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Biomedical subjects

Steven E Nissen

Publications and source records attributed to Steven E Nissen.

At least 19 recordsLinked to original sources
PubMed2026

Bempedoic Acid and First and Recurrent Limb Outcomes in Statin-Intolerant Patients With Peripheral Artery Disease: Insights From the CLEAR Outcomes Trial.

BACKGROUND: Patients with peripheral artery disease (PAD) are at high risk of major adverse limb events (MALE) and major adverse cardiovascular events (MACE). Recently, bempedoic acid was shown to reduce MACE in primary and secondary prevention patients. Whether bempedoic acid reduces the risk of MALE in patients with PAD is unknown. METHODS: CLEAR Outcomes (Cholesterol Lowering via Bempedoic Acid [ETC1002], an ACL-Inhibiting Regimen) randomized 13 970 patients to bempedoic acid 180 mg or placebo from December 22, 2016, to August 14, 2019. The trial primary end point was MACE-4, defined as death resulting from cardiovascular causes, nonfatal myocardial infarction, nonfatal stroke, or coronary revascularization. A clinical history of PAD was reported by investigators at baseline. Two blinded vascular medicine specialists independently adjudicated MALE, including adverse events indicating worsening PAD symptoms leading to revascularization, chronic limb-threatening ischemia, and acute limb ischemia. Outcomes were assessed as time to first event and total (including recurrent) events with a negative binomial approach. RESULTS: A total of 1624 of the enrolled patients (mean±SD age, 63.9±9.9 years; 915 [56.3%] female) had PAD at baseline. In patients with PAD in the placebo group, 69 (8.3%) had MALE over a median of 40.6 months, with rate of recurrent events of 4.0%/y. Bempedoic acid reduced the risk of MALE by 36% (hazard ratio, 0.64 [95% CI, 0.44-0.93]; P=0.018). Bempedoic acid reduced total MALE by 45% (relative risk, 0.55 [95% CI, 0.35-0.85]; P=0.007). First MACE-4 or MALE was reduced overall by 13% (hazard ratio, 0.87 [95% CI, 0.80-0.95]) with consistent effects with PAD (hazard ratio, 0.82 [95% CI, 0.64-1.04]) and without PAD (hazard ratio, 0.87 [95% CI, 0.79-0.86]; Pinteraction=NS) but not statistically significant within the PAD subgroup alone. Total MACE-4 or MALE was reduced (relative risk, 0.81 [95% CI, 0.73-0.90]) overall with consistent effects in PAD (relative risk, 0.71 [95% CI, 0.54-0.95]) and without PAD (relative risk, 0.82 [95% CI, 0.73-0.92]; Pinteraction=NS). CONCLUSIONS: Patients with PAD are at high risk of MALE and MACE. Bempedoic acid reduces both MACE and MALE in patients with atherosclerotic vascular disease, with notable absolute benefits in patients with PAD. These findings support (1) the importance of lowering low-density lipoprotein cholesterol in patients with PAD to reduce overall vascular risk and (2) the benefits of bempedoic acid in this population.

Humans↗
PubMed2006

The DREAM trial.

Explore the source record for details and available documents.

Cardiovascular Diseases↗
PubMed2006

Coronary artery calcification and changes in atheroma burden in response to established medical therapies.

OBJECTIVES: This study sought to determine the relationship between coronary calcification and plaque progression in response to established medical therapies. BACKGROUND: Coronary calcification correlates with the extent of atherosclerosis and predicts clinical outcome. METHODS: Atheroma volume was determined in serial intravascular ultrasound pullbacks in matched arterial segments of 776 patients with angiographic coronary artery disease. A calcium grade at baseline was assigned for each image (total 28,876) (0 = no calcium, 1 = calcium with acoustic shadowing <90 degrees and 2 = calcium with shadowing >90 degrees). Patients with a calcium index (average of calcium scores in a pullback) below versus above the median were compared with regard to plaque burden and progression. RESULTS: Patients with a high calcium index were older (59 vs. 54 years, p < 0.001), more likely to be male (80% vs. 68%, p < 0.001), and more likely to have a history of hypertension (71% vs. 64%, p = 0.03). These patients had a greater percentage atheroma volume (PAV) (45% vs. 34%, p < 0.001), total atheroma volume (TAV) (210 vs. 151 mm3, p < 0.001), and percentage of images with maximal plaque thickness >0.5 mm (93% vs. 72%, p < 0.001). The continuous rate of change in PAV (1.1 +/- 0.4% vs. 0.8 +/- 0.4%, p = 0.34) and TAV (1.7 +/- 2.1% vs. -0.1 +/- 2.2%, p = 0.37) was similar in patients with a lower and higher calcium index, respectively. A lower calcium index was associated with a higher rate of patients showing substantial change in atheroma burden (at least 5% change in PAV, 70% vs. 53%, p < 0.001). CONCLUSIONS: Calcific plaques are more resistant to undergoing changes in size in response to systemic interventions targeting atherosclerotic risk factors.

Adult↗
PubMed2006

Effects of normal, pre-hypertensive, and hypertensive blood pressure levels on progression of coronary atherosclerosis.

OBJECTIVES: The purpose of this study was to evaluate the effects of normal blood pressure (BP), pre-hypertension, and hypertension on progression of coronary atherosclerosis. BACKGROUND: The Seventh Report of the Joint National Committee on the Prevention, Detection, Evaluation, and Treatment of High Blood Pressure (JNC-7) classifies BP as normal, pre-hypertension, and hypertension. The effects of these categories on progression of coronary atherosclerosis are unknown. METHODS: The 274 patients who completed the intravascular ultrasound (IVUS) substudy of the CAMELOT (Comparison of Amlodipine Versus Enalapril to Limit Occurrences of Thrombosis) trial were included. The entry criteria were > or =1 angiographic coronary stenosis >20% and diastolic BP <100 mm Hg. Patients underwent a baseline coronary IVUS, which was repeated after 2 years of amlodipine, enalapril, or placebo therapy. The BP was evaluated periodically, and the averages of the measurements were used in the analyses. RESULTS: Mean BP throughout the study was 127.0 +/- 12.0/75.5 +/- 6.8 mm Hg. In multivariable analysis, significant determinants of progression included systolic BP (r = 0.16; p = 0.006) and pulse pressure (r = 0.14; p = 0.02). Patients with "hypertensive" average BP had a 12.0 +/- 3.6 mm3 (least-square mean +/- SE) increase in atheroma volume, those with "pre-hypertensive" BP had no major change (0.9 +/- 1.8 mm3), and those with "normal" BP had a decrease of 4.6 +/- 2.6 mm(3) (p < 0.001 by analysis of covariance; p < 0.05 for comparison of all pairs). CONCLUSIONS: The most favorable rate of progression of coronary atherosclerosis is observed in patients whose BP falls within the "normal" JNC-7 category (i.e., systolic BP <120 mm Hg and diastolic BP <80 mm Hg). This study suggests that in patients with coronary artery disease, the optimal BP goal may be substantially lower than the <140/90 mm Hg level.

Adult↗
PubMed2006

Determinants of arterial wall remodeling during lipid-lowering therapy: serial intravascular ultrasound observations from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial.

BACKGROUND: Coronary plaque progression and instability are associated with expansive remodeling of the arterial wall. However, the remodeling response during plaque-stabilizing therapy and its relationship to markers of lipid metabolism and inflammation are incompletely understood. METHODS AND RESULTS: Serial intravascular ultrasound (IVUS) data from the Reversal of Atherosclerosis with Aggressive Lipid Lowering Therapy (REVERSAL) trial were obtained during 18 months of intensive versus moderate lipid-lowering therapy. In a subgroup of 210 patients, focal coronary lesions with mild luminal narrowing were identified. Lumen area, external elastic membrane (EEM) area, and plaque area were determined at the lesion and proximal reference sites at baseline and during follow-up. The remodeling ratio (RR) was calculated by dividing the lesion EEM area by the reference EEM area. The relationship between the change in remodeling, change in plaque area, lipid profile, and inflammatory markers was examined. At the lesion site, a progression in plaque area (8.9+/-25.7%) and a decrease in the RR (-3.0+/-11.2%) occurred during follow-up. In multivariable analyses, the percentage change in plaque area (P<0.0001), baseline RR (P<0.0001), baseline lesion lumen area (0.019), logarithmic value of the change in high-sensitivity C-reactive protein (P=0.027), and hypertension at baseline (P=0.014) showed a significant, direct relation with the RR at follow-up. Lesion location in the right coronary artery (P=0.006), percentage change in triglyceride levels (P=0.049), and age (P=0.037) demonstrated a significant, inverse relation with the RR at follow-up. Changes in LDL cholesterol, HDL cholesterol, and treatment group demonstrated no significant associations. CONCLUSIONS: Constrictive remodeling of the arterial wall was observed during plaque-stabilizing therapy with statin medications and appears related to their antiinflammatory effects.

Adaptation, Physiological↗
PubMed2006

Application of intravascular ultrasound in anti-atherosclerotic drug development.

The background use of a number of established therapies presents a key challenge for the development of novel anti-atherosclerotic agents: how to predict potential efficacy before the completion of long-term trials with endpoints such as mortality. This challenge has stimulated the search to develop intermediate measures of efficacy. Recent advances now allow intravascular ultrasound (IVUS) to provide an accurate assessment of atheroma accumulation within the arterial wall. Here we describe how IVUS can be applied to the serial assessment of atheroma burden in response to treatment with a range of anti-atherosclerotic strategies, which has resulted in its emergence as a key technology in the evaluation and approval of novel drugs.

Animals↗
PubMed2006

Relationship between cardiovascular risk factors and atherosclerotic disease burden measured by intravascular ultrasound.

OBJECTIVES: The goal of this study was to determine the relationship between established cardiovascular risk factors and the extent of coronary atherosclerotic plaque. BACKGROUND: Few data exist correlating cardiovascular risk factors with volumetric measurements of coronary atheroma burden in patients with coronary artery disease. METHODS: Clinical characteristics, quantitative coronary angiography, and intravascular ultrasound (IVUS) were evaluated in subjects enrolled in a study comparing atorvastatin and pravastatin. Plaque areas were measured at 1-mm intervals to compute atheroma volume. The percent of cross sections with an abnormal intimal thickness (>0.5 mm) was determined. Data on cardiovascular risk factors were collected. RESULTS: In 654 subjects, atheroma volume averaged 174.5 mm3 and percent atheroma volume 38.9%. Atherosclerosis was present in 81.2% of 25,897 cross sections. In univariate analysis, there was a strong association between diabetes, male gender, and a history of either prior revascularization or stroke with percent atheroma volume. Hypertension or prior myocardial infarction was also predictive of more severe disease. Low-density lipoprotein and C-reactive protein were not significant predictors of greater disease burden. In multivariate analysis, diabetes, male gender, and a history of a prior interventional procedure remained strong predictors of increased atheroma volume. History of stroke, non-Caucasian race, and smoking status remained significant. Although multiple measures of IVUS disease burden were worse in subjects with diabetes, angiographic stenosis severity was not different. CONCLUSIONS: Male gender, diabetes, and a history of prior revascularization are strong independent predictors of atherosclerotic burden in coronary disease patients. Many risk factors did not predict angiographic disease severity, suggesting different mechanisms drive stenosis development and atheroma accumulation.

Anatomy, Cross-Sectional↗