The sulfhydryl group of
clopidogrel metabolite could induce
insulin autoimmune syndrome (IAS) with
hypoglycemia as the major symptom. For patients with
cardiovascular disease taking
clopidogrel for vascular protection, this adverse event
hypoglycemia increases the risk of cardiovascular events. However, discontinuing
clopidogrel leaves patients without appropriate antiplatelet
therapy. Treating IAS with
glucocorticoids is also risky for these patients' primary
cardiovascular diseases. Early recognition and appropriate treatment of
clopidogrel-induced IAS (CIAS) would be beneficial for patients. This research aimed to discover the clinical features and investigate optimal therapeutic management of CIAS. We systematically searched for cases of CIAS in PubMed and Embase and performed data mining in Food and Drug Administration Adverse Event Reporting System (FAERS). In the CIAS series, clinical features were summarized and compared to 287 IAS cases, including demographic information, HLA alleles, onset, and symptoms. The
therapeutic effect of
glucocorticoids was compared between the receiving group and the not-receiving group. The possibilities of common
antiplatelet drugs to induce
hypoglycemia/IAS were investigated with chemical structure and FAERS reports. A CIAS series of 51 patients was established. CIAS had an onset age of 74.8±8.6 years old, 92.2% male, and a balanced proportion of East Asians and non-East Asians.
Confusion occurred more frequently in CIAS than in IAS from various causes, while the other symptoms and
hypoglycemia types were similar. The recovery time was approximately the same whether using
glucocorticoids/
immunotherapy in CIAS or not. Among common
antiplatelet drugs,
ticagrelor and
rivaroxaban were unlikely to induce
hypoglycemia/IAS.
Clopidogrel is a distinctive cause of IAS featuring an elderly male presenting
confusion as the symptom of
hypoglycemia.
Glucocorticoids/
immunotherapy might not be necessary for the long-term recovery of CIAS. To balance the risks of
hypoglycemia and cardiovascular events, substituting
clopidogrel with
ticagrelor and
rivaroxaban might be considered.