Nearly three-quarters of patients who are initially "statin-intolerant" are able to re-start therapy on a graduated-dosing schedule and continue on an intermittent dosing regimen.
A report from the CDC estimates that of the 71 million patients with hyperlipidemia in the United States, only 34 million are treated. Of these patients, 12 million have uncontrolled lipid levels and 1.4 million are refractory or “intolerant” to statins.1 Treating these patients is a significant challenge, since effective alternative treatment options, while under study, are limited. There is increasing evidence, however, that some of these patients may benefit from a drug holiday and rechallenge.
Results from the largest statin re-challenge study to date (Cleveland Clinic)2 suggest that in 72.5% of patients with previous statin intolerance, the drug can be successfully restarted. The retrospective analysis reviewed records of 1605 patients referred to the clinic for evaluation of adverse effects of statins, including myalgias, arthralgias, transaminitis, weakness, and GI intolerance, that necessitated drug cessation; a daily statin regimen was restarted in 1014 patients, and they achieved a 21.3% reduction in LDL level at a median follow-up of 31 months. There were 149 patients who remained on an intermittent dosing strategy, and surprisingly, they achieved a 27.7% reduction in LDL level. An important caveat is that the statin re-challenge in all patients was accomplished gradually with a once-weekly dosing schedule that was then increased to twice-weekly and so on until the patients reached the maximally tolerated regimen. There was a positive trend in the reduction of all-cause mortality for those patients who were able to restart the statin regimen (daily or intermittent dosing) but this did not achieve statistical significance. The most commonly used statin for re-challenge was rosuvastatin.
For primary care providers and their patients, the study provides convincing evidence that there may be some degree of tachyphylaxis to the adverse effects of statin therapy. So, before giving up on statin therapy and labeling a patient as “statin-intolerant,” it is worth re-challenging after a drug holiday to see whether this lifesaving therapy can be tolerated the second time around.
1. Centers for Disease Control and Prevention. Vital signs: prevalence, treatment, and control of high levels of low-density lipoprotein cholesterol-United States, 1999-2002 and 2005-2008. MMWR Morbid Mortal Wkly Rep. 2011;60:109-114. (Full text)
2. Mampuya WM, Frid D, Rocco M, et al. Treatment strategies in patients with statin intolerance: The Cleveland Clinic experience. Am Heart J. 2013;166:597-603. doi:10.1016/j.ahj.2013.06.004. (Abstract)