In patients with a heart attack, it is of important to restore the blood flow to the heart muscle as early as possible. Primary percutaneous catheter intervention (PCI) is the recommended treatment to restore blood supply. To reduce the complication risk of PCI and of having another heart attack it is recommended to provide a combination of 2 antiplatelet drugs, known as dual antiplatelet therapy (DAPT) to patients for at least 1 year. DAPT combines aspirin and a P2Y12 inhibitor drug, such as clopidogrel.
Changes in antiplatelet medication over time are common. Reasons for these changes might be multiple, including the risk of bleeding and of a new heart attack, socioeconomic factor and/or genetics. To date, data from large clinical studies to guide the optimal approach to change DAPT are limited. In addition, concerns surrounding the safety of switching between different types of P2Y12 inhibitors have emerged recently.
This study aims to understand, in a real-world setting, how and when antiplatelet medication is changed in patients with a heart attack who are treated with PCI and DAPT, describe groups of patients who receive different types of DAPT, and to evaluate how changes in DAPT affect the risk of occurrence of new cardiovascular diseases (heart attack, stroke, major bleeding, cardiovascular revascularisation, all cause death and cardiovascular death) and major bleeding. The study will be conducted in seven countries, including the UK, and findings will be used to guide and improve the clinical care of patients who have a heart attack.
This study aims to describe the switch patterns between P2Y12 inhibitors in patients treated with percutaneous catheter intervention (PCI) and dual antiplatelet therapy (DAPT: combining aspirin with a P2Y12 inhibitor) for ST-elevation myocardial infarction (STEMI) or non-STEMI (NSTEMI). The study will also evaluate the impact that these switches have on the risk of cardiovascular events and major bleeding and describe characteristics of DAPT users. The study will use CPRD data linked to HES and ONS to create a cohort of all PCI-treated patients for STEMI or NSTEMI, aged ?18 years and initiating DAPT between 2015 and 2018. Diagnoses and procedures will be obtained from CPRD or HES data, drug information from CPRD and death data from ONS.
First switch between P2Y12 inhibitors will be described in terms of counts, percentages and incidence rates with 95% confidence intervals (CI) and median time to switch estimated using Kaplan-Meier methods. In secondary analyses, time to all-cause death and cardiovascular outcomes (myocardial infarction, ischaemic stroke, coronary revascularisation and cardiovascular death), will be assessed using Kaplan-Meier analysis amongst patients experiencing different patterns of medication switch. In patients initiated with prasugrel/ticagrelor-based DAPT, the associations between MACE and major bleeding with P2Y12 inhibitor de-escalation (i.e. switching from more to less potent P2Y12 inhibitors from prasugrel or ticagrelor to clopidogrel) will be assessed using time-dependent exposure Cox proportional hazards models; and the net clinical benefit determined by subtracting aggregate incidence rate of major bleeding from the aggregated incidence rate of MACE over one year of follow-up in de-escalating patients versus patients remaining on prasugrel or ticagrelor. Patient characteristics will also be described, overall, by switch pattern and outcome.
Primary outcomes are:
The occurrence and the time to the following switches between P2Y12 inhibitors:
? escalation to prasugrel or ticagrelor in patients treated with clopidogrel at baseline index date;
? de-escalation to clopidogrel in patients treated with prasugrel or ticagrelor at baseline index date.
To account for uncertainty in the estimation of the duration of drug exposure, patients will be considered as switching between P2Y12 inhibitors if the new antiplatelet is prescribed for a period of [-7 days; +7 days] from the end date of exposure to the former antiplatelet.
Secondary outcomes are:
All-cause death; Cardiovascular death; Non-fatal myocardial infarction; Non-fatal ischemic stroke; MACE (Major Adverse Cardiac Event, i.e. first occurrence of non-fatal ischemic stroke, non-fatal myocardial infarction or all-cause death); Major bleeding (i.e. hospitalisation with a primary diagnosis of bleeding); Coronary revascularisation (i.e. PCI or coronary artery bypass graft surgery [CABG])
Joseph Kim - Chief Investigator - IQVIA Ltd ( UK )
Mounika Parimi - Corresponding Applicant - IQVIA - UK
- Collaborator -
Bharat Thakrar - Collaborator - IQVIA
Catrina Richards - Collaborator - IQVIA Ltd ( UK )
Jessica Lundbom - Collaborator - IQVIA Ltd ( UK )
Mar Pujades Rodriguez - Collaborator - IQVIA
Jessica Lundbom - Collaborator - IQVIA Ltd ( UK )
Mar Pujades Rodriguez - Collaborator - IQVIA
HES Admitted Patient Care;ONS Death Registration Data