Final updated NICE guidance released on Thursday confirmed earlier plans to lower the threshold for statin therapy in England, despite opposition from some doctors.
NICE insisted the drugs are safe and effective, and that wider use will save an extra 4,000 lives over three years while reducing rates of MI and stroke.
But the GPC said there was not enough evidence of benefit in low-risk people to give GPs confidence in prescribing statins more widely.
A senior GPC figure said NICE's claim that GP workload would be unaffected was 'incomprehensible'.
NICE has chosen to finalise the guidance, which also addresses lipid modification in people with established cardiovascular disease, with few changes from the draft version, despite significant controversy.
When the guidance first launched in February, the GPC said the plans would affect consultation workload and warned the drugs may not benefit low-risk people but expose them to side-effects.
In June, a group of senior doctors including prominent GPs urged NICE to abandon the plans, saying there was too little evidence of benefit and harms of treatment in low-risk groups.
NICE's guideline will lower the 10-year cardiovascular risk threshold for starting preventive treatment to 10% from 20%.
An additional 4.5m people in England will be eligible for statin therapy as a result, although the guidance stresses that statins should be considered only 'if lifestyle modification is ineffective or inappropriate'.
GPs will be required to screen practice lists to identify people who may be at risk, and use the QRISK2 tool in a formal risk assessment for many of their patients. Where a statin is required for primary prevention, GPs should prescribe atorvastatin 20mg.
NICE said most people aged over 65 in England would now be eligible for statin therapy under the new risk threshold.
Unveiling the final guidance, Dr Anthony Wierzbicki, chair of the guideline development group, said: 'We've got the best evidence base on huge numbers and the biggest set of clinical trials ever done. Statins work; we know that they are very safe drugs, they are now becoming cheaper as they go off-patent.
'For people at risk of heart disease, if lifestyle measures fail - and actually implementing lifestyle changes can be very difficult - we have a second option, and that is to give them a statin if they want it.'
Professor Mark Baker, director of the centre for clinical practice at NICE, downplayed fears over extra GP workload. 'We're not suggesting that there is a big campaign to get all these people on statins, we're saying it should be opportunistic over the next five years.
'Most of these people, if not all, should already be under surveillance by their GPs on a periodic basis for assessment of their cardiac risk, and we will just see consideration of this guidance as part of that process.'
He said that for GPs to object to the guidance on the basis it will increase workload was 'not really justified'.
Over-treatment claims 'ludicrous'
Professor Baker strongly rejected claims from critics that the guideline could over-medicalise the population: 'There are some people who, for their own reasons, and not necessarily related to the good of the population, have sought to make a thing of this where a big thing does not exist.
'I think it is ludicrous to suggest that we are over-medicalising the population when the whole point of using modern, safe and effective drugs in an economic way is to prevent bad things happening in the future.'
A GPC statement said: 'The GPC believe that there is insufficient evidence of significant overall benefit to low-risk individuals to allow GPs to have confidence in the recommendation to reduce the risk-threshold for prescribing cholesterol-lowering drugs, and that doing so might distort health spending priorities and disadvantage other patients.'
It added: 'In advocating drug therapy for people who are at normal (or lower) levels of risk than those expected for their age group this guidance represents a step-change in medical practice which deserved wider public debate and more robust evidence of benefit.'
The GPC said NICE's lack of access to full trial data meant it had 'only made an assessment of the likelihood of unseen data affecting their conclusions'.
Many studies referenced by the guideline showed no or limited benefit, while treatment in low-risk patients had not been shown to reduce mortality, the GPC said.
'In low-risk patients, the number of people benefiting by reduction in risk of non-fatal MI is balanced by those harmed by increased risk of developing diabetes,' it added.
Workload denial 'incomprehensible'
The GPC said the analysis had not taken into account the impact of the guidance on other patients in a cash-limited health service.
However, it stressed: 'It is important to note that these concerns apply to low-risk people only and those at higher risk or with existing disease should continue treatment.'
Dr Andrew Green, chairman of the GPC's clinical and prescribing subcommittee, told GP that GPs must be prepared 'to justify their actions' if they deviate from NICE's new guidance.
'Where there are differing professional views GPs should explore these with patients in a way they can understand, come to a joint decision about management, and record this in the notes.'
He refuted NICE's claim that implementing the guidance would have little effect on GP workload: 'The idea that this can be done for the entire adult population over 40 without an impact on practice workload, and hence without a impact on the quality of care given for other conditions, is incomprehensible.'
Overview: why NICE wants wider statin use
Existing guidance published in 2008 affects 13m people in England and uses a 20% risk threshold as the level for initiating primary preventive treatment. Around 5-10m people currently take statins.
Lowering the risk threshold to 10% will add a further 4.5m to this at-risk group, of whom around half, over 2m people, are expected to be placed on statins. This will cost the NHS around £52m more per year based on 80% long-term uptake, although NICE says this figure is less than spending on statins in 2012 as prices have fallen after some statins went off-patent.
NICE said trial evidence suggests that treating these additional 2m patients over three years would avoid around 4,000 cardiovascular deaths, 8,000 strokes and 14,000 MIs.
This equates to an additional two lives saved, four strokes avoided and seven non-fatal MIs prevented for every 1,000 patients treated - an NNT of 77.
Professor Baker said this NNT was lower than other well-established medical interventions such as treatment for hypertension. 'We're looking at a significant advance in primary preventive medicine,' he said.
In people with existing cardiovascular disease, high-intensity statin treatment with atorvastatin 80mg, advised by the new guidance, would avoid 16 cardiovascular deaths, 11 strokes and 22 non-fatal MIs per 1,000 treated patients, according to NICE.
Dr Wierzbicki said the guidance also simplified the measures and tests needed to assess cardiovascular disease risk. 'It's now much easier for patients to have these screens done, and for GPs and nurses and even hospital doctors to look at all the results and make sense of the results,' he said.