Disturbances in lipid metabolism are at the very core of several major health issues in modern society, including cardiovascular disease (CVD), obesity and diabetes.
Elevated levels of cholesterol in the blood are a major risk factor in cardiovascular disease development, the most common cause of death in the western world. Most people are aware of the importance of monitoring cholesterol, which can be done at a GP’s practice.
In people with established heart disease, adherence to medication regimes remains a problem. A number of observational studies, principally in the UK, have shown a significant number of patients do not adhere to their drug regimes.
There is a range of responses to statins and some people do not respond as well as others. There may be a biological basis for this: patients might require a higher dose. Other people simply may not take their tablets.
“Non-adherence is multi-factorial. In a certain proportion of people, recognised side-effects are the cause. About 10 per cent of people get myalgic pains. However, many people simply forget to take their medicines; they don’t view them as important,” said Prof Tom Fahey, Head of the Division of Population Health Sciences, RCSI Medical School.
MJ Murphy et al published a paper in the British Journal of Clinical Pharmacology, demonstrating that the benefits of statins (shown in randomised controlled trials) are also apparent in community settings.
The paper, ‘Real-life reduction in cholesterol with statins, 1993 to 2002’, assessed the effectiveness of lipid-lowering treatment in the general population. Total cholesterol concentration fell by 23.5 per cent in those treated with lipid-lowering medication and by 13.9 per cent in those who were untreated.
Average cholesterol concentration fell by 25.9 per cent in patients judged to be taking their lipid-lowering medication, compared with 18.2 per cent in those judged not to be taking treatment, the study found.
The impact of lipid-lowering drugs on cholesterol concentrations in normal care-settings was significant, the study found. This was despite a significant proportion of the population receiving low-dose treatment. In those subjects judged to be taking their medication, the benefits achieved were substantial.
Record linkage studies have shown that people who are not taking their medicines, particularly statins, are more likely to experience a second cardiovascular event. There is evidence to support putting people on moderate-to-high doses of statins, followed by a ‘light touch’ in terms of monitoring.
Randomised controlled trials assessing two strategies are needed, in terms of the surrogate outcome of cholesterol lowering, plus the harder endpoint of whether patients get heart attacks or not, Prof Fahey said.
Most of the evidence in this area has been based on observational research. There may be tolerance problems with higher-dose statins, and there is a trade off between getting the maximum physiological benefit from reducing cholesterol levels and increased symptoms as a result of drug side-effects. Some older data has demonstrated the benefits of higher, as opposed to lower, adherence to statins.
A six-year follow-up study of adherence to statin treatment and re-admission of patients to hospital after heart attacks (L Wei et al, based at Ninewells Hospital in Dundee) found that good adherence to statin treatment was associated with lower risk of recurrent myocardial infarction.
Patients who experienced their first heart attack between January 1990 and November 1995 were examined. Compared with those not taking statins, those who had 80 per cent or better adherence to statin treatment had their risk of a further heart attack reduced by 80 per cent. Their all-cause mortality risk was cut by half. There was no significant reduction in either endpoint for those who were less than 80 per cent adherent to statins.
Currently, high-risk patients are treated to a target cholesterol concentration. An alternative prescribing strategy (the ‘fire and forget’ approach) would instead deploy low-dose statins more widely. It has been suggested that for the same cost, this approach might prevent more cardiovascular events.
With fire-and-forget, if patients tolerate the drug, treatment is regarded as effective. The dosage of the statin is not titrated to the patient’s individual response. A certain proportion of people will not respond as well as expected and these people will thus be undertreated.
Observational research favours the ‘treat to target’ approach, involving titration of dose against extent of cholesterol lowering, rather than the ‘fire and forget’ method. A further study by L Wei et al of the two statin-prescribing strategies, with respect to adherence and cardiovascular outcomes, was carried out at Dundee.
Adherence to statin treatment in patients treated to target was two-and-a-half times better than in patients treated on a fire-and-forget basis. A 60 per cent lower CVD event rate was found in patients treated to target than in fire-and-forget patients.
The findings suggest that adherence to statins is worse in patients treated on a fire-and-forget basis than in patients treated to a target cholesterol concentration, and that this prescribing strategy is associated with worse cardiovascular outcomes.
The evidence is that age should not be an issue, as there have been randomised trials showing the benefits of statins in the elderly. Once somebody reaches their eighties, however, the balance of benefits from treatment has to be weighed against increasing frailty and the fact that they have multiple medications. The risks of drug interactions increase.