Does Switching Statins Increase the Risk for Adverse Events?
Does Switching Statins Increase the Risk for Adverse Events?
Patients on statin therapy sometimes must switch from one statin to another, such as when the insurer or hospital insists. Does switching statins increase the risk of developing adverse reactions that will generalize to all of the statins, including ones initially tolerated?
Statins are one of the most widely prescribed classes of medications for hypercholesterolemia in the United States. Included within this class are several agents: lovastatin, pravastatin, simvastatin; and the newer agents -- atorvastatin, fluvastatin, and rosuvastatin. The mechanism of action for each statin centers on the inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, resulting in a decrease in low-density lipoproteins (LDL). The numerous benefits of statins have been well established in several landmark trials, including a reduction in the relative risk of coronary events by about 23% to 37%.
As newer statins have been developed, a greater disparity in their relative potencies has been demonstrated. But for a large majority of agents, equipotent doses are available with respect to their ability to lower LDL. Another difference between the statins is related to their hydrophilic or lipophilic nature. It has been suggested that lipophilic statin agents, such as lovastatin and simvastatin, potentially increase muscle-related adverse drug events (ADEs) in patients.
While statins are generally safe, they are not innocuous and there have been several ADEs associated with their use. The most common ADEs, which usually subside without discontinuing the medication, include constipation, diarrhea, dizziness, headache, heartburn, and upset stomach. The most worrisome potential ADE and a common reason for patients to discontinue treatment is statin-induced myopathies. The statin-induced muscle effects vary in intensity and severity and are categorized by symptomatic muscle weakness and/or pain, elevated creatine kinase (CK -- an enzyme found in skeletal muscle that becomes elevated when the muscle is injured), and dark-colored urine (associated with a breakdown of muscle tissue). Statin-induced myopathies can range from myalgia (muscle ache or weakness without elevations in CK) to myositis (muscle complaints with elevated CK) to the most severe -- rhabdomyolysis (markedly elevated levels of CK).
Factors that may predispose individuals to be more susceptible to myopathy-related ADEs appear to be dependent on the statin used, as well as the dose, coexistence of factors that generally predispose a patient to myopathies (eg, advanced age, female gender, renal insufficiency, hepatic dysfunction, complex medical problems), and being on multiple medications (because of the risk of drug interactions).
Individuals who experience intolerable myopathies but have a high benefit-to-risk ratio for remaining on a statin may benefit from switching to a lower potency statin. To date, there are no clinical trials directly comparing the rates of myopathies with the agents currently available. Nor are there data evaluating the risk of developing ADEs when switching statins that can be generalized as a class effect. If a person is switched from a statin that they were tolerating to a statin that they do not tolerate, one could consider switching them back to the previously tolerated statin. For those patients who report intolerance to multiple statins despite trying various members of the class, new dosing strategies are being evaluated (eg, every other day or once weekly).
In conclusion, the current data are limited with regard to switching statins and increasing the risk for ADEs. That risk, particularly regarding myopathies, appears to be related to the factors described above. Additional research is needed on alternate dosing schedules and strategies to reduce these ADEs.
The author wishes to acknowledge the help of Patrick Galuski, PharmD student, at Northeastern University School of Pharmacy in Boston, Massachusetts.
Question
Patients on statin therapy sometimes must switch from one statin to another, such as when the insurer or hospital insists. Does switching statins increase the risk of developing adverse reactions that will generalize to all of the statins, including ones initially tolerated?
Response from the Expert
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Jenny Van Amburgh, PharmD, CDE
Associate Clinical Professor, School of Pharmacy, Northwestern University, Boston, Massachusetts; Director of the Clinical Pharmacy Team and Residency Director, Harbor Health Services, Inc., Boston, Massachusetts |
Statins are one of the most widely prescribed classes of medications for hypercholesterolemia in the United States. Included within this class are several agents: lovastatin, pravastatin, simvastatin; and the newer agents -- atorvastatin, fluvastatin, and rosuvastatin. The mechanism of action for each statin centers on the inhibition of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase, resulting in a decrease in low-density lipoproteins (LDL). The numerous benefits of statins have been well established in several landmark trials, including a reduction in the relative risk of coronary events by about 23% to 37%.
As newer statins have been developed, a greater disparity in their relative potencies has been demonstrated. But for a large majority of agents, equipotent doses are available with respect to their ability to lower LDL. Another difference between the statins is related to their hydrophilic or lipophilic nature. It has been suggested that lipophilic statin agents, such as lovastatin and simvastatin, potentially increase muscle-related adverse drug events (ADEs) in patients.
While statins are generally safe, they are not innocuous and there have been several ADEs associated with their use. The most common ADEs, which usually subside without discontinuing the medication, include constipation, diarrhea, dizziness, headache, heartburn, and upset stomach. The most worrisome potential ADE and a common reason for patients to discontinue treatment is statin-induced myopathies. The statin-induced muscle effects vary in intensity and severity and are categorized by symptomatic muscle weakness and/or pain, elevated creatine kinase (CK -- an enzyme found in skeletal muscle that becomes elevated when the muscle is injured), and dark-colored urine (associated with a breakdown of muscle tissue). Statin-induced myopathies can range from myalgia (muscle ache or weakness without elevations in CK) to myositis (muscle complaints with elevated CK) to the most severe -- rhabdomyolysis (markedly elevated levels of CK).
Factors that may predispose individuals to be more susceptible to myopathy-related ADEs appear to be dependent on the statin used, as well as the dose, coexistence of factors that generally predispose a patient to myopathies (eg, advanced age, female gender, renal insufficiency, hepatic dysfunction, complex medical problems), and being on multiple medications (because of the risk of drug interactions).
Individuals who experience intolerable myopathies but have a high benefit-to-risk ratio for remaining on a statin may benefit from switching to a lower potency statin. To date, there are no clinical trials directly comparing the rates of myopathies with the agents currently available. Nor are there data evaluating the risk of developing ADEs when switching statins that can be generalized as a class effect. If a person is switched from a statin that they were tolerating to a statin that they do not tolerate, one could consider switching them back to the previously tolerated statin. For those patients who report intolerance to multiple statins despite trying various members of the class, new dosing strategies are being evaluated (eg, every other day or once weekly).
In conclusion, the current data are limited with regard to switching statins and increasing the risk for ADEs. That risk, particularly regarding myopathies, appears to be related to the factors described above. Additional research is needed on alternate dosing schedules and strategies to reduce these ADEs.
The author wishes to acknowledge the help of Patrick Galuski, PharmD student, at Northeastern University School of Pharmacy in Boston, Massachusetts.
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