ECG signal

Dr Diana R Holdright

Consultant Cardiologist

Dr Diana Holdright

Drug Therapy - High Cholesterol

The recognition that cholesterol played a pivotal role in the development of coronary artery disease was made in 1915 by a Russian doctor, Nicolai Anitchkov. Since that time we have learned that LDL cholesterol in particular increases the risk of coronary artery disease, and that HDL cholesterol is protective to the vascular system. Other components, such as the lipoprotein (a) and apolipoproteins A-1 and B, are also being extensively investigated. The arithmetic sum of LDL and HDL cholesterol comprises most but not all of the total cholesterol level measured in a blood test, and as such it is important to consider these components both individually and together, rather than simply responding to a total cholesterol level reading in isolation. The higher the LDL and the lower the HDL cholesterol, the greater the risk of coronary artery disease.

Because an adverse cholesterol profile is just one risk factor for coronary artery disease, we use various scoring systems to estimate an individual’s future risk of coronary artery disease and/or stroke, collectively termed cardiovascular disease. The QRISK2 system is one such tool, which can be used in patients who are not known to have had a prior heart attack or stroke, and is specific to the UK population. By inputting a number of variables in addition to the LDL and HDL cholesterol, such as age, gender, blood pressure smoking history, presence of diabetes or kidney disease, a family history of cardiovascular disease, and socioeconomic factors, a patient’s ten year risk of developing heart disease and stroke can be calculated. It is typically at the 20% threshold when specific drug therapy, such as a statin to lower cholesterol, is recommended; at lower scores emphasis will be more on lifestyle changes that a patient can make to lower their risk.

Familial hypercholesterolaemia is a genetic condition where there are mutations in the genes which regulate the clearance of LDL cholesterol from the blood.  Familial hypercholesterolaemia causes premature atherosclerosis and heart disease, and as it is due to an abnormal dominant gene first degree relatives (siblings, parents and children) have a 50% chance of inheriting the condition. It greatly increases the risk of heart attack at a young age, and so screening is important; the advent of genetic testing and developments in screening tools have improved our ability to detect carriers of the gene at a young age and begin treatment early to reduce their risk of future heart problems.

The statins, which first became available in the late 1980s, are the most effective drugs at lowering LDL cholesterol and reducing cardiovascular risk. A vast number of international clinical trials have shown that the more the LDL cholesterol is lowered, the lower the risk of heart attack and stroke. Cholesterol is measured in units called mmol/L (in the US, mg/dL) and for every 1 mmol/L the LDL cholesterol is lowered by a statin there is a 22% reduction in the risk of heart attack, stroke and sudden death *.  Therefore the average patient on an appropriate statin at the right dose might expect their future risk to be halved; not many drugs in medicine are associated with such profound benefit.  However, as with all drug therapy, there is a risk of side-effects, which increases with higher doses of statins. Side-effects are fortunately rare but a minority of patients develop muscle or joint aches on statins; sometimes switching to a different statin or lowering the dose resolves this, but there are some patients who are simply unable to take them. Very rarely statins can cause a serious muscle problem called rhabdomyolysis; in one study this occurred in 1 in 1000 patients taking a high-dose statin but in no patients on lower doses. We have previously been concerned that statins may affect liver function adversely, although the latest studies suggest that this is not the case and, in fact, statins may actually improve liver function. As with all drug therapy, it is important to consider both the potential for benefit and potential for harm before embarking on what is ideally life-long therapy.

There are also other drugs classes to treat cholesterol, although they have not been shown to have the same magnitude of benefit as the statins; they include fibrates, ezetimibe, nicotinic acid and bile acid sequestrants.

* Cholesterol Treatment Trialists’ (CTT) Collaborators. Efficacy and safety of more intensive lowering of LDL cholesterol.  Lancet 2010; 376: 1670-81


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Drug Therapy - High Cholesterol