Prevalence of Cardiovascular Drugs and Oral Anticoagulant Use among Persons with and without Parkinson's Disease.

INTRODUCTION: Cardio- and cerebrovascular diseases are common among persons with Parkinson's disease (PD), but it is unknown how the prevalence of cardiovascular drug and oral anticoagulant use changes in relation to PD diagnosis. METHODS: We investigated the prevalence of cardiovascular drug and oral anticoagulant use among persons with and without PD among 17,541 persons who received incident PD diagnosis in 2001-2015 in Finland and their 116,829 matched comparison persons. Prevalence was calculated in 6-month time windows from 5 years before to 5 years after PD diagnosis (index date) and compared to a matched cohort without PD using generalized estimating equations. RESULTS: Persons with PD had higher prevalence of any cardiovascular drugs (unadjusted OR = 1.15; 95% CI: 1.11-1.18) and oral anticoagulants (unadjusted OR = 1.16; 95% CI: 1.11-1.22) before index date than those without PD. After index date, persons with PD had lower prevalence of cardiovascular drugs (0.94; 95% CI: 0.91-0.96), and no difference was observed for oral anticoagulants. Prevalence of any cardiovascular drugs on the index date was 66 and 61% for persons with and without PD, respectively. ß-blockers were the most common cardiovascular drugs in both cohorts. Warfarin was the most common oral anticoagulant, but the use of direct oral anticoagulants increased during the last years of follow-up. CONCLUSION: Orthostatic hypotension and weight loss likely explain the decreased cardiovascular drug use after PD diagnosis. Results with oral anticoagulants may reflect clinical assessment of benefits being larger than risks, despite the risks associated with their use in persons with PD.

Prevalence of heart failure and trends in its pharmacological treatment between 2000 and 2017 among very old people.

PURPOSE: The aim of this study was to describe a population of very old people with heart failure (HF), to analyse the use of cardiovascular drugs over time, and to explore factors influencing cardiovascular drug treatment for this group. METHODS: All participants with information regarding HF diagnosis were selected from the Umeå 85+/Gerontological Regional Database (GERDA). The people in GERDA are all ≥85 years old. Trained investigators performed structured interviews and assessments. Information regarding medications and diagnoses was obtained from the participants and from medical records. Medical diagnoses were reviewed and confirmed by an experienced geriatrician. RESULTS: In this very old population, the prevalence of HF was 29.6% among women and 30.7% among men. Between 2000 and 2017, there was an increase in the use of renin-angiotensin (RAS) inhibitors (odds ratio [OR] 1.107, 95% confidence interval [CI] 1.072-1.144) and beta-blockers (BBs) (OR 1.123, 95% CI 1.086-1.161) among persons with HF, whereas the prevalence of loop diuretics (OR 0.899, 95% CI 0.868-0.931) and digitalis (OR 0.864, 95% CI 0.828-0.901) decreased (p < 0.001 for all drug classes). Higher age was associated with lower use of RAS inhibitors and BBs. CONCLUSION: In this HF population, the use of evidence-based medications for HF increased over time. This may be a sign of better awareness among prescribers regarding the under-prescribing of guidelines-recommended treatment to old people. Higher age associated with a lower prevalence of RAS inhibitors and BBs. This might indicate that further improvement is possible but could also represent a more cautious prescribing among frail very old individuals.

Italian Association of Hospital Cardiologists Position Paper 'Gender discrepancy: time to implement gender-based clinical management'.

It has been well assessed that women have been widely under-represented in cardiovascular clinical trials. Moreover, a significant discrepancy in pharmacological and interventional strategies has been reported. Therefore, poor outcomes and more significant mortality have been shown in many diseases. Pharmacokinetic and pharmacodynamic differences in drug metabolism have also been described so that effectiveness could be different according to sex. However, awareness about the gender gap remains too scarce. Consequently, gender-specific guidelines are lacking, and the need for a sex-specific approach has become more evident in the last few years. This paper aims to evaluate different therapeutic approaches to managing the most common women's diseases.

Novel drug design and repurposing: An opportunity to improve translational research in cardiovascular diseases?

Drug repurposing is defined as the use of approved therapeutic drugs for indications different from those for which they were originally designed. Repositioning diminishes both the time and cost for drug development by omitting the discovery stage, the analysis of absorption, distribution, metabolism, and excretion routes, as well as the studies of the biochemical and physiological effects of a new compound. Besides, drug repurposing takes advantage of the increased bioinformatics knowledge and availability of big data biology. There are many examples of drugs with repurposed indications evaluated in in vitro studies, and in pharmacological, preclinical, or retrospective clinical analyses. Here, we briefly review some of the experimental strategies and technical advances that may improve translational research in cardiovascular diseases. We also describe exhaustive research from basic science to clinical studies that culminated in the final approval of new drugs and provide examples of successful drug repurposing in the field of cardiology.

Keeping It "Current": A Review of Treatment Options for the Management of Supraventricular Tachycardia.

OBJECTIVE: To review treatment options and updates that exist for the management of paroxysmal supraventricular tachycardia (PSVT). DATA SOURCES: A literature search of PubMed was performed including articles from 1974 to June 2023 using the terms: arrhythmias, adenosine, verapamil, diltiazem, esmolol, propranolol, metoprolol, beta-blockers, amiodarone, PSVT, synchronized cardioversion, methylxanthines, dipyridamole, pediatrics, heart transplant, and pregnancy. Primary literature and guidelines were reviewed. STUDY SELECTION AND DATA EXTRACTION: Studies were considered if they were available in English and conducted in humans. DATA SYNTHESIS: PSVT is a subset of supraventricular tachycardia (SVT) that presents as a rapid, regular tachycardia with an abrupt onset and termination. Due to frequent emergency department (ED) visits annually with symptoms of PSVT, appropriate and efficient management of these patients is vital. This review provides an overview of the pathophysiology of PSVT, while also describing the literature behind nonpharmacologic and pharmacologic management of PSVT. RELEVANCE TO PATIENT CARE AND CLINICAL PRACTICE: This review describes new literature regarding the improved success of the modified Valsalva maneuver as a nonpharmacologic therapy in PSVT. In addition, it describes a new technique in administration of adenosine that has improved outcomes, defines dose adjustments needed for drug interactions with adenosine, compares the utilization of nondihydropyridine calcium channel blockers with adenosine, and provides management recommendations for patients in special populations. CONCLUSIONS: With high annual rates of ED visits for SVT, providers should be aware of the data behind management and modifications of therapy based on patient-specific factors (ie, patient preference, pharmacokinetics/pharmacodynamics, drug interactions, and special populations).

Perioperative Antiplatelet Bridging With Cangrelor: A Cohort Study and Narrative Review.

BACKGROUND: In patients who received a cardiac stent, practice guidelines recommend dual antiplatelet therapy (DAPT). However, an urgent procedure may be required necessitating interruption of DAPT. Intravenous cangrelor was previously shown to be an alternative due its short-half life and quick onset/offset. OBJECTIVE: To determine the safety and effectiveness of cangrelor bridging for patients undergoing invasive procedures in a veteran population. METHODS: Retrospective cohort of patients from Michael E. DeBakey VA Medical Center and the VA North Texas Health Care Systems who underwent perioperative cangrelor bridging. The primary outcome was the incidence of bleeding using the Bleeding Academic Research Consortium (BARC) criteria. The secondary outcome was a composite of nonfatal stroke, myocardial infarction (MI), mortality, and unplanned revascularization within 30 days. A narrative review was also performed to summarize cangrelor bridging for noncardiac invasive procedure. RESULTS: There were 41 patients that met the eligibility criteria. Patients were predominantly Caucasian (57.5%) men with a median age of 70 years. The median duration on cangrelor bridging was 2.6 days with 11 and 30 patients undergoing cardiac and noncardiac invasive procedures, respectively. Nine patients (22%) had a bleeding event of which 8 were minor. One was severe due to significant iliopsoas hematoma following drain placement. All bleeding events occurred postoperatively except for 2 perioperative events that occurred during orthopedic procedures. Ischemic events up to 30 days occurred in 3 patients (7.3%) which consisted of 1 (2.4%) nonfatal MI requiring revascularization and 2 (4.9%) deaths, 1 of which was sudden cardiac. CONCLUSION AND RELEVANCE: This study suggests that cangrelor bridging may be a reasonable alternative to holding oral P2Y12 inhibitors in patients requiring interruption of antiplatelet therapy for an urgent surgery/invasive procedure.

The Inflation Reduction Act: How Will Medicare Negotiating Drug Prices Impact Patients with Heart Disease?

PURPOSE OF REVIEW: Cardiovascular medications improve health and prevent early death. However, high drug prices reduce the use of these medications and strain the health system. The Inflation Reduction Act (IRA) of 2022 allows Medicare to negotiate drug prices with manufacturers and reduces out-of-pocket drug costs for Medicare beneficiaries. This article explores the potential impact that the IRA will have on the treatment of cardiovascular disease. RECENT FINDINGS: Cardiovascular disease medications are likely to be selected for price negotiations under the IRA, leading to savings for patients and for Medicare. Recent work suggests that the IRA's reforms to the Medicare Part D drug benefit will meaningfully reduce out-of-pocket costs for important cardiovascular medications. The IRA is expected to impact cardiovascular disease treatments via price negotiations and through the broader access to medications afforded by improvements to Part D coverage design.

Prognostic Impact of Multiple Drug Use at Discharge in Patients Hospitalized with Heart Failure.

The association between polypharmacy/multiple drug use (MDU) and prognosis in patients hospitalized with heart failure (HF) is unclear. It is also unknown whether the prognostic values of MDU vary depending on the presence/absence of a previous history of HF and preserved/reduced left ventricular ejection fraction (LVEF). We analyzed consecutive 1,034 patients hospitalized with HF (age, 74.9 ± 11.5 years; 58.7% male). MDU was defined as ≥5 drugs at discharge. The primary endpoint was a composite of all-cause death and HF readmission. MDU was observed in 695 patients (67.2%). Patients with MDU use had higher prevalences of a previous history of HF, reduced LVEF, and comorbidities than those without MDU. Cox proportional hazard analysis showed that MDU was significantly associated with the primary endpoint after adjustment for possible confounders (hazard ratio [HR], 1.36; 95% confidence interval [CI], 1.03-1.79; P = 0.030). There was significant interaction between the presence/absence of a history of HF and the prognostic impact of MDU (HF history [-]: HR, 0.86; 95% CI, 0.54-1.40; P = 0.553; HF history [+]: HR, 1.72; 95% CI, 1.16-2.55; P = 0.007; P for interaction = 0.005). However, there was no significant interaction between preserved/reduced LVEF and the prognostic impact of MDU (P for interaction = 0.274). In conclusion, MDU at discharge is an independent risk factor for the composite of death or HF readmission in patients hospitalized with HF. We observed a significant interaction between the presence of de novo versus recurrent HF and the prognostic value of MDU.

Can Pharmaceutical Excipients Threaten the Aquatic Environment? A Risk Assessment Based on the Microtox® Biotest.

The ecotoxicological impact of pharmaceuticals has received considerable attention, primarily focusing on active pharmaceutical ingredients (APIs) while largely neglecting the potential hazards posed by pharmaceutical excipients. Therefore, we analyzed the ecotoxicity of 16 commonly used pharmaceutical excipients, as well as 26 API-excipient and excipient-excipient mixtures utilizing the Microtox® test. In this way, we assessed the potential risks that pharmaceutical excipients, generally considered safe, might pose to the aquatic environment. We investigated both their individual ecotoxicity and their interactions with tablet ingredients using concentration addition (CA) and independent action (IA) models to shed light on the often-overlooked ecotoxicological consequences of these substances. The CA model gave a more accurate prediction of toxicity and should be recommended for modeling the toxicity of combinations of drugs with different effects. A challenge when studying the ecotoxicological impact of some pharmaceutical excipients is their poor water solubility, which hinders the use of standard aquatic ecotoxicity testing techniques. Therefore, we used a modification of the Microtox® Basic Solid Phase protocol developed for poorly soluble substances. The results obtained suggest the high toxicity of some excipients, i.e., SLS and meglumine, and confirm the occurrence of interactions between APIs and excipients. Through this research, we hope to foster a better understanding of the ecological impact of pharmaceutical excipients, prompting the development of risk assessment strategies within the pharmaceutical industry.

Visfatin and Subclinical Atherosclerosis in Type 2 Diabetes: Impact of Cardiovascular Drugs.

Background and Objectives: The role of adipokines in the development of atherosclerosis in type 2 diabetes (T2DM) has not yet been fully elucidated. The effects of drugs on adipokine concentrations have only been evaluated in very few studies, although they may be of clinical importance. This study aimed to assess whether the concentrations of circulating adipokines could predict subclinical atherosclerosis in patients with T2DM, as well as their interactions with commonly used cardiovascular drugs. Materials and Methods: Our population-based cross-sectional multicentric study included 216 participants with T2DM but without previously diagnosed atherosclerosis. The carotid artery intima-media thickness (IMT), plaque and ankle-brachial index (ABI) metrics were measured. Resistin, visfatin, retinol-binding protein 4, high molecular weight adiponectin and leptin levels were evaluated using Luminex's xMAP technology. Results: Visfatin and resistin concentrations correlated positively with IMT (p = 0.002 and p = 0.009, respectively). The correlation of visfatin to IMT ≥ 1.0 mm was significant in males (p < 0.001). Visfatin had a positive correlation with IMT ≥ 1.0 mm or plaque (p = 0.008) but resistin only correlated with plaque (p = 0.049). Visfatin predicted IMT ≥ 1.0 mm or plaque in patients on ß-blocker monotherapy (p = 0.031). Visfatin lost its ability to predict subclinical atherosclerosis in patients taking angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, calcium channel blockers or statins. After adjustments for risk factors for atherosclerosis and cardiovascular drugs, visfatin maintained an independent association with mean IMT (p = 0.003), IMT ≥ 1.0 mm or plaque (p = 0.005) and ABI ≤ 0.9 (p = 0.029). Conclusions: Visfatin could be used as a marker of subclinical atherosclerosis in patients with T2DM, especially in males. The assessment of visfatin concentration could aid in identifying individuals who could benefit from implementing preventive measures against atherosclerosis.

Marketing research of combined drugs for treatment of cardiovascular diseases.

The work is devoted to the results of complex marketing research of all combined cardiovascular drugs. The market of combined drugs from group C according to the ATC classification in 41 countries of the world during 2019-2022 was analyzed. Segment markets of the 27 European Union countries, Albania, Belarus, Bosnia and Hercegovina, Canada, Colоmbia, Great Britain, India, Moldova, Norway, Russian Federation, Switzerland, and Ukraine, were studied. The pharmaceutical market of Australia and the United States were also studied. The structure of this group of drugs was characterized, and the most common combinations in the analyzed markets were identified. It was found that group C09 is the most filled with combined drugs, and the number of combinations is most diverse in C09 drug groups that act on the renin-angiotensin system, C10 hypolipidemic drugs, C07 beta-blockers, and C03 diuretics, which are the drugs of the first choice for arterial hypertension and coronary heart disease. There are two promising areas for expanding the range of drugs that affect the cardiovascular system.

Sex, Permanent Drug Discontinuation, and Study Retention in Clinical Trials: Insights From the TIMI trials.

BACKGROUND: Women are underrepresented across cardiovascular clinical trials. Whether women are more likely than men to prematurely discontinue study drug or withdraw consent once enrolled in a clinical trial is unknown. METHODS: Eleven phase 3/4 TIMI (Thrombolysis in Myocardial Infarction) trials were included (135 879 men and 51 812 women [28%]). The association between sex and premature study drug discontinuation and withdrawal of consent were examined by multivariable logistic regression after adjusting for potential confounders in each individual trial and combining the individual point estimates in random effects models. RESULTS: After adjusting for baseline differences, women had 22% higher odds of premature drug discontinuation (adjusted odds ratio [ORadj], 1.22 [95% CI, 1.16-1.28]; P<0.001) compared with men. Qualitatively consistent results were observed for women versus men in the placebo arms (ORadj, 1.20 [95% CI, 1.13-1.27]) and active therapy arms (ORadj, 1.23 [95% CI, 1.17-1.30)]; there was some evidence for regional heterogeneity (P interaction <0.001). Of those who stopped study drug prematurely, a similar proportion of men and women in the active arm stopped because of an adverse event (36% for both; P=0.60). Women were also more likely to withdraw consent compared with men (ORadj, 1.26 [95% CI, 1.17-1.36]; P<0.001). CONCLUSIONS: Women were more likely than men to prematurely discontinue study drug and withdraw consent across cardiovascular outcome trials. Premature study drug discontinuation was not explained by baseline differences by sex or a higher proportion of adverse events. Future trials should better capture reasons for drug discontinuation and withdrawal of consent to understand barriers to continued study drug use and clinical trial participation, particularly among women.

The association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease: A meta-analysis.

This study aimed to investigate the association between cardiovascular drugs and depression/anxiety in patients with cardiovascular disease (CVD). This meta-analysis was registered in PROSPERO (International Prospective Register of Systematic Reviews; CRD42020197839) and conducted in accordance with the MOOSE (Meta-analysis of Observational Studies in Epidemiology) guidelines. The PubMed, EMBASE, Web of Science, China National Knowledge Infrastructure, Wanfang, and VIP databases were systematically searched to identify all available studies on this topic. Random-effects multivariate meta-regression was performed to investigate the sources of study heterogeneity. Review Manager version 5.3 and Stata 12.0 were used for data analyses. This meta-analysis included 54 studies with a total number of 212,640 patients. Overall, in patients with CVD, aspirin (odds ratio [OR]:0.91, 95% confidence interval [CI]:0.86-0.96, P = 0.02) was associated with a lower risk of depression, while calcium channel blockers (CCB) (OR:1.21, 95%CI:1.05-1.38, P = 0.008), diuretics (OR:1.34, 95%CI:1.14-1.58, P = 0.0005), and nitrate esters (OR:1.32, 95%CI:1.08-1.61, P = 0.006) were associated with a higher risk of depression, additionally, statin (OR:0.79, 95%CI:0.71-0.88, P < 0.0001) was associated with a lower risk of anxiety, but diuretics (OR:1.39, 95%CI:1.26-1.52, P < 0.00001) was associated with a higher risk of anxiety. Subgroup analysis presented that, in patients with hypertension, ß-blockers were associated with a higher risk of depression (OR:1.45, 95%CI:1.26-1.67, P < 0.00001); in patients with coronary artery disease (CAD), statin (OR:0.77, 95%CI:0.59-0.99, P = 0.04), and aspirin (OR:0.85, 95%CI:0.75-0.97, P = 0.02) were associated with a lower risk of depression, while CCB (OR:1.32, 95%CI:1.15-1.51, P < 0.0001) and diuretics (OR:1.36, 95%CI:1.12-1.64, P = 0.002) were associated with a higher risk of depression, additionally, diuretics was associated with a higher risk of anxiety (OR:1.41, 95%CI:1.28-1.55, P < 0.00001); in patients with heart failure, nitrate esters (OR:1.93, 95%CI:1.19-3.13, P = 0.007), and diuretics (OR:1.58, 95%CI: 1.02-2.43, P = 0.04) were associated with a higher risk of depression. The use of cardiovascular drugs should be considered when evaluating depression or anxiety in patients with CVD to improve the care and treatment of these patients.

Cardiovascular drugs and COVID-19 clinical outcomes: a systematic review and meta-analysis of randomized controlled trials.

AIMS: To update our previously reported systematic review and meta-analysis of observational studies on cardiovascular drug exposure and COVID-19 clinical outcomes by focusing on newly published randomized controlled trials (RCTs). METHODS: More than 500 databases were searched between 1 November 2020 and 2 October 2021 to identify RCTs that were published after our baseline review. One reviewer extracted data with other reviewers verifying the extracted data for accuracy and completeness. RESULTS: After screening 22 414 records, we included 24 and 21 RCTs in the qualitative and quantitative syntheses, respectively. The most investigated drug classes were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blocker (ARBs) and anticoagulants, investigated by 10 and 11 studies respectively. In meta-analyses, ACEI/ARBs did not affect hospitalization length (mean difference -0.42, 95% confidence interval [CI] -1.83; 0.98 d, n = 1183), COVID-19 severity (risk ratio/RR 0.90, 95% CI 0.71; 1.15, n = 1661) or mortality (risk ratio [RR] 0.92, 95% CI 0.58; 1.47, n = 1646). Therapeutic anticoagulation also had no effect (hospitalization length mean difference -0.29, 95% CI -1.13 to 0.56 d, n = 1449; severity RR 0.86, 95% CI 0.70; 1.04, n = 2696; and, mortality RR 0.93, 95% CI 0.77; 1.13, n = 5689). Other investigated drug classes were antiplatelets (aspirin, 2 trials), antithrombotics (sulodexide, 1 trial), calcium channel blockers (amlodipine, 1 trial) and lipid-modifying drugs (atorvastatin, 1 trial). CONCLUSION: Moderate- to high-certainty RCT evidence suggests that cardiovascular drugs such as ACEIs/ARBs are not associated with poor COVID-19 outcomes, and should therefore not be discontinued. These cardiovascular drugs should also not be initiated to treat or prevent COVID-19 unless they are needed for an underlying currently approved therapeutic indication.

Residues of Cardiovascular and Lipid-Lowering Drugs Pose a Risk to the Aquatic Ecosystem despite a High Wastewater Treatment Ratio in the Megacity Shanghai, China.

The residues of pharmaceuticals in surface waters of megacities and ecotoxicological implications are of particular concern. In this study, we combined field investigations and model simulations to explore the contamination of cardiovascular and lipid-lowering drugs, one group of the most prescribed medications globally, in surface waters of a typical megacity, Shanghai, with a high wastewater treatment ratio (≈96%). Among 26 target substances, 19 drugs were detected with aqueous concentrations ranging from 0.2 (ketanserin) to 715 ng/L (telmisartan). Of them, angiotensin II receptor antagonists, telmisartan and irbesartan, were dominant besides ß-blockers. Spatial distribution analysis demonstrated their much higher levels in tributaries compared to the mainstream. The results of model simulations and field investigation revealed relatively low concentrations of cardiovascular and lipid-lowering drugs in surface waters of Shanghai compared to other cities in highly developed countries, which is associated with low per capita usage in China. Ecotoxicological studies in zebrafish embryos further revealed developmental effects, including altered hatching success and heart rate, by irbesartan, telmisartan, lidocaine, and their mixtures at ng/L concentrations, which are typical levels in surface waters. Overall, the present results suggest that the high wastewater treatment ratio was not sufficient to protect fish species in the aquatic ecosystem of Shanghai. Exposure to cardiovascular and lipid-lowering drugs and associated risks will further increase in the future due to healthcare improvements and population aging.

A Pharmacovigilance Study of Adverse Drug Reactions Reported for Cardiovascular Disease Medications Approved Between 2012 and 2017 in the United States Food and Drug Administration Adverse Event Reporting System (FAERS) Database.

PURPOSE: Between 2012 and 2017, the FDA approved 29 therapies for a cardiovascular disease (CVD) indication. Due to the limited literature on patient safety outcomes for recently approved CVD medications, this study investigated adverse drug reports (ADRs) reported in the FDA Adverse Event Reporting System (FAERS). METHODS: A disproportionality analysis of spontaneously reported ADR was conducted. Reports in FAERS from Quarter 1, 2012, through Quarter 1, 2019, were compiled, allowing a 2-year buffer following drug approval in 2017. Top 10 reported ADRs and reporting odds ratios (ROR; confidence interval (CI)), a measure of disproportionality, were analyzed and compared to drugs available prior to 2012 as appropriate. RESULTS: Of 7,952,147 ADR reports, 95,016 (1.19%) consisted of reports for newly approved CVD medications. For oral anticoagulants, apixaban had significantly lower reports for anemia and renal failure compared to dabigatran and rivaroxaban but greater reports for neurological signs/symptoms, and arrhythmias. Evaluating heart failure drugs, sacubitril/valsartan had greater reports for acute kidney injury, coughing, potassium imbalances, and renal impairment but notably, lower for angioedema compared to lisinopril. Assessing familial hypercholesterolemia drugs, alirocumab had greater reports for joint-related-signs/symptoms compared to other agents in this category. A newer pulmonary arterial hypertension treatment, selexipag, had greater reports of reporting for bone/joint-related-signs/symptoms but riociguat had greater reports for hemorrhages and vascular hypotension. CONCLUSION: Pharmacovigilance studies allow an essential opportunity to evaluate the safety profile of CVD medications in clinical practice. Additional research is needed to evaluate these reported safety concerns for recently approved CVD medications.

Opioid poisoning cases aged 50+ in the 2015-2020 National Poisoning Data System: suspected suicides versus unintentional poisoning and other intentional misuse/abuse.

High rates of opioid overdose and suicide among the 50+ age group call for an examination of suicidal intent in overdose incidents. Using 2015-2020 National Poison Data System opioid poisoning cases aged 50+ (n = 83 153), we examined the types of opioids and other substances associated with suspected suicides compared to intentional misuse/abuse without suicidal intent. During the six years, prescription opioid cases decreased, while illicit opioid cases increased. Among both types of opioid poisoning cases, the proportions of suspected suicides decreased and those of intentional misuse/abuse without suicidal intent increased. However, due to the large increase in illicit opioid cases, the number of suspected suicide cases involving illicit opioids increased. Multivariable analyses showed that among prescription opioids, acetaminophen with opioid (IRR = 1.17, 95% CI = 1.11-1.24) and tramadol (IRR = 1.12, 95% CI = 1.06-1.47) were associated with higher risk of suspected suicides than intentional misuse/abuse without suicidal intent. Among illicit opioid cases, fentanyl poisoning cases were associated with lower risk of suspected suicides (IRR = 0.40, 95% CI = 0.17-0.94). Of other medications, use of benzodiazepines and antipsychotics was consistently associated with higher risk of suspected suicides in both prescription and illicit opioid cases. Alcohol and cocaine were also associated with higher risk of suspected suicide. Along with continued reductions in opioid prescribing, more effective monitoring of individual patient misuse/abuse behaviors and suicide risk assessment are needed. Healthcare professionals should also review other prescription medications frequently co-prescribed with opioids that may have additive effects on suicidal behaviors among older adults.

Mitochondrial Effects of Common Cardiovascular Medications: The Good, the Bad and the Mixed.

Mitochondria are central organelles in the homeostasis of the cardiovascular system via the integration of several physiological processes, such as ATP generation via oxidative phosphorylation, synthesis/exchange of metabolites, calcium sequestration, reactive oxygen species (ROS) production/buffering and control of cellular survival/death. Mitochondrial impairment has been widely recognized as a central pathomechanism of almost all cardiovascular diseases, rendering these organelles important therapeutic targets. Mitochondrial dysfunction has been reported to occur in the setting of drug-induced toxicity in several tissues and organs, including the heart. Members of the drug classes currently used in the therapeutics of cardiovascular pathologies have been reported to both support and undermine mitochondrial function. For the latter case, mitochondrial toxicity is the consequence of drug interference (direct or off-target effects) with mitochondrial respiration/energy conversion, DNA replication, ROS production and detoxification, cell death signaling and mitochondrial dynamics. The present narrative review aims to summarize the beneficial and deleterious mitochondrial effects of common cardiovascular medications as described in various experimental models and identify those for which evidence for both types of effects is available in the literature.

Prevention of Complications in the Cardiac Intensive Care Unit: A Scientific Statement From the American Heart Association.

Contemporary cardiac intensive care units (CICUs) have an increasing prevalence of noncardiovascular comorbidities and multisystem organ dysfunction. However, little guidance exists to support the development of best-practice principles specific to the CICU. This scientific statement evaluates strategies to avoid the potentially preventable complications encountered within contemporary CICUs, focusing on those that are most applicable to the CICU environment. This scientific statement reviews evidence-based practices derived in non-CICU populations, assesses their relevance to CICU practice, and highlights key knowledge gaps warranting further investigation to attenuate patient risk.

Initial cardiovascular treatment patterns during the first 90 days following an incident cardiovascular event.

AIMS: The aim of this study was to investigate the initial cardiovascular prescription patterns in patients after their first cardiovascular events, and to identify factors associated with cardiovascular polypharmacy. METHODS: This was a cross-sectional study including patients aged ≥ 45 years with the first record of coronary heart disease (CHD) or stroke between 2007 and 2016 using The Health Improvement Network database. This study investigated the patterns of cardiovascular drugs prescribed during the first 90 days after the first cardiovascular events. Logistic regression was used to examine the association between patients' baseline characteristics and cardiovascular polypharmacy (≥5 cardiovascular drugs). RESULTS: A total of 121,600 (59,843 CHD and 61,757 stroke) patients were included in the study. The mean age was 69.5 ± 11.9 years. The proportion of patients who were prescribed 0-1, 2-3, 4-5 drugs and ≥6 drugs were 11.0%, 29.8%, 38.6% and 20.5%, respectively. Factors associated with cardiovascular polypharmacy were sex (female: OR 0.74, 95% CI 0.72-0.76 vs male), age (75-84 years old: OR 0.50, 0.47-0.53 vs 45-54 years old), smoking status (current smoking: OR 1.29, 1.15-1.24 vs never), body mass index (obesity: OR 1.38, 1.34-1.43 vs normal), deprivation status (most deprived: OR 1.09, 1.04-1.14 vs least deprived) and Charlson comorbidity index (index ≥5: OR 1.25, 1.16-1.35 vs index 0). CONCLUSION: Multiple cardiovascular drugs treatment was common in patients with CVD in the UK. High-risk factors of CVD were also associated with cardiovascular polypharmacy. Further studies are warranted to assess the impact of cardiovascular polypharmacy and its interaction on CVD recurrence and mortality.