Does Green Brazilian Propolis Extract Improve Functional Capacity in Symptomatic Chronic Coronary Disease? -- a Pilot Randomized Trial.

Does Green Brazilian Propolis Extract Improve Functional Capacity in Symptomatic Chronic Coronary Disease? -- a Pilot Randomized Trial. | Authorea try { document.documentElement.classList.add('js'); } catch (e) { } var _gaq = _gaq || []; _gaq.push(['_setAccount', 'G-8VDV14Y67G']); _gaq.push(['_trackPageview']); (function() { var ga = document.createElement('script'); ga.type = 'text/javascript'; ga.async = true; ga.src = ('https:' == document.location.protocol ? 'https://ssl' : 'http://www') + '.google-analytics.com/ga.js'; var s = document.getElementsByTagName('script')[0]; s.parentNode.insertBefore(ga, s); })(); Skip to main content Preprints Collections Wiley Open Research IET Open Research Ecological Society of Japan All Collections About About Authorea FAQs Contact Us Quick Search anywhere Search for preprint articles, keywords, etc. Search Search ADVANCED SEARCH SCROLL This is a preprint and has not been peer reviewed. Data may be preliminary. 17 February 2025 V1 Latest version Share on Does Green Brazilian Propolis Extract Improve Functional Capacity in Symptomatic Chronic Coronary Disease? -- a Pilot Randomized Trial. Authors : Clara Figueiredo 0000-0002-7722-9087 [email protected] , Luiz Carlos Passos , Caio Cafezeiro , Rodrigo de Melo , Marcelo Augusto Silveira , Taina Viana , and Eduardo Jorge de Oliveira Authors Info & Affiliations https://doi.org/10.22541/au.173976865.53918317/v1 Published Pharmaceuticals Version of record Peer review timeline 378 views 135 downloads Contents Abstract Information & Authors Metrics & Citations View Options References Figures Tables Media Share Abstract Background: Inflammation plays a critical role in coronary heart disease progression. Low-dose colchicine has shown promise in reducing cardiovascular events, and Green Brazilian propolis extract (EPP-AF®), with anti-inflammatory properties, may offer benefits in its treatment. This pilot study evaluates whether six weeks of EPP-AF improves functional capacity assessed by treadmill test. Methods: the PRAIA trial was a randomized, double-blind, placebo-controlled pilot study conducted at a coronary disease clinic in an outsourced center in Brazil. Patients aged ≥18 years with stable coronary artery disease, receiving optimized medical therapy, were randomized 2:1 to receive either 200 mg of EPP-AF® or placebo twice daily for six weeks. The primary outcome was the change, measured in seconds, in treadmill exercise duration. Secondary outcomes included total exercise time, METs, hs-CRP levels, Seattle Angina Questionnaire (SAQ), and CCS score. Statistical analysis was performed on an intention-to-treat basis. Results: A total of 59 patients were randomized, with a median follow-up of 6.5 weeks. The primary endpoint, median change in treadmill test time, showed no difference between the propolis (39 seconds) and placebo (30 seconds) groups (p = 0.83). There were no improvements in functional capacity, hs-CRP levels, or angina symptoms assessed by SAQ in the propolis group. No major adverse cardiovascular events occurred during the study. Conclusion: EPP-AF® did not improve functional capacity, inflammation markers, or angina symptoms assessed by SAQ in patients with stable coronary artery disease compared to placebo. Introduction Coronary heart disease (CHD) remains the primary global cause of death. Its chronic manifestation as stable angina is associated with reduced quality of life and significant disability-adjusted life years(1,2). Optimal medical therapy (OMT) according to current guidelines to chronic coronary disease (CCD) involves administration of lipid-lowering medications and antiplatelet agents to slow the progression of atherosclerosis, along with antianginal medications for symptom management (1,3). Inflammation plays a critical role in CHD and has emerged as a promising therapeutic target, as evidenced by numerous recent clinical trials (4,5) particularly those investigating low-dose colchicine (6), which has been shown to reduce rates of myocardial infarction, stroke, and revascularization due to unstable angina(7). These findings ultimately led to the recent FDA approval of low-dose colchicine for this population. Standardized Brazilian green propolis extract (EPP-AF®) is a natural product derived from resins and plant exudates, exhibiting anti-inflammatory and immunomodulatory effects proven in in vitro and in vivo studies (8,9). The cardiovascular effects of EPP-AF are not yet fully understood, but some of its known properties, such as lipid profile modulation and protection of endothelial injury, suggest its potential utility in CHD treatment(10). Other non-traditional therapies with anti-inflammatory properties have also been studied in CHD, demonstrating some efficacy, albeit with limited evidence (4). The aim of this study was to conduct a randomized controlled, double-blind, pilot trial to assess whether the use of EPP-AF for six weeks in symptomatic patients with CCD and OMT would be associated with an improvement in functional capacity, as demonstrated by treadmill tests. Study designed and patients The PRAIA (Effect of Green PRopolis Extract in Chronic Stable AngIna PAtients. A Randomized, Double-Blind, Pilot Study ) trial was conducted in a coronary disease clinic in an outsourced center in Salvador, Bahia, Brazil. The trial was registered with the Brazilian Registry of Clinical Trials (RBR-87w38c) and received ethical approval from the local ethical committee (registration number 36882820.9.000.0045) on October 1, 2020. The present study was conducted in accordance with the principles of the Good Clinical Practice guidelines of the International Conference on Harmonization. The provision of EPP-AF® active drug or placebo was funded by the Collaborating Institution for the Production and Distribution of Propolis: Apis Flora Industria Comercial LTDA. The provision of EPP-AF® active drug or placebo was funded by the Collaborating Institution for the Production and Distribution of Propolis: Apis Flora Industria Comercial LTDA. Patient recruitment took place from May 2021 to January 2023. The patients were identified consecutively during outpatient care carried out from clinics specialized in coronary artery disease at the study center. Potential participants were invited for a screening visit and underwent comprehensive assessment. All patients provided informed consent and were enrolled if all inclusion criteria and none of the exclusion criteria were met. Patients were eligible if they were aged 18 years or older, any evidence of coronary disease on invasive coronary angiography or computed tomography angiography (≥ 50% narrowing in at least one coronary artery) and experienced stable angina symptoms (or ischemic equivalents such as dyspnea or arm pain with exertion) despite optimized treatment with lipid-lowering drugs, antiplatelets and anti-anginal medications (betablockers, calcium channel blockers, long and short acting nitrates and/or trimetazidine) for at least 4 weeks. Exclusion criteria included patients scheduled for myocardial revascularization within 30 days, those with left main coronary artery obstruction more than 50%, recent acute coronary syndrome (less than 3 months), baseline electrocardiogram (ECG) abnormalities that might interfere with the interpretation of ECG ST segment changes, physical limitations for treadmill testing, symptomatic NYHA III-IV heart failure with reduced ejection fraction, and participation in another research protocol. Randomization and Follow-up Patients were randomly assigned by computer and managed by a research assistant who was not involved in the evaluation or management of study patients. Randomization was performed in a double-blind manner in a 2:1 allocation ratio to receive 200 mg twice a day of propolis extract (EPP-AF®) or matching placebo, with stratification according to diabetes status, angina severity by The Canadian Cardiovascular Society Classification for Angina (CCS) and number of anti-anginal drugs prescribed. Clinical assessments and maximal treadmill exercise tests were performed at initial assessment and at the end of the follow-up period (6 weeks). Patients were encouraged to contact investigators by telephone with any questions or in the presence of clinical changes. All other treatments for CCD remained unchanged and dose adjustments were prohibited during the six-week follow-up period. End Points The primary endpoint was to evaluate the median change, measured in seconds, from baseline to week 6 in exercise duration on the treadmill test. Secondary outcomes included the total exercise time achieved on the treadmill test, functional capacity calculated by METs, measurement of high-sensitivity C-reactive protein (hs-CRP) levels, the mean score on the Seattle Angina Questionnaire (SAQ) in the angina domains (SAQ-angina), as well as the total score obtained in all domains, and angina symptoms by the CCS assessment. Any unfavorable clinical outcomes, such as cardiovascular death, myocardial infarction (MI), stroke, and need for urgent revascularization, were documented during the study period. The exercise test was performed following the Bruce protocol by a single research assistant. The intensity of anginal pain during exercise was assessed using the Borg scale. Positive exercise tests were defined by horizontal or downward depression ≥1 mm in the ST segment (60 ms after the J point) accompanied by anginal pain, or depression ≥ 1.5 mm without anginal pain. In addition, the duration of the exercise test, total workload in metabolic equivalents (METs) and maximum depression of the ST segment were recorded. High sensitivity C-reactive protein (hs-CRP) levels were quantified by the hospital laboratory using the VITROS Chemistry Products . Operators were blinded to treatment group. To assess angina-specific health status, the 7-item Seattle Angina Questionnaire (SAQ) was administered before randomization and at the 6-week follow-up. The SAQ is a validated tool, known for its reliability and sensitivity to clinical changes(11). It measures angina frequency, physical limitation due to angina, angina stability, treatment satisfaction, and quality of life (QoL) over the preceding 4 weeks. These scores are averaged to derive the SAQ Summary score, representing overall disease-specific health status. SAQ scores range from 0 to 100, with higher scores indicating less frequent angina, improved function, and better QoL. Statistical analysis The Kolmogorov-Smirnov test verified the normal distribution of continuous variables. Normally distributed variables were described by means and standard deviations, while non-symmetrically distributed ones were described by medians and 25th/75th percentiles. Categorical variables were reported as frequency and percentage. Chi-square tests compared categorical variables. Paired t-tests and Wilcoxon tests compared scores and domains from baseline to follow-up for parametric and non-parametric variables, respectively. Independent samples t-tests and Mann-Whitney tests compared score differences between intervention groups. Statistical significance was set at p < 0.05. Data was analyzed using SPSS version 20.0. Given the exploratory nature of our study as a pilot investigation, we estimated a total sample size of 60 patients. The analysis was conducted on an intention-to-treat basis, including all randomized patients regardless of adherence to the treatment protocol. Results A total of 64 patients were initially enrolled in the study, but five did not meet the primary inclusion criteria. Consequently, 59 patients were randomized and received at least one dose of either propolis or placebo. Five participants were lost to follow-up. In addition, one patient declined to undergo the baseline and follow-up exercise tests, and two patients could not complete the final treadmill test due to mobility issues after six weeks of treatment (Figure 1). The baseline characteristics of the patients were well balanced between the trial groups (Table 1). The median age of patients was 61 years (57 - 67), and 37 (62.7%) were male; 30 (50.8%) had diabetes, 26 (54%) had previous STEMI, and 34 (57.6%) had multi-vessel coronary disease. At baseline, patients were receiving appropriate treatment for CAD, with a median LDL-c of 79 mg/dL (60–105), and 56 (95%) were on aspirin. Moreover, 33 (56%) of patients reported angina symptoms classified as CCS grade 2 or 3, despite the use of multiple antianginal medications, including beta-blockers (57, 96.6%), CCB (42, 71%), nitrates (27, 46%), and trimetazidine (25, 42.3%). The median follow-up duration was 6.5 weeks (5.8–7.5 weeks). Two patients permanently discontinued the intervention due to adverse events related to gastric intolerance. Outcomes The primary endpoint, defined as the median treadmill test time from baseline to week 6, showed an increase of 39 seconds (IQR: -59 to 128) in the propolis group and an increase of 30 seconds (IQR: -10 to 101) in the placebo group (p = 0.83) (Figure 2). The treadmill test duration showed a numerical improvement in both groups, with no difference in the propolis group, increasing from 367 seconds (IQR: 273–555) to 378 seconds (IQR: 232–558) (p = 0.47). Functional capacity, measured in METs, also increased numerically in the second exercise test for both groups, though this change was not statistically significant compared to baseline (Table 2). Additionally, there were no significant differences in hs-CRP levels between baseline and the follow-up period in either the propolis or placebo groups (Table 2). At the end of the follow-up period, 10 (31%) of patients in the propolis group and 10 (41%) in the placebo group were classified as having CCS grade 2 or 3 angina, with no statistically significant differences from baseline (p = 0.21 for propolis and p = 0.06 for placebo). No changes were observed in the Seattle Angina Questionnaire 7-item (SAQ-7) scores across all domains for patients receiving propolis over the six-week follow-up (Table 3). Discussion The PRAIA trial did not show that standardized Brazilian green propolis extract improved functional capacity in symptomatic patients with stable coronary artery disease, already on guideline-based medical therapy. Specifically, there was no improvement in treadmill exercise duration compared to placebo. Additionally, this intervention was not associated with improvements in other outcomes, such as total exercise duration, functional capacity measured in METs, reductions in hs-CRP levels, or symptom relief as assessed by the CCS score and SAQ-7. Inflammation plays a central role in atherosclerosis, contributing to endothelial dysfunction and plaque rupture (5,12,13). Recent studies have demonstrated the benefits of targeting inflammation to reduce major adverse cardiac events in CAD patients. (7,14,15). Additionally, elevated inflammatory markers have been shown to correlate with the severity and prognosis of stable angina(16,17). The main goal in treating chronic coronary syndrome is to improve quality of life and life expectancy (3). However, the range of available treatments remains limited, highlighting the need for new alternatives. Recently, low-dose colchicine, an established anti-inflammatory drug, has shown significant cardiovascular benefits in some randomized, placebo-controlled trials. It has been linked to fewer hospitalizations for worsening angina and is now included in guidelines for managing chronic coronary disease (14). Propolis, a natural product created by bees from a mixture of resin and plant-derived bioactive compounds, has long been recognized for its anti-inflammatory, antioxidant, and immunomodulatory properties(18,19). Its cardiovascular effects have been studied primarily in experimental in vitro models and animal studies(20). Evidence suggests that propolis acts as an anti-inflammatory agent by preventing vascular endothelial dysfunction and reducing inflammatory markers(21). These promising effects underscore the potential of EPP-AF as a therapeutic agent for cardiovascular diseases. A recent study with EPP-AF in patients with high cardiovascular risk on hemodialysis showed a significant reduction in hs-CRP (9). This is the first clinical trial to evaluate propolis as an anti-inflammatory and anti-anginal therapy in patients with coronary heart disease. While the PRAIA trial did not demonstrate the efficacy of propolis, interest in alternative therapies for cardiovascular diseases has grown. Several compounds derived from plant, animal, and mineral sources have shown promise in this field (4). Traditional Chinese Medicine (TCM), for example, has gained increasing attention, with numerous clinical trials registered to assess its efficacy (22). Tongxinluo, a compound of 12 plant, insect, and mineral ingredients, is approved in China for the treatment of angina. A large, randomized trial demonstrated that Tongxinluo significantly reduced cardiac events in post-myocardial infarction patients. Similarly, the Guanxin Danshen Dropping Pill, a TCM herbal product, is widely used for angina, coronary artery disease, and myocardial infarction(24). Another TCM was evaluated in 144 patients with unstable angina. After four weeks, both the experimental and control groups showed improvements in angina pectoris scores and the SAQ; however, these differences were not statistically significant. Nevertheless, the experimental TCM was more strongly associated with a decline in inflammatory markers(26). Another natural compound, Terminalia arjuna , a plant-based product recognized for its anti-inflammatory and antioxidant properties, has shown potential clinical benefits in the treatment of cardiovascular diseases. In a study involving 116 individuals with CAD over six months, Terminalia arjuna was found to reduce inflammatory cytokine levels. However, it did not demonstrate an impact on clinical events such as myocardial infarction, stroke, or coronary revascularization(27). Although our results were negative, it is important to note that both groups showed an improvement in total exercise time at the end of the follow-up period. This effect may be attributed to the Hawthorne phenomenon, where patients tend to alter their behavior simply due to the awareness of being observed. Another possible explanation is the ischemic preconditioning effect, where brief periods of ischemia trigger protective mechanisms that enhance the heart’s tolerance to subsequent ischemic events, potentially improving exercise performance. The PRAIA trial did not demonstrate the clinical efficacy of Green Brazilian propolis in CAD; however, its significance as a randomized study evaluating potential treatments for angina should not be overlooked. There is a lack of robust evidence from large, randomized trials for the primary antianginal medications recommended in recent guidelines. Most of these drugs have only been tested in smaller trials comparing them to beta-blockers, with a notable gap in head-to-head studies. Therefore, this area of care demands more attention, particularly given the poor prognosis and diminished quality of life for these patients. The study has limitations, including a small sample size, which may have limited statistical power and contributed to potential type I and type II errors. Secondly, the 6-week follow-up period, though typical for antianginal therapy trials(28), may have been too short to capture the long-term effects of the intervention. Future studies should address these issues by increasing sample size, extending follow-up, and using a multicenter approach to improve validity The sample size for this pilot study was calculated based on the assumption that it would be sufficient to detect differences in functional capacity in patients with CAD based on previous anti-anginal trials(29,30). In conclusion, the administration of standardized Brazilian green propolis extract (EPP-AF®) did not lead to significant improvements in functional capacity in treadmill, reduction of inflammation marker tested by hsCRP, or angina symptoms compared to placebo in patients with stable coronary artery disease. However, its safety profile and known bioactive properties justify further investigation into cardiovascular diseases through larger, multicenter trials with extended follow-up periods. References 1. 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Combination of Activating Blood Circulation and Detoxifying Chinese Medicines Played an Anti-Inflammatory Role in Unstable Angina Patients after Percutaneous Coronary Intervention: A Multicenter, Open-Labeled, Randomized Controlled Trial. Chin J Integr Med. 2021 Nov 1;27(11):803–10. 26. Wu M, Yang S, Liu G, Gu C, Ren P, Zhao R, et al. Treating unstable angina with detoxifying and blood-activating formulae: A randomized controlled trial. J Ethnopharmacol. 2021 Dec 5;281. 27. Kapoor D, Vijayvergiya R, Dhawan V. Terminalia arjuna in coronary artery disease: Ethnopharmacology, pre-clinical, clinical & safety evaluation. Vol. 155, Journal of Ethnopharmacology. Elsevier Ireland Ltd; 2014. p. 1029–45. 28. Vrints C, Andreotti F, Koskinas KC, Rossello X, Adamo M, Ainslie J, et al. 2024 ESC Guidelines for the management of chronic coronary syndromes. Eur Heart J [Internet]. 2024 Sep 29;45(36):3415–537. Available from: https://academic.oup.com/eurheartj/article/45/36/3415/7743115 29. Pavasini R, Camici PG, Crea F, Danchin N, Fox K, Manolis AJ, et al. Anti-anginal drugs: Systematic review and clinical implications. Int J Cardiol. 2019 May 15;283:55–63. 30. Manchanda SC, Krishnaswami S. Combination treatment with trimetazidine and diltiazem in stable angina pectoris. Vol. 78, Heart. 1997. Conflict of Interest The authors declare no conflict of interest related to this publication. Acknowledgments We would like to express our gratitude to Ana Nery Hospital for their support and contributions to this work. We also appreciate the assistance provided by Apis Flora Industrial Comercial LTDA. Supplementary Archives Table 1. Baseline characteristics Age (IQR) 59 (53 - 65) 64 (59-71) Male (%) 68.6% 54.2% Body Mass Index (IQR) 27.3 (25.3 – 28.3) 26.7 (26 – 28.6) SBP (IQR) 130 (112 - 154) 131 (120 - 150) Heart rate (IQR) 71 (64 - 77) 65 (62 - 69) Total cholesterol (IQR) 140 (93 -171) 132 (114 – 181) LDLc (IQR) 73 (45 – 104) 76 (58 – 90) Creatinine clearance (IQR) 87 (75 – 101) 86 (60 – 98) Hypertension (n) 31 (88.6%) 22 (91.7%) Diabetes (n) 17 (48.6%) 13 (54.2%) LVEF (IQR) 63 (53 – 67) 66 (55 – 74) LVEDd (IQR) 50 (46 – 53) 47 (44 – 51) LVESd (IQR) 31 (31 – 37) 31 (26 - 33) STEMI (n) 15 (42.9%) 11 (45.8%) PCI (n) 14 (40%) 8 (33.3%) CABG surgery (n) 1 (2.9%) 0 ADA disease (n) 30 (85.7%) 20 (83.3%) CAD multiarterial (n) 20 (57.1%) 14 (58.3%) Angina symptoms (n) CCS grade 1 CCS grade 2 CCS grade 3 Atypical angina 13 (37.1%) 11 (31.4%) 7 (20%) 4 (4.2%) 8 (33.3%) 8 (33.3%) 7 (29.2%) 1 (11.4%) Aspirin (n) 34 (97.1%) 22 (91.7%) Clopidogrel (n) 10 (28.6%) 8 (33.3%) Statins (n) 34 (97.1%) 24 (100%) Ezetimibe (n) 12 (34.3%) 7 (29.2%) IECA/ARB (n) 33 (94.3%) 19 (79.2%) Antianginal medications Nitrate (n) Betablockers (n) CCB (n) Trimetazidine (n) 13 (37.1%) 34 (97.1%) 25 (71.4%) 14 (40%) 14 (58.3%) 23 (95.8%) 17 (70.8%) 11 (45.8%) hs-CRP (IQR) 1.43 (0.38 – 2.90) 1.22 (0.49 – 3.62) CABG – coronary arterial bypass graft; CCB - calcium channel blockers; IQR – interquartile range; hs-CRP – high-sensitivity C reactive protein; LDLc – low density level cholesterol; LVEDs - Left Ventricular End-Diastolic Diameter; LVESd - Left Ventricular End-SistolicDiameter; LVEF – Left Ventricular Ejection Fraction; PCI – percutaneous coronary intervention; SBP – systolic blood pressure. Table 2. Secondary End Points after Randomization, According to study group. Before treatment (n = 34) After treatment (n = 31) Before treatment (n=24) After treatment (n=23) Duration on the treadmill test (seconds) (IQR) 367 (273 – 555) 378 (232 – 558) 0,24 341 (217 – 380) 355 (232 – 443) 0.03 Functional capacity in METs (IQR) 6.70 (4.93 – 9.80) 7.16 (4.98 -9.98) 0,36 5.98 (3.94 – 7.16) 6.36 (4.31 – 7.75) 0.06 Propolis Placebo Before treatment (n=35) After treatment (n=31) p Before treatment (n=24) After treatment (n=23) p hsCRP (IQR) 0.92 (0.44 -2.45) 1.14 (0.34 -3.99) 0,65 1.53 (0.735 – 4.40) 1.24 (0.68 – 5.59) 0,42 IQR – interquartile range; hs-CRP – high-sensitivity C reactive protein; METs – metabolic equivalents. Table 3 - Effect of propolis and placebo on the domain scores of the Seattle Angina Questionnaire (SAQ) Before treatment (n=35) After treatment (n=31) p Before treatment (n=24) After treatment (n=23) p SAQ-7 Angina Frequency Score, median (IQR) 80 (70 – 85) 90 (80 -100) 0.43 80 (60 – 80) 90 (80 - 100) 0.002 SAQ-7 Physical Limitation Score, median (IQR) 55.5 (41.6 – 88.8) 62.5 (40.3 – 87.5) 0.84 66.6 (41.6 – 85.1) 69.4 (55.5 – 91.6) 0.36 SAQ-7 Quality-of-Life Score, median (IQR) 58.3 (41.7 – 66.7) 50 (33.3 – 66.7) 0.52 50 (41.6 – 70.8) 66.6 (50 – 75) 0.055 SAQ-7 Angina Stability Score, median (IQR) 75 (50 – 87.5) 75 (50 - 100) 0.77 50 (50 -100) 100 (75 – 100) 0.015 SAQ-7 Treatment Satisfaction Score, median (IQR) 93.7 (78.1 – 100) 93.7 (78.1 – 100) 0.73 87.5 (75 – 100) 100 (87.5 – 100) 0.162 SAQ-7 Summary Score, median (IQR) 61.3 (47.4 -75.3) 62.7 (50.2 – 75.2) 0.38 63.7 (50.2 – 70.5) 76.3 (59.5 – 84.2) 0.001 Figure 1. Enrollment, Randomization and Follow-up. * Patients did not undergo the exercise test due to refusal or the presence of any mobility impairment. Figure 2. Primary End Point Information & Authors Information Version history V1 Version 1 17 February 2025 Peer review timeline Published Pharmaceuticals Version of Record 31 May 2025 Published Copyright This work is licensed under a Non Exclusive No Reuse License. Keywords anti-oxidants atherosclerosis cardiac pharmacology clinical pharmacology endothelium inflammation Authors Affiliations Clara Figueiredo 0000-0002-7722-9087 [email protected] Ana Nery Hospital View all articles by this author Luiz Carlos Passos Ana Nery Hospital View all articles by this author Caio Cafezeiro Ana Nery Hospital View all articles by this author Rodrigo de Melo Federal University of Bahia View all articles by this author Marcelo Augusto Silveira Hospital São Rafael View all articles by this author Taina Viana Hospital Ana Nery View all articles by this author Eduardo Jorge de Oliveira Ana Nery Hospital View all articles by this author Metrics & Citations Metrics Article Usage 378 views 135 downloads .FvxKWukQNSOunydq8rnd { width: 100px; } Citations Download citation Clara Figueiredo, Luiz Carlos Passos, Caio Cafezeiro, et al. Does Green Brazilian Propolis Extract Improve Functional Capacity in Symptomatic Chronic Coronary Disease? -- a Pilot Randomized Trial.. 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