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Clopidogrel – bad on the rebound?
After stopping aspirin or heparin treatment for an acute coronary syndrome (ACS), a clustering of thrombotic events has been described–the so-called “rebound phenomenon”. Could the same phenomenon occur with clopidogrel, and might this explain recent reports of late stent thrombosis following its discontinuation?
Three thousand, one hundred and thirty-one patients were retrospectively selected from the Department of Veterans Affairs (VA) Veterans Health Administration Cardiac Care Follow-up Clinical Study, which uses national data for quality monitoring in the United States. All had had an ACS and had been discharged on clopidogrel treatment. The authors examined the rates of all-cause mortality or acute myocardial infarction after stopping clopidogrel treatment.
Among medically treated patients, the mean duration of clopidogrel treatment was 302 days, and death or myocardial infarction occurred in 17.1% (n = 268). 60.8% (n = 163) of events occurred 0–90 days after cessation of clopidogrel treatment, 21.3% (n = 57) occurred at 91–180 days, and 9.7% (n = 26) occurred 181–270 days later. In multivariable analysis (including adjustment for the length of clopidogrel treatment), the first 90-day interval after stopping treatment with clopidogrel was associated with a significantly higher risk of adverse events (incidence rate ratio 1.98 compared with the 90–180 day interval). Among patients with ACS who underwent percutaneous coronary intervention, death or myocardial infarction occurred in 7.9% (n = 124) of patients in the first 90 days after stopping treatment, again giving a significantly higher risk of adverse events (incidence rate ratio 1.82).
The increased incidence of adverse effects in the first 90 days after stopping clopidogrel, regardless of whether the ACS was treated medically or with intervention, suggests the possibility of a clopidogrel rebound effect. This finding will need to be confirmed by other databases, but further investigation into the mechanisms of this effect would seem warranted.
▸ Ho PM, Peterson ED, Wang L, . Incidence of death …
American Journal of Medicine; American Journal of Physiology: Heart and Circulatory Physiology; Annals of Emergency Medicine; Annals of Thoracic Surgery; Archives of Internal Medicine; BMJ; Chest; European Journal of Cardiothoracic Surgery; JAMA; Journal of Clinical Investigation; Journal of Diabetes and its Complications; Journal of Immunology; Journal of Thoracic and Cardiovascular Surgery; Lancet; Nature Medicine; New England Journal of Medicine; Pharmacoeconomics; Thorax
Dr Alistair C Lindsay, Dr Katie Qureshi