Lipid-Lowering Therapy Seen Through the Lens of Experts: Expectations Thwarted by Reality

Abstract

Lipid-Lowering Therapy Seen Through the Lens of Experts: Expectations Thwarted by Reality L ow-density lipoprotein cholesterol (LDLc) is a key determinant of atherosclerotic cardiovascular disease (ASCVD) worldwide. 1,2 Statins reduce mortality and morbidity regardless of LDLc baseline levels, either in primary or secondary prevention. 3,4 Non-statin LDLc lowering therapies are equally effective in reducing the risk of several outcomes and follow statins along the same linear relationship: For every 39 mg/dL reduction in LDLc levels, the relative risk of cardiovascular events decreases by 22%-24%. 5 Patients with previous ischemic events, diabetic individuals with either target organ lesions or 3 or more risk factors, and those with familial hypercholesterolemia and 1 additional risk factor, comprise a cohort exposed to a very high risk of events and need persistent and aggressive LDLc lowering. 3,6 Such patients, provided that goals be achieved and maintained in the long run, derive the highest absolute risk reduction from LDLc-lowering therapy. 4 Furthermore, statins-the backbone of lipid-lowering therapy (LLT)-show a very favorable safety profile. 4,7,8 Notwithstanding the radical change in the natural history of atherosclerotic disease promoted by statins, their long-term adherence all across the globe, as well as the compliance to LDLc goals set by various guidelines, seems way too far from ideal, which in turn, frustrates much of the expectations toward their benefits. 7,[9][10][11][12][13][14] Although Turkey has the highest prevalence of premature coronary artery disease among European countries, 15 rates of statin discontinuation continuously mount along a period of 6 months past the first prescription, and only 18% of patients in secondary prevention achieve LDLc goals <70 mg/dL: Surprising data, given the countrywide reimbursement of statins by the Turkish health system. Reasons for the low adherence and high discontinuation rate may vary among countries or regions in the same country, and the most commonly reported causes are fear of side effects by patients, coupled with low awareness of benefits, dissemination of negative or fake news, and therapeutic inertia.Worthy of mention is the inertia to associate ezetimibe as an add-on to statins when goals are not achieved: Despite its proven value to further reduce LDLc levels and cardiovascular outcomes, 6,16 data from registries have shown that its addition to statins in patients with ASCVD remains very low 9,13,17,18 and does not progress during a 2-year follow-up. 19 PCSK9 inhibitors (PCSK9i) are the most efficacious non-statin LDLc-lowering agents 20 and were proven capable of reducing cardiovascular outcomes when added to maximally tolerated statin doses (MTD) in very high-risk patients. 21,22 Recently, important contributions were added to the body of data demonstrating the usefulness of PCSK9i in the secondary prevention of ASCVD. In a randomized double-blind trial of 300 patients who underwent percutaneous coronary intervention for acute myocardia...