NEW ORLEANS – Alternative dosing regimens solve the common problem of statin-induced muscle pain in most cases.
Lowering the daily dose of the statin, dropping down to alternate-day or even once-weekly therapy, or switching to another statin having a better track record with regard to myalgia all have been shown to improve tolerability while maintaining reasonably effective lipid-lowering, according to Dr. Karol E. Watson, codirector of the University of California, Los Angeles, Program in Preventive Cardiology.
Dr. Karol E. Watson
It must be emphasized, however, that none of the alternative dosing regimens have proved to reduce cardiovascular events. The issue hasn’t been studied. That being said, alternative dosing strategies do provide an option for patients who would otherwise go without the proven benefits of statin therapy, she noted at the annual meeting of the American College of Physicians.
Statin-induced muscle pain, cramping, or weakness is far more common than rates from major clinical trials would suggest. Statin-induced myalgia occurs in 10%-20% of treated patients in everyday practice. In contrast, in the landmark clinical trials, where patients were carefully preselected and there was often an active run-in phase, myalgia rates were far lower and similar to placebo.
Factors that increase the likelihood of statin-induced myopathy include advanced age, diabetes, hypothyroidism, renal insufficiency, alcohol abuse, liver disease, and smaller muscle mass, as is common in patients of smaller body size, including women. But people who experience more muscle side effects also tend to get the biggest lipid responses to statin therapy, Dr. Watson noted.
Of all the statins, rosuvastatin (Crestor) has been shown to have the most favorable ratio of LDL lowering to creatine kinase elevation (Cleve. Clin. J. Med. 2011;78:393-403). It’s a good option in patients experiencing problematic myalgia on another statin.
Also, fluvastatin XL performed exceptionally well in the large French observational Prediction of Muscular Risk in Observational Conditions (PRIMO) study, the cardiologist continued. Among nearly 8,000 French patients on high-dose statins for at least 3 months, 10.5% reported muscle-related symptoms. The lowest rate, at 5.1%, was in patients on fluvastatin XL at 80 mg/day. The highest rate, 18.2%, was in patients on simvastatin at 40-80 mg/day. PRIMO participants on atorvastatin at 40-80 mg/day had a 14.9% incidence of muscle symptoms, while those on 40 mg/day of pravastatin had a 10.9% rate (Cardiovasc. Drugs Ther. 2005:19:403-14).
Alternate-day dosing as an answer for statin-intolerant patients only can be carried out effectively with rosuvastatin or atorvastatin, drugs with half-lives markedly longer than the other statins. Alternate-day dosing with 5 or 10 mg of rosuvastatin was studied in a retrospective analysis involving 51 patients, 37 (73%) of whom were able to tolerate the regimen. Among those who tolerated every-other-day dosing, the mean reduction in LDL was 34.5%, enabling half of them to achieve their LDL target (Ann. Pharmacother. 2008;42:341-6).
In another retrospective study, once-weekly dosing of rosuvastatin at 2.5-20 mg was introduced to 50 previously statin-intolerant patients. Thirty-seven patients (74%) were able to tolerate the once-weekly therapy at a mean dose of 10 mg. They responded with a 23% reduction in LDL from a baseline of 167 mg/dL (Am. J. Cardiol. 2009;103:393-4).
In a prospective pilot study, 61 consecutive patients intolerant to other statins were placed on rosuvastatin at 5 mg/day if they were moderately high risk and 10 mg/day if they were at very high risk. Only 1 of the 61 patients discontinued rosuvastatin because of muscle pain. From a baseline mean LDL of 177 mg/dL, patients in the 5-mg/day group dropped their LDL by a mean of 75 mg/dL and those on 10 mg/day lowered their LDL by 79 mg/dL (Clin. Ther. 2006;28:933-42).
The National Lipid Association advises that it’s not routinely necessary to get a baseline creatine kinase level before starting statin therapy, nor is it necessary to obtain one during treatment in asymptomatic patients, Dr. Watson noted. But patients on statin therapy need to be counseled about the associated increased risk of muscle complaints and the importance of contacting their physicians should they arise (Am. J. Cardiol. 2006;97:89C-94C).
Those who develop tolerable muscle symptoms may continue with therapy, according to the National Lipid Association Statin Safety Task Force. But patients who experience intolerable symptoms with or without a creatine kinase elevation should stop treatment. Once they’re asymptomatic, the same drug can be restarted at the same dose, or one of the alternative strategies Dr. Watson described can be employed.
She reported serving as a consultant to Pfizer and on the Merck clinical trials adjudication committee.