Candesartan cilexetil is not associated with cough in hypertensive patients with enalapril-induced cough

Abstract

The aim of this study was to evaluate the occurrence of dry cough during treatment with candesartan cilexetil, enalapril, or placebo in patients with hypertension and a history of angiotensin converting enzyme (ACE)-inhibitor-related cough. Patients with confirmed cough during an enalapril (10 mg) challenge period, followed by no cough during a placebo dechallenge period were randomized to 8 weeks of double-blind treatment with candesartan cilexetil (8 mg) (n = 62), enalapril (10 mg) (n = 66), or placebo (n = 26). Incidence and severity of dry cough was evaluated by the symptom assessment questionnaire, frequency of dry cough by a visual analog scale, and the possible impact on quality of life by the minor symptom evaluation (MSE) profile. The percentage of patients with cough was significantly lower with candesartan cilexetil (35.5%) than with enalapril (68.2%, P < .001), and did not differ between candesartan cilexetil and placebo (26.9%, P > .20). Patients coughed less frequently and with less severe cough with candesartan cilexetil than with enalapril, and similarly with candesartan cilexetil and placebo. Changes in the MSE profile were minor, although candesartan cilexetil had better scores for contentment than placebo (P = .03), and also tended to be associated with better sleep than enalapril (P = .08). In hypertensive patients with ACE-inhibitor-induced cough, the incidence, frequency, and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril, and no different from that found with placebo.

Using Routinely Collected Prescribing Data to Determine Drug Persistence for the Purpose of Pharmacovigilance

“…Using routinely collected primary care data, we are able to demonstrate that the 1, 2–3, and 4–6 month discontinuation rates for ramipril, simvastatin, and ARBs are similar to previously published ADR rates obtained from large clinical trials and postmarketing studies 20 – 32 …”

“…Using routinely collected primary care data, we are able to demonstrate that the 1, 2-3, and 4-6 month discontinuation rates for ramipril, simvastatin, and ARBs are similar to previously published ADR rates obtained from large clinical trials and postmarketing studies. [20][21][22][23][24][25][26][27][28][29][30][31][32] We identified that approximately 10% of patients prescribed ramipril discontinued within 31 days of their first prescription, a figure similar to previously published data, suggesting that between 13% and 18% of patients prescribed ramipril suffer an ADR and 8% discontinue treatment within 8 weeks of starting. [20][21][22] Similarly for simvastatin, 13.0% of patients discontinued within 3 months and 16% within 6 months of starting, figures similar to previous reports suggesting that 16% to 18% of patients prescribed simvastatin suffer an adverse drug event (ADE) and 18% discontinue therapy over a 3-to 6-month period.…”

Indications for and utilization of ACE inhibitors in older individuals with diabetes

“…Contraindications to treatment were considered rare because most individuals not tolerating an ACE can receive an ARB with a low likelihood of side effects. 29,30…”

Candesartan

“…Cough was infrequent in comparison with placebo (1.6% with candesartan vs. 1.1% with placebo) (8). In a placebo-controlled trial of 154 patients with a confirmed history of ACEI-induced cough, treatment with candesartan cilexetil, 8 mg/day over 8 weeks, significantly lowered the frequency and severity of dry cough to a level not significantly different from that reported in placebo recipients (97). This finding has been confirmed in a comparative trial of enalapril and calcium antagonists.…”

“…In hypertensive patients with confirmed enalapril-induced cough, the incidence (35.5% vs. 68.2%) frequency and severity of dry cough was significantly lower with candesartan cilexetil than with enalapril and not different from that found with placebo (97).…”