isotretinoin and Myocardial-Infarction

Case reports have suggested isotretinoin exposure may be associated with adverse cardiac events. There are limited data where the cardiovascular safety of isotretinoin is systematically evaluated.. The aim of this study was to determine the strength of association between isotretinoin exposure and adverse cardiovascular events.. This was a population-based retrospective cohort study within an integrated healthcare delivery system. Adults ≥ 18 years of age with acne between 2009 and 2018 were included. Exposure to isotretinoin was identified using pharmacy records, and propensity score 1:1 matching was performed. The primary outcome was a composite of cardiovascular outcomes, including acute myocardial infarction, heart failure, and all-cause death.. The cohort consisted of 12,140 adults (10.5%) exposed to isotretinoin and 103,126 adults who were never exposed. Mean follow-up was 7.1 ± 2.9 years. After propensity score 1:1 matching, 23,844 patients were included. The rates of the composite cardiovascular outcomes were 0.47 versus 0.48 per 1000 person-years in the isotretinoin and non-exposed groups, respectively. No significant association was observed between isotretinoin treatment and the composite cardiovascular outcomes (adjusted hazard ratio [HR] 0.99, 95% confidence interval [CI] 0.62-1.58), all-cause mortality (adjusted HR 1.10, 95% CI 0.62-1.95), acute myocardial infarction (adjusted HR 1.00, 95% CI 0.33-3.09), congestive heart failure (adjusted HR 0.45, 95% CI 0.14-1.40), or atrial fibrillation (adjusted HR 0.44, 95% CI 0.12-1.65).. Among adult patients with acne, no association was found between exposure to isotretinoin and an increased risk of cardiovascular events. Physicians should not be discouraged from prescribing isotretinoin out of concern for cardiovascular effects.

Topics: Acne Vulgaris; Adolescent; Adult; Aged; California; Case-Control Studies; Female; Follow-Up Studies; Heart Disease Risk Factors; Heart Failure; Humans; Isotretinoin; Male; Middle Aged; Myocardial Infarction; Prevalence; Retrospective Studies; Risk Factors; Young Adult

The use of isotretinoin has been associated with mild changes in the metabolic profile of adolescents. In very rare cases, a possible association with myocardial infarction, stroke and thromboembolic events has been reported. In this report we describe the potential association of isotretinoin with the occurrence of an acute myocardial infarction in a very young girl. OCT provided unique visualization of the culprit lesion.

Topics: Acne Vulgaris; Adult; Coronary Angiography; Coronary Vessels; Dermatologic Agents; Female; Humans; Isotretinoin; Myocardial Infarction; Thrombectomy; Tomography, Optical Coherence; Treatment Outcome

Redox imbalance elicited by oxidative stress contributes to pathogenic remodeling of ion channels that underlies arrhythmogenesis and contractile dysfunction in the failing heart. This study examined whether the expression of K(+) channels in the remodeled ventricle is controlled by the thioredoxin system, a principal oxidoreductase network regulating redox-sensitive proteins. Ventricular dysfunction was induced in rats by coronary artery ligation, and experiments were conducted 6-8 wk postinfarction. Biochemical assays of tissue extracts from infarcted hearts showed that thioredoxin reductase activity was decreased by 32% from sham-operated controls (P < 0.05), whereas thioredoxin activity was 51% higher postinfarction (P < 0.05). These differences in activities paralleled changes in protein abundance as determined by Western blot analysis. However, whereas real-time PCR showed thioredoxin reductase mRNA levels to be significantly decreased postinfarction, thioredoxin mRNA was not altered. In voltage-clamp studies of myocytes from infarcted hearts, the characteristic downregulation of transient-outward K(+) current density was reversed by exogenous pyruvate (5 mmol/l), and this effect was blocked by the specific inhibitors of the thioredoxin system: auranofin or 13-cis-retinoic acid. Real-time PCR and Western blot analyses of myocyte suspensions from infarcted hearts showed that pyruvate increased mRNA and protein abundance of Kv4.2 and Kv4.3 channel alpha-subunits as well as the accessory protein KChIP2 when compared with time-matched, untreated cells (P < 0.05). The pyruvate-induced increase in Kv4.x expression was blocked by auranofin, but the upregulation of KChIP2 expression was not affected. These data suggest that the expression of Kv4.x channels is redox-regulated by the thioredoxin system, which may be a novel therapeutic target to reverse or limit electrical remodeling of the failing heart.

Topics: Animals; Auranofin; Blotting, Western; Disease Models, Animal; Heart Failure; Isotretinoin; Kv Channel-Interacting Proteins; Male; Membrane Potentials; Myocardial Infarction; Myocardium; Oxidation-Reduction; Oxidative Stress; Patch-Clamp Techniques; Potassium; Pyruvic Acid; Rats; Rats, Sprague-Dawley; Reverse Transcriptase Polymerase Chain Reaction; Shal Potassium Channels; Thioredoxin-Disulfide Reductase; Thioredoxins; Ventricular Remodeling

Topics: Acne Vulgaris; Administration, Oral; Canada; Dermatologic Agents; France; Humans; Isotretinoin; Myocardial Infarction; Stroke; Thromboembolism