Evidence map›Paper›PMID 23444397›Full record

Trial reportEuropean heart journal2013

HPS2-THRIVE randomized placebo-controlled trial in 25 673 high-risk patients of ER niacin/laropiprant: trial design, pre-specified muscle and liver outcomes, and reasons for stopping study treatment.

HPS2-THRIVE Collaborative Group

Open access · bronzeAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in European heart journal, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 225 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
225citing papers in PubMed, 11 pooled it
80.3field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

225 citing papers in PubMed, 11 syntheses or guidelines pooled it, 668 citations in OpenAlex.

  1. American Association of Clinical Endocrinology Clinical Practice Guideline: Developing a Diabetes Mellitus Comprehensive Care Plan-2022 Update.Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists · 2022
    Guideline
  2. Pooled it
  3. Guideline
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  5. Niacin for primary and secondary prevention of cardiovascular events.The Cochrane database of systematic reviews · 2017 · on this map
    Pooled it
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  9. Statins for primary prevention of venous thromboembolism.The Cochrane database of systematic reviews · 2014
    Pooled it
  10. Guideline
  11. Guideline
  12. Trial
  13. Trial
  14. Trial
  15. Trial
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165 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

1 author.

HPS2-THRIVE Collaborative GroupClinical Trial Service Unit & Epidemiological Studies Unit, University of Oxford, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK. thrive@ctsu.ox.ac.uk

Funding

British Heart Foundation RE/08/004Cancer Research UKDepartment of Health CDF-2013-06-012Medical Research Council MC_EX_G0801669Medical Research Council MC_U137686853Medical Research Council MC_U137686855
6 · The paper itself

Abstract

aimsNiacin has potentially favourable effects on lipids, but its effect on cardiovascular outcomes is uncertain. HPS2-THRIVE is a large randomized trial assessing the effects of extended release (ER) niacin in patients at high risk of vascular events. METHODS AND

resultsPrior to randomization, 42 424 patients with occlusive arterial disease were given simvastatin 40 mg plus, if required, ezetimibe 10 mg daily to standardize their low-density lipoprotein (LDL)-lowering therapy. The ability to remain compliant with ER niacin 2 g plus laropiprant 40 mg daily (ERN/LRPT) for ~1 month was then assessed in 38 369 patients and about one-third were excluded (mainly due to niacin side effects). A total of 25 673 patients were randomized between ERN/LRPT daily vs. placebo and were followed for a median of 3.9 years. By the end of the study, 25% of participants allocated ERN/LRPT vs. 17% allocated placebo had stopped their study treatment. The most common medical reasons for stopping ERN/LRPT were related to skin, gastrointestinal, diabetes, and musculoskeletal side effects. When added to statin-based LDL-lowering therapy, allocation to ERN/LRPT increased the risk of definite myopathy [75 (0.16%/year) vs. 17 (0.04%/year): risk ratio 4.4; 95% CI 2.6-7.5; P < 0.0001]; 7 vs. 5 were rhabdomyolysis. Any myopathy (definite or incipient) was more common among participants in China [138 (0.66%/year) vs. 27 (0.13%/year)] than among those in Europe [17 (0.07%/year) vs. 11 (0.04%/year)]. Consecutive alanine transaminase >3× upper limit of normal, in the absence of muscle damage, was seen in 48 (0.10%/year) ERN/LRPT vs. 30 (0.06%/year) placebo allocated participants.

conclusionThe risk of myopathy was increased by adding ERN/LRPT to simvastatin 40 mg daily (with or without ezetimibe), particularly in Chinese patients whose myopathy rates on simvastatin were higher. Despite the side effects of ERN/LRPT, among individuals who were able to tolerate it for ~1 month, three-quarters continued to take it for ~4 years.

Indexed as

Arterial Occlusive DiseasesChemical and Drug Induced Liver InjuryDeath, Sudden, CardiacDelayed-Action PreparationsDrug Therapy, CombinationFemaleHumansHypolipidemic AgentsIndolesMaleMiddle AgedMuscular DiseasesMyocardial InfarctionMyocardial ReperfusionNiacinSimvastatinDelayed-Action PreparationsHypolipidemic AgentsIndolesMK-0524NiacinSimvastatincardiovascular diseaseER niacin/laropiprantHDL-cholesterolLDL-cholesterolsecondary prevention

Identifiers

PMID23444397
PMCPMC3640201
OpenAlexW2410405995

What Socratic holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.