High-Dose Atorvastatin vs Usual-Dose Simvastatin for Secondary Prevention After Myocardial Infarction<SUBTITLE>The IDEAL Study: A Randomized Controlled Trial</SUBTITLE>

Abstract

Context Evidence suggests that more intensive lowering of low-density lipoprotein cholesterol (LDL-C) than is commonly applied clinically will provide further benefit in stable coronary artery disease. Objective To compare the effects of 2 strategies of lipid lowering on the risk of cardiovascular disease among patients with a previous myocardial infarction (MI). Design, Setting, and Participants The IDEAL study, a prospective, randomized, open-label, blinded end-point evaluation trial conducted at 190 ambulatory cardiology care and specialist practices in northern Europe between March 1999 and March 2005 with a median follow-up of 4.8 years, which enrolled 8888 patients aged 80 years or younger with a history of acute MI. Interventions Patients were randomly assigned to receive a high dose of atorvastatin (80 mg/d; n=4439), or usual-dose simvastatin (20 mg/d; n=4449). Main Outcome Measure Occurrence of a major coronary event, defined as coronary death, confirmed nonfatal acute MI, or cardiac arrest with resuscitation. Results During treatment, mean LDL-C levels were 104 (SE, 0.3) mg/dL in the simvastatin group and 81 (SE, 0.3) mg/dL in the atorvastatin group. A major coronary event occurred in 463 simvastatin patients (10.4%) and in 411 atorvastatin patients (9.3%) (hazard ratio [HR], 0.89; 95% CI, 0.78-1.01; P=.07). Nonfatal acute MI occurred in 321 (7.2%) and 267 (6.0%) in the 2 groups (HR, 0.83; 95% CI, 0.71-0.98; P = .02), but no differences were seen in the 2 other components of the primary end point. Major cardiovascular events occurred in 608 and 533 in the 2 groups, respectively (HR, 0.87; 95% CI, 0.77-0.98; P=.02). Occurrence of any coronary event was reported in 1059 simvastatin and 898 atorvastatin patients (HR, 0.84; 95% CI, 0.76-0.91; PϽ.001). Noncardiovascular death occurred in 156 (3.5%) and 143 (3.2%) in the 2 groups (HR, 0.92; 95% CI, 0.73-1.15; P=.47). Death from any cause occurred in 374 (8.4%) in the simvastatin group and 366 (8.2%) in the atorvastatin group (HR, 0.98; 95% CI, 0.85-1.13; P=.81). Patients in the atorvastatin group had higher rates of drug discontinuation due to nonserious adverse events; transaminase elevation resulted in 43 (1.0%) vs 5 (0.1%) withdrawals (PϽ.001). Serious myopathy and rhabdomyolysis were rare in both groups. Conclusions In this study of patients with previous MI, intensive lowering of LDL-C did not result in a significant reduction in the primary outcome of major coronary events, but did reduce the risk of other composite secondary end points and nonfatal acute MI. There were no differences in cardiovascular or all-cause mortality. Patients with MI may benefit from intensive lowering of LDL-C without an increase in noncardiovascular mortality or other serious adverse reactions. Trial Registration ClinicalTrials.gov Identifier: NCT00159835.

Safety of atorvastatin in Asian patients within clinical trials

“…1) so that the several large trials did not confound results from the smaller trials. Six long‐term trials18, 20, 21, 22, 23, 28 (see footnote to Table 1 for trial details) investigating the effect of atorvastatin on CV outcomes were analyzed both individually and pooled according to treatment group; the median study duration was 3.1–4.9 years. The remaining 52 short‐term studies (≤2 years) were pooled according to treatment group; the median study duration was 4–72 weeks.…”

“…Long‐term CV outcomes trials with atorvastatin,17, 18, 19, 20, 21, 22, 23 as well as other statins,24, 25 have demonstrated the safety of this class in a range of populations. However, compared with the wealth of evidence from Western populations, the availability of statin safety data from Asian populations is limited, which may be a contributing factor in the underutilization of statins for the treatment of dyslipidemia in this ethnic group.…”

Cost‐Effectiveness of Intensifying Lipid‐Lowering Therapy With Statins Based on Individual Absolute Benefit in Coronary Artery Disease Patients

“…Given that CAD patients differ widely in history of and risk factors for vascular disease, there is a potential range in absolute benefit from intensification of LLT. Previously, we derived a prediction model in the Treating to New Targets (TNT) trial population that estimates 5‐year absolute treatment effect of intensive versus standard LLT with statins on recurrent vascular events for an individual patient, which was validated in the Incremental Decrease in End point through Aggressive Lipid‐lowering (IDEAL) trial population 7, 8, 9. With this model, we are able to estimate the individual 5‐year absolute risk reduction (ARR) for vascular events based on simple patient characteristics 7, 10.…”

Statin Use and Adverse Effects Among Adults >75 Years of Age: Insights From the Patient and Provider Assessment of Lipid Management (PALM) Registry

“…The 2013 American College of Cardiology (ACC)/American Heart Association (AHA) Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults acknowledges the limitations of existing data on older individuals and recommends individualizing the decision to initiate statins for primary prevention in adults >75 years 1. For secondary prevention, 3 trials found that high‐intensity statin therapy reduced cardiovascular events more than moderate‐intensity statin therapy, but these trials enrolled few patients >75 years and none >80 years8, 9, 10; however, there was sufficient evidence for moderate‐intensity statin therapy in secondary prevention patients of any age 11. The most recent 2016 US Preventive Services Task Force Recommendation Statement on Statin Use for the Primary Prevention of Cardiovascular Disease similarly avoids firm recommendations about statins for older adult patients (>75 years old), as do the European Society of Cardiology/European Atherosclerosis Society guidelines for the management of dyslipidemias in patients >80 years old, with insufficient evidence to make a recommendation in this population 12, 13…”