Adverse event with first-dose perindopril in congestive heart failure

Abstract

The first-dose effect of perindopril, a long-acting angiotensin-converting-enzyme inhibitor (ACEI), has been reported to influence blood pressure (BP) to the same extent as placebo. Therefore, perindopril has been suggested as the drug of choice when initiating ACEI therapy in heart failure. I report a patient with a serious complication after the first dose of perindopril. A 61-year-old man with episodes of mild chest pain for 3 weeks was admitted with increasing dyspnoea. He had lung rales, raised jugular venous pressure, no heart or carotid murmurs, and no liver enlargement or peripheral oedema. On admission he was treated with intravenous diuretics and a low-dose dopamine infusion. The BP was never lower than 130/90 mm Hg and dopamine was stopped the following morning. Creatine kinase MB fraction rose to 70 IU (normal <12 IU) and electrocardiograms indicated an inferior myocardial infarction. Echocardiography revealed inferolateral left ventricular dyskinesia. Previously, he had been treated with antihypertensive drugs for 5 years. 4 months before admission he took captopril (unknown dosage), which was stopped after 1 month due to a skin rash. During hospital admission his BP remained stable at 130–150/80–90 mm Hg measured three times daily and he was in constant sinus rhythm. ACEI therapy was initiated with a single dose of 2 mg perindopril 5 days after admission. The evening BP was 130/80 mm Hg 5–6 h after perindopril. The next morning he had visual disturbances. The BP that had been 90/60 mm Hg before the patient expressed any complaints normalised spontaneously. Neurological examination revealed left-sided hemianopia and no other neurological disturbances. Computed tomography showed an ischaemic infarct of the region supplied by the right posterior cerebral artery. Laboratory values before start of perindopril were: sodium 137 mmol/L, potassium 3·8 mmol/L, and creatinine 138 mol/L. The patient was on oral furosemide 40 mg four times daily, spironolactone 25 mg daily, potassium supplement, aspirin 150 mg daily, and phenoxymethylpenicillin 800 mg three times daily (pneumonia was initially suspected but not verified and the patient was afebrile when perindopril was given). The visual defect remained the same at his discharge 9 days later. Severe and moderate hypotension after initiation of 2·5 mg enalapril occurred in 0·5% and 4·7%, respectively, of 1210 heart failure patients. In the studies of left ventricular dysfunction (7487 eligible patients), 0·04% developed a stroke and 2·2% became hypotensive when enalapril 2·5 mg twice daily was initiated with most patients on diuretics. Although withdrawal of diuretics has been recommended before initiation of ACEI, such action does not always prevent severe hypotension. Perindopril has a long half-life Sunscreen alone with SPF after 15 min