Does the long-term administration of proton pump inhibitors increase the risk of adverse cardiovascular outcomes? A ChatGPT powered umbrella review.

BACKGROUND: Proton pump inhibitors (PPIs) are commonly prescribed for the treatment of acid-related disorders. In the context of coronary artery disease (CAD), PPIs are commonly prescribed along with antiplatelet medications. In fact, the potential interaction between these two classes of medications has been subject to much debate. This review aimed to summarise the findings from systematic reviews and meta-analyses on the casual relationship between PPI use (alone) and major adverse cardiovascular events (MACE). Furthermore, the recent release of ChatGPT has provided reviewers with a powerful natural language processing tool. We therefore aimed to assess the utility of ChatGPT in the systematic review process. METHODS: A comprehensive search of PubMed was conducted to identify relevant systematic reviews and meta-analyses published up to March 2023. Two independent reviewers assessed the eligibility of the studies, extracted the data, and assessed the methodological quality using AMSTAR 2.0. The population of interest was adults that received the medications of interest (PPIs) for a minimum of three months, regardless of indication. Control groups were defined as placebo or active comparators. The outcomes of interest were described under the general term MACE, which include cardiovascular death, non-fatal myocardial infarction, and non-fatal stroke. There were no restrictions with regards to time, but we only included reports in English. A different group of independent reviewers simultaneously ran the same process using ChatGPT. The results were then compared with the human generated results. RESULTS: Seven systematic reviews and meta-analyses were included, involving a total of 46 randomised controlled trials and 33 observational studies. The studies examined the association between PPI use and MACE, including stroke, myocardial infarction, and all-cause mortality. The results of the individual studies were conflicting, with some showing a positive association between PPI use and MACE, some showing no association, and others showing mixed results. However, the majority of the studies that included observational data reported a positive association between PPI use and MACE. Sensitivity analyses conducted in some studies did not significantly alter the primary results, suggesting that the findings were robust. Furthermore, ChatGPT was successfully prompted to execute most tasks involved in this review. We therefore present text that was generated by ChatGPT, including the abstract, introduction, results, and discussion sections. CONCLUSION: The findings of this umbrella review suggest that a causal relationship between PPI use and an increased risk of MACE cannot be ruled out. Further research is needed to better understand this relationship, particularly the underlying mechanisms and potential confounding factors. Healthcare professionals should consider the long-term use of PPIs and carefully weigh the risks and benefits for each patient. Finally, ChatGPT was successfully prompted to execute most of the tasks involved in this review. We therefore feel that this tool will be of great assistance in the field of evidence synthesis in the near future.

The role of cardiopulmonary exercise testing in risk stratification and prognosis of atrial fibrillation: a scoping review of the literature.

BACKGROUND: Cardiopulmonary exercise testing (CPET) is a significant tool for evaluating exercise capacity in healthy individuals and in various pulmonary and cardiovascular conditions, quantifying symptoms and predicting outcomes. Atrial fibrillation (AF) poses a significant burden on patients and health systems; a research marathon is ongoing for discovering the pathophysiologic substrate, natural history, prognostic tools and optimal treatment strategies for AF. Among the plethora of variables measured during CPET, there is a series of parameters of interest concerning AF. METHODS: We conducted a scoping review aiming to identify significant CPET-related parameters linked to AF, as well as indicate the impact of other cardiac disease-related variables. We searched PubMed from its inception to 12 January 2022 for reports underlining the contribution of CPET in the assessment of patients with AF. Only clinical trials, observational studies and systematic reviews were included, while narrative reviews, expert opinions and other forms of manuscripts were excluded. RESULTS: In our scoping review, we report a group of heterogeneous, thus noteworthy parameters relevant to the potential contribution of CPET in AF. CPET helps phenotype AF populations, evaluates exercise capacity after cardioversion or catheter ablation, and assesses heart rate response to exercise; peak VO2 and VE/VCO2, commonly measured indices during CPET, also serve as prognostic tools in patients with AF and heart failure. CONCLUSIONS: CPET seems to hold a clinically important predictive value for future cardiovascular events both in patients with pre-existing cardiac conditions and in healthy individuals. CPET variables may play a fundamental role in the prediction of future AF-related events.

Meta-analysis of cardiovascular outcome trials assessing the impact of glucagon-like peptide-1 receptor agonists on major cardiac arrhythmias.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP-1RAs), a group of novel antidiabetic agents, demonstrated beneficial cardiovascular effects in recent large, placebo-controlled randomised clinical trials (RCTs); their clear antiarrhythmic benefit has not been yet underlined. The purpose of the present meta-analysis is to clarify the impact of GLP-1RAs on different types of cardiac arrhythmias. METHODS: We searched PubMed from its inception up to 8 October 2020 for all available cardiovascular and renal outcome, placebo-controlled RCTs utilising GLP-1RAs versus placebo. The present meta-analysis is reported according to the Preferred Reporting Items for Systematic reviews and Meta-analyses (PRISMA) statement. RESULTS: We included data from 7 RCTs with GLP-1RAs in a total of 55,943 participants. Treatment with GLP-1RAs did not provide significant benefit in the risk for atrial fibrillation (RR = 0.81, 95%CI; 0.78-1.15, I2 = 51%), atrial flutter (RR = 0.79, 95%CI; 0.53-1.16, I2 = 0%), ventricular fibrillation (RR = 0.99, 95%CI; 0.48-2.04, I2 = 0%), ventricular tachycardia (RR = 1.41, 95%CI; 0.87-2.28, I2 = 10%), atrial tachycardia (RR = 0.63, 95%CI; 0.10-3.90, I2 = 24%), sinus node dysfunction (RR = 0.70, 95%CI; 0.40-1.23, I2 = 0%), ventricular extrasystoles (RR = 1.37, 95%CI; 0.56-3.30, I2 = 0%), second-degree atrioventricular block (RR = 0.96, 95%CI; 0.52-1.74, I2 = 0%) or complete atrioventricular block (RR = 0.78, 95%CI; 0.39-1.54, I2 = 38%). CONCLUSIONS: In patients with type 2 diabetes mellitus, treatment with GLP-1RAs does not significantly affect the risk for major cardiac arrhythmias.

Homocysteine as a Predictor of Paroxysmal Atrial Fibrillation-Related Events: A Scoping Review of the Literature.

High levels of homocysteine (Hcy) have been linked with adverse cardiovascular outcomes, such as arrhythmias and stroke. In the context of paroxysmal atrial fibrillation (PAF), hyperhomocysteinemia has been demonstrated to be an independent predictor of future events. The aim of this report was to address the potential value of Hcy levels in predicting future paroxysms of atrial fibrillation (AF), as well as to identify the potential mechanisms of action. We searched PubMed and the Cochrane Database on 16 January 2022. Keywords used were homocysteine or hyperhomocysteinemia paired with a total of 67 different keywords or phrases that have been implicated with the pathogenesis of AF. We included primary reports of clinical and non-clinical data in the English language, as well as systematic reviews with or without meta-analyses. We placed no time constraints on our search strategy, which yielded 3748 results. Following title review, 3293 reports were excluded and 455 reports were used for title and abstract review, after which 109 reports were finally used for full-text review. Our review indicates that Hcy levels seem to hold a predictive value in PAF. Herein, potential mechanisms of action are presented and special considerations are made for clinically relevant diagnostic procedures that could complement plasma levels in the prediction of future PAF events. Finally, gaps of evidence are identified and considerations for future clinical trial design are presented.

5-Fluorouracil, capecitabine and vasospasm: a scoping review of pathogenesis, management options and future research considerations.

BACKGROUND: 5-Fluorouracil (5-FU) is a widely used chemotherapeutic agent that can cause cardiotoxicity manifesting, among others, as chest pain. Capecitabine is an oral prodrug of 5-FU, with reported preferential activation in malignant cells that may also cause cardiotoxic reactions. Standard treatment of 5-FU and capecitabine induced chest pain with vasodilators is mostly effective, but there are several cases of patients unresponsive to these agents. METHODS: We performed a PubMed search on 31st May 2020. We used a three keyword search strategy using Boolean search operators. More specifically, we included fluorouracil or 5-FU or capecitabine and chest pain or angina and mechanism or treatment or management. We included primary reports of clinical and non-clinical data, as well as systematic reviews. Narrative reviews, expert opinions, letters to the editor and other forms of non-primary literature were excluded. RESULTS: Our search yielded a total of 1595 reports. Of these, 1460 were narrative reviews or irrelevant to the topic and were excluded. A total of 135 reports were used for our review. We used 81 reports for data extraction, which included 13 clinical trials, 4 retrospective reports, 61 case reports, and 3 systematic reviews. CONCLUSION: We report the incidence and predisposing factors, the value of available diagnostic procedures, and standard medical and invasive treatments. We also speculate on the potential benefit of arginine as a promising option both in prevention as well as treatment of 5-FU-induced chest pain. Finally, gaps of evidence are identified and proposals are made in terms of future research.

Cardiovascular efficacy and safety of dipeptidyl peptidase-4 inhibitors: A meta-analysis of cardiovascular outcome trials.

BACKGROUND: Dipeptidyl peptidase-4 (DPP-4) inhibitors are a generally safe and well tolerated antidiabetic drug class with proven efficacy in type 2 diabetes mellitus (T2DM). Recently, a series of large, randomized controlled trials (RCTs) addressing cardiovascular outcomes with DPP-4 inhibitors have been published. AIM: To pool data from the aforementioned trials concerning the impact of DPP-4 inhibitors on surrogate cardiovascular efficacy outcomes and on major cardiac arrhythmias. METHODS: We searched PubMed and grey literature sources for all published RCTs assessing cardiovascular outcomes with DPP-4 inhibitors compared to placebo until October 2020. We extracted data concerning the following "hard" efficacy outcomes: fatal and non-fatal myocardial infarction, fatal and non-fatal stroke, hospitalization for heart failure, hospitalization for unstable angina, hospitalization for coronary revascularization and cardiovascular death. We also extracted data regarding the risk for major cardiac arrhythmias, such as atrial fibrillation, atrial flutter, ventricular fibrillation and ventricular tachycardia. RESULTS: We pooled data from 6 trials in a total of 52520 patients with T2DM assigned either to DPP-4 inhibitor or placebo. DPP-4 inhibitors compared to placebo led to a non-significant increase in the risk for fatal and non-fatal myocardial infarction [risk ratio (RR) = 1.02, 95%CI: 0.94-1.11, I 2 = 0%], hospitalization for heart failure (RR = 1.09, 95%CI: 0.92-1.29, I 2 = 65%) and cardiovascular death (RR = 1.02, 95%CI: 0.93-1.11, I 2 = 0%). DPP-4 inhibitors resulted in a non-significant decrease in the risk for fatal and non-fatal stroke (RR = 0.96, 95%CI: 0.85-1.08, I 2 = 0%) and coronary revascularization (RR = 0.99, 95%CI: 0.90-1.09, I 2 = 0%), Finally, DPP-4 inhibitors demonstrated a neutral effect on the risk for hospitalization due to unstable angina (RR = 1.00, 95%CI: 0.85-1.18, I 2 = 0%). As far as cardiac arrhythmias are concerned, DPP-4 inhibitors did not significantly affect the risk for atrial fibrillation (RR = 0.95, 95%CI: 0.78-1.17, I 2 = 0%), while they were associated with a significant increase in the risk for atrial flutter, equal to 52% (RR = 1.52, 95%CI: 1.03-2.24, I 2 = 0%). DPP-4 inhibitors did not have a significant impact on the risk for any of the rest assessed cardiac arrhythmias. CONCLUSION: DPP-4 inhibitors do not seem to confer any significant cardiovascular benefit for patients with T2DM, while they do not seem to be associated with a significant risk for any major cardiac arrhythmias, except for atrial flutter. Therefore, this drug class should not be the treatment of choice for patients with established cardiovascular disease or multiple risk factors, except for those cases when newer antidiabetics (glucagon-like peptide-1 receptor agonists and sodium-glucose co-transporter-2 inhibitors) are not tolerated, contraindicated or not affordable for the patient.

Colchicine as a Potential Therapeutic Agent Against Cardiovascular Complications of COVID-19: an Exploratory Review.

Coronavirus disease-19 (COVID-19) may result in serious complications involving several organ systems, including myocardial tissue. An exaggerated host inflammatory response, described as a cytokine storm, has been linked to play a major role in these complications. Colchicine and other pharmaceutical agents have been proposed to counter the cytokine storm and improve outcomes. In this exploratory review, we utilized a PubMed and Cochrane Database search aiming to identify the biochemical characteristics of the cytokine storm as well as to identify the potential effect of colchicine on these inflammatory biomarkers. The research yielded 30 reports describing the characteristics of the cytokine storm and 44 reports describing the effect of colchicine on various inflammatory biomarkers. According to our research, colchicine may be an agent of interest in the treatment of COVID-19 via its anti-inflammatory properties. However, there are potential drug interactions with cytochrome P450 3A4 inhibitors resulting in acute colchicine toxicities. Additionally, there is scarce evidence regarding the efficacy of colchicine in the acute phase of disease, since most trials evaluated its effect in chronic conditions. In this direction, our team proposes three different hypotheses for evaluating the place of colchicine in the treatment of COVID-19.

Hypotension associated with menaquinone.

PURPOSE: A case of mild symptomatic hypotension after treatment with menaquinone (vitamin K(2)) is reported. SUMMARY: A 62-year-old white man with a medical history of hyperlipidemia, coronary artery disease, and benign prostatic hyperplasia was started on a regimen of menaquinone 100 µg daily as a supplement to his medications for coronary artery disease. Approximately two hours after taking the first dose of menaquinone, the patient experienced sudden weakness and dizziness. At that time, his blood pressure was 110/55 mm Hg. On day 2 of treatment, his blood pressure was 105/50 mm Hg two hours after taking menaquinone; however the patient was asymptomatic. On day 3, the patient's blood pressure was 100/50 mm Hg two hours after menaquinone ingestion, with symptoms of generalized weakness and dizziness, at which point menaquinone was discontinued. All of the patient's heart rate measurements were within normal limits during this time. The day after discontinuing menaquinone, the patient's blood pressure was 115/65 mm Hg, after which his readings were within normal limits on subsequent days. After a 10-day menaquinone-free period, the patient was rechallenged. On rechallenge day 1, the patient's blood pressure was 115/60 mm Hg two hours after menaquinone ingestion; on rechallenge day 2, his blood pressure was 100/55 mm Hg. The patient was asymptomatic on both days of the rechallenge. The Naranjo et al. adverse drug reaction probability scale score was 7, indicating a probable adverse reaction to menaquinone. The drug interaction probability scale score for this case was 6, indicating that a drug interaction was probable. CONCLUSION: A 62-year-old white man developed mild symptomatic hypotension while receiving menaquinone therapy.