Dual antiplatelet therapy (DAPT) is a combination of drugs that prevents clots from forming in the heart's arteries. DAPT is given to people who have had a heart attack and had a coronary stent put in (a wire-mesh tube placed in the coronary arteries that supply blood to the heart, to keep them open) or heart bypass surgery (a type of surgery that improves blood flow to the heart). Some people are prescribed an anticoagulant, another type of drug that also prevents blood clots, at the same time.
DAPT and anticoagulants increase the risk of bleeding. Some people experience major bleeding that needs hospitalisation. Many more people experience minor bleeding, such as bleeding in the stomach or bowel, nosebleeds, bleeding from gums, and excessive bruising. This can cause discomfort and anxiety, take up consultations with GPs and may cause patients to stop taking their medications as prescribed.
We propose to use CPRD GOLD, a large GP database of routinely collected data, and Hospital Episode Statistics, a database describing patients' attendances and admissions to hospital, to determine how many people experience bleeding after being prescribed DAPT. We will compare patients who take different combinations of DAPT (with or without an anticoagulant).
Objective: To quantify the incidence of all bleeding events in patients exposed to different regimens of dual antiplatelet therapy (DAPT) or triple therapy (DAPT and an anticoagulant) and to estimate hazard ratios for bleeding for different antiplatelet regimens.
Methods: Retrospective population-based cohort study. We will identify three patient cohorts, percutaneous coronary intervention (PCI), coronary artery bypass grafting (CABG), and acute coronary syndrome (ACS) treated by medication only, in Hospital Episode Statistics (HES). We will follow all patient cohorts through CPRD GOLD. For the PCI cohort we will compare aspirin and clopidogrel (AC, reference) vs. aspirin and prasugrel (AP) or aspirin and ticagrelor (AT). For the CABG and ACS cohorts we will compare aspirin (reference) vs. AC. (For all three cohorts we will also compare AC, AP or AT (reference) vs. triple therapy, TT). The primary outcome will be any bleeding event. Secondary outcomes will be all-cause mortality; cardiovascular mortality; mortality from bleeding; hospital admission.
Data analysis: We will calculate crude and adjusted rates of bleeding (events/person time) with 95% confidence intervals (CIs) for each exposure group and use Cox proportional hazards models to estimate adjusted hazard ratios (HRs) with 95% CIs for time to first bleeding event.
Health Outcomes to be Measured:
Primary: any bleeding event (classified as minor or major using the Bleeding Academic Research Consortium (BARC) bleeding scale). For each patient we will define all bleeding events in HES and CPRD (and cross-validate hospital admissions in HES) during follow-up. Secondary outcomes will be: any major bleeding event; any minor bleeding event; all-cause mortality; cardiovascular mortality; mortality from bleeding (these will be identified from linked Office for National Statistics (ONS) data) and hospital admission for a bleeding event (Inpatient HES).
HES Admitted Patient Care;HES Admitted Patient Care;HES Outpatient;HES Outpatient;ONS Death Registration Data;ONS Death Registration Data;Patient Level Index of Multiple Deprivation;Patient Level Index of Multiple Deprivation;Practice Level Index of Multiple Deprivation