Table 5.

Potential clinical (event) endpoints, including advantages and limitations

Clinical Endpoints	Details	Advantages	Limitations
AS-RELATED END POINTS
Aortic Valve Replacement	TAVI or SAVR with or without coronary bypass grafting / aortic root replacement	- Clinical endpoint attributable to the disease process being modified - Easy and accurate to capture – may be available from electronic patient records and data linkage - The major intervention that patients and physicians are keen to avoid	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Optimal timing of AVR not yet established (strategies may differ between institutions and likely to change within the follow up period of future trials)
Unplanned aortic stenosis related hospital admission	An unplanned hospital admission with syncope, heart failure, chest pain, or arrhythmia (ventricular arrhythmia or second- or third-degree heart block) attributed to AS.10	- Clinical endpoint attributable to the disease process being modified	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Patients with AS often have comorbid conditions that may account for the clinical events, rather than being due to AS.
AS-related death	Death related to aortic stenosis (sudden cardiac death, death due to heart failure, ventricular arrhythmia or AV conduction disease in a patient with severe aortic stenosis)	- Clinical endpoint attributable to the disease process being modified	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Adjudication may be challenging in the context of co-morbidities such as coronary artery disease
SYMPTOMS, DISABILITY & QUALITY OF LIFE
Symptoms	Shortness of breath Chest pain Presyncope and syncope	Important to patients	- Requires large trials and/or prolonged follow up (∼5–10 yrs) - May be attributable to co-morbidities rather than AS
Quality of Life Assessments	Kansas City Questionnaire 6-minute walk test	Important to patients	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Changes may be attributable to co-morbidities or frailty rather than AS
Disability Free Years	Number of years a patient lives free from disability	Important to patients	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Changes may be attributable to co-morbidities or frailty rather than AS
SAFETY ENDPOINTS
Atherothrombotic events	Myocardial infarction Stroke	Important safety data for drugs without a safety profile	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Events are related to atherosclerosis not AS
Coronary Revascularization	Coronary artery bypass grafting Percutaneous coronary intervention	- Important safety data for drugs without a safety profile - Decisions to proceed with revascularization may be triggered by progression in AS	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Events are related to atherosclerosis not AS
Death	All-cause mortality	- Important safety data for drugs without a safety profile - Potentially available from electronic patient records and data linkage - No need for adjudication	- Requires large trials and/or prolonged follow-up (∼5–10 yrs) - Events may not be related to AS but rather co-morbidity