Evidence map›Paper›PMID 21067805›Full record

Trial reportLancet (London, England)2010

Intensive lowering of LDL cholesterol with 80 mg versus 20 mg simvastatin daily in 12,064 survivors of myocardial infarction: a double-blind randomised trial.

Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative Group, Jane Armitage, Louise Bowman, Karl Wallendszus, Richard Bulbulia, Kazem Rahimi, Richard Haynes, Sarah Parish, Richard Peto, Rory Collins

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

Trial report in Lancet (London, England), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 183 papers, 33 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
183citing papers in PubMed, 33 pooled it
54.3field-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

183 citing papers in PubMed, 33 syntheses or guidelines pooled it, 563 citations in OpenAlex.

  1. Pooled it
  2. Pooled it
  3. Pooled it
  4. Pooled it
  5. Pooled it
  6. [Efficacy and safety of atorvastatin in major cardiovascular events: Meta-analysis].Revista medica del Instituto Mexicano del Seguro Social · 2023
    Pooled it
  7. Pooled it
  8. Pooled it
  9. Pooled it
  10. Pooled it
  11. Prevalence of statin intolerance: a meta-analysis.European heart journal · 2022 · on this map
    Pooled it
  12. Pooled it
  13. Pooled it
  14. Pooled it
  15. Pooled it
  16. Pooled it
  17. Pooled it
  18. Pooled it
  19. Pooled it
  20. Pooled it

123 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors.

Study of the Effectiveness of Additional Reductions in Cholesterol and Homocysteine (SEARCH) Collaborative GroupSEARCH Study, Clinical Trial Service Unit and Epidemiological Studies Unit, Richard Doll Building, Old Road Campus, Roosevelt Drive, Oxford OX3 7LF, UK.
Jane Armitage
Louise Bowman
Karl Wallendszus
Richard Bulbulia
Kazem Rahimi
Richard Haynes
Sarah Parish
Richard Peto
Rory Collins

Funding

British Heart Foundation PG/12/32/29544Medical Research Council MC_EX_G0801669Medical Research Council MC_U137686853
6 · The paper itself

Abstract

backgroundLowering of LDL cholesterol reduces major vascular events, but whether more intensive therapy safely produces extra benefits is uncertain. We aimed to establish efficacy and safety of more intensive statin treatment in patients at high cardiovascular risk.

methodsWe undertook a double-blind randomised trial in 12,064 men and women aged 18-80 years with a history of myocardial infarction. Participants were either currently on or had clear indication for statin therapy, and had a total cholesterol concentration of at least 3·5 mmol/L if already on a statin or 4·5 mmol/L if not. Randomisation to either 80 mg or 20 mg simvastatin daily was done centrally using a minimisation algorithm. Participants were assessed at 2, 4, 8, and 12 months after randomisation and then every 6 months until final follow-up. The primary endpoint was major vascular events, defined as coronary death, myocardial infarction, stroke, or arterial revascularisation. Analysis was by intention to treat. This study is registered, number ISRCTN74348595.

findings6031 participants were allocated 80 mg simvastatin daily, and 6033 allocated 20 mg simvastatin daily. During a mean follow-up of 6·7 (SD 1·5) years, allocation to 80 mg simvastatin produced an average 0·35 (SE 0·01) mmol/L greater reduction in LDL cholesterol compared with allocation to 20 mg. Major vascular events occurred in 1477 (24·5%) participants allocated 80 mg simvastatin versus 1553 (25·7%) of those allocated 20 mg, corresponding to a 6% proportional reduction (risk ratio 0·94, 95% CI 0·88-1·01; p=0·10). There were no apparent differences in numbers of haemorrhagic strokes (24 [0·4%] vs 25 [0·4%]) or deaths attributed to vascular (565 [9·4%] vs 572 [9·5%]) or non-vascular (399 [6·6%] vs 398 [6·6%]) causes. Compared with two (0·03%) cases of myopathy in patients taking 20 mg simvastatin daily, there were 53 (0·9%) cases in the 80 mg group.

interpretationThe 6% (SE 3·5%) reduction in major vascular events with a further 0·35 mmol/L reduction in LDL cholesterol in our trial is consistent with previous trials. Myopathy was increased with 80 mg simvastatin daily, but intensive lowering of LDL cholesterol can be achieved safely with other regimens.

fundingMerck; The Clinical Trial Service Unit also receives funding from the UK Medical Research Council and the British Heart Foundation.

Indexed as

AdultAgedAged, 80 and overAnticholesteremic AgentsCholesterol, HDLCholesterol, LDLDouble-Blind MethodFemaleHumansHypercholesterolemiaMaleMiddle AgedMyocardial InfarctionSimvastatinTriglyceridesYoung AdultAnticholesteremic AgentsCholesterol, HDLCholesterol, LDLSimvastatinTriglycerides

Identifiers

PMID21067805
PMCPMC2988223
OpenAlexW1523152575

What Socratic holds

Textmetadata
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.