the time of admission (group C+) to standard therapy or to remain just on standard therapy (group C-). Blood samples for determination of troponin I (TI), CRP, IL-6 and IL-8 were collected at admission (entry level) and 24 h later (final level). Patients with non-physiological baseline levels of TI, as well as patients with progression to Q wave MI were excluded. All baseline, clinical and demographic data and final values of TI were comparable in the two groups. In patients treated with cerivastatin (group C+, n = 13) we observed decrease in the CRP level (-6.73 +/- 3.93 mg/L); on the other hand, in group C- (n = 17) the CRP level increased (+7.92 +/- 2.77 mg/L, p = 0.004). Similar differences were observed also in IL-6: in group C+ the level was significantly reduced as compared with the increase in group C- (-0.76 +/- 0.52 vs. 4.58 +/- 1.49 ng/L, p = 0.005). The level of IL-8 was not affected. Our results suggest that early treatment with cerivastatin can decrease the serum level of CRP and IL-6 in patients with UAP/NQMI; this might positively influence their prognosis. Nevertheless, further studies are needed to support this hypothesis.

Topics: Aged; Angina, Unstable; C-Reactive Protein; Female; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Interleukin-6; Interleukin-8; Male; Middle Aged; Myocardial Infarction; Pyridines

Active surveillance of population-based health networks may improve the timeliness of detection of adverse drug events (ADEs). Active monitoring requires sequential analysis methods. Our objectives were to (1) evaluate the utility of automated healthcare claims data for near real-time drug adverse event surveillance and (2) identify key methodological issues related to the use of healthcare claims data for real-time drug safety surveillance.. We assessed the ability to detect ADEs using historical data from nine health plans involved in the HMO Research Network's Center for Education and Research on Therapeutics (CERT). Analyses were performed using a maximized sequential probability ratio test (maxSPRT). Five drug-event pairs representing known associations with an ADE and two pairs representing 'negative controls' were analyzed.. Statistically significant (p < 0.05) signals of excess risk were found in four of the five drug-event pairs representing known associations; no signals were found for the negative controls. Signals were detected between 13 and 39 months after the start of surveillance. There was substantial variation in the number of exposed and expected events at signal detection.. Prospective, periodic evaluation of routinely collected data can provide population-based estimates of medication-related adverse event rates to support routine, timely post-marketing surveillance for selected ADEs.

Topics: Adverse Drug Reaction Reporting Systems; Algorithms; Celecoxib; Competitive Medical Plans; Health Maintenance Organizations; Humans; Insurance Claim Review; Lactones; Medical Records Systems, Computerized; Myocardial Infarction; Naproxen; Population Surveillance; Product Surveillance, Postmarketing; Pyrazoles; Pyridines; Retrospective Studies; Rhabdomyolysis; Sulfonamides; Sulfones; Time Factors; Treatment Outcome; United States

To characterize the relationship between hydroxymethylglutaryl-CoA reductase inhibitors (statins) and outcomes in older persons with acute myocardial infarction (AMI).. Observational study.. Acute care hospitals in the United States from April 1998 to June 2001.. Medicare patients aged 65 and older with a principal discharge diagnosis of AMI (N=65,020) who did and did not receive a discharge prescription for statins.. The primary outcome of interest was all-cause mortality at 3 years after discharge.. Of 23,013 patients with AMI assessed, 5,513 (24.0%) were receiving a statin at discharge. Nearly 40% of eligible patients (n=8,452) were aged 80 and older, of whom 1,310 (15.5%) were receiving a statin at discharge. In a multivariable model taking into account demographic, clinical, physician and hospital characteristics, and propensity score, discharge statin therapy was associated with significantly lower 3-year mortality (hazard ratio (HR)=0.89 (95% confidence interval (CI)=0.83-0.96)). In an analysis stratified by age, discharge statins were associated with lower mortality in patients younger than 80 (HR=0.84, 95% CI=0.76-0.92) but not in those aged 80 and older (HR=0.97, 95% CI=0.87-1.09).. Statin therapy is associated with lower mortality in older patients with AMI younger than 80 but not in those aged 80 and older, as a group. This finding questions whether statin efficacy data in younger patients can be broadly applied to the very old and indicates the need for further study of this group.

Topics: Age Factors; Aged, 80 and over; Atorvastatin; Cholesterol, LDL; Drug Prescriptions; Fatty Acids, Monounsaturated; Female; Fluvastatin; Follow-Up Studies; Heptanoic Acids; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Indoles; Lovastatin; Male; Myocardial Infarction; Odds Ratio; Pravastatin; Pyridines; Pyrroles; Retrospective Studies; Survival Rate; Treatment Outcome

Topics: Anti-Inflammatory Agents, Non-Steroidal; Clinical Trials as Topic; Cyclooxygenase 2 Inhibitors; Drug and Narcotic Control; Drug Approval; Health Policy; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Lactones; Myocardial Infarction; Probability; Product Surveillance, Postmarketing; Pyridines; Research Design; Rhabdomyolysis; Risk Assessment; Stroke; Sulfones; Treatment Outcome; United States; United States Food and Drug Administration

Although statins are reported to have a cardioprotective effect, their immediate direct influence on ischemia-reperfusion injury and the underlying mechanisms remain obscure. We investigated these issues an in vivo canine model.. Dogs were subjected to coronary occlusion (90 minutes) and reperfusion (6 hours) immediately after injection of pravastatin (0.2, 2, or 10 mg/kg), pitavastatin (0.01, 0.1, or 0.5 mg/kg), or cerivastatin (0.5, 5, or 50 microg/kg). Then myocardial phosphatidylinositol 3-kinase (PI3-K) and 5'-nucleotidase activities were measured, as well as infarct size. After 15 minutes of reperfusion, pravastatin caused dose-dependent activation of Akt and ecto-5'-nucleotidase in the ischemic zone, and the effect was significant at higher doses. Pitavastatin also significantly increased these activities, and its optimal dose was within the clinical range, whereas cerivastatin caused activation at the lowest dose tested. In all cases, both Akt and ecto-5'-nucleotidase showed activation in parallel, and this activation was completely abolished by wortmannin, a PI3-K inhibitor. The magnitude of the infarct-limiting effect paralleled the increase in Akt and ecto-5'-nucleotidase activity and was blunted by administration of wortmannin, alpha,beta-methyleneadenosine-5'-diphosphate, or 8-sulfophenyltheophylline during reperfusion. Both collateral flow and the area at risk were comparable for all groups.. Activation of ecto-5'-nucleotidase after ischemia by PI3-K activation may be crucial for immediate infarct-size limitation by statins. There seems to be an optimal dose for each statin that is independent of its clinical cholesterol-lowering effect.

Topics: 5'-Nucleotidase; Adenosine Triphosphate; Androstadienes; Animals; Cardiotonic Agents; Chromones; Coronary Disease; Dogs; Dose-Response Relationship, Drug; Enzyme Activation; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Morpholines; Myocardial Infarction; Myocardial Reperfusion Injury; Phosphatidylinositol 3-Kinases; Phosphoinositide-3 Kinase Inhibitors; Pravastatin; Pyridines; Quinolines; Signal Transduction; Theophylline; Wortmannin

Topics: Clinical Trials as Topic; Drug and Narcotic Control; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Hyperlipidemias; Myocardial Infarction; Myocardial Ischemia; Practice Guidelines as Topic; Pyridines; Research Design

The aim of this study was to test the feasibility of cine magnetic resonance imaging (MRI) for assessment of the infarcted rat and mouse heart and to compare the results with established methods. These models have been proven to predict genesis and prevention of heart failure in patients. The value of cine MRI was tested in studies investigating interventions to change the course of the remodeling process. MRI was performed for determination of left ventricular (LV) volumes and mass, myocardial infarct (MI) size and cardiac output. LV wet weight was determined after MRI. Rats underwent conventional hemodynamic measurements for determination of cardiac output and LV volumes by electromagnetic flowmeter and pressure-volume curves. Infarct size was determined by histology. MRI-acquired MI-size (18.5+/-2%) was smaller than that found by histology (22.8+/-2.5%, p<0.05) with close correlation (r=0.97). There was agreement in LV mass between MRI and wet weight (r=0.97, p<0.05) and in the MRI- and flowmeter measurements of cardiac output (r=0.80, p<0.05). Volume by MRI differed from pressure-volume curves with good correlation (r=0.96, p<0.05). In a serial study of mice after coronary ligation, LV hypertrophy at 8 weeks was detected (Sham 105.1+/-7.9 mg, MI 144.4+/-11.7 mg, p<0.05). Left ventricles were enlarged in infarcted mice (end-diastolic volume, week 8: Sham 63.5+/-4 microl, MI 94.2 microl, p<0.05). In conclusion, cine MRI is a valuable diagnostic tool applicable to the rat and mouse model of MI. Being non-invasive and exact it offers new insights into the remodeling process after MI because serial measurements are possible. The technique was applied to study several interventions and proved its usefulness.

Topics: Animals; Cardiac Output; Disease Models, Animal; Heart Failure; Heart Ventricles; Humans; Ischemia; Magnetic Resonance Imaging, Cine; Mice; Myocardial Infarction; Myocardial Ischemia; Pyridines; Rats; Reproducibility of Results; Sensitivity and Specificity; Species Specificity; Statistics as Topic; Stroke Volume; Testosterone; Ventricular Dysfunction, Left; Ventricular Remodeling

We sought to assess the influence of long-term hydroxymethylglutaryl coenzyme A reductase inhibition (statin) therapy on left ventricular (LV) remodeling after myocardial infarction (MI) by use of serial cardiac magnetic resonance imaging (CMRI) studies.. Statin therapy has been shown to reduce cardiac hypertrophy in vitro and in vivo, but the influence on LV post-MI remodeling is largely unknown.. The CMRI measurements were taken four and 12 weeks after left coronary artery ligation in a 7.05-tesla Biospec. The MI size, LV mass and volumes, cardiac output (CO), and ejection fraction were determined. Rats were treated for 12 weeks with either placebo (P), cerivastatin (C; 0.6 mg/kg body weight per day) as a dietary supplement, or cerivastatin plus the nitric oxide synthase (NOS) inhibitor N-methyl-L-arginine methyl ester (L-NAME, 76 mg/100 ml) and hydralazine (8 mg/100 ml) in drinking water (CLH) to assess the contribution of endogenous nitric oxide formation.. Administration of cerivastatin attenuated hypertrophy after MI, and this effect was completely abolished by NOS inhibition (increase of LV mass from 4 to 12 weeks after MI: 235.3 +/- 33.7 mg with P vs. 59.8 +/- 20.5 mg with C vs. 239.5 +/- 16.0 mg with CLH; p < 0.05 vs. P and CLH). Left ventricular dilation was not changed (increase of end-diastolic volume from 4 to 12 weeks after MI: 108.7 +/- 28.8 with P vs. 126.6 +/- 20.5 with C vs. 173.7 +/- 25.1 with CLH; p = NS). The CO was higher in the cerivastatin group (12 weeks: 76.1 +/- 2.9 ml/min with P vs. 95.8 +/- 4.8 ml/min with C; p < 0.05). The effects of cerivastatin were abolished by NOS inhibition in the CLH group (CO at 12 weeks: 69.3 +/- 2.8 ml/min, p < 0.05 vs. C).. Left ventricular remodeling was profoundly changed by statin treatment. Hypertrophy was attenuated, and global function was improved. These positive effects were abolished by NOS inhibition.

Topics: Animals; Disease Models, Animal; Hydralazine; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Magnetic Resonance Imaging; Male; Myocardial Infarction; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Pyridines; Rats; Rats, Wistar; Ventricular Function, Left; Ventricular Remodeling

Hydroxymethylglutaryl coenzyme A reductase inhibitors (statins) attenuate angiotensin II-induced cellular signaling. Because angiotensin II is involved in left ventricular (LV) remodeling after myocardial infarction (MI), we examined the effects of statin treatment in an experimental model of chronic heart failure after MI.. Rats with extensive MI were treated with placebo or cerivastatin (0.3 mg/kg per day) as a dietary supplement or via gavage for 11 weeks starting on the 7th postoperative day. Infarct size and cholesterol levels were similar among all groups. LV cavity area, an index of LV dilatation, was reduced in MI rats on cerivastatin compared with placebo. LV end-diastolic pressure was increased in MI rats on placebo (24.1+/-4.1 mm Hg versus sham: 5.1+/-0.3 mm Hg; P<0.01), and it was significantly reduced by cerivastatin treatment (13.7+/-2.7 mm Hg; P<0.05 versus placebo). Cerivastatin partially normalized LV dP/dt(max) and dP/dt(min), indices of LV systolic and diastolic function, which were significantly reduced in MI rats on placebo. Improvement of LV function by cerivastatin was accompanied by a reduced expression of collagen type I and beta-myosin heavy chain. LV endothelial nitric oxide synthase was increased, whereas the nitrotyrosine protein level was decreased in MI rats by cerivastatin treatment.. Cerivastatin improved LV remodeling and function in rats with heart failure. This effect was associated with an attenuated LV expression of fetal myosin heavy chain isoenzymes and collagen I. Statin treatment may retard the progression of chronic heart failure.

Topics: Animals; Blotting, Northern; Blotting, Western; Collagen; Gene Expression Regulation; Heart Failure; Heart Ventricles; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Male; Myocardial Contraction; Myocardial Infarction; Myosin Heavy Chains; Nitric Oxide Synthase; Nitric Oxide Synthase Type III; Pyridines; Rats; Rats, Wistar; RNA, Messenger; Tyrosine

Topics: Anticholesteremic Agents; Anuria; Clopidogrel; Coronary Artery Bypass; Humans; Hypercholesterolemia; Intracranial Thrombosis; Male; Middle Aged; Muscle Weakness; Myocardial Infarction; Platelet Aggregation Inhibitors; Postoperative Complications; Pyridines; Rhabdomyolysis; Ticlopidine

Topics: Cost-Benefit Analysis; Economics, Pharmaceutical; Humans; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Models, Economic; Myocardial Infarction; Pyridines