Table 1.
Disease area | Potential surrogate endpoint | Validity as a true surrogate |
---|---|---|
Hypertension/vascular physiology | Blood pressure8 | ++++ |
Carotid intima-media thickness8 | ++ | |
Microalbuminuria8,15 | ++/? | |
Flow-mediated dilatation58,59 | ++ | |
Left ventricular hypertrophy8 | ++ | |
Lipid disorders/atherosclerosis | Low-density lipoprotein cholesterol9,10,15,57 | ++++ |
High-density lipoprotein cholesterol11,12 | − | |
Carotid magnetic resonance imaging60 | ++ | |
Intravascular ultrasound20 | ++ | |
Coronary computed tomography61 | ? | |
Optical coherence tomography62 | ? | |
Diabetes | Serum glucose | ++ |
Haemoglobin A1c | ++ | |
Microalbuminuria | ++ | |
Obstructive coronary artery disease | Quantitative coronary angiography63 | ++ |
Intravascular ultrasound20 | ++ | |
Coronary computed tomography61 | ? | |
Optical coherence tomography62 | ? | |
Restenosis after PCI28–30 | ++ | |
Angiographic variables to predict restenosis31,32 | + | |
Acute coronary syndromes | Troponins64 | ++ |
Brain natriuretic peptide64 | ++ | |
Infarct size65 | ? | |
Return of TIMI flow66,67 | ? | |
Resolution of ST elevation67 | ? | |
Heart failure | Exercise capacity68,69 | − |
Haemodynamics (e.g. cardiac output)69 | − | |
Ejection fraction33 | ++ | |
Remodelling (e.g. LV volume)70 | ++ | |
Brain natriuretic peptide69,71 | − | |
Electrophysiology | Premature ventricular beats36 | − |
Late potentials72 | − | |
Non-sustained ventricular tachycardia36 TTaTachycardia | − |
The symbols ‘−‘ and ‘+’ to ‘+ ++ +’ indicate the reliability of the potential surrogate; the symbol ‘?’ indicates currently unknown. A valid surrogate or true surrogate will be on the causal path to and have a strong, consistent statistical relationship with the clinical endpoint.