The efficacy of statin monotherapy uptitration versus switching to ezetimibe/simvastatin:results of the EASEGO study

Objective: To assess the incremental low-density lipoprotein-cholesterol (LDL-C) lowering efficacy of doubling the statin dose or switching to the ezetimibe/simvastatin 10/20 mg combination tablet (EZE/SIMVA) in patients on simvastatin 20 mg or atorvastatin 10 mg not at LDL-C target <2.5 mmol/L. Study design and methods: Patients with documented coronary heart disease (CHD) and/or type 2 diabetes (DM2) with LDL-C >= 2.5 and <5.0 mmol/L despite treatment with atorvastatin 10 mg or simvastatin 20 mg were randomized to (1) double statin dose or (2) switch to ezetimibe/simvastatin 10/20, according to a PROBE study design. LDL-C, lipoprotein subfractions and safety data were assessed during the study. Results: 119 of 178 (67%) patients in the EZE/SIMVA group and 49 of 189 (26%) in the doubling statin group reached target LDL-C <2.5 mmol/L. The odds ratio of success for EZE/SIMVA versus doubling statin treatment in reaching the LDL-C target of <2.5 mmol/L was 5.7 (95% Cl: 3.7-9.0, p <0.0001). A reduction in total cholesterol (TC), total/high density lipoprotein (HDL) cholesterol ratio and apolipoprotein B was observed in both groups, but this reduction was significantly more pronounced in the EZE/SIMVA group as compared with the doubling statin dose group. Treatment was well tolerated and no difference was observed between the two groups with regard to adverse effects. Conclusions: In CHD/DM2 patients treated with simvastatin or atorvastatin with LDL-C persistently >= 2.5 mmol/L, switching to the EZE/SIMVA was more effective in attaining the LDL-C target of <2.5 mmol/L than doubling the statin dose

Clinical course of isolated stable angina due to coronary heart disease

Aims To describe the clinical course of patients with stable angina due to coronary heart disease without a history of cardiovascular (CV) events or revascutarization (isolated angina). Methods and results Of 7665 patients in a trial comparing long-acting nifedipine with placebo, 2170 (28%) had isolated angina. During a mean follow-up of 4.9 years, 147 of these died (1.4/100 patient-years), white 761 (8.7/100 patient-years) either died, or had a cardiac event or procedure. The first event was death in 82, myocardial infarction or heart failure in 112, coronary revascularization in 171, and chest pain requiring hospitalization in 396. Six hundred and twelve patients (6.8/100 patient-years) underwent coronary angiography (CAG), followed by revascularization in 371. Sixty-eight of 262 deaths or major cardiac events were preceded by chest pain requiring hospitalization or revascularization. Event-rates after CAG were higher than before. The stroke rate was 0.7/100 patient-years (75 patients). Conclusion Patients with stable isolated angina have tow rates of death and major cardiac events, but relatively high rates of chest pain requiring hospitalization despite contemporary management. Since the majority of deaths and major CV clinical events are not preceded by clear warning symptoms, the main clinical implication is that measures to prevent such events must target all patients

Resource utilization implications of treatment were able to be assessed from appropriately reported clinical trial data

Background and Objective: Published clinical trial data rarely allow assessment of the health care resource utilization implications of treatment. We give an example of how these can be assessed given appropriate tabulation of data. Methods: Data from a trial comparing long-acting nifedipine gastrointestinal therapeutic system to placebo in 7,665 patients with stable angina pectoris was analyzed. Results: Relative to placebo, nifedipine significantly increased mean cardiovascular (CV) event-free survival by 41 days but had no effect on mean survival. Per 100 years of follow-up, 78.1 patient-years of double-blind nifedipine administration reduced use of another calcium antagonist, an angiotensin converting enzyme inhibitor, an angiotensin receptor blocker, a diuretic and a cardiac glycoside by 1.54, 3.73, 2.63, 2.23, and 0.64 years, respectively, whereas 0.21 less hospitalization for overt heart failure, 0.47 less hospitalization for any stroke or transient ischemic attack, 0.8 less coronary angiogram, 0.38 less coronary bypass procedure, and 0.13 additional orthopedic procedure was required. Combining resource utilization with cost data for one particular hospital showed that one additional year of CV event-free survival costs an average additional EURO3,036 in the setting considered. Conclusion: Appropriately tabulated clinical trial data allows clinicians to judge the resource utilization implications and economic effect of treatment decisions. (c) 2007 Elsevier Inc. All rights reserved

Presence and development of atrial fibrillation in chronic heart failure - Experiences from the MERIT-HF Study

Background: Atrial fibrillation is common in heart failure, but data regarding beta-blockade in these patients and its ability to prevent new occurrence of atrial fibrillation are scarce. Methods: Baseline ECGs in MERIT-HF were coded regarding baseline rhythm, and outcome was analyzed in relation to rhythm. Occurrence of atrial fibrillation during follow-up was also analyzed. Results: At baseline atrial fibrillation was diagnosed in 556patients (13.9%). Mean metoprolol CR/XL dose in patients in atrial fibrillation (154 mg) and sinus rhythm (15 8 mg) was similar, as well as decrease in heart rate (14.8 and 13.7 bpm, respectively). Only 61 (total of 3 62) deaths occurred in those in atrial fibrillation at baseline, 31 on placebo and 30 on metoprolol (RR 1.0; 95% CI 0.61-1.65). During follow-up, new atrial fibrillation was observed in 85 patients on placebo and 47 patients on metoprolol (RR 0.53; 95% CI 0.37-0.76; p = 0.0005). Conclusion: First, given the wide confidence interval, it was impossible to detect an interaction between metoprolol and mortality in patients with atrial fibrillation and heart failure. Second, in patients with sinus rhythm at baseline, metoprolol reduced the incidence of atrial fibrillation during follow-up. However, we must be extremely cautious in over-interpreting effects in these subgroups. (c) 2006 European Society of Cardiology. Published by Elsevier B.V. All rights reserved

Effects of Rosuvastatin on Coronary Flow Reserve and Metabolic Mismatch in Patients With Heart Failure (from the CORONA Study)

In patients with heart failure (HF), statin treatment might improve myocardial perfusion, but could also have detrimental effects on myocardial metabolism. A predefined substudy of the Controlled Rosuvastatin Multinational Trial in Heart Failure (CORONA) trial sought to determine the effects of statin treatment on myocardial blood flow reserve and cardiac metabolism. Sixteen patients with HF (New York Heart Association class II or III) were randomized to rosuvastatin 10 mg/day (n = 8) or placebo treatment (n = 8). At baseline and after 6 months of treatment, nitrogen-13 ammonia at rest and after dipyridamole stress and 18-fluorodeoxyglucose positron emission tomography were performed. Rosuvastatin treatment significantly lowered total (-36%,

Diagnostic criteria and adjudication process both determine published event-rates:The ACTION trial experience

Objective: Few trials report event-adjudication procedures in detail. Using data from the ACTION (A Coronary disease Trial Investigating Outcome with Nifedipine GITS) study, we compared the impact on event-rates of an adjudication strategy based on systematic screening of all reported serious adverse events (SAEs) with a strategy based on investigator diagnoses. The final diagnosis was always made by a critical events committee (CEC) using standard criteria. Methods: ACTION randomized 7665 patients with stable angina to either nifedipine or placebo. Pre-specified events included acute or procedural myocardial infarction (MI), refractory angina, heart failure and debilitating stroke. Clinically related SAEs including in-hospital procedures were combined into episodes independent from the investigator diagnoses entered on SAE reports. All fatal episodes and those episodes suggestive of pre-specified events were adjudicated by the CEC. Results: During follow-up, 17,081 episodes were reported in 5312 patients. The SAE descriptions ruled out the occurrence of a pre-specified event in 28%. The remaining 72% were adjudicated by the CEC and 616 cases of MI, 361 of refractory angina, 275 of heart failure and 190 of debilitating stroke were diagnosed (total=1442). Had adjudication by the CEC been limited to the 3924 episodes (2397 patients) that were fatal or for which the investigator had reported any of the diagnoses mentioned, 98 cases of MI, 35 of refractory angina, 81 of heart failure and 14 of debilitating stroke would have been missed (total=228). Conclusion: Both the diagnostic criteria used and the adjudication process determine event-rates and conclusions about treatment effects in clinical trials. Published trial reports should always state if event-adjudication was independent of the diagnoses of investigators, and if all events of interest were adjudicated or only the first one. (c) 2007 Elsevier Inc. All rights reserved