Is it possible to get rid of the atherosclerotic plaques and open coronary arteries?

I am not talking about primary PCI, a life-saving emergency procedure to re-open a blocked coronary artery during a heart attack. What I have in mind is whether it is possible to remove the atherosclerotic plaques that develop in the lining of the coronary arteries due to cardiovascular risk factors. The underlying pathogenetic process, which leads from risk factors such as genetic disposition, hypertension, hyperlipidaemia, smoking, diabetes, stress and physical inactivity, to a heart attack, is inflammation. Anything that inflames the coronary endothelium results in plaques, which can then rupture and lead to a heart attack or even sudden death. The plaques are not static; their properties depend on their structure, density, cholesterol content, and degree of inflammation.

We know that lifestyle changes and medication can, in patients with coronary artery disease, improve symptoms and prognosis by reducing the risk of heart attack, but is it possible to reverse the process of coronary atherosclerosis?

Yes and no. It is doable, but it is not easy. Also, what matters is not so much if it is possible to ‘clean up’ the coronary arteries but whether doing so will improve quality and length of life.

Not all atherosclerotic plaques are created equal. There are lipid-rich plaques that can be relatively easily influenced with medication, although actual volume regression is much harder to achieve. Since the landmark 4S trial, multiple clinical studies showed that whilst there is substantial prognostic benefit in the treatment of coronary artery disease with statins and other drugs, the regression of atherosclerosis is only modest. More recent clinical trials that showed a meaningful reduction in the volume of atherosclerotic plaques, such as GLAGOV, used very aggressive treatments with expensive drugs; in this case a PCSK9 inhibitor evolocumab. Then there are calcified plaques (as in ‘hardening of the arteries'), and removing calcium proved impossible in studies such as the TACT trial.

The key in understanding the mismatch between pronounced prognostic benefit with only borderline effect on plaque regression is the vulnerable plaque theory. The vulnerable coronary artery plaques have a thin fibrous cap and a large liquid lipid core. In case of erosion and rupture of the cap, the contact of the liquid core with blood triggers platelet aggregation and acute thrombosis, which occludes the coronary artery and causes myocardial infarction. The drug treatments and lifestyle changes work by stabilising the plaques making them less susceptible to rupture without significantly reducing their size. In fact, successful removal of cholesterol from the liquid lipid core and no effect on calcium will make the density of plaques go up whilst improving prognosis; the MESA trial demonstrated that calcium density is inversely associated with risk of myocardial infarction.

OK, so back to the original question: What can be done to remove coronary plaques? Well, crucial is to reduce plasma cholesterol and thus remove the cholesterol component from the plaques. Clinical trials with PCSK9 inhibitors and high-dose statins showed that reduction in LDL cholesterol to very low levels - below 1.55 mmol/l - leads to significant regression of lipid-rich plaques. That is not easy to achieve; in primary prevention LDL 3 mmol/l or less is normally considered acceptable. The other large area is prevention and good old-fashioned lifestyle changes: smoking cessation, treatment of high blood pressure, keeping a healthy weight, good sleep, regular physical activity and avoidance of stress; easier said than done! A healthy diet is essential: fruit and veg, whole grains and legumes reduce inflammation, whereas red meat, processed meat, sweet beverages and sugar increase it.

All in all, we may not be able to get rid of coronary plaques - at least not entirely - but we can change their structure and stabilise them, which is what matters in terms of prognosis. Sophisticated drugs and hi-tech treatments have a role to play, but so does exercise and a healthy diet.