Effects of atorvastatin on serum lipids, serum inflammation and plaque morphology in patients with stable atherosclerotic plaques

Abstract

Statin treatment in patients with coronary heart disease is associated with a reduced incidence of short-term adverse events and endpoint cardiac events. However, the effects of statin treatment on atherosclerotic plaques, particularly stable plaques, remain poorly defined. In total, 228 consecutive patients with stable atherosclerotic plaques who had undergone coronary arteriography (CAG) and intravascular ultrasound (IVUS) were randomly assigned to receive placebo (placebo group, n=54) or atorvastatin (ATOR) at a single daily dose of 10 mg (ATOR 10 mg group, n=47), 20 mg (ATOR 20 mg group, n=45), 40 mg (ATOR 40 mg group, n=43) or 80 mg (ATOR 80 mg group, n=39). Endpoints, including serum lipids, serum inflammation, plaque volume and percentage of plaque necrosis were assessed after 3–6 months. At baseline, mean low-density lipoprotein (LDL), high-density lipoprotein (HDL) and high-sensitivity C-reactive protein (hs-CRP) levels, as well as plaque volumes and percentages of plaque necrosis, were similar between all groups. At 6 months of follow-up, the LDL levels in the ATOR groups were below those at their respective baselines (P<0.01). HDL levels in the ATOR 80 mg group following treatment were significantly higher compared with baseline (P=0.001). Additionally, they were significantly higher compared with those in the placebo, ATOR 10, 20 and 40 mg groups (P<0.01, P=0.001, P=0.048, P=0.047, respectively). Hs-CRP levels in the placebo group following treatment were higher compared with baseline levels (6.87±2.62 vs. 5.07±1.80, P<0.01), but hs-CRP levels in the ATOR 80 mg group following treatment were lower compared with baseline (3.59±1.07 vs. 6.10±2.12, P<0.01). According to the virtual histology (VH) of IVUS, the percentages of plaque necrosis following treatment in the placebo and ATOR 10 mg groups rose above baseline levels (15.51±12.56 vs. 7.69±1.31%, 13.54±11.76 vs. 7.83±1.43%, P<0.01) and conformed to the diagnostic criteria for unstable plaques (15.51±12.56, 13.54±11.76%). By contrast, in the ATOR 20, 40 and 80 mg groups, percentages of plaque necrosis remained stable following treatment compared with baseline (P=0.069, 0.846 and 0.643, respectively). Plaque volumes following treatment in the placebo, ATOR 10 and 20 mg groups were similar to baseline levels. However, in the ATOR 40 and 80 mg groups, plaque volumes decreased following treatment compared with baseline plaque volumes (30.69±8.12 vs. 37.09±12.01 mm3, 24.99±1.01 vs. 36.47±14.68 mm3, P=0.019, P<0.01, respectively). ATOR (20 mg/day) is able to lower LDL to standard levels while ATOR 40 mg/day was superior to 20 mg/day and had similar effects to 80 mg/day. Only ATOR 80 mg/day was able to increase HDL levels. Hs-CRP in patients without ATOR was higher and ATOR 80 mg/day decreased levels. ATOR ≥20 mg/day is able to stabilize plaques and ATOR 80 mg/day was superior to 20 and 40 mg/day. Thus, ATOR 40–80 mg/day reduces the volume of plaques.

Use of Atorvastatin in Lipid Disorders and Cardiovascular Disease in Chinese Patients

“…Plaque volumes in the atorvastatin 40 and 80 mg groups decreased significantly compared with baseline plaque volumes (30.69 ± 8.12 vs. 37.09 ± 12.01 mm 3 , P = 0.019; 24.99 ± 1.01 vs. 36.47 ± 14.68 mm 3 , P < 0.01, respectively). [ 38 ]…”

Regional evidence and international recommendations to guide lipid management in Asian patients with type 2 diabetes with special reference to renal dysfunction

“…Furthermore, hyperlipidemia could worsen inflammation of the kidney, whereas lowering LDL‐C levels may potentially preserve renal function . In support of these findings, atorvastatin treatment has been shown to dose‐dependently decrease not only LDL‐C levels, but also oxidative stress and inflammatory markers, atheromatous plaques and the rate of decline in renal function …”

“…50 In support of these findings, atorvastatin treatment has been shown to dose-dependently decrease not only LDL-C levels, but also oxidative stress and inflammatory markers, atheromatous plaques and the rate of decline in renal function. 49,[51][52][53][54] Although the biological and genetic mechanisms underlying the increased incidence of diabetic kidney disease in Asia remain to be clarified, there is an urgent need to implement diabetes detection and prevention strategies to reduce disease burden. It is recommended that patients with diabetes, hypertension, a family history of CKD, or a past history of acute kidney injury should undergo regular screening for detection of CKD.…”

A double‐blind, randomized, placebo‐controlled pilot trial of atorvastatin for nephrogenic diabetes insipidus in lithium users

“…Although the dose range 20‐40 mg/d have similar therapeutic effects for other indications (eg, LDL cholesterol management), 29‐32 40 mg has a higher risk of side effects 33 . In terms of duration, clinical trials of atorvastatin for cardiovascular outcomes have shown therapeutic effects within 6‐12 weeks 29‐32 . Similarly, trials for treatment of lithium‐induced NDI with other agents have shown effects within 12 weeks 17,18 .…”

“…Clinically relevant safety measures were monitored throughout the study including creatine kinase, liver function (AST, ALT levels), LDL cholesterol levels, glomerular renal function (eGFR), lithium serum levels, and electrolytes (sodium and potassium). Liver function, creatine kinase, and LDL levels were monitored for any risk of liver and muscle injury and dangerously low levels of LDL 30,45 . The effects of statins on glomerular renal function (eGFR) remain controversial and were thus monitored 46 …”