Cardiovascular disorders and exposure to chemical pollutants.

Introduction: Exposure with some chemical can cause cardiovascular disorders. Occupational exposures with chemicals are modifiable risk factors for cardiovascular diseases. The Objective of this study was the determination of cardiovascular disorders in industries with occupational exposures. Materials and methods: Study was a cross-sectional method and was done on workers of related industries. The study was done with a physical examination and checklist by getting health and illness history and clinical tests about the risk factors and cardiovascular disorders. According to exposures the population of the study was divided into 3 groups. Data were analyzed with SPSS 16, by considering p < 0.05 as significant. Results: The frequency of unstable angina and stable angina were the most in group 1. The relative risk for unstable angina was 1.55 (1.46-1.61) in group 1 and for stable angina was 1.54 (1.47-1.62) in this group. The risk of thrombophlebitis was 8.48 (7.07-10.17) in group 2. Conclusions: Workers in industry with chemical pollutants had cardiovascular disorders. The occupational exposures, especially chemical agents are effective on cardiovascular system.

Comparative cardiovascular safety of LABA/LAMA FDC versus LABA/ICS FDC in patients with chronic obstructive pulmonary disease: a population-based cohort study with a target trial emulation framework.

BACKGROUND: Use of combinations of long-acting ß2 agonists/long-acting muscarinic antagonists (LABA/LAMA) in patients with chronic obstructive pulmonary disease (COPD) is increasing. Nevertheless, existing evidence on cardiovascular risk associated with LABA/LAMA versus another dual combination, LABA/inhaled corticosteroids (ICS), was limited and discrepant. AIM: The present cohort study aimed to examine comparative cardiovascular safety of LABA/LAMA and LABA/ICS with a target trial emulation framework, focusing on dual fixed-dose combination (FDC) therapies. METHODS: We identified patients with COPD who initiated LABA/LAMA FDC or LABA/ICS FDC from a nationwide Taiwanese database during 2017-2020. The outcome of interest was a hospitalized composite cardiovascular events of acute myocardial infarction, unstable angina, heart failure, cardiac dysrhythmia, and ischemic stroke. Cox regression models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for composite and individual cardiovascular events after matching up to five LABA/LAMA FDC initiators to one LABA/ICS FDC initiator using propensity scores (PS). RESULTS: Among 75,926 PS-matched patients, use of LABA/LAMA FDC did not show a higher cardiovascular risk compared to use of LABA/ICS FDC, with a HR of 0.89 (95% CI, 0.78-1.01) for the composite events, 0.80 (95% CI, 0.61-1.05) for acute myocardial infarction, 1.48 (95% CI, 0.68-3.25) for unstable angina, 1.00 (95% CI, 0.80-1.24) for congestive heart failure, 0.62 (95% CI, 0.37-1.05) for cardiac dysrhythmia, and 0.82 (95% CI, 0.66-1.02) for ischemic stroke. The results did not vary substantially in several pre-specified sensitivity and subgroup analyses. CONCLUSION: Our findings provide important reassurance about comparative cardiovascular safety of LABA/LAMA FDC treatment among patients with COPD.

Comparison of ticagrelor and clopidogrel on platelet function and prognosis in unstable angina.

PURPOSE: This study aims to compare the effects of ticagrelor and clopidogrel on platelet function, cardiovascular prognosis, and bleeding in patients with unstable angina pectoris. METHODS: Patients with unstable angina pectoris undergoing percutaneous coronary intervention (PCI) were enrolled (January 2018-December 2019). In total, 212 patients were treated with ticagrelor (90 mg twice daily) and 210 patients were treated with clopidogrel (75 mg once daily). Thromboelastography and light transmission aggregometry were used to measure the platelet aggregation rate (PAR). High-sensitivity troponin T (hs-TnT), pro-brain natriuretic peptide (NT-proBNP), high-sensitivity C-reactive protein (CRP), and heart-type fatty acid-binding protein (h-FABP) were measured to assess myocardial injury after PCI. Cardiovascular prognosis and bleeding events were evaluated in hospital and 12 months after discharge. RESULTS: The PAR was significantly slower with ticagrelor (P < 0.001). hs-TnT, NT-proBNP, CRP, and h-FABP increased after compared with before PCI in both groups (P < 0.05). hs-TnT (P < 0.001) and h-FABP (P < 0.001) increased more significantly with clopidogrel. The in-hospital and 12-month major adverse cardiovascular event (MACE) rates were not significantly different between the two groups. The in-hospital total bleeding event rate was higher with ticagrelor (P < 0.05). Minor bleeding and total bleeding were more frequent at the 12-month follow-up in the ticagrelor group (P < 0.05). CONCLUSION: Ticagrelor was more effective in suppressing the PAR than clopidogrel and reduced PCI-induced myocardial injury in patients with unstable angina pectoris. However, it increased in-hospital and 12-month bleeding events and had no benefit on in-hospital and 12-month MACEs.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial.

BACKGROUND: High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown. OBJECTIVE: The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated. DESIGN, PARTICIPANTS AND INTERVENTION: This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone. MAIN OUTCOME MEASURES: The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3. RESULTS: A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/µL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups. CONCLUSION: STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only. TRIAL REGISTRATION: This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Tramadol versus codeine and the short-term risk of cardiovascular events in patients with non-cancer pain: A population-based cohort study.

AIMS: The effect of tramadol on the cardiovascular system is largely unknown. There is concern that, with its multimodal mechanism of action to increase serotonin and norepinephrine levels in the body, it could increase the risk of arterial ischaemia and cardiovascular events. We aimed to compare the short-term risk of cardiovascular events with the use of tramadol to that of codeine among patients with non-cancer pain. METHODS: We conducted a retrospective population-based cohort study using data from the Clinical Practice Research Datalink (CPRD) with new users of tramadol or codeine from April 1998 to March 2017. Exposure was defined using an approach analogous to an intention-to-treat, with a maximum follow-up of 30 days. The primary endpoint was myocardial infarction, and secondary endpoints were unstable angina, ischaemic stroke, coronary revascularization, cardiovascular death and all-cause mortality. Hazard ratios (HRs) were estimated using Cox proportional hazards models, adjusted for high-dimensional propensity score. RESULTS: The final cohort included 123 394 tramadol users and 914 333 codeine users. When tramadol was compared to codeine, the adjusted hazard ratio (HR) of myocardial infarction was 1.00 (95% CI 0.81-1.24). There was also no evidence of elevated risks of unstable angina (0.92; 95% CI 0.67-1.27), ischaemic stroke (0.98; 95% CI 0.82-1.17), coronary revascularization (0.97; 95% CI 0.69-1.38), cardiovascular death (1.07; 95% CI 0.93-1.23) or all-cause mortality (1.03; 95% CI 0.94-1.14) when tramadol was compared to codeine. CONCLUSIONS: Short-term use of tramadol, compared with codeine, was not associated with an increased risk of cardiac events among patients with non-cancer pain.

Antiplatelet and myocardial protective effect of Shexiang Tongxin Dropping Pill in patients undergoing percutaneous coronary intervention: A randomized controlled trial / 中西医结合学报

BACKGROUND@#High on-clopidogrel platelet reactivity could be partially explained by loss-of-function alleles of CYP2C19, the enzyme that converts clopidogrel into its active form. Shexiang Tongxin Dropping Pill (STDP) is a traditional Chinese medicine to treat angina pectoris. STDP has been shown to improve blood flow in patients with slow coronary flow and attenuate atherosclerosis in apolipoprotein E-deficient mice. However, whether STDP can affect platelet function remains unknown.@*OBJECTIVE@#The purpose of this study is to examine the potential effects of STDP on platelet function in patients undergoing percutaneous coronary intervention (PCI) for unstable angina. The interaction between the effects of STDP with polymorphisms of CYP2C19 was also investigated.@*DESIGN, PARTICIPANTS AND INTERVENTION@#This was a single-center, randomized controlled trial in patients undergoing elective PCI for unstable angina. Eligible subjects were randomized to receive STDP (210 mg per day) plus dual antiplatelet therapy (DAPT) with clopidogrel and aspirin or DAPT alone.@*MAIN OUTCOME MEASURES@#The primary outcome was platelet function, reflected by adenosine diphosphate (ADP)-induced platelet aggregation and platelet microparticles (PMPs). The secondary outcomes were major adverse cardiovascular events (MACEs) including recurrent ischemia or myocardial infarction, repeat PCI and cardiac death; blood biomarkers for myocardial injury including creatine kinase-MB isoenzyme (CK-MB) and high-sensitive troponin I (hsTnI); and biomarkers for inflammation including intercellular cell adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1), monocyte chemoattractant protein-1 (MCP-1) and galectin-3.@*RESULTS@#A total of 118 subjects (mean age: [66.8 ± 8.9] years; male: 59.8%) were included into analysis: 58 in the control group and 60 in the STDP group. CYP2C19 genotype distribution was comparable between the 2 groups. In comparison to the control group, the STDP group had significantly lower CK-MB (P < 0.05) but similar hsTnI (P > 0.05) at 24 h after PCI, lower ICAM-1, VCAM-1, MCP-1 and galectin-3 at 3 months (all P < 0.05) but not at 7 days after PCI (P > 0.05). At 3 months, the STDP group had lower PMP number ([42.9 ± 37.3] vs. [67.8 ± 53.1] counts/μL in the control group, P = 0.05). Subgroup analysis showed that STDP increased percentage inhibition of ADP-induced platelet aggregation only in slow metabolizers (66.0% ± 20.8% in STDP group vs. 36.0% ± 28.1% in the control group, P < 0.05), but not in intermediate or fast metabolizers. The rate of MACEs during the 3-month follow-up did not differ between the two groups.@*CONCLUSION@#STDP produced antiplatelet, anti-inflammatory and cardioprotective effects. Subgroup analysis indicated that STDP inhibited residual platelet reactivity in slow metabolizers only.@*TRIAL REGISTRATION@#This study was registered on www.chictr.org.cn: ChiCTR-IPR-16009785.

Association Between Early Severe Cardiovascular Events and the Initiation of Treatment With the Anti-Interleukin 12/23p40 Antibody Ustekinumab.

Importance: Ustekinumab, a monoclonal antibody targeting interleukin 12/23p40 (IL-12/23p40), is effective in the treatment of moderate to severe psoriasis, psoriatic arthritis, and Crohn disease. In 2011, a meta-analysis of randomized clinical trials reported a potential risk of severe cardiovascular events (SCEs) within the first few months after the initiation of anti-IL-12/23p40 antibodies. Objective: To assess whether the initiation of ustekinumab treatment is associated with increased risk of SCEs. Design, Setting, and Participants: This case-time-control study used data from the French national health insurance database, covering 66 million individuals, on all patients exposed to ustekinumab between April 1, 2010, and December 31, 2016, classified according to their cardiovascular risk level (high- and low-risk strata). The risk period was the 6 months before the SCE, defined as acute coronary syndrome or stroke, and the reference period was the 6 months before the risk period. Statistical analysis was performed from September 20, 2017, to July 6, 2018. Exposure: The initiation of ustekinumab treatment was screened during the risk and reference periods. Main Outcomes and Measures: Odds ratios for the risk of SCE after the initiation of ustekinumab treatment were calculated. Results: Of the 9290 patients exposed to ustekinumab (4847 men [52%]; mean [SD] age, 43 [14] years), 179 experienced SCEs (65 cases of acute coronary syndrome, 68 cases of unstable angina, and 46 cases of stroke). Among patients with a high cardiovascular risk, a statisically significant association between initiaton of ustekinumab treatment and SCE occurrence was identified (odds ratio, 4.17; 95% CI, 1.19-14.59). Conversely, no statistically significant association was found among patients with a low cardiovascular risk (odds ratio, 0.30; 95% CI, 0.03-3.13). Conclusions and Relevance: This study suggests that the initiation of ustekinumab treatment may trigger SCEs among patients at high cardiovascular risk. In line with the current mechanistic models for atherosclerotic disease, the period after the initiation of anti-IL-12/23p40 may be associated with atherosclerotic plaque destabilization via the inhibition of helper T cell subtype 17. Although the study interpretation is limited by its observational design, these results suggest that caution may be needed in the prescription of ustekinumab to patients at high cardiovascular risk.

Vascular safety of erenumab for migraine prevention.

OBJECTIVE: To examine the cardiovascular, cerebrovascular, and peripheral vascular safety of erenumab across migraine prevention studies. METHODS: Vascular adverse events (AEs) and blood pressure data were integrated across 4 double-blind, placebo-controlled studies of erenumab and their open-label extensions in patients with chronic or episodic migraine. Subgroup analyses were conducted by acute migraine-specific medication use and number of vascular risk factors at baseline. Standardized search terms were used to identify vascular AEs (cardiovascular, cerebrovascular, or peripheral). An independent committee adjudicated whether targeted events were vascular in origin. RESULTS: In placebo-controlled studies, 2,443 patients received placebo (n = 1,043), erenumab 70 mg (n = 893), or erenumab 140 mg (n = 507) subcutaneously once monthly. Regardless of acute migraine-specific medication use or vascular risk factors at baseline, AE incidence was similar across the placebo and erenumab treatment groups. Hypertension AEs were reported for 0.9% (placebo), 0.8% (erenumab 70 mg), and 0.2% (erenumab 140 mg) of patients. Vascular AEs, which were similar across double-blind and open-label treatment, generally were confounded, with plausible alternative etiologies. In 18 patients with events reviewed by the independent committee, 4 events were positively adjudicated as cardiovascular in origin: 2 deaths and 2 vascular events. All 4 positively adjudicated cardiovascular events occurred during open-label erenumab treatment. CONCLUSION: Selective blockade of the canonical calcitonin gene-related peptide receptor with erenumab for migraine prevention had a vascular safety profile comparable to that of placebo over 12 weeks, with no increased emergence of events over time. Further study of long-term safety of erenumab in patients with migraine is needed. CLINICALTRIALSGOV IDENTIFIERS: NCT02066415, NCT02456740, NCT01952574, NCT02483585, NCT02174861, and NCT01723514. CLASSIFICATION OF EVIDENCE: This analysis provides Class II evidence that for patients with migraine, erenumab does not increase the risk of vascular AEs.

A Destabilized Case of Stable Effort Angina Pectoris Induced by Low-dose Adenosine Triphosphate.

A 79-year-old man was diagnosed with sudden deafness. He had previously experienced a suspected episode of angina pectoris. At a local hospital, after 500 mg of hydrocortisone and 80 mg adenosine triphosphate (ATP) were administered, he became aware of chest discomfort. An electrocardiogram revealed serious ST-segment depressions. He was diagnosed with a non-ST elevated myocardial infarction (NSTEMI). Emergency coronary angiography revealed triple vessel disease, and the lesion was successfully stented. The mechanisms whereby the stable effort angina pectoris destabilized in this case were thought to include a reduction of the local blood flow because of an ATP product and probable thrombus formation in response to the administered steroids.

Unstable Angina: A Serious Adverse Event following Gemcitabine-Cisplatin Based Chemotherapy.

A 29 year male, with an inoperable adenocarcinoma of gall bladder was initiated on gemcitabine and a platinum compound based chemotherapy. During 4th cycle of chemotherapy, patient complained of chest pain following cisplatin and gemcitabine infusion. ECG was suggestive of acute coronary syndrome, which was successfully managed by antianginal therapy. Fifth cycle of chemotherapy was uneventful. Patient died of cardiovascular collapse before receiving the 6th cycle of chemotherapy. As per Naranjo adverse drug reaction probability scale, causal association of the event with cisplatin and gemcitabine was probable and possible respectively. It is advised to routinely assess the cardiovascular status of patients before and during cisplatin and/or gemcitabine based chemotherapy.

Short-Term Exposure to Fine Particulate Matter Air Pollution Is Preferentially Associated With the Risk of ST-Segment Elevation Acute Coronary Events.

BACKGROUND: Air pollution is associated with greater cardiovascular event risk, but the types of events and specific persons at risk remain unknown. This analysis evaluates effects of short-term exposure to fine particulate matter air pollution with risk of acute coronary syndrome events, including ST-segment elevation myocardial infarction, non-ST-segment elevation myocardial infarction, unstable angina, and non-ST-segment elevation acute coronary syndrome. METHODS AND RESULTS: Acute coronary syndrome events treated at Intermountain Healthcare hospitals in urban areas of Utah's Wasatch Front were collected between September 1993 and May 2014 (N=16 314). A time-stratified case-crossover design was performed matching fine particulate matter air pollution exposure at the time of each event with referent periods when the event did not occur. Patients served as their own controls, and odds ratios were estimated using nonthreshold and threshold conditional logistic regression models. In patients with angiographic coronary artery disease, odds ratios for a 10-µg/m(3) increase in concurrent-day fine particulate matter air pollution >25 µg/m³ were 1.06 (95% CI 1.02-1.11) for all acute coronary syndrome, 1.15 (95% CI 1.03-1.29) for ST-segment elevation myocardial infarction, 1.02 (95% CI 0.97-1.08) for non-ST-segment elevation myocardial infarction, 1.09 (95% CI 1.02-1.17) for unstable angina, and 1.05 (95% CI 1.00-1.10) for non-ST-segment elevation acute coronary syndrome events. Excess risk from fine particulate matter air pollution exposure was not observed in patients without angiographic coronary artery disease. CONCLUSIONS: Elevated fine particulate matter air pollution exposures contribute to triggering acute coronary events, especially ST-segment elevation myocardial infarction, in those with existing seriously diseased coronary arteries but not in those with nondiseased coronary arteries.

Cardioprotective effects of voluntary exercise in a rat model: role of matrix metalloproteinase-2.

BACKGROUND: Regular exercise at moderate intensity reduces cardiovascular risks. Matrix metalloproteinases (MMPs) play a major role in cardiac remodeling, facilitating physiological adaptation to exercise. The aim of this study was to examine the influence of voluntary physical exercise on the MMP-2 enzyme activity and to investigate the cardiac performance by measurement of angina susceptibility of the heart, the basal blood pressure, the surviving aorta ring contraction, and the cardiac infarct size after I/R-induced injury. METHODS: Male Wistar rats were divided into control and exercising groups. After a 6-week period, the serum level of MMP-2, basal blood pressure, cardiac angina susceptibility (the ST segment depression provoked by epinephrine and 30 s later phentolamine), AVP-induced heart perfusion and aorta ring contraction, infarct size following 30 min ischemia and 120 min reperfusion, and coronary effluent MMP-2 activity were measured. RESULTS: Voluntary wheel-running exercise decreased both the sera (64 kDa and 72 kDa) and the coronary effluent (64 kDa) MMP-2 level, reduced the development of ST depression, improved the isolated heart perfusion, and decreased the ratio of infarct size. CONCLUSION: 6 weeks of voluntary exercise training preserved the heart against cardiac injury. This protective mechanism might be associated with the decreased activity of MMP-2.

Long term exposure to ambient air pollution and incidence of acute coronary events: prospective cohort study and meta-analysis in 11 European cohorts from the ESCAPE Project.

OBJECTIVES: To study the effect of long term exposure to airborne pollutants on the incidence of acute coronary events in 11 cohorts participating in the European Study of Cohorts for Air Pollution Effects (ESCAPE). DESIGN: Prospective cohort studies and meta-analysis of the results. SETTING: Cohorts in Finland, Sweden, Denmark, Germany, and Italy. PARTICIPANTS: 100 166 people were enrolled from 1997 to 2007 and followed for an average of 11.5 years. Participants were free from previous coronary events at baseline. MAIN OUTCOME MEASURES: Modelled concentrations of particulate matter <2.5 µm (PM2.5), 2.5-10 µm (PMcoarse), and <10 µm (PM10) in aerodynamic diameter, soot (PM2.5 absorbance), nitrogen oxides, and traffic exposure at the home address based on measurements of air pollution conducted in 2008-12. Cohort specific hazard ratios for incidence of acute coronary events (myocardial infarction and unstable angina) per fixed increments of the pollutants with adjustment for sociodemographic and lifestyle risk factors, and pooled random effects meta-analytic hazard ratios. RESULTS: 5157 participants experienced incident events. A 5 µg/m(3) increase in estimated annual mean PM2.5 was associated with a 13% increased risk of coronary events (hazard ratio 1.13, 95% confidence interval 0.98 to 1.30), and a 10 µg/m(3) increase in estimated annual mean PM10 was associated with a 12% increased risk of coronary events (1.12, 1.01 to 1.25) with no evidence of heterogeneity between cohorts. Positive associations were detected below the current annual European limit value of 25 µg/m(3) for PM2.5 (1.18, 1.01 to 1.39, for 5 µg/m(3) increase in PM2.5) and below 40 µg/m(3) for PM10 (1.12, 1.00 to 1.27, for 10 µg/m(3) increase in PM10). Positive but non-significant associations were found with other pollutants. CONCLUSIONS: Long term exposure to particulate matter is associated with incidence of coronary events, and this association persists at levels of exposure below the current European limit values.

Cardiovascular safety of varenicline: patient-level meta-analysis of randomized, blinded, placebo-controlled trials.

Smoking is a major modifiable risk factor for cardiovascular (CV) disease. Varenicline is a pharmacological aid for smoking cessation. To explore the CV safety of varenicline, we investigated the incidence of CV events in varenicline-treated subjects across all phase 2-4 randomized placebo-controlled clinical trials of ≥12-week treatment duration conducted in smokers aged ≥18 years and sponsored by the drug manufacturer. This manuscript reports a subject-level meta-analysis of time to major adverse cardiovascular events (MACE; defined as CV-related death, nonfatal myocardial infarction, nonfatal stroke) and time to MACE+ (defined as MACE plus worsening or any procedure for peripheral vascular disease, hospitalization for angina, or performance of coronary revascularization). All events were adjudicated by an independent adjudication committee, blind to treatment assignment. Events were assessed during treatment and up to 30 days after the last treatment dose. The primary analytical method was a stratified logrank time-to-event analysis; secondary analyses were meta-analyses of incidence rate ratios and rate differences. Overall, 7002 subjects were included (varenicline: 4190; placebo: 2812) from 15 studies. MACE were reported by 13 varenicline subjects (0.31%) and 6 placebo subjects (0.21%) [hazard ratio, 1.95; 95% confidence interval (CI): 0.79-4.82; P = 0.15; risk difference, 0.006 events per subject-year; 95% CI: -0.003, 0.015, P = 0.19]. MACE+ were reported by 26 varenicline subjects (0.62%) and 12 placebo subjects (0.43%) (hazard ratio, 1.74; 95% CI: 0.91-3.34, P = 0.10; risk difference, 0.010; 95% CI: -0.002, 0.022, P = 0.11). This subject-level meta-analysis of MACE or MACE+ up to 30 days posttreatment in placebo-controlled clinical trials of varenicline found a trend toward increased incidence of these events in varenicline-treated patients that did not reach statistical significance. The overall number of events was low and the absolute risk of CV events with varenicline was small.

Síndrome colinérgico y síndrome intermedio confluyentes en una intoxicación por organofosforados / Simultaneous cholinergic and intermediate syndromes in organophosphate poisoning

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