P1873Incidence rates of oedema with triple therapy amlodipine/valsartan/HCTZ as compared to valsartan/amlodipine and valsartan/HCTZ dual combination therapy

Abstract

Background: With increasing prevalence of hypertension and lower treatment thresholds and targets, more patients will need single‐pill triple combination treatment. To achieve a long‐term adherence with the prescribed medication, a good favourable tolerability profile is an another crucial prerequisite. Peripheral oedema, a known side effect of CCBs, like amlodipine, is one of the most frequent adverse events (AEs) reported in hypertensive patients and is often associated with lower adherence or even treatment discontinuation. Purpose: We present the safety profile of triple therapy focusing on the incidence rate of oedema for amlodipine/valsartan/hydrochlorothiazide (Aml/Val/HCTZ) high dose (10/320/25 mg) as compared with the respective dual combinations observed in a large double‐blind, controlled phase III study. Results: The study enrolled patients with systolic BP (SBP) ≥145 mmHg and diastolic BP (DBP) ≥100 mmHg. After a single‐blind treatment run‐in phase, patients received double‐blind treatment during a 2 week force‐titration phase followed by Val/Aml/HCTZ (320/10/25 mg; n=583), Val/Aml (320/10 mg; n=568), HCTZ/Aml (25/10 mg; n=561) or Val/HCTZ (320/25 mg; n=559) for 6 weeks. Treatment groups were comparable with respect to demographic characteristics: 71.6% of randomized population were Caucasian, 55.3% were male and mean age was 53.2 years with 14.0% ≥65 years. Mean sitting SBP/DBP was 169.9/106.5 mmHg at baseline. Over 90% of patients completed the study with completion rates being similar across the treatment groups. Most frequently reported AEs in the total safety population (N=2268) were peripheral oedema (5.7%), headache (5.4%), and dizziness (5.2%). The incidence rates of peripheral oedema with Aml/Val/HCTZ (4.5%) was significantly lower than Aml/Val (8.5%; p=0.0057) and Aml/HCTZ (8.9%; p=0.0029) but greater than that reported with Val/HCTZ (0.9%; p=0.0002). Peripheral oedema suspected to be related to study drug occurred in 3.3%, 6.2%, 7.3%, 0.4% of patients on triple therapy, Aml/Val, Aml/HCTZ and Val/HCTZ and led to discontinuation of 0.2%, 0.4%, 0.9%, 0% of patients, respectively. The majority of cases of peripheral oedema were mild or moderate in severity. Results between treatment groups were generally consistent regardless of age, gender and race. An analysis in which multiple preferred terms related to oedema (e.g., generalized oedema, pitting oedema, peripheral oedema, eyelid oedema, gravitational oedema, periorbital oedema, joint swelling, swelling and swelling face) were pooled (oedema pooled) demonstrated consistent results: triple therapy (6.7%) vs Aml/Val (12.4%, p=0.0012) vs Aml/HCTZ (11.9%, p=0.0030) and vs Val/HCTZ (1.6%; p<0.0001). Conclusion: High‐dose Aml/Val/HCTZ was generally well tolerated in patients within stage II hypertension range. The most frequent AE with Aml/Val/HCTZ was peripheral oedema. However, the absolute incidence of peripheral oedema was small and lower as compared with Aml/Val or Aml/HCTZ.