Table 1.
Potential surrogate endpoints in clinical trials
| 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.