Efficacy of Combination Drug Pulse Therapy in Maintaining Lipid Levels in Patients Intolerant of Daily Statin Use

Abstract

The objective of this study was to evaluate the efficacy of combination drug pulse therapy in maintaining lipid levels in patients intolerant of a daily dose of statins. Twenty‐three patients, previously receiving aggressive statin therapy, were treated twice weekly with rosuvastatin or atorvastatin in different dosages along with ezetimibe as well as daily doses of bile acid sequestrant for a mean period of 4.5 months. The recommended National Cholesterol Education Program Adult Treatment Panel III goals had already been achieved in 78% of patients (n=18) before starting combination pulse therapy. This combination therapy significantly increased high‐density lipoprotein cholesterol values by 5.82% (t=2.138, P=.044), while the increases in total cholesterol, low‐density lipoprotein cholesterol, triglyceride, and apolipoprotein B levels compared with baseline were not statistically significant. Overall, 3 of 23 patients (13%) discontinued the combination therapy because of muscle‐related symptoms over a mean course of 4.5 months of treatment.

Statin-associated muscle symptoms: impact on statin therapy—European Atherosclerosis Society Consensus Panel Statement on Assessment, Aetiology and Management

“…If LDL-C remains above target despite maximally tolerated statin dosage, addition of an alternative LDL-C lowering agent should be considered in patients at high CVD risk to improve LDL-C reduction. 38 , 39 Ezetimibe reduces LDL-C by 15–20%, is easy to take with few side effects, 40 and has been shown to reduce CVD events. 41 In patients with SAMS, the combination of ezetimibe plus fluvastatin XL reduced LDL-C by 46% and was as well tolerated as ezetimibe alone.…”

Strategies to preserve the use of statins in patients with previous muscular adverse effects

“…The highest rate of tolerance was found in the prospective study by Athyros et al, 10 which evaluated atorvastatin 10 mg twice weekly, a rather low total exposure to a statin, although the weekly statin dose did not correlate strongly with tolerability ( Figure 1). [10][11][12][13][14] Higher rates of myalgia were observed in the four trials using rosuvastatin; however, based on rosuvastatin-equivalent doses, these four studies used a higher weekly total statin dose. In all of the trials, the correlation between dosing intensity based on LDL cholesterol or TC lowering and recurrent myalgia could not be evaluated due to patients' use of other lipid-altering medications.…”

“…To evaluate the effects of twiceweekly use of rosuvastatin or atorvastatin, Reddy et al 13 retrospectively identified 23 patients previously intolerant of daily doses of one of those statins due to myalgia who subsequently received the same statin twice weekly (along with twice-weekly ezetimibe 10 mg and colesevelam 625 mg twice daily). Patients received either rosuvastatin 5-40 mg (n = 14) or atorvastatin 20-40 mg (n = 9).…”

“…[10][11][12][13][14] Our review identified five published trials that evaluated the effects, including musculoskeletal adverse effects, of extending the statin dosing interval in patients intolerant of daily statin use. None of the five trials was randomized or controlled, and all but the study by Athyros et al 10 were chart reviews.…”

“…[22][23][24][25] Summary information on the methodology and quality of each included trial or research report is given in Table 1. [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25] Many of the studies included patients with prior statin intolerance due to adverse effects other than myalgia or patients who required treatment with an alternative agent because goal lowdensity lipoprotein (LDL) levels were not achieved; for those studies, only data on the patients with a history of previous myalgia were reviewed and included in the evaluation described here.…”