Comparing the risk of metoprolol-related adverse drug reactions between women and men with heart failure using effectiveness outcomes as a proxy: a population-based cohort study using CPRD

Study identification

• PURI:
  https://redirect.ema.europa.eu/resource/105419
• EU PAS number:
  EUPAS105418
• Study ID:
  105419
• Official title and acronym:
  Comparing the risk of metoprolol-related adverse drug reactions between women and men with heart failure using effectiveness outcomes as a proxy: a population-based cohort study using CPRD
• DARWIN EU® study:
  No
• Study countries:
  Netherlands
• Study description:
  Women are approximately 1.5 times more likely than men to have adverse drug reactions (ADRs). Although sex differences in cardiovascular medicine are well known, clinical relevance of these differences remains mostly unproven. One of the relevant medications are beta-blockers, that represent a pillar in the pharmacological treatment of patients with chronic heart failure (CHF). Current guidelines advise the use of bisoprolol, metoprolol, nebivolol and carvedilol interchangeably in the treatment of CHF. Despite this, beta-blockers are not a homogeneous class, with differences in beta-1/beta-2-receptor selectivity as well as vasodilatory action. Moreover, different drugs behind each generation exhibits unique pharmacokinetic and pharmacodynamic characteristics, which can lead to differential responses to the treatment. However, it has been shown that women with HF are underrepresented in the randomized controlled trials (RCTs). Sex differences with respect to the ADRs are also insufficiently investigated. From 155 eligible HF trials identified in a systematic review, only 11 reported ADR data for women and men separately. Despite the sex-neutral approach of HF guidelines, findings from clinical practice suggest that a sex-specific recommendations should be addressed. This study aims to determine if sex appears to modify the safety of metoprolol and carvedilol in CHF by using data from general practitioner offices from across the UK. We will apply the Active Comparator, New User design to analyse effectiveness outcomes of metoprolol and carvedilol as a proxy of ADRs in women and men with HF.
• Study status:
  Ongoing

Research institution and networks

Institutions

Division of Pharmacoepidemiology & Clinical Pharmacology (PECP), Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University

Netherlands

Contact details

Sophie Bots

Study contact

[e-mail]

Olaf Klungel

Primary lead investigator

Study timelines

Date when funding contract was signed

Planned: 15/04/2023

Actual: 15/04/2023

Data collection

Planned: 26/06/2023

Actual: 26/06/2023

Date of final study report

Planned: 15/10/2023

Sources of funding

Other

More details on funding

University

Regulatory

• Was the study required by a regulatory body?:
  No
• Is the study required by a Risk Management Plan (RMP)?:
  Not applicable