Statins given to Scottish men 20 years ago still show benefit now (WOSCOPS trial)
When I was a senior registrar in Glasgow in 1995 my mentor published the West of Scotland Coronary Prevention Study (WOSCOPS). This study took 6595 men aged 45 to 64 years who had not had a previous heart attack and treated them for 5 years with pravastatin 40 mg or placebo (a tablet with nothing in). The results were remarkable and along with a trial looking at treatment of patients with heart attacks with Simvastatin (4S trial) changed the way we treat people with actual or potential cardiovascular disease.
The study showed that treatment for 5 years significantly reduced the risk of nonfatal myocardial infarction or death from cardiovascular disease by 31% compared with placebo. As at that time the incidence of coronary artery disease in Glasgow was very high the effects were dramatic.
After the 5 year trial was completed all patients were invited to go on pravastatin 40mg because of the beneficial effects. What seems amazing is that 20 years later the original benefit of taking the pravastatin for the original 5 year period was still evident.
1. This is shown in the table below.
Patients had been tracked using mortality statistics and these will be highly accurate. Death is a hard end point. Patients are either dead or alive and the statistic can’t be fiddled. Notice how the curves remain separated. This means if you were given pravastatin 40mg 20 years ago for 5 years you would still be having the benefit of this 20 years later and would be less likely to be dead compared to someone who had not been given the tablet.
The authors have tried to analyse this data in more detail by tracking the hospital admissions related to the patients. Here the follow up data for the patients is only 90% complete but still remarkably good reflecting the fact that people in this part of Scotland do not move around much. Again the figures are striking.
Having been treated with pravastatin for five years 20 years ago means that you have a 19% less chance of having a PCI (percutaneous intervention =stent) or CABG (coronary artery bypass graft) and a 31% less chance of having a heart failure. So not only do you have a better chance of living longer but you have a better chance of not having to have invasive cardiac surgery or developing heart failure.
We do not know how many people were treated with pravastatin 40mg after the trial formally ended after 5 years. All would have been advised about the results of the trial as would their general practitioners. One would have hoped that all would have been offered the pravastatin to take and we would assume that equal numbers in each group would have taken up the offer to take it. The benefits that we are seeing 20 years later are still therefore likely to be due to the pravastatin that was taken 20 years before.
The divergence of the curves with time is in contra distinction to other long term follow up from other cardiovascular trials. After all if you follow up patients for long enough they will all be dead and the curves will converge at a point of 100%s death. An example of this convergence is the RITA 3 trial (see news) where it appeared that treating people early following a presentation with unstable angina reduced event rates and possibly death rates. At 5 years following the treatment the effect was most marked but at 10 years the effect had disappeared.
Harvey White a renowned cardiologist from Auckland New Zealand commenting on the 20 year follow up data said “the legacy effect of statins appeared to be an ongoing, carry over effect related to a slowing of the progression of the disease and/or the stabilization of existing coronary artery plaque.”
Many of my cardiology colleagues have been taking statins for many years with the hunch that benefits accumulated with time. We now have the data to support this… and if anybody asks – yes I do take a statin!
1. Packard CJ et al. Circulation.2014; 130: 2105-2126Lifetime Clinical and Economic Benefits of Statin-Based LDL Lowering in the 20-Year Followup of the West of Scotland Coronary Prevention Study