Prognostic value of normal positron emission tomography myocardial perfusion imaging in patients with known or suspected coronary artery disease: a meta-analysis.

OBJECTIVE: Several studies have confirmed high diagnostic performance of positron emission tomography (PET) myocardial perfusion imaging (MPI) in patients with known or suspected coronary artery disease. However, whether the superior diagnostic accuracy could translate into improved mortality outcomes remains unknown. The aim of this study was to define the prognostic value of normal PET MPI. METHODS: PubMed and EMBASE were searched to identify related studies up to June 2016. All studies using PET MPI to evaluate subjects with known or suspected coronary artery disease and providing absolute number of patients with a negative test and primary data on clinical outcomes with a follow-up time ≥3 months were included for analysis. RESULTS: The search yielded 11 studies comprising 20,471 patients for final analysis. The negative-predictive value (NPV) for cardiac death, all-cause death and major adverse cardiovascular events (MACE) were 98.80% [95% confidence interval (CI), 97.64%-99.39%], 94.89% (95% CI: 92.99-96.30%) and 90.26% (95% CI: 78.01-96.03%), over 36.9 months of follow-up for cardiac death, over 26.8 months for all-cause death and 35.7 months for MACE. The corresponding annualized event rates were 0.39%, 2.29% and 3.27%, respectively. In subgroup analyses of different imaging analysis methods for PET MPI, studies using perfusion abnormity had a similar NPV as compared with those using coronary flow reserve (98.46% vs 98.86%, p-value = NS), with a corresponding annualized event rate after negative tests (equal to 1 - NPV) as 0.45% and 0.42%, respectively. CONCLUSION: Normal PET has a high NPV for cardiac death, MACE and all-cause mortality. Different indexes used for PET imaging analysis have a comparable prognostic value. Advances in knowledge: A normal PET MPI conferred a very low risk of cardiac death of 0.39% per year, which is close to that of a normal aged-matched population.

The effect of Danshen extract on lipoprotein-associated phospholipase A2 levels in patients with stable angina pectoris: study protocol for a randomized controlled trial - the DOLPHIN study.

BACKGROUND: Lipoprotein-associated phospholipase A2 (Lp-PLA2), a biomarker of oxidation and inflammation, has been associated with increased coronary artery disease risk. To date, very few studies have examined the Chinese herbal drug Danshen or its extract on Lp-PLA2 in patients with stable angina pectoris. In this study, we aim to investigate the effect of Danshen extract on Lp-PLA2 level in patients with stable angina. METHODS/DESIGN: This is a randomized, single-blind, placebo-controlled, adaptive clinical trial. A total of 156 patients meeting the eligibility criteria will be randomly assigned to either the Danshen extract (DanshenDuofensuanyan injection and Danshen drop spill) group or the placebo group in a 1:1 ratio. Participants will then undergo treatment with DanshenDuofensuanyan injection or placebo (glucose) during hospitalization, followed by open-label Danshen drop spill (30 pills/day) in Danshen extract group for 60 days after discharge. Because this is an adaptive trial, two interim analyses are prospectively planned. These will be performed after one-third and two-thirds of the patients, respectively, have completed the trial. On the basis of the results of these interim analyses, a data monitoring committee will determine how to modify aspects of the study without undermining the validity and integrity of the trial. The primary outcome measure is the serum level of Lp-PLA2 in the Danshen extract group and the placebo group. The secondary outcomes include the proportion of patients who show a clinically significant change, which is defined as at least a 20-point improvement in angina frequency score on the Seattle Angina Questionnaire and the carotid intima-media thickness, which will be measured using ultrasound. Other secondary efficacy and safety outcomes will also be assessed. DISCUSSION: This study will provide evidence that Danshen extract is beneficial for stable angina and may establish a possible mechanism of Danshen treatment effects on cardiovascular disease. This study may also validate an objective blood test (LP-PLA2 level) for assessing the effectiveness of Danshen therapy in patients with stable angina pectoris. TRIAL REGISTRATION: ClinicalTrials.gov, NCT02870764 . Registered on 13 August 2016.