High burden of drug therapy in adult congenital heart disease: polypharmacy as marker of morbidity and mortality

AIMS: To assess medication use in adult congenital heart disease (ACHD) patients compared to the age- and sex-matched general population, identify patterns of pharmacotherapy, and analyse associations between pharmacotherapy and adverse outcomes in ACHD. METHODS AND RESULTS: Data of 14 138 ACHD patients from the CONCOR registry [35 (24–48) years, 49% male] and age- and sex-matched referents (1:10 ratio) were extracted from the Dutch Dispensed Drug Register for the years 2006–14. Adult congenital heart disease patients had more cardiovascular and non-cardiovascular drugs than referents (median 3 vs. 1, P < 0.001). Polypharmacy, defined as ≥5 dispensed drug types yearly, was present in 30% of ACHD and 15% of referents {odds ratio [OR] = 2.47 [95% confidence interval (CI) 2.39–2.54]}. Polypharmacy was independently associated with female sex [OR = 1.92 (95% CI 1.88–1.96)], older age [for men: OR = 2.3/10 years (95% CI 2.2–2.4) and for women: OR = 1.6/10 years (95% CI 1.5–1.6); P(interaction) < 0.001], and ACHD severity [mild: OR = 2.51 (95% CI 2.40–2.61), moderate: OR = 3.22 (95% CI 3.06–3.40), severe: OR = 4.87 (95% CI 4.41–5.38)]. Cluster analysis identified three subgroups with distinct medication patterns; a low medication use group (8-year cumulative survival: 98%), and a cardiovascular and comorbidity group with lower survival (92% and 95%, respectively). Cox regression revealed a strong association between polypharmacy and mortality [hazard ratio (HR) = 3.94 (95% CI 3.22–4.81)], corrected for age, sex, and defect severity. Polypharmacy also increased the risk of hospitalization for adverse drug events [HR = 4.58 (95% CI 2.04–10.29)]. CONCLUSION: Both cardiovascular and non-cardiovascular medication use is high in ACHD with twice as much polypharmacy compared with the matched general population. Patients with polypharmacy had a four-fold increased risk of mortality and adverse drug events. Recognition of distinct medication patterns can help identify patients at highest risk. Drug regimens need repeating evaluation to assess the appropriateness of all prescriptions. More high-quality studies are needed to improve ACHD care with more evidence-based pharmacotherapy.