Patrick J. Devine

Extended-Release Niacin or Ezetimibe and Carotid Intima–Media Thickness

BACKGROUND Treatment added to statin monotherapy to further modify the lipid profile may include combination therapy to either raise the high-density lipoprotein (HDL) cholesterol level or further lower the low-density lipoprotein (LDL) cholesterol level. METHODS We enrolled patients who had coronary heart disease or a coronary heart disease risk equivalent, who were receiving long-term statin therapy, and in whom an LDL cholesterol level under 100 mg per deciliter (2.6 mmol per liter) and an HDL cholesterol level under 50 mg per deciliter for men or 55 mg per deciliter for women (1.3 or 1.4 mmol per liter, respectively) had been achieved. The patients were randomly assigned to receive extended-release niacin (target dose, 2000 mg per day) or ezetimibe (10 mg per day). The primary end point was the between-group difference in the change from baseline in the mean common carotid intima-media thickness after 14 months. The trial was terminated early, on the basis of efficacy, according to a prespecified analysis conducted after 208 patients had completed the trial. RESULTS The mean HDL cholesterol level in the niacin group increased by 18.4% over the 14-month study period, to 50 mg per deciliter (P < 0.001), and the mean LDL cholesterol level in the ezetimibe group decreased by 19.2%, to 66 mg per deciliter (1.7 mmol per liter) (P < 0.001). Niacin therapy significantly reduced LDL cholesterol and triglyceride levels; ezetimibe reduced the HDL cholesterol and triglyceride levels. As compared with ezetimibe, niacin had greater efficacy regarding the change in mean carotid intima-media thickness over 14 months (P = 0.003), leading to significant reduction of both mean (P = 0.001) and maximal carotid intima-media thickness (P < or = 0.001 for all comparisons). Paradoxically, greater reductions in the LDL cholesterol level in association with ezetimibe were significantly associated with an increase in the carotid intima-media thickness (R = -0.31, P < 0.001). The incidence of major cardiovascular events was lower in the niacin group than in the ezetimibe group (1% vs. 5%, P = 0.04 by the chi-square test). CONCLUSIONS This comparative-effectiveness trial shows that the use of extended-release niacin causes a significant regression of carotid intima-media thickness when combined with a statin and that niacin is superior to ezetimibe. (ClinicalTrials.gov number, NCT00397657.)

The ARBITER 6-HALTS Trial (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6–HDL and LDL Treatment Strategies in Atherosclerosis): Final Results and the Impact of Medication Adherence, Dose, and Treatment Duration

OBJECTIVES This report describes the final results of the ARBITER 6-HALTS (Arterial Biology for the Investigation of the Treatment Effects of Reducing Cholesterol 6-HDL and LDL Treatment Strategies in Atherosclerosis) trial. BACKGROUND The ARBITER 6-HALTS trial was terminated early on the basis of a pre-specified interim analysis showing superiority of niacin over ezetimibe on change in carotid intima-media thickness (CIMT). After termination, an additional 107 subjects completed a close-out assessment. METHODS Patients with coronary heart disease (CHD) or CHD equivalent with low-density lipoprotein cholesterol <100 mg/dl and high-density lipoprotein cholesterol <50 mg/dl for men or 55 mg/dl for women while receiving stable statin treatment were randomly assigned to ezetimibe (10 mg/day) or extended-release niacin (target dose, 2,000 mg/day). The primary end point was change in mean CIMT, analyzed according to a last observation carried forward method. The relationships of study medication adherence, dosage, and cumulative exposure (product of adherence, dose, and time) with change in CIMT were explored. RESULTS Results in 315 patients included 208 with 14-month follow-up and 107 after mean treatment of 7 +/- 3 months. Niacin (n = 154) resulted in significant reduction (regression) in mean CIMT (-0.0102 +/- 0.0026 mm; p < 0.001) and maximal CIMT (-0.0124 +/- 0.0036 mm; p = 0.001), whereas ezetimibe (n = 161) did not reduce mean CIMT (-0.0016 +/- 0.0024 mm; p = 0.88) or maximal CIMT (-0.0005 +/- 0.0029 mm; p = 0.88) compared with baseline. There was a significant difference between ezetimibe and niacin treatment groups on mean changes in CIMT, favoring niacin, for both mean CIMT (p = 0.016) and maximal CIMT (p = 0.01). Increased cumulative drug exposure was related to regression of CIMT with niacin, and progression of CIMT with ezetimibe. CONCLUSIONS Niacin induces regression of CIMT and is superior to ezetimibe for patients taking statins. (Comparative Study of the Effect of Ezetimibe Versus Extended-Release Niacin on Atherosclerosis; NCT00397657).

Real-world application of coronary computed tomography angiography and its potential effect on downstream resource utilization in evaluating angina

BACKGROUND Evaluating low-risk outpatients with chest pain is a common clinical problem and poses significant demand on clinical resource utilization. Despite the impressive performance characteristics of coronary multislice computed tomography (MSCT) angiography, its implementation in the diagnostic evaluation of outpatient chest pain and its effect on downstream resource utilization remains undefined. OBJECTIVE We compared the effect of a strategy that used MSCT with a traditional strategy (pre-MSCT strategy) in which MSCT was not available on clinical downstream resource utilization, defined as the need for further stress testing or cardiac catheterization. METHODS We retrospectively identified 75 patients without known disease who had undergone MSCT angiography for the primary indication of possible angina. The review of clinical vignettes of these 75 patients and completion of surveys assessing diagnostic strategy by two general cardiologists represented the pre-MSCT diagnostic strategy. Survey responses were compared with the number of cardiac catheterizations and stress tests that actually resulted after MSCT angiography (MSCT strategy). RESULTS A strategy that used MSCT angiography in the evaluation of patients with possible angina would have significantly reduced the need for further stress testing and cardiac catheterizations (58 vs 11; P < 0.005). Furthermore, this strategy would have resulted in significantly fewer unnecessary cardiac catheterizations (6 vs 23; P < 0.005). CONCLUSIONS Coronary MSCT angiography can potentially reduce the need for further stress tests or cardiac catheterizations in the evaluation of low- to intermediate-risk patients with possible angina. Prospective studies are needed to validate these findings and to assess the overall cost effectiveness of implementing MSCT early in the outpatient evaluation of angina.

Comparison of Coronary CT Angiography Image Quality With and Without Breast Shields.

OBJECTIVE The purpose of this study is to compare the image quality of coronary CT angiography performed with and without breast shields. MATERIALS AND METHODS This study involved a retrospective cohort of 72 women with possible angina who underwent 64-MDCT retrospective ECG-gated coronary CT angiography at a single academic tertiary medical center. Images of 36 women scanned while wearing bismuth-coated latex breast shields and 36 control subjects scanned without shields, matched by heart rate and body mass index, were graded on a standardized Likert scale for image quality, stenosis, and plaque by two independent board-certified readers blinded to breast shields. RESULTS Seventy-two patients (mean [± SD] age, 53 ± 9 years) were included. The pre scan heart rate, body mass index, and Agatston score did not differ between groups. The median estimated radiation dose was 13.4 versus 16.1 mSv for those with and without breast shields (p = 0.003). For shielded versus unshielded scans, 86% versus 83% of coronary segments were rated excellent or above average (p = 0.4), median image quality was 2.0 for both groups, mean signal was 474 ± 75 and 452 ± 91 HU (p = 0.27), mean noise was 33.9 ± 8.5 and 29.8 ± 8.3 HU (p = 0.04), and median signal-to-noise ratio was 14.4 and 14.7 (p = 0.56), respectively. CONCLUSION Breast shields for women undergoing coronary CT angiography slightly increased noise but did not negatively affect signal, signal-to-noise ratio, quality, or interpretability. Breast shield use warrants further study.

Partial anomalous pulmonary venous return presenting as pseudo-pulmonic stenosis

Partial anomalous pulmonary venous return (PAPVR) is rare condition that can be discovered incidentally or lead o significant right heart overload if untreated. We report the ase of a patient who presented with symptoms and signs of n atrial septal defect (ASD), but whose initial evaluation as remarkable only for pulmonic stenosis by Doppler chocardiography. Computed tomography (CT) eventually ssisted with making the diagnosis of an anomalous LUL ein that was surgically corrected. We discuss this case and eview the pathophysiology, diagnosis, and management of APVR.