Effect of icosapent ethyl on progression of coronary atherosclerosis in patients with elevated triglycerides on statin therapy: a prospective, placebo-controlled randomized trial (EVAPORATE): interim results.

AIMS: Though statin therapy is known to slow coronary atherosclerosis progression and reduce cardiovascular (CV) events, significant CV risk still remains. In the REDUCE-IT study, icosapent ethyl (IPE) added to statin therapy reduced initial CV events by 25% and total CV events by 30%, but its effects on coronary atherosclerosis progression have not yet been fully investigated. Therefore, this study is to determine whether IPE 4 g/day will result in a greater change from baseline in plaque volume measured by serial multidetector computed tomography than placebo in statin-treated patients. METHODS AND RESULTS: EVAPORATE is a randomized, double-blind, placebo-controlled trial. Patients had to have coronary atherosclerosis by coronary computed tomographic angiography (CCTA) (≥1 angiographic stenoses with ≥20% narrowing), on stable statin therapy with low-density lipoprotein cholesterol levels 40-115 mg/dL, and persistently high triglyceride levels (135-499 mg/dL). Patients underwent an interim scan at 9 months and were followed for an additional 9 months with CCTA at 0, 9, and 18 months. Here, we present the protocol-specified interim efficacy results. A total of 80 patients were enrolled, with 67 completing the 9-month visit and having interpretable CCTA at baseline and at 9 months (age = 57 ± 6 years, male = 36, 63%). At the 9-month interim analysis, there was no significant change in low attenuation plaque (LAP) between active and placebo groups (74% vs. 94%, P = 0.469). However, there was slowing of total non-calcified plaque (sum of LAP, fibrofatty, and fibrous plaque) (35% vs. 43%, P = 0.010), total plaque (non-calcified + calcified plaque) (15% vs. 26%, P = 0.0004), fibrous plaque (17% vs. 40%, P = 0.011), and calcified plaque (-1% vs. 9%, P = 0.001), after adjustment by baseline plaque, age, sex, diabetes, baseline triglyceride levels, and statin use. CONCLUSION: EVAPORATE is the first study using CCTA to evaluate the effects of IPE as an adjunct to statin therapy on atherosclerotic plaque characteristics in a high-risk CV population with persistently high triglyceride levels. It provides important mechanistic data in regards to the reduction in CV events in the REDUCE-IT clinical trial. CLINICALTRIALS. GOVIDENTIFIER: NCT029226027.

Effect of a plant-based bioequivalent inorganic nitrate (NO3-) complex with vitamins, antioxidants and phytophenol rich food extracts in hypertensive individuals - A randomized, double-blind, placebo-controlled study.

BACKGROUND: This study assessed efficacy of plant based bioequivalent nitrate complex, consist of vitamins, natural antioxidants and phytophenol rich food extracts to elevate nitric oxide (NO) bioavailability as determined by saliva conversion of nitrate (NO3-) to nitrite (NO2-) a required step to produce NO, in relationship to lowering blood pressure (BP) in both men and women. METHODS: 67 individuals (26 men; mean age of 59.3 ± 9.0 yrs) with mean baseline systolic and diastolic BP >120 and 80 mmHg respectively were randomized to receive daily dosing of 314 mM NO3- or NO3- free (placebo) tablets in double-blinded study for 12 weeks (wks). Inorganic NO3- tablets consist of NO3- rich beetroot extract, thiamine nitrate, and potassium nitrate in the presence of ascorbic acid, to facilitate NO bioavailability. RESULTS: The primary endpoint of the study was reduction in BP at 12 wks by improving endothelial function. At study conclusion, mean ± SD reduction in systolic BP (SBP) in the inorganic NO3- group was 12.5 ± 13.3 mmHg (p = 0.0007), as compared to 6.19 ± 11.39 mmHg (p = 0.004) in the placebo group, for a placebo-corrected reduction of -6.31 mmHg (95% CI 10.89-2.31, p = 0.04). NO3- also reduced diastolic BP by 4.7 ± 10.3 mmHg (p = 0.01), while no significant reduction in placebo group (1.98 ± 9.38 mmHg, p = 0.24) was noted. Endothelial function improved at 12 weeks by 0.8 ± 3.1 (p = 0.03) in active group when compared to 0.1 ± 1.8 (p = 0.82) in placebo group. CONCLUSION: Endothelial function improved robustly reducing both systolic and diastolic BP in hypertensive individuals with daily supplementation of dietary NO3-. CLINICALTRIALS. GOV ID: NCT03909789.

Calcification of the heart: mechanisms and therapeutic avenues.

INTRODUCTION: Coronary artery calcification (CAC) is reflective of atherosclerotic disease and incrementally predictive of future cardiovascular events (CVE), independent of traditional risk factors. Extra coronary calcium such as aortic valve calcification, which can be identified and quantified by computed tomography (CT) imaging, has shown to predict future CVE in both asymptomatic and symptomatic (i.e. stable angina and acute coronary syndrome [ACS]) settings. It has hence been a vital tool in studies involving new therapies for cardiovascular disease. Areas covered: In this review, promising therapies on the horizon are reviewed, along with the role of cardiac CT and coronary calcification in these studies. A Medline search for peer-reviewed publications using keywords related to coronary calcium score, aortic valve calcium, and therapies targeting the same was carried out. Expert commentary: CT scanning provides a distinct means of detecting and quantifying coronary plaque as well as valvular calcification with excellent reproducibility. Based on voluminous data available, the absence of coronary calcium serves as a factor to de-risk patients for cardiovascular risk stratification and management algorithms. Newer therapies have shown to lower progression of coronary calcification, thus being beneficial in slowing progression of atherosclerotic disease. As British Epidemiologist Geoffrey Rose states, the best predictor of a life-threatening disease is the early manifestation of that disease. As CAC represents the early manifestation of atherosclerosis, it is the best-known stratifier of risk today, and its clinical use will continue to rise.