Guidelines on who is eligible for statins may need to be rewritten after an international trial found benefits in "healthy" adults, experts say.
The study of 17,800 men and women with normal cholesterol levels found rosuvastatin cut deaths from heart attacks and strokes.
Currently statins are offered to people with a moderate to high risk of a cardiovascular "event".
The results are published in the New England Journal of Medicine.
The patients in the trial, funded by AstraZeneca, had cholesterol levels below those usually indicating a need for treatment and had no other signs of heart disease.
But they did have increased levels of a C-reactive protein, which indicates inflammation in the body and is believed to be a marker of future cardiovascular events.
After an average follow-up of two years, 20mg a day of rosuvastatin was found to have cut cholesterol by 50% and C-reactive protein by 37%.
Overall, the chance of a heart attack, stroke, hospital admission for chest pain or death from cardiovascular disease was cut by 44%, researchers said.
The risk of one of those outcomes was 0.77 per 100 person-years of follow-up with rosuvastatin and 1.36 with placebo.
A reduction was even seen in those with the lowest chance of a cardiovascular event over the next decade, they said.
Researchers found a higher incidence of physician-reported diabetes in the statin group but could not explain it as blood glucose levels were similar between those taking rosuvastatin and those taking a dummy pill.
Statins are already prescribed to millions of adults in the UK.
The UK's National Institute of Clinical and Health Excellence (NICE) recommends doctors carry out a risk calculation based on an individual's blood pressure, cholesterol, weight and other risk factors, such as whether or not they smoke.
Those with a 20% risk of a heart attack or stroke in the next 10 years should be prescribed a daily dose of simvastatin - the cheapest of the statin class.
Dr Terry McCormack, a GP in Whitby, North Yorkshire, and ex-chairman of the Primary Care Cardiovascular Society, said the results were "astonishing" and much stronger than he would have expected.
He added that NICE should redo their cost-effectiveness calculation on the basis of the latest figures.
"These are people who have an intermediate risk and you wouldn't normally prescribe statins for them in the UK," he said.
"It opens up a whole new debate and the trial probably raises more questions than it answers."
Professor Peter Sever, an expert in clinical pharmacology at Imperial College in London, said the results backed other studies which had shown statins had the same proportional benefit however low an individual's cholesterol.
But he added: "The thing to remember is that the 20% threshold is arbitrary - it is essentially based on economic issues.
"Most nations have a finite pot and if you're going to treat everyone with a 10% risk, that's billions of pounds extra and somewhere along the line someone else is going to miss out."
Professor Peter Weissberg, medical director at the British Heart Foundation, said: "The findings raise questions about who should receive treatment to prevent a heart attack, how aggressively they should be treated and with which drug.
"These important issues have profound implications for future NICE guidelines."
However, Professor Weissberg added that further studies were needed to determine if measuring C-reactive protein was the right way to identify people likely to gain most from treatment.
Dr Alan McDougall, from AstraZeneca, said there was "no question" the trial would raise some important issues about statin use but that they would recommend doctors still follow existing guidance.
NICE is due to consult on plans to review their statin guidance shortly.