Effect of Two Intensive Statin Regimens on Progression of Coronary Disease

Nicholls, Stephen J.; Ballantyne, Christie M.; Barter, Philip J.; Chapman, M. John; Erbel, Raimund; Libby, Peter; Raichlen, Joel S.; Uno, Kiyoko; Borgman, Marilyn; Wolski, Kathy; Nissen, Steven E.

doi:10.1056/nejmoa1110874

Cited by 753 publications

(332 citation statements)

References 29 publications

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“…This result suggests that worsened clinical presentation and vulnerable plaque features at baseline may result in more favorable responses among nonculprit plaques to statin. Similar results were reported in several previous studies using intravascular ultrasonography and OCT 10, 38, 39. Takarada et al demonstrated that the efficacy of statin therapy on improving FCT, assessed by serial OCT, was significantly greater in plaques with thinner caps than in those with thicker caps 10.…”

Section: Discussionsupporting

confidence: 86%

“…Takarada et al demonstrated that the efficacy of statin therapy on improving FCT, assessed by serial OCT, was significantly greater in plaques with thinner caps than in those with thicker caps 10. In the SATURN (Study of Coronary Atheroma by Intravascular Ultrasound: Effect of Rosuvastatin Versus Atorvastatin) trial, which aimed to compare the efficacy of 2 different statins on the regression of plaque volume assessed by intravascular ultrasonography,38 the greater change was observed in larger plaques than in smaller plaques. In addition, most studies that tested the efficacy of statin therapy on plaque stabilization in patients with ACS demonstrated improvement in plaque phenotype 10, 11, 40, 41.…”

Section: Discussionmentioning

confidence: 99%

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Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Minami

Wang

Aguirre

et al. 2017

JAHA

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BackgroundPrevious studies have demonstrated that statin therapy improves cardiac outcomes, probably by stabilizing thin‐cap fibroatheroma in patients with coronary artery disease. However, major adverse cardiac events still occur in some patients, despite statin therapy. The aim of this study is to identify clinical predictors for the lack of a favorable vascular response to statin therapy in patients with coronary artery disease.Methods and ResultsA total of 140 nonculprit plaques from 84 patients with coronary artery disease who were treated with a statin and had serial optical coherence tomography imaging (median interval, 6.3 months) were included. Thin‐cap area (fibrous cap thickness, <200 μm) was measured using a novel 3‐dimensional computer‐aided algorithm. Overall, the thin‐cap area significantly decreased from baseline (median, 2.852 mm2; 25th–75th percentile, 1.023–6.157 mm2) to follow‐up (median, 1.210 mm2; 25th–75th percentile, 0.250–3.192 mm2; P<0.001), and low‐density lipoprotein cholesterol significantly decreased from baseline (mean±SD, 92.9±30.1 mg/dL) to follow‐up (mean±SD, 76.3±23.3 mg/dL; P<0.001). The general linear model with multiple predictor variables revealed that the thin‐cap area was significantly higher in patients with chronic kidney disease than in those without it (regression coefficient b, 1.691 mm2; 95% confidence interval, 0.350–3.033 mm2; P=0.013) and lower in patients with acute coronary syndrome (regression coefficient b, −1.535 mm2; 95% confidence interval, −2.561 to −0.509 mm2; P=0.003).ConclusionsChronic kidney disease is an independent predictor for the lack of a favorable vascular response to statin therapy, whereas acute coronary syndrome is an independent predictor for favorable vascular response to statin therapy. These findings should be further warranted in future prospective studies.Clinical Trial RegistrationURL: http://www.clinicaltrials.gov. Unique identifier: NCT01110538.

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Section: Discussionsupporting

confidence: 86%

Section: Discussionmentioning

confidence: 99%

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Minami

Wang

Aguirre

et al. 2017

JAHA

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“…These findings provide mechanistic support for the possible roles of non-HDLC and TG to more definitively emerge as future therapeutic targets, especially in statin-treated patients requiring secondary prevention. Although the benefits of LDLC lowering are well established, 1,20 many patients continue to experience cardiovascular events, despite achieving low LDLC levels. 2 The global obesity, diabetes mellitus, and metabolic syndrome epidemic is increasing the prevalence of atherogenic TG-rich remnant lipoproteins, 21 which are more effectively accounted for by measuring the non-HDLC, but not the LDLC fraction.…”

Section: Discussionmentioning

confidence: 99%

Non-HDL Cholesterol and Triglycerides

Puri

Nissen

Shao

et al. 2016

ATVB

Self Cite

126

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Objectives-Non-high-density lipoprotein cholesterol (non-HDLC) levels reflect the full burden of cholesterol transported in atherogenic lipoproteins. Genetic studies suggest a causal association between elevated triglycerides (TGs)-rich lipoproteins and atherosclerosis. We evaluated associations between achieved non-HDLC and TG levels on changes in coronary atheroma volume. Approach and Results-Data were analyzed from 9 clinical trials involving 4957 patients with coronary disease undergoing serial intravascular ultrasonography to assess changes in percent atheroma volume (∆PAV) and were evaluated against on-treatment non-HDLC and TG levels. The effects of lower (<100 mg/dL) versus higher (≥100 mg/dL) achieved non-HDLC levels and lower (<200 mg/dL) versus higher (≥200 mg/dL) achieved TG levels were evaluated in populations with variable on-treatment low-density lipoprotein cholesterol (LDLC) 0) was associated with achieved TG levels >200 mg/dL, respectively. Lower on-treatment non-HDLC and TG levels associated with significant PAV regression compared with higher non-HDLC and TG levels across all levels of LDLC and C-reactive protein and irrespective of diabetic status (P<0.001 across all comparisons). ∆PAV were more strongly influenced by changes in non-HDLC (β=0.62; P<0.001) compared with changes in LDLC (β=0.51; P<0.001). Kaplan-Meier sensitivity analyses demonstrated significantly greater major adverse cardiovascular event rates in those with higher versus lower non-HDLC and TG levels, with an earlier separation of the non-HDLC compared with the LDLC curve. Conclusions-Achieved non-HDLC levels seem more closely associated with coronary atheroma progression than LDLC.Plaque progression associates with achieved TGs, but only above levels of 200 mg/dL. These observations support a more prominent role for non-HDLC (and possibly TG) lowering in combating residual cardiovascular risk. 14 Accordingly, the relationship between achieved non-HDLC and TG levels upon coronary atheroma progression rates has yet to be defined.Coronary intravascular ultrasound is a sensitive imaging tool for measuring coronary atheroma volume and continues to play an important role for evaluating the antiatherosclerotic effects of novel therapies on serial measures of coronary disease progression. 15,16 Post hoc analyses of serial intravascular ultrasound trials demonstrated significant associations between measures of disease progression and incident cardiovascular events. 17-19The present analysis aimed to define the relationship between achieved non-HDLC and TG levels with rates of coronary atheroma progression. The effects of higher versus lower non-HDLC and TG levels on plaque progression rates were specifically explored within patients stratified according to varying degrees of residual metabolic risk (defined according to achieved LDLC, C-reactive prot...

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“…However, given the presence of both LM disease and a higher baseline plaque burden, one would expect that if either group were to be the recipients of a more intensive treatment regime, it would be the LM disease group. As statin use causes a reduction in total plaque volume, and a fall in the prevalence of HRP, 38,39 ), this would cause a resultant reduction in the magnitude of between group differences. Finally, as the study focused on those with non-obstructive LM disease it is possible that as the stenosis becomes more severe, local hemodynamic effects and flow destabilization may occur resulting in a regional pattern of plaque progression secondary to this over and above the globalized pattern observed in the current study.…”

Section: Discussionmentioning

confidence: 99%

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy

Weir‐McCall

Blanke

Sellers

et al. 2018

Journal of Cardiovascular Computed Tomography

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Background: The aim of the study is examine the impact of non-obstructive (< 50%stenosis) left main (LM) disease on the natural history of coronary artery disease using serial coronary computed tomography angiography (CTA). Methods: CTAs from the PARADIGM (Progression of atherosclerotic plaque determined by computed tomographic angiography imaging) study, a prospective multinational registry of patients who underwent serial CTA at a ≥2 year interval were analyzed. Those without evidence of CAD on their baseline scan were excluded, as were those with obstructive left main disease. Coronary artery vessels and their branches underwent quantification of: plaque volume and composition; diameter stenosis; presence of high-risk plaque. Results: Of 944 (62 ± 9 years, 60% male) who had evidence of CAD at baseline, 444 (47%) had LM disease. Those with LM disease had a higher baseline plaque volume (194.8 ± 221mm3 versus 72.9 ± 84.3mm3, p < 0.001) and a higher prevalence of high-risk plaque (17.5% versus 13%, p < 0.001) than those without LM disease. On multivariable general linear model, patients with LM disease had greater annual rates of progression of total (26.5 ± 31.4mm3/yr versus 14.9 ± 20.1mm3/yr, p < 0.001) and calcified plaque volume (17 ± 24mm3/yr versus 7 ± 11mm3/yr, p < 0.001), with no difference in fibrous, fibrofatty or necrotic core plaque components. Conclusion: The presence of non-obstructive LM disease is associated with greater rates of plaque progression and a higher prevalence of high-risk plaque throughout the entire coronary artery tree compared to CAD without LM involvement. Our data suggests that non-obstructive LM disease may be a marker for an aggressive phenotype of CAD that may benefit from more intensive treatment strategies.

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Effect of Two Intensive Statin Regimens on Progression of Coronary Disease

Cited by 753 publications

References 29 publications

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Clinical Predictors for Lack of Favorable Vascular Response to Statin Therapy in Patients With Coronary Artery Disease: A Serial Optical Coherence Tomography Study

Non-HDL Cholesterol and Triglycerides

Impact of Non-obstructive left main disease on the progression of coronary artery disease: A PARADIGM substudy

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