Addressing the Side Effects of Using Statin
Myopathy, increased incidence of diabetes, renal failure, cataracts, cognitive impairment, and impaired liver function are adverse side effects of statin use. Myopathy, although not serious, can cause disability or affect the patient’s daily life.
Efficacy In Elderly Patients
Statins in elderly patients are effective for secondary prevention of cardiovascular events. However, there are no data recommending the use of high-dose or potent statins in patients over 75 years of age. There is little evidence available on the role of statins in primary prevention in people over 80 years of age.
The pathophysiological mechanisms of cardiovascular disease change over the life course, and some studies have shown that low total cholesterol is associated with increased mortality in people over 80 years of age. On the other hand, the importance of hypercholesterolemia as a cardiovascular risk factor decreases with age. In addition, this population is underrepresented in clinical trials, so the recommendation to continue statin therapy beyond this age group would be an extrapolation of the younger adult studies.
- The PROSPER 4 trial was the only clinical trial in older patients (70 years of age or older) that showed a reduction in the combined variables of cardiovascular mortality, nonfatal myocardial infarction, and stroke with pravastatin compared with placebo; however, no such benefit was observed in primary prevention.
- A meta-analysis of primary prevention clinical trials5 in patients at high cardiovascular risk, which evaluated the benefits of statins across age groups, found that statin use was not associated with a reduction in overall mortality or major coronary or cerebrovascular events in those aged 65 years or older.
- In secondary prevention, studies and meta-analyses of people over 65 years of age have shown a reduced risk of all-cause mortality and cardiovascular death, stroke and heart attack. There are no data to recommend the use of high-dose statins in patients over 75 years of age. In the Prosper 4 study, patients treated with high-dose statins (31%) had similar outcomes to those treated with moderate doses (MACE: RR 1.02 95% CI 0.97-1.08, all-cause mortality: HR 1.00 95% CI 0.93-1.08).
- In the European Community, statins only produce benefits after one to two years of continuous treatment.
Therefore, for the elderly as primary prevention, the preferred approach is non-pharmacological, multifactorial management of risk factors, such as avoidance of smoking, adherence to a healthy diet, regular physical activity and elimination of overweight. If there is a history of cardiovascular disease (secondary prevention), moderate-intensity statin therapy is recommended. For patients with limited life expectancy (<2 years), initiation of therapy is not recommended 8.
Safety Of Statins
Myopathy, increased incidence of diabetes, renal failure, cataracts, cognitive impairment, and impaired liver function are adverse side effects associated with statin use. Myopathy, although not serious, can cause disability or affect the patient’s daily life.
The incidence of adverse events is higher in older patients and is also greater due to associated co-morbidities and frequent coexistence of polypharmacy, a greater potential for drug interactions, and impaired renal and/or hepatic function. In addition, age is a risk factor for the development of cognitive impairment.
High doses of statins, potent statins, and duration of exposure increase the risk of adverse reactions in older adults and are no longer effective.
There is also an increased incidence of concomitant use of statins with gemfibrozil, antipsychotics, amiodarone, verapamil, cyclosporine, macrolides, or azole antifungals. Pravastatin is an option for patients treated with other drugs metabolized by cytochrome P450. Concomitant use of gemfibrozil with any statin is not recommended because of the increased risk of myopathy.
Treatment should be discontinued when the physician and patient agree that there is no clinical benefit or that the risks outweigh the potential benefits.
Prescribing should be considered
- When the potential benefit is no longer clinically meaningful.
- Patients with severe physical impairment, cognitive impairment, or short life expectancy, as reduced risk of CV events or mortality is not relevant.
- In patients with adverse events (myositis, rhabdomyolysis, or severe hepatic impairment).
- In patients with signs or symptoms consistent with statin side effects (myalgia, moderate to severe transaminase elevation, cognitive impairment, or fatigue).
- In patients without a history of cardiovascular disease requiring treatment with drugs that interact with statins (increased risk of toxicity.
- Statin therapy is recommended in elderly patients.
- In primary prevention, assess the need for continued therapy.
- In secondary prevention, use moderate intensity therapy and avoid intensive therapy; reduce dose or change statins if necessary.