Prevention – SAMSON

The clinical question

BHF-funded studies have led the world in showing that statins save lives by reducing the risk of heart attack and stroke. But side effects, most notably muscle weakness or pain, are reported by up to a third of people taking statins. Because these symptoms are common, it has been difficult to work out whether they are a side effect of the statin or caused by something else.

In clinical trials these side effects are reported in similar numbers by participants receiving a statin or a placebo (a dummy pill). Despite this, some people worry about the side effects of statins and in some cases, this means they are reluctant to take them when their doctor recommends it. And a significant proportion stop taking their pills and lose the protection that the statin provides. 

To explore this in more detail, the BHF-funded SAMSON trial took a personalised approach to understanding more about the side effects people experience while taking statins.

What did the study involve?

Between June 2016 and March 2019, the study recruited 60 people who had been prescribed statins, but had recently stopped taking the medication due to side effects – some of whom came forward after the study was featured in BHF’s Heart Matters magazine.  

Over the course of a year, participants were randomly assigned every month to take either a statin (atorvastatin), identical placebo tablets, or no tablets. Each day, they recorded whether they’d taken their pill and how they felt on a scale of 0 (no symptoms) to 100 (worst imaginable) using a smartphone app. If the symptoms became too severe, they were able to stop taking the tablets for that month. 49 participants completed all 12 months of the trial.

What did the study show?

• 90 per cent of the symptoms that people reported while taking a statin were also experienced while they were taking a placebo. 
• People experienced more symptoms when they were taking a tablet (either statin or the placebo) than when they were not taking a pill.
• Participants were just as likely to temporarily stop taking their placebo tablets due to side effects as they were with statins.
• After participants received an explanation of their results at the end of the study, half of them successfully restarted their statin.
  
  

Why is the study important?

It has been estimated that between half and three-quarters of people prescribed a statin stop taking it within two years, with symptoms such as muscle pain being the most common reason. And many more people decide not to take statins in the first place because of concerns about side effects. 

The results of SAMSON suggest that the symptoms participants experienced are nearly all linked to the “nocebo” effect – where people experience side effects from a treatment because of a negative association with it, rather than the actual biological effect of the drug. It also showed that the type of personalised approach exemplified by the SAMSON trial can help to empower people to get back onto a life-saving therapy, and allows the small number of people who do experience side effects that are directly linked to statins the chance to explore other treatment options.

The SAMSON trial was also featured in a collection of the BHF’s research successes to mark 60 years since the BHF was founded. 

The participant voice

One of the participants in SAMSON was Janice Richardson, a retired nurse from West Yorkshire. Janice was originally prescribed statins in 2015 but stopped taking them several times due to developing various aches and pains, which she was convinced were because of the statin. After reading a BHF Heart Matters article about the SAMSON trial, Janice signed up. Her results showed that she experienced the same symptoms when taking the placebo as she did when taking a statin.

Janice said: “I was so surprised that my aches and pains were not due to the statins themselves – you can convince yourself of anything! I’m now very happy to be taking my statins again. Looking back, I walk a lot in the valley where I live and have plenty of stairs in my home that I go up and down multiple times a day. No wonder my body was feeling these pains!”.

Study details

“Statin side effect or not? A patient-empowering within-subject randomized controlled trial and development of a practical technology to support 21st century primary prevention decisions.”
Award reference:  PG/15/7/31235
Principal investigator: Professor Darrel Francis

Publication details

Wood FA, Howard JP, Finegold JA, Nowbar AN, Thompson DM, Arnold AD, Rajkumar CA, Connolly S, Cegla J, Stride C, Sever P, Norton C, Thom SAM, Shun-Shin MJ, Francis DP. N-of-1 Trial of a Statin, Placebo, or No Treatment to Assess Side Effects. N Engl J Med. 2020; 383(22):2182-2184.