Quantitative evaluation of statin effectiveness versus intolerance and strategies for management of intolerance

There is disquiet about statin effectiveness and side effects in both the medical and lay media.

We searched the literature for reports on the incidence of statin intolerance (SI) in which control rates of similar events were also recorded. The number of people who must receive treatment (NNT) to prevent one atherosclerotic cardiovascular disease (ASCVD) event at 5-50% 10-year risk and LDL cholesterol 2-7 mmol/l was compared with the number of those who would experience harm attributable to statin (NNH). Using a similar method, the effectiveness of various strategies to overcome SI in preventing CVD was then compared.

Observational studies with non-randomised control groups report higher rates of statin adverse events than randomised trials. Overall, at least 75 patients must be treated for one to experience a side effect. In contrast, the NNT to prevent one ASCVD event with statins as monotherapy or in combination with other cholesterol-lowering medications to achieve at least 50% decrease in LDL cholesterol and <1.8 mmol/l was between 3 and 61, depending on risk and LDL cholesterol. NNH for adverse events of severity equivalent to ASCVD was >750 (<0.1333%). When SI is encountered, the most effective current management for most patients in terms of ASCVD reduction is to rechallenge with low dose potent statin and then up-titrate until the cholesterol target has been achieved with, if necessary, the addition of ezetimibe 10 mg daily.

The most severe complication of SI is discontinuation of effective cholesterol-lowering treatment in patients who, by virtue of their CVD risk and cholesterol level, might otherwise benefit.