Introduction
Biology of PCSK9
Available inhibitors of PCSK9
Study | Inhibitor |
N
| % with diabetes | Intervention | Population | Planned follow-up at start of trial | Primary outcome | Expected year of completion |
---|---|---|---|---|---|---|---|---|
FOURIER (TIMI-59) [12], Clinical.trials.gov NCT01764633 | Evolocumab | 27,564 | ∼34 | Evolocumab 140 mg every 2 weeks or 420 mg monthly or placebo | Prior vascular event; LDL-cholesterol ≥1.8 mmol/l or non–HDL-cholesterol ≥2.6 mmol/l | ∼4 years | Cardiovascular death, MI, stroke, coronary revascularisation | 2017 |
ODYSSEY OUTCOMES [13], Clinical.trials.gov NCT01663402 | Alirocumab | 18,000 | Not available | Alirocumab 75 mg or 150 mg every 2 weeks; or placebo | ACS in last 12 months; LDL-cholesterol ≥1.8 mmol/l or non-HDL-cholesterol ≥2.6 mmol/l, or apolipoprotein B ≥0.8 g/l | Until >1613 events occur and >2 years follow-up | Coronary events or ischaemic stroke | 2018 |
SPIRE-1 [15], Clinical.trials.gov NCT01975376 | Bococizumaba
| 17,000 | ∼40 | Bococizumab 150 mg every 2 weeks; or placebo | High risk or prior vascular event; LDL-cholesterol 1.8–2.5 mmol/l or non-HDL-cholesterol 2.6–3.3 mmol/l | ∼5 years | Cardiovascular death, MI, stroke, urgent coronary revascularisation | – |
SPIRE-2 [15], Clinical.trials.gov NCT01975389 | 9000 | Bococizumab 150 mg every 2 weeks; or placebo | High risk or prior vascular event, LDL-cholesterol ≥2.6 mmol/l or non-HDL-cholesterol ≥3.4 mmol/l | ∼4 years | Cardiovascular death, MI, stroke, urgent coronary revascularisation | – |
Effects of monoclonal antibodies to PCSK9 in people with and without diabetes
Monoclonal antibody | Trial | Population |
N
| Duration (weeks) | Dose | LDL-cholesterol | Total cholesterol | HDL-cholesterol | Triacylglycerols | Lp(a) |
---|---|---|---|---|---|---|---|---|---|---|
Evolocumab | DESCARTES [38], Clinical.trials.gov NCT01516879 | LDL-cholesterol ≥1.9 mmol (with or without atorvastatin depending on baseline risk) | 901 | 52 | 420 mg every 4 weeks; or placebo | −57 (2)a
| −34 (1)a
| +5 (1)a
| −12 (3)a
| −22 (2)a
|
Alirocumab | ODYSSEY-LT [36], Clinical.trials.gov NCT01507831 | Elevated cardiovascular risk on statin with LDL-cholesterol ≥1.8 mmol/l | 2341 | 24 | 15 mg every 2 weeks; or placebo | −62 (−64, −59) | −38 (−39, −36) | +5 (+3, +6) | −17 (−20, −15) | −26 (−28, −23) |
Bococizumab | Clinical.trials.gov NCT0159224 [30] | Adults on stable statin with LDL-cholesterol ≥2.1 mmol/l | 93 | 24 | 150 mg every 2 weeks; or placebo | −53 (−63, −43) | −30 (−37, −24) | +1 (−4, +7) | −19 (−35, +5.0)b
| −9 (−27, +3)b
|
Adults on stable statin with LDL-cholesterol ≥2.1 mmol/l | 97 | 24 | 300 mg every 4 weeks; or placebo | −41 (−52, −30) | −24 (−31, −17) | +7 (0, +13) | −14 (−33, +11)b
| −11 (−27, 0)b
|
Safety profile of monoclonal antibodies to PCSK9
PCSK9 inhibitors: their potential place in clinical practice
Characteristic | Moderate riska
| High riskb
| ||
---|---|---|---|---|
On statin? | Yes | No | Yes | No |
Baseline LDL-cholesterol (mmol/l)c
| 2 | 4 | 2 | 4 |
Reduction in LDL-cholesterol (mmol/l) with PCSK9 inhibitor | 1 | 2 | 1 | 2 |
HR (excluding first year)d
| 0.75 | 0.56 | 0.75 | 0.56 |
Individuals protected from a cardiovascular event (no. per 1000 treated for 5 years) | 13–19 | 22–33 | 38–50 | 66–88 |