Cardiovascular outcome trial · N Engl J Med 2017
SPIRE-1/2 trial
Cardiovascular Efficacy and Safety of Bococizumab in High-Risk Patients.
The bottom line
Bococizumab substantially lowered LDL cholesterol but showed no significant reduction in major cardiovascular events overall, with benefit seen only in the higher-risk trial, and the drug's development was discontinued due to high rates of antidrug antibodies and injection-site reactions.
No significant benefit (program stopped)US status: Discontinued
At a glance
- Medicine
- Bococizumab 150 mg subcutaneously every 2 weeks
- Compared with
- Placebo
- People
- 27,438
- Who took part
- High cardiovascular risk patients; SPIRE-1 (lower-risk) baseline LDL ≥70 mg/dl; SPIRE-2 (higher-risk) baseline LDL ≥100 mg/dl; 93% on statin therapy at baseline
- Design
- randomized, placebo-controlled (two parallel multinational trials, SPIRE-1 and SPIRE-2), stopped early
- Follow-up
- Median follow-up 10 months (combined); 7 months (SPIRE-1); 12 months (SPIRE-2)
- Main question
- Nonfatal myocardial infarction, nonfatal stroke, hospitalization for unstable angina requiring urgent revascularization, or cardiovascular death
Main result
Combined trials hazard ratio 0.88 (95% CI, 0.76 to 1.02; P=0.08); SPIRE-1 (lower-risk): hazard ratio 0.99 (95% CI, 0.80 to 1.22; P=0.94); SPIRE-2 (higher-risk): hazard ratio 0.79 (95% CI, 0.65 to 0.97; P=0.02)
Effect on LDL cholesterol
Mean change from baseline in LDL cholesterol at 14 weeks: -56.0% bococizumab vs +2.9% placebo, between-group difference -59.0 percentage points (P<0.001); median reduction from baseline of 64.2% (P<0.001)
Other results
Major cardiovascular events occurred in 173 patients each in the bococizumab group and the placebo group in SPIRE-1; major cardiovascular events occurred in 179 and 224 patients, respectively, in SPIRE-2
Safety
Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001); trials stopped early owing in part to development of high rates of antidrug antibodies
In the trial's own words
“The hazard ratio for the primary end point in the combined trials was 0.88 (95% CI, 0.76 to 1.02; P=0.08). Injection-site reactions were more common in the bococizumab group than in the placebo group (10.4% vs. 1.3%, P<0.001).”
Quoted from the abstract of N Engl J Med 2017, checked word for word against PubMed. PubMed 28304242 · Full paper (DOI)
Common questions
What did the SPIRE-1/2 trial find?
Bococizumab substantially lowered LDL cholesterol but showed no significant reduction in major cardiovascular events overall, with benefit seen only in the higher-risk trial, and the drug's development was discontinued due to high rates of antidrug antibodies and injection-site reactions.
Who was in SPIRE-1/2?
27,438 people. High cardiovascular risk patients; SPIRE-1 (lower-risk) baseline LDL ≥70 mg/dl; SPIRE-2 (higher-risk) baseline LDL ≥100 mg/dl; 93% on statin therapy at baseline.
What was SPIRE-1/2's main result?
Combined trials hazard ratio 0.88 (95% CI, 0.76 to 1.02; P=0.08); SPIRE-1 (lower-risk): hazard ratio 0.99 (95% CI, 0.80 to 1.22; P=0.94); SPIRE-2 (higher-risk): hazard ratio 0.79 (95% CI, 0.65 to 0.97; P=0.02)
How much did LDL cholesterol change in SPIRE-1/2?
Mean change from baseline in LDL cholesterol at 14 weeks: -56.0% bococizumab vs +2.9% placebo, between-group difference -59.0 percentage points (P<0.001); median reduction from baseline of 64.2% (P<0.001)
Related trials
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- FOURIER (2017)Adding evolocumab to statin therapy substantially lowers LDL cholesterol and reduces cardiovascular events in patients with atherosclerotic cardiovascular disease, with injection-site reactions being the main added safety concern.
- ORION-1 (2017)In this phase 2 trial, inclisiran produced substantial, dose-dependent, and durable reductions in LDL cholesterol and PCSK9 levels in high cardiovascular risk patients, with an acceptable safety profile, but the trial was not designed to assess cardiovascular outcomes.
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