Statin intolerance, while not very common, is typically seen more often in special populations such as women, Asian patients, and the elderly. For a patient to be considered intolerant to statins, they need to have documented muscle symptoms or an elevated creatine phosphokinase level. Although not well defined, many clinicians consider improvement of symptoms with statin withdrawal as a diagnosis for statin intolerance. Typically patients are then rechallenged with 1 to 2 other statins and if still unable to tolerate, then different lipid-lowering therapies may be utilized [40]. In the elderly, it is important to rule out other causes for myalgia and monitor for significant drug interactions that may lead to muscle pain, particularly if the patient is requiring secondary prevention with statin therapy, before discontinuation.
Dementia
In 2012, the FDA issued a warning about the potential risk of cognitive impairment with the use of statins, which was based on case reports, not clinical trial data [41]. The NLA guidelines do not recommend baseline cognitive assessments prior to starting therapy and recommend that if patients do report cognitive impairment, other contributing factors and the risk associated with stopping statin therapy must be considered. Statin therapy may be discontinued to assess reversibility of symptoms, and if symptoms resolve, then it may be more beneficial to keep the patient off statin therapy. Clinicians may also consider lowering the dose or switching to another statin if they feel it is necessary for the patient to continue with a statin, particularly if the patient requires secondary prevention. Evidence suggests that statins are not associated with adverse effects on cognition and should not be withheld due to the potential for causing cognitive impairment alone [42]. The prevalence of cognitive impairment increases with age, so it is important for a clinician to rule out age-related processes or other disease states, such as Alzheimer’s, before discontinuation of previously tolerated statin therapy.
Renal Impairment
Kidney function must be evaluated prior to initiation of a statin in an elderly person as well as during the time the patient is taking a statin. Because statins are eliminated via the kidney, and because most elderly patients have decreased kidney function, the potential for drug build-up in the body is higher than in a younger patient and may lead to more adverse effects. Atorvastatin is the only option that does not require dose adjustment. All other statins should be adjusted based upon the level of renal impairment. The results from the SHARP study, published in 2011, showed that the combination of ezetimibe and simvastatin versus placebo significantly reduced ASCVD events in patients with moderate to severe chronic kidney disease, including those receiving dialysis. Specifically, this trial showed a significant reduction of ischemic events and occurrence of arterial revascularization procedures. Although the trial did not show a significant difference in incidence of MI or CHD-related mortality, the trial was not adequately powered to show differences in results among the individual ASCVD events and it is not clear whether the results can guide the use of statin therapy in all patients with chronic kidney disease [43]. Statins may be beneficial in renal insufficiency to lower LDL-C, but more studies are needed to assess CVD outcomes related to statin use in patients with a history of kidney disease [44].
Hepatic Function
Statins have been known to increase liver enzymes and in rare cases lead to liver injury, which typically has led to underutilization of therapy in clinical practice. Risk factors associated with this include preexisting hepatitis, advanced age, chronic alcohol use, and use of concomitant medications that may also cause hepatotoxicity, such as acetaminophen. When a statin-induced hepatic effect is suspected, it is important to first rule out other causes or disease states that may be undiagnosed. If no other cause can be found, clinicians may choose to reduce the statin dose, switch the statin, or discontinue the statin altogether if the risk outweighs the benefit. Additionally, statins do not have to be held in patients who have preexisting hepatic dysfunction if use is clearly indicated because the cardiovascular benefits typically outweigh the risks of causing liver injury. Clinical judgement is still warranted and patients with preexisting liver conditions should be monitored regularly [45].
Cost Considerations
Several studies have demonstrated that statin therapy, in the general population, is economical for both primary and secondary prevention of CVD [46,47]. The 4S study found simvastatin therapy to be cost-effective; for example, the cost per life year gained for a 70-year-old man with high chlesterol was $3800 [48]. In contrast, primary prevention in middle-aged men, based on the West of Scotland trial, averages about $35,000 per year of life gained [46]. In a 2015 study that utilized an established Markov simulation model, researchers studied adults 75 to 94 years and examined the cost-effectiveness of generic statins for primary prevention in this population. The authors estimated treating this population with statins over the next decade would be cost-effective. However, the researchers cautioned that the CV benefits and cost-effectiveness would be offset with even a modest increased risk of cognitive impairments or functional limitations. Statin use was not cost-effective in diabetes patients who did not have elevated LDL-C levels [49].
