How I Treat statin-associated Side Effects in an Outpatient Setting

Abstract

Dyslipidemia promotes atherosclerosis and causes cardiovascular diseases. Statins are potent lipid-lowering medications with a cardiovascular mortality benefit. They are generally safe and well tolerated but sometimes can be associated with side effects of variable severity. The most common side effect is statin-associated muscle symptoms. Uncommon side effects include new-onset diabetes mellitus and elevation in liver enzymes. These effects can lead to noncompliance and premature discontinuation of the medication. Hence, it is crucial to identify patients with true statin-associated side effects (SASE) to ensure optimal statin use. The appropriate evaluation of the patient before starting statins and proactive utilization of available diagnostic tests to rule out alternate etiologies mimicking adverse effects are essential for accurate diagnosis of SASE. In patients with true SASE, timely intervention with modified statin or non-statins is beneficial. Herein, we discuss key clinical trial data on statins and non-statins, and describe our center’s approach toward patients with SASE.

Step‐by‐step diagnosis and management of the nocebo/drucebo effect in statin‐associated muscle symptoms patients: a position paper fromthe International Lipid Expert Panel(ILEP)

“…Where known reversible factors that predispose to SAMS exist, these should be corrected or discussed with the patient prior to commencing statin therapy. 38 A comprehensive overview of reversible risk factors has been provided elsewhere, 39 and these are briefly summarized below in this section.…”

“…Bearing in mind the fact that any AEs that occur during treatment (causal or otherwise) may limit adherence and compliance, every effort should be made to avoid muscle symptoms and the misattribution of symptoms to statin therapy. Where known reversible factors that predispose to SAMS exist, these should be corrected or discussed with the patient prior to commencing statin therapy 38 . A comprehensive overview of reversible risk factors has been provided elsewhere, 39 and these are briefly summarized below in this section.…”

The impact of lipid-lowering medications on coronary artery plaque characteristics

“…Statin-mediated inhibition results in reduced intracellular cholesterol, which in turn causes a compensatory increase in LDL receptor expression on the cell membrane to promote uptake of circulating LDL-C. Statins are the most used lipid-lowering therapy with strong evidence of safety and efficacy in primary and secondary CVD prevention. They can lead to a 22–63% reduction in LDL-C and may exert additional CV protective effects independent of LDL-C lowering, so-called pleiotropic effects [32] . Non-lipid lowering effects of statins in CVD include reducing inflammatory cytokines, reducing oxidation-sensitive inflammatory pathways, and modulating leukocyte-endothelial cell interactions [33] .…”

“…Ezetimibe inhibits the absorption of cholesterol at the brush border of the small intestine via the sterol transporter named Niemann–Pick C1-like intracellular cholesterol transporter 1 (NPC1L1). Ezetimibe monotherapy can yield an 18–20% reduction in LDL-C with good safety and tolerability [32] . Angioscopy and IVUS in stable CAD patients receiving elective percutaneous coronary intervention (PCI) noted significant plaque volume reduction with the addition of ezetimibe 10 mg/day to background statin therapy [54] .…”

“…The U.S. FDA has approved two PCSK9 inhibitors: evolocumab and alirocumab. PCSK9 inhibitor monotherapy can cause a 43–64% reduction in LDL-C with good safety and tolerability [32] . In the ATHEROREMO-IVUS (the European collaborative project on inflammation and vascular wall remodeling in atherosclerosis-IVUS) study, 581 participants underwent ICA for acute coronary syndrome or stable angina, and PCSK9 inhibition was associated with smaller necrotic cores by VH-IVUS, independent of statin use [58] .…”