March 2017: FOURIER trial results published: inhibition of PCSK9 with evolocumab on a background of statin therapy
December 2016: LSHTM StatinWISE trial assessing muscle symptoms recruits first patients
October 2016: ASCOT-LLA publishes adverse event analyses
September 2016: The Lancet publishes major review about the use of statins
July 2016: Impact of renal function on the effects of LDL-cholesterol with statin based regimens published in Lancet Diabetes Endrocrinol
June 2016: Adverse impact on public health of misleading information about statin safety
June 2016: Renewed call to retract BMJ articles that mislead on statin effects
May 2016: Adverse event protocol published in AHJ
May 2016: Tabular data (all Serious Adverse Events by MedDRA classification) now available for HPS and SEARCH trials
The Cholesterol Treatment Trialists’ (CTT) Collaboration was established in 1994, with its initial protocol being published in 1995. It was set up after it was recognized that no single lipid intervention trial would be likely to have a sufficient number of trial participants (and hence statistical power) to reliably assess mortality outcomes or look at events in particular types of patient. Its aim is to conduct periodic meta-analyses of large-scale (≥1000 participants), long-term (≥2 years scheduled treatment duration) unconfounded, randomized controlled trials of lipid intervention therapies.
The Collaboration's work to date has largely focused on statin therapy, with individual participant data on major vascular events, cancers and mortality having been collected from about 30 major statin trials (equating to approximately 175,000 trial participants). The analyses of such data have been published in a series of publications, sequentially adding to the body of evidence for the efficacy and safety of statins. These analyses have shown that:
- Reduction of LDL cholesterol using statin therapy substantially reduces the risk of major vascular events (major coronary events, strokes or the need for coronary revascularization) and vascular mortality by about one fifth for each 1 mmol/L reduction in LDL cholesterol achieved
- Further reductions in LDL cholesterol with more intensive statin therapy produce further reductions in the incidence of major vascular events
In addition, the CTT analyses have shown that statin therapy:
- Has no effect on the incidence of, or death from, any type of cancer
- Is effective in a wide range of people including those with diabetes, those at low risk of vascular disease, and in both women and men
A new programme of work is currently underway to collect and analyze individual participant data on all other types of adverse event that were recorded in large-scale statin trials, in order that comprehensive analyses of all possible effects (either adverse or beneficial) of statin therapy in these trials can be conducted.
The CTT Collaboration also has plans to combine data from randomized trials of other lipid modification therapies, both for established drugs (such as fibrates) and emerging interventions (such as PCSK9 or CETP inhibitors).