Article on statin safety makes unproven assertions

With publication of the review article in The Lancet on 8 September 2016 looking at the efficacy and safety of statin therapy, the pressure on GPs to prescribe high-intensity statins to low-risk people has become even greater. Under the heading ‘Proven beneficial effects of statin therapy’, the review states: “Lowering low-density lipoprotein (LDL) cholesterol by 2mmol/L with an effective statin regimen for about five years in 10,000 patients would typically prevent major vascular events in about… 500 (5%) patients at lower risk (e.g. primary prevention).”^[1]

Not only is this assertion not proven, it has not been tested. The appendix to the Cholesterol Treatment Trialists’ (CTT) Collaboration meta-analysis, published in May 2012, shows that the mean difference in LDL for low-risk patients (<10% five-year risk of major vascular event) in the trials of statin versus placebo is less than 1 mmol/L.^[2]
The assertion that 500 major vascular events would be prevented over five years is based on projections that rely upon the assumption that benefits of statin therapy in low-risk people increase linearly with LDL reduction beyond the boundaries of clinical trial data. It also relies on the assumption that harms do not increase with higher intensity therapy.

More importantly, the CTT has been unfairly faulted for not making patient-level statin trial data available for independent analyses. The CTT protocol, published in 1995, clearly states that “trial data submitted to the CTT’s secretariat will be held in strict confidence and will not be used in any publication without the permission of the responsible trialists”. CTT made an agreement that it would not release the data, and it has kept that agreement.

At this point, GPs are being advised to treat people with <20% 10-year risk of CVD with high-intensity statins without having evidence of net health benefit (reduction in overall mortality and serious adverse events) from the clinical trials as reported, and without the underlying data being available for independent analysis.

In around 1663, the Royal Society of London adopted the motto Nullius in verba, meaning ‘Take nobody’s word for it’. As reported by the Royal Society, the motto “is an expression of the determination of Fellows to withstand the domination of authority and to verify all statements by an appeal to facts determined by experiment”.

Nonetheless, 350 years later, physicians are being directed to take the word of the CTT and the trialists — including drug manufacturer-sponsors in most cases — to treat low-risk people with statins. It is now time to make all the data from all the major statin trials available for analysis by independent organisations so that doctors can practise truly evidence-based medicine.

John Abramson

Lecturer in healthcare policy

Harvard Medical School

Declaration of interest: Dr Abramson serves as a consultant to plaintiffs’ attorneys in pharmaceutical litigation, including cases involving statins.