164
VOLUME 8 NUMBER 4 • NOVEMBER 2011
CASE STUDY 2
SA JOURNAL OF DIABETES & VASCULAR DISEASE
ised muscle aches and pains should first be investigated for possible
statin intolerance, as this may influence her treatment options. In this
case, measurement of CK and thyroid function in the context of muscle
pain, as well as liver-function tests, were all within the normal reference
range. She was advised to discontinue statin therapy for one month to
investigate whether her muscle aches resolved.
After checking for statin intolerance, there are three options for her
management (Table 1).
South African guidelines recommend statin therapy for CVD preven-
tion in patients with type 2 diabetes, so it is important to continue treat-
ment. (See South African lipid guidelines on page 155.) Switching to a
hydrophilic statin such as rosuvastatin or pravastatin may be less likely
to cause muscle pain compared to a lipophilic statin. In one study, nearly
two-thirds of patients who were intolerant to a particular statin were able
to tolerate an alternative statin without side effects.
Alternatively, simvastatin could be re-introduced at a lower dose
(10 mg) and slowly up-titrated to the optimal dose that does not cause
muscle symptoms. Titration to target LDL cholesterol levels could also be
achieved by adding ezetimibe to low-dose statin therapy, in accordance
with European Society of Cardiology (ESC) guidance. If muscle symptoms
persist, ezetimibe monotherapy could be considered and the patient re-
ferred for ankle-brachial pressure tests for possible peripheral arterial
disease.
Glycaemic control, blood pressure and BMI are all good in this patient,
suggesting that she is following lifestyle advice appropriately. She is be-
ing treated with low-dose aspirin, based on guideline recommendations
for treatment in patients with type 2 diabetes aged over 50 years and
with blood pressure below 145/90 mmHg. However, it is also important
to consider whether the risks associated with aspirin therapy are justified
in this patient, given that her 10-year estimated CHD risk is 7.5% and her
10-year risk for stroke is 3.8%.
EXPERT CONSENSUS
A well-established body of evidence supports the benefits of CVD preven-
tion including LDL cholesterol lowering with a statin in patients with type
2 diabetes. However, this case of possible statin intolerance highlights
the need to consider non-statin options for lipid management.
Discussing treatment options with the patient to help her to make in-
formed decisions about her therapy is clearly important, as highlighted
by South African guidelines. This should involve discussion of the risks
and benefits of the various treatment options, as well as the importance
of concordance in achieving recommended LDL cholesterol targets and
preventing CVD events, including stroke.
The importance of adherence to a healthy lifestyle, as already adopted
by this patient, in CVD prevention should also be re-emphasised, sup-
ported by evidence from the STENO-2 study. If, as in this case, the patient
has a low risk score, this information should be communicated care-
fully to avoid any misperception by the patient that she does not need
cholesterol-lowering medication.
If muscle symptoms return after re-introducing a statin and are likely
to influence patient compliance, non-statin treatment options should
be considered. In this patient, these would involve a choice between
ezetimibe, or a nicotinic acid formulation – ideally one with reduced
flushing potential (i.e. in combination with laropiprant, an anti-flushing
agent). Although no general recommendations for the use of nicotinic
acid in type 2 diabetes patients are given in recent guidelines, this
treatment may be considered for Rose as she has good glycaemic
control. Nicotinic acid medicinal products have been associated with
increases in fasting blood glucose levels, so the patient should be
monitored closely, with adjustment of diet and/or hypoglycaemic therapy
as necessary. A fibrate is not indicated as a non-statin alternative in
this patient because her triglyceride levels are not sufficiently elevated
(~1.8 mmol/l).
After discussing the risks and benefits of nicotinic acid, the patient
might prefer re-introduction of a low dose of statin with add-on ezetimibe
therapy for improved LDL cholesterol-lowering efficacy. This approach,
which is recommended, may represent the preferred option in this pa-
tient.
Finally, from a practical viewpoint, the physician should be aware of
the risk of relying on ‘normal’ results, especially given the lack of stand-
ardisation in measurement of liver function tests across different labo-
ratories. Any elevation in CK needs to be considered in the context of
the patient’s usual activities, which in this case include regular exercise.
This underscores the need for measurement of CK before starting lipid-
modifying treatment to obtain appropriate baseline levels.
• Investigate for possible statin intolerance
• Consider switching to a hydrophilic statin or add on ezetimibe to low-dose
statin therapy
• If symptoms persist, consider non-statin options
Take-home messages: type 2 diabetes patient with muscle aches on
a statin
SUMMING UP: TAKE-HOME MESSAGES
• Lowering cholesterol to recommended targets (4 mmol/l for total
cholesterol and 1.8 mmol/l LDL cholesterol) is essential in high-risk
patients, including in secondary prevention cases, prior CABG, and
primary prevention in most type 2 diabetes patients
• Treatment options should be discussed with the patient, taking into
account informed preference, co-morbidities, multiple drug therapy
and the benefits and risks of treatment. The importance of concord-
ance with therapy and lifestyle management should be emphasised
• Switching to higher-intensity statins is preferable to up-titrating sim-
vastatin dosage to optimise LDL-lowering efficacy and tolerability.
Add-on ezetimibe is an option if targets are not achieved
• Where there is evidence of possible statin intolerance, ezetimibe may
be a useful non-statin option.
