Nicotinic AcidNicotinic Acid
Treatment of dyslipidaemia in patients with adequately controlled LDL cholesterol and inadequately controlled HDL cholesterol (HDL-C <1 mmol/L) despite monotherapy with a statin, used in combination with an HMG CoA reductase inhibitor.
Access path
- TGA registered · Nicotinic Acid
TGA label narrower than the PBS population
- Jul 2006Not recommended
Inappropriate comparator selection (ezetimibe rejected); lack of clinical trial evidence that raising HDL-C improves…
- Jul 2006Not recommended
inappropriate comparator (ezetimibe not accepted by PBAC as the appropriate comparison); lack of clinical evidence…
- ↻ resubmittedMar 2007Recommended
Comparator changed: ezetimibe (primary comparator nominated by sponsor; PBAC also…
- Mar 2007Recommended
Comparator changed: ezetimibe (primary comparator nominated by sponsor; PBAC also…
- PBS listing
From the public summary
The PBAC also noted that although only limited toxicity data were presented, prolonged release nicotinic acid appeared to be associated with more toxicity, compared with placebo, with more than two-thirds of patients treated with prolonged release nicotinic acid experiencing flushing.PSD · Mar 2007
The use of changes in CIMT as a surrogate outcome for change in HDL-C was not considered by the PBAC to be adequately validated at this time. The PBAC noted this matter would be discussed at the March 2007 meeting of American College of Cardiology. Further, the PBAC noted the epidemiological data suggest that raising HDL-C may provide independent and additive cardiovascular benefit and that the clinical trial evidence is weakly supportive.PSD · Mar 2007
Cost-effectiveness
A modelled economic evaluation was not presented. Trial-based incremental cost/additional patient avoiding a cardiovascular event was estimated at less than $15,000, but this was based on uncertain surrogate endpoint and weak clinical evidence.
A modelled economic evaluation was not presented. A modelled economic evaluation using long term mortality and morbidity data would have provided more information to the PBAC on which to base its decision. PBAC · 2007
Decision context
PopulationPatients with dyslipidaemia with adequately controlled LDL-C and inadequately controlled HDL-C (HDL-C <1 mmol/L) despite at least 3 months' treatment with a statin, for combination therapy with a statin.
Why it was knocked back
- no statistically significant benefit demonstrated for prolonged release nicotinic acid over placebo on the key trial outcome (CIMT), uncertainty that CIMT change is a validated surrogate for improved cardiovascular outcomes, uncertainty associated with the impact of raising HDL-C on cardiovascular outcomes, weak epidemiological evidence for HDL-raising benefit
Submission history
| Decided | Outcome | Comparator | ICER | Evidence |
|---|---|---|---|---|
| Mar 2007 | Recommended | placebo plus ongoing statin therapy | — | RCT, Meta-analysis · CIMT |
| Mar 2007 | Recommended | placebo plus ongoing statin therapy | — | RCT · CIMT |
| Jul 2006 | Not recommended | ezetimibe (submission's nomination); placebo as add-on to statin (PBAC's preferred comparator) | $15k–45k | RCT | Other (indirect comparison) · TC: HDL-C ratio |
| Jul 2006 | Not recommended | ezetimibe (primary comparator nominated by sponsor; PBAC also considered placebo as appropriate comparator) | — | RCT |
Similar precedents
Regulatory · TGA
Label narrower than PBS population — PBAC restricts to type 2 diabetics with inadequate HDL-C despite statin monotherapy; TGA label covers broader dyslipidaemia populations without these specific constraints.