STOCKHOLM -- A third of patients on cholesterol-lowering therapy received inadequate doses of generic simvastatin after being switched from atorvastatin (Lipitor), an analysis of a large pharmacy database showed.
Because of differences in potency between brand-name statins and generic versions, doctors must adjust the number of pills patients take. What researchers found was that fewer than half of patients who switched from brand-name statins to generci received doses of equal potency after the switch. The switching occurred after a government-mandated change in rules for using branded statins in the Netherlands.
Statistical models suggested inadequate dosing would lead to a 5.6 percent increase in LDL (or bad) cholesterol, possibly increasing the risk of heart problems, according to a study that will be reported here at the European Society of Cardiology meeting next week.
"The predicted net effect of this would be at least a 5 percent to 6 percent increase in low-density lipoprotein cholesterol, which translates to a 3 percent average increase in the risk of heart disease and stroke," Dr. Danny Liew of the University of Melbourne in Australia said in a statement.
"Our study highlights the need for health policymakers to be conscious of the potential adverse and unintended consequences of policy changes and for clinicians to be aware of dose equivalences among statins," Liew added in an e-mail to MedPage Today.
The findings came from an analysis of a nationwide pharmacy database and included 39,031 patients switched from atorvastatin to simvastatin during the first quarter of 2009. The switches occurred after the Dutch government began requiring physicians to justify prescriptions for branded statins.
Liew and colleagues conducted the analysis after prescription data suggested that switching often resulted in simvastatin doses that did not have potency equivalent to that of atorvastatin. They determined relative potency on the basis of a published meta-analysis of randomized clinical trials comparing the two drugs.
Their analysis showed that 33.7 percent of patients received less than equally potent doses of simvastatin after switching from atorvastatin, 19.1 percent received more potent doses of simvastatin, and 47.2 percent received doses of the same potency.
"Patients on higher doses of initial atorvastatin were more likely to switch to less potent doses of simvastatin," Liew commented. "It may be that clinicians may be reluctant to prescribe high doses of simvastatin."
A recent study showed that every 25 mg/dL reduction in LDL lowers the risk of any cardiovascular disease (CVD) event by 14 percent, a coronary event by 16 percent, stroke by 10 percent, and cardiovascular death by 11 percent. Given that inadequate simvastatin dosing was modeled to lead to a 5.6 percent increase in LDL, the investigators estimated that inadequate dosing of simvastatin would increase cardiovascular risk by 3 percent.
A U.S. cardiologist echoed Liew's cautionary statements regarding the possible risks associated with switching to an inadequate statin dose.
"The consequences of switching from Lipitor to simvastatin on LDL cholesterol on any CVD event, coronary event, stroke, and CVD death in the Dutch population are noteworthy and of concern," said Dr. Robert Eckel of the University of Colorado. "Despite the cost-saving benefits of such a change, the increased risk demands better guidance on how to prescribe equipotent doses."
Eckel is a spokesperson for the American Heart Association and was not involved in the study.
Liew and Eckel reported no relevant disclosures. Liew's co-investigators included employees of Pfizer.