New guidelines advance anti-cholesterol therapy and expand primary cardiovascular prevention

For instance, whereas previous guidelines started considering the initiation of anti-cholesterol therapy with statins in the presence of a 10-year cardiovascular risk of 7.5 per cent (intermediate risk), the advice now is to start treatment as early as in the presence of a 3 per cent risk (low risk) and this would bring at least another 25 million Americans in the US alone on board the treatment.

The new risk calculator is also more precise than its predecessors and tends to estimate a lower risk than before. But this also means that the intervention thresholds are lowered. Thus, the range of people to be monitored is broadened and the start of therapy is brought forward, with people between 30 and 40 years of age also being targeted.

Risk amplifiers, such as an episode of heart attack or stroke at an early age in a parent or sibling, a high polygenic risk, being affected by chronic inflammatory diseases, lipoprotein(a) levels ≥50 mg/dL, high-sensitivity C-reactive protein levels ≥ 2mg/L on several occasions, triglycerides persistently ≥150 mg/dL, also enter into the new cardiovascular risk calculation.

In short, these guidelines represent a medical and cultural turning point. Prevention is becoming more and more early and proactive, instead of reactive, which is the typical attitude of secondary prevention, which takes place when a cardiovascular event has already occurred.

The principle behind this change is simple: keeping LDL-cholesterol levels as low as possible for as long as possible provides better protection against strokes and heart attacks over time.

In short, experts are no longer satisfied with 'acceptable' cholesterol values 'today'. What also counts is the duration of exposure to this risk factor, which can be present even at an age hitherto considered 'exempt' of pharmacological prevention interventions (except, of course, for severe forms of familial hypercholesterolaemia). And this is because the less risk one accumulates over the years, the fewer cardiovascular events one will have in the future. A concept of 'early' prevention that has long since been cleared in the field of arterial hypertension, but not yet in that of dyslipidaemia, also 'silent killers' and enemies of the arteries.

If until now all interventions for the prevention and treatment of dyslipidaemia have focused on 'bad' cholesterol (LDL), the new guidelines broaden the horizon to 'new kids on the block'. In fact, new biomarkers, new key examinations enter the recommendations: the Lipoprotein(a), to be measured at least once in a lifetime, the high-sensitivity C-reactive protein to measure inflammation, the apolipoprotein B: indicated in patients already on therapy, when residual risk is suspected or in the presence of hypertriglyceridemia. Finally, among the instrumental examinations, in case of doubt, the assessment of the presence of calcium in the coronary arteries (CAC score) is indicated (for men over 40 and women over 45), by means of chorotreatment.

All this because, cardiovascular risk can be increased even in the case of 'normal' cholesterol. It is therefore necessary to introduce new assessment parameters that go beyond the limits of this pseudo-normality.

While statins remain a fundamental pillar of the anti-cholesterol therapeutic armamentarium, they have long since ceased to be the only option.

The new guidelines also put three other therapies on the same level as statins: ezetimibe, anti-PCSK9 monoclonal antibodies (PCSK9 inhibitors) and bempedoic acid. Incisiran is also in the game, but with a weaker strength of recommendation. While the new guidelines give a firm stop to the use of anti-cholesterol 'supplements', writing in black and white that they are not recommended for lowering cholesterol or triglycerides.

And the reason is that the scientific evidence of their benefit in reducing cardiovascular risk (which is the real goal of therapy) is weak: documented benefits are limited or inconsistent.

A message that marks a clear stance after years of ambiguity.

When it is necessary to act decisively on cholesterol, only drugs can help.

And even recent studies such as VESALIUS-CV show that lowering LDL-cholesterol a lot (below 55 mg/dL) with a PCSK9 inhibitor reduces cardiovascular risk even in patients who have not yet had a heart attack or stroke, i.e. in primary prevention.

These results could lead to a blurring of the boundary between primary and secondary prevention in terms of treatment targets, leading towards a single treatment model (and goals to be pursued): aiming to bring LDL-cholesterol below 55 mg/dl (in primary prevention & 70 mg/dl) for almost all patients at risk: fewer categories, more simplicity, greater therapeutic intensity.

In conclusion, summarising the main changes contained in the American guidelines on cholesterol management, what is changing for doctors and patients is: anticipating treatment even around the age of 30; customising the assessment of the risk profile by including new tests, intensifying treatment, adopting lower treatment targets and widening the choice to more treatment options.

Strategies that take cardiovascular medicine into the era of a continuum of prevention, ever earlier. With the goal of preventing millions of people from having a stroke or heart attack.