Humans ; Cardiovascular Diseases/chemically induced* ; East Asian People ; Risk Factors ; Heart Disease Risk Factors ; Lipids ; Anticholesteremic Agents/adverse effects* ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Treatment Outcome

Statins are a kind of prescription drug that is widely used to treat hyperlipidemia, coronary artery disease, and other atherosclerotic diseases. A common side effect of statin use is a mild rise in liver aminotransferases, which occurs in less than 3% of patients. Statin-related liver injury is most commonly caused by atorvastatin and simvastatin, but severe liver injury is uncommon. Therefore, understanding and evaluating hepatotoxicity and weighing the benefits and risks is of great significance to better realize the protective effect of statins.
Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Atorvastatin/adverse effects* ; Simvastatin/adverse effects* ; Chemical and Drug Induced Liver Injury/drug therapy* ; Drug-Related Side Effects and Adverse Reactions/drug therapy*

OBJECTIVE: To identify mitochondrial gene variants associated with statin-induced myalgia in Chinese patients with coronary artery disease (CHD). METHODS: This study was conducted in a cohort of 403 patients with CHD receiving rosuvastatin therapy, among whom 341 patients had complete follow-up data concerning myalgia and 389 patients had documented measurements of plasma creatine kinase (CK) level. All these patients underwent genetic analysis using GSA chip for detecting mitochondria gene variants associated with myalgia. A logistic regression model was used to assess the association between 69 mitochondrial single-nucleotide polymorphisms (SNPs) and myopathy in 341 patients. The impact of these mutation sites on CK levels in 389 patients was evaluated by linear regression analysis. RESULTS: G12630A variant was identified to correlate with an increased risk of myalgia in CHD patients (OR: 8.689, 95% CONCLUSIONS Mitochondrial G12630A variation is associated with statin-induced myalgia in patients with CHD, indicating the necessity of different treatment strategies for patients who carry this risk allele.
China ; Coronary Artery Disease/genetics* ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects* ; Mitochondria ; Myalgia ; Polymorphism, Single Nucleotide

Atorvastatin is one of the most widely prescribed medications for dyslipidemia treatment. In Korea, post combined therapy with ezetimibe, a 73-year-old woman was reported by a community pharmacy to have experienced visual field defect, which recovered after drug discontinuation. She had never experienced this symptom before, and several studies have reported an association between use of statins and visual disorders such as blurred vision, diplopia, and cataract. Blockage of cholesterol accumulation, oxidative stress, or myopathy is expected to be a cause of this symptom. Naranjo scale, Korean causality assessment algorithm (Ver.2), and World Health Organization-Uppsala Monitoring Center (WHO-UMC) criteria were the three tools used to determine causality between the visual disorder and atorvastatin. The results represent ‘probable’, ‘certain’, and ‘probable/likely’ causality, respectively. Our results, in combination with a review of literature, indicate that ocular adverse effects are highly likely related to atorvastatin.
Aged ; Atorvastatin Calcium ; Cataract ; Cholesterol ; Diplopia ; Drug-Related Side Effects and Adverse Reactions ; Dyslipidemias ; Ezetimibe ; Female ; Global Health ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Muscular Diseases ; Oxidative Stress ; Pharmacies ; Vision Disorders ; Visual Fields

Gynecomastia is a common benign disease characterized by the progressive enlargement of the glandular tissue of the male breast due to an imbalance between the levels of estrogen and androgen in the blood. The etiology may vary and may be physiological, pharmacological, pathological, or even idiopathic. Among men, drug-induced gynecomastia may account for 10% to 20% of cases. The literature contains six case reports of rosuvastatin-induced gynecomastia. Withdrawal of statin or switching to a less potent statin can lead to symptom improvement and avoidance of unnecessary tests and patient anxiety. A 62-year-old male patient developed unilateral gynecomastia after 13 months of rosuvastatin therapy. After switching to a different statin (pravastatin), his symptoms improved within 2 months. Thus, clinicians should be aware of the possibility of occurrence of gynecomastia when statins are prescribed.
Anxiety ; Breast ; Drug-Related Side Effects and Adverse Reactions ; Estrogens ; Gynecomastia ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Male ; Middle Aged ; Rosuvastatin Calcium

OBJECTIVES: To enable early detection of adverse drug reactions (ADRs) in patients using HMG-CoA reductase inhibitors (statins), we developed an algorithm that automatically detects liver injury caused by statins from Electronic Medical Record (EMR) data. We verified the performance of our algorithm through manual ADR assessment and a direct chart review. METHODS: The subjects in this study were patients who had been prescribed a statin for the first time among outpatients in Seoul St. Mary's Hospital in Korea between January 2009 and December 2012. We extracted basic information about the patients, including laboratory information, underlying disease, diagnosis information, prescription information, and concomitant drugs. We developed an automatic ADR detection algorithm by using EMR data. We validated the results of the algorithm through a chart review. RESULTS: We developed the algorithm to assess ADR occurrences based on alanine transaminase (ALT) and alkaline phosphatase (ALP) levels. According to the proposed algorithm, any of these result options could be attained: ADR-free, little association, strong association, and weak association or indeterminable. The results of the ADR assessments obtained using the proposed algorithm showed that the data of 126 patients (1.4% of all 9,241 patients) included suspicious figures, thus indicating the possibility of an ADR. In the EMR chart review for verifying the algorithm, ADRs of 33 patients were not associated with statin use; therefore, the ADR occurrence rate was found to be 1.0% (93/9,241). Therefore, the positive predictive value was calculated to be 73.8% (93/126; 95% confidence interval, 69.2%–77.6%). No differences were observed between statin types (p = 0.472). CONCLUSIONS: For early detection of statin-induced liver injury, we developed an automatic ADR assessment algorithm. We expect that algorithms that are more reliable can be developed if we conduct supplement clinical studies with a focus on adverse drug effects.
Alanine Transaminase ; Alkaline Phosphatase ; Diagnosis ; Drug-Induced Liver Injury ; Drug-Related Side Effects and Adverse Reactions ; Electronic Health Records ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; Korea ; Liver ; Outpatients ; Oxidoreductases* ; Prescriptions ; Seoul

Drug-induced liver injury (DILI) remains a significant clinical challenge and is the leading cause of acute liver failure in most countries. An aging population that uses more medications, a constant influx of newly developed drugs and a growing risk from unfamiliar herbal and dietary supplements will make DILI an increasing part of clinical practice. Currently, the most effective strategy for disease management is rapid identification, withholding the inciting agents, supportive care and having a firm understanding of the expected natural history. There are resources available to aid the clinician, including a new online "textbook" as well as causality assessment tools, but a heightened awareness of risk and the disease's varying phenotypes and good history-taking remain cornerstones to diagnosis. Looking ahead, growing registries of cases, pharmacoepidemiology studies and translational research into the mechanisms of injury may produce better diagnostic tools, markers for risk and disease, and prevention and therapeutics.
Age Factors ; Anti-Infective Agents/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anticonvulsants/adverse effects ; Biopsy ; Dietary Supplements/adverse effects ; Drug-Induced Liver Injury/*diagnosis/epidemiology ; Drugs, Chinese Herbal/adverse effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Incidence ; Liver/pathology ; Liver Function Tests ; Risk Factors ; Tumor Necrosis Factor-alpha/antagonists & inhibitors

BACKGROUND/AIMS: This study was designed to evaluate the dose-effect relationship of statins in patients with ischemic congestive heart failure (CHF), since the role of statins in CHF remains unclear. METHODS: The South koreAn Pitavastatin Heart FaIluRE (SAPHIRE) study was designed to randomize patients with ischemic CHF into daily treatments of 10 mg pravastatin or 4 mg pitavastatin. RESULTS: The low density lipoprotein cholesterol level decreased by 30% in the pitavastatin group compared with 12% in the pravastatin (p < 0.05) group. Left ventricular systolic dimensions decreased significantly by 9% in the pitavastatin group and by 5% in the pravastatin group. Left ventricular ejection fraction (EF) improved significantly from 37% to 42% in the pitavastatin group and from 35% to 39% in the pravastatin group. Although the extent of the EF change was greater in the pitavastatin group (16% vs. 11%) than that in the pravastatin group, no significant difference was observed between the groups (p = 0.386). Exercise capacity, evaluated by the 6-min walking test, improved significantly in the pravastatin group (p < 0.001), but no change was observed in the pitavastatin group (p = 0.371). CONCLUSIONS: Very low dose/low potency pravastatin and high dose/high potency pitavastatin had a beneficial effect on cardiac reverse remodeling and improved systolic function in patients with ischemic CHF. However, only pravastatin significantly improved exercise capacity. These findings suggest that lowering cholesterol too much may not be beneficial for patients with CHF.
Aged ; Biological Markers/blood ; Cholesterol, LDL/*blood ; Down-Regulation ; Dyslipidemias/blood/diagnosis/*drug therapy/epidemiology ; Exercise Tolerance/drug effects ; Female ; Heart Failure/diagnosis/*drug therapy/epidemiology/physiopathology ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/*administration & dosage/adverse effects ; Male ; Middle Aged ; Myocardial Ischemia/diagnosis/*drug therapy/epidemiology/physiopathology ; Pravastatin/*administration & dosage/adverse effects ; Prospective Studies ; Quinolines/*administration & dosage/adverse effects ; Recovery of Function ; Republic of Korea ; Stroke Volume/drug effects ; Time Factors ; Treatment Outcome ; Ventricular Function, Left/drug effects ; Ventricular Remodeling/drug effects

A post-marketing study is an integral part of research that helps to ensure a favorable risk-benefit profile for approved drugs used in the market. Because most of post-marketing studies use observational designs, which are liable to confounding, estimation of the causal effect of a drug versus a comparative one is very challenging. This article focuses on methodological issues of importance in designing and analyzing studies to evaluate the safety of marketed drugs, especially marketed traditional Chinese medicine (TCM) products. Advantages and limitations of the current designs and analytic methods for postmarketing studies are discussed, and recommendations are given for improving the validity of postmarketing studies in TCM products.
Anaphylaxis ; chemically induced ; Drug-Related Side Effects and Adverse Reactions ; Drugs, Chinese Herbal ; adverse effects ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors ; adverse effects ; Neural Networks (Computer) ; Product Surveillance, Postmarketing ; Research Design ; Rhabdomyolysis ; chemically induced

Hepatic adverse drug reactions (ADRs) to certain drugs may differ within each country, reflecting different patterns of prescription, socioeconomic status, and culture. The purpose of this study was to assess the suspected cause of hepatic ADRs using the spontaneously reported pharmacovigilance data from Korea. A total of 9,360 spontaneously reported adverse drug events (ADEs) from nine Pharmacovigilance Centers were analyzed. Risk of hepatic ADEs was assessed by calculating the reporting odds ratio (ROR). Of the 9,360 cases, 567 hepatic ADEs were reported. The most frequently prescribed drug classes inducing hepatic ADEs were anti-tuberculotics, cephalosporins, valproic acids, penicillins, quinolones, non-steroidal anti-inflammatory drugs (NSAIDs), anti-viral agents, and statins. ROR values were especially high in anti-tuberculosis drugs, systemic antifungal drugs for systemic use, anti-epileptics, propylthiouracil, and herbal medicines. Underlying diseases such as tuberculosis (6.9% vs 0.9%), pneumonia (4.9% vs 1.7%), intracranial injury including skull fracture (4.5% vs 0.9%), HIV (3.4% vs 0.4%), subarachnoid hemorrhage (2.8% vs 0.5%), and osteoporosis (2.4% vs 1.4%) were significantly more common in hepatic ADE group. In conclusion, anti-infective drugs, anti-epileptics, NSAIDs and statins are the most common suspects of the spontaneously reported hepatic ADEs, in Korea. Careful monitoring for such reactions is needed for the prescription of these drugs.
Adult ; *Adverse Drug Reaction Reporting Systems/statistics & numerical data ; Aged ; Anti-Infective Agents/adverse effects ; Anti-Inflammatory Agents, Non-Steroidal/adverse effects ; Anticonvulsants/adverse effects ; Drug Monitoring ; Drug-Induced Liver Injury/*epidemiology/*etiology ; Female ; Humans ; Hydroxymethylglutaryl-CoA Reductase Inhibitors/adverse effects ; Male ; Middle Aged ; Odds Ratio ; Pharmacovigilance ; Republic of Korea/epidemiology ; Risk Factors