D. Layton, N. Qayum, C. Doe, S. Freemantle, S. Shakir.
At launch (2005), ivabradine (Procoralan©) was indicated for treatment of chronic stable angina pectoris in patients with normal sinus rhythm, with a contraindication and/or intolerance for beta-blockers. A drug utilisation study was conducted to support risk management of the drug. Study objectives included examining contraindications, warnings for use and incidence of two adverse events: visual phosphenes and bradycardia (persistent heart rate <50bpm).
To develop a tool for use to support assessment of prescribing discordance with prescribing recommendations and explore impact on phosphenes and bradycardia incidence.
An observational single exposure cohort study. Exposure data were collected from dispensed prescriptions issued by primary care physicians November 2005 and May 2009; outcome data (including pre-existing patient medical conditions and/or drugs which carried contraindications and/or warnings for use) from forms sent to physicians ≥6 months after each patient’s first prescription. An algorithm based prescribing framework was developed and assisted with the assessment of available information according to the contraindications and warnings for use in the Summary of Product Characteristics. To explore impact of prescriber discordance, risk (%; + 95% Confidence Interval (CI)) of phosphenes and bradycardia were calculated by framework group (≥1 contraindication; ≥1 warnings for use; combination of >1 contraindication/>1 warning for use; concordant; unknown). Descriptive statistics were also calculated.
Final cohort comprised 4624 patients, median age 68 years (IQR 60, 77); 57% (n=2663) male. Contraindications and warnings for use were assessed for 3357 patients: 74% (n=2491) were concordant, 21% (n=701) had warnings for use, 4% (n=124) had contraindications and 1% (n=41) had a combination of contraindications and warnings for use. Bradycardia was reported for 96 patients (2.1% (1.6, 2.5) cohort) of which 73 were assessed by framework group: n=4 (3.2% (0.9, 8.3)) were contraindicated, n=17 (2.4% (1.4, 3.9)) had warnings for use, n=1 had combination of both, and n=51 (2.0% (1.5, 2.7)) were concordant. Phosphenes were reported for 140 patients (3.0% (2.5, 3.6) cohort), of which 104 were assessed by framework group: n=2 (1.6% (0.2, 5.8)) were contraindicated, n=23 had warnings for use (3.3% (2.1, 4.9)), n=1 had a combination of both, and n=78(3.1% (2.5, 3.9)) were concordant.
In this study, the incidence of bradycardia and phosphenes was common in all concordance groups, although estimates lacked precision. This study demonstrates the feasibility of using a framework to assess prescribing discordance as reported in drug utilisation studies to identify at-risk populations, which may help support post-marketing risk:benefit evaluations.