Very Low Levels of Atherogenic Lipoproteins and the Risk for Cardiovascular Events

Abstract

Objectives To evaluate (1) the inter-individual variability of reductions in low-density lipoprotein cholesterol (LDL-C), non-high-density lipoprotein cholesterol (non-HDL-C) or apolipoprotein B (apoB) levels achieved with statin therapy, (2) the proportion of patients not reaching guideline-recommended lipid levels on high-dose statin therapy, and (3) the association between very low levels of atherogenic lipoproteins achieved with statin therapy and CVD risk. Background Levels of atherogenic lipoproteins achieved with statin therapy are highly variable, but the consequence of this variability for cardiovascular disease (CVD) risk is not well documented. Methods Meta-analysis of individual patient data from 8 randomized controlled statin trials in which conventional lipids and apolipoproteins were determined in all study participants at baseline and at 1-year follow-up. Results Among 38,153 patients allocated to statin therapy, a total of 6,286 major cardiovascular events occurred in 5,387 study participants during follow-up. There was large inter-individual variability in the reductions of LDL-C, non-HDL-C and apoB achieved with a fixed statin dose. Over 40% of trial participants assigned to high-dose statin therapy did not reach an LDL-C target below 70 mg/dL. Compared to patients who achieved an LDL-C > 175 mg/dL, those who reached an LDL-C 75-100 mg/dL, 50-75 mg/dL and < 50 mg/dL had adjusted hazard ratios for major cardiovascular events of 0.56 (95%CI 0.46-0.67), 0.51 (95%CI 0.42-0,62) and 0.44 (95%CI 0.35-0.55), respectively. Similar associations were observed for non-HDL-C and apoB. Conclusions The reduction of LDL-C, non-HDL-C and apoB levels achieved with statin therapy displays large inter-individual variation. Among trial participants treated with high-dose statin therapy, over 40% do not reach an LDL-C target <70 mg/dL. Patients who achieve very low LDL-C levels have a lower risk of major cardiovascular events than those achieving moderately low levels.

Therapeutic strategies for atherosclerosis and atherothrombosis: Past, present and future

“…A recent meta-analysis of multiple statin trials confirmed the sharp reductions in LDL levels (up to 55-60 % for the most potent statins and higher doses) and significant reductions in cardiovascular risk in several patient groups treated with statins (17). However, over the last years a debate has arisen around the increased risk of diabetes due to statin treatment, which has been shown to be 9 % in a meta-analysis (18).…”

Defining the Place of Ezetimibe/Atorvastatin in the Management of Hyperlipidemia

“…A large variability in individual response has been demonstrated for several different statins and doses [13,14]. A recent meta-analysis using individual subject data collected from 32,258 patients treated with atorvastatin 10-80 mg, rosuvastatin 5-40 mg, or simvastatin 10-80 mg showed that the standard deviation of LDL-C reduction for all statins and doses ranged from 13 to 18%, whereas the percentage of patients experiencing a suboptimal response (\30% reduction in LDL-C) ranged from 5 to 53% [15].…”

“…Even though the strategy of treating patients to a specific level of LDL-C has never been formally tested in large trials assessing cardiovascular morbidity and mortality, treatment goals might still be useful as a means to ensure that the aggressiveness of therapy is matched to absolute risk for an event [34]. LDL-C levels achieved with treatment correlated well with the incidence of major atherosclerotic cardiovascular events in four meta-analyses [7][8][9]13] and a large analysis of 40,000 patient records [35]. Acknowledging the new evidence of cardiovascular event reduction with ezetimibe and the potential role of the recently approved monoclonal antibodies to proprotein convertase subtilisin/kexin 9 (PCSK9), the American College of Cardiology issued an expert consensus document on the role of non-statin therapies for LDL-C lowering [36].…”

“…In a recent meta-analysis of eight RCTs including 18,677 patients treated with high-dose statins (defined as either rosuvastatin 20 mg or atorvastatin 80 mg), 40% of patients did not reach an LDL-C \70 mg/dl [13].…”

Lipidek és az agyérbetegség – Új lehetőségek az LDL-koleszterin-szint csökkentésére

“…Egy nyolc nagy klinikai vizsgálat eredményeit kiértékelő metaanalízis rámutatott, hogy a bevont alanyok több mint 40%-a nagy dózisú statinkezelés mellett sem érte el a kívánatos LDL-C-célértéket (1,8 mmol/l). Azoknál a betegeknél azonban, akiknél célér-ték alatti LDL-C-szintet sikerült elérni, tovább csökkent a major cardiovascularis események rizikója [32]. A statinterápiát ezetimibbel kiegészítve további 26%-os LDL-C-szint-csökkenést érhetünk el [26], így az ezetimibet akár közepes dózisú statinhoz adva célértékre hozható a beteg, ugyanakkor a magasabb dózisú statinkezelés mellékhatásait és rizikóit (diabetes, vérzéses stroke) elkerülhetjük vagy csökkenthetjük.…”