Artificial intelligence in cardiovascular prevention: new ways will open new doors.

Prevention and effective treatment of cardiovascular disease are progressive issues that grow in tandem with the average age of the world population. Over recent decades, the potential role of artificial intelligence in cardiovascular medicine has been increasingly recognized because of the incredible amount of real-world data (RWD) regarding patient health status and healthcare delivery that can be collated from a variety of sources wherein patient information is routinely collected, including patient registries, clinical case reports, reimbursement claims and billing reports, medical devices, and electronic health records. Like any other (health) data, RWD can be analysed in accordance with high-quality research methods, and its analysis can deliver valuable patient-centric insights complementing the information obtained from conventional clinical trials. Artificial intelligence application on RWD has the potential to detect a patient's health trajectory leading to personalized medicine and tailored treatment. This article reviews the benefits of artificial intelligence in cardiovascular prevention and management, focusing on diagnostic and therapeutic improvements without neglecting the limitations of this new scientific approach.

Racial and ethnic differences in pharmacotherapy to prevent coronary artery disease and thrombotic events.

Awareness of racial/ethnic disparities represents a key challenge for healthcare systems that attempt to provide effective healthcare and to reduce existing inequalities in the use of and adherence to guideline-recommended cardiovascular drugs to improve clinical outcomes for cardiovascular disease (CVD). In this review, we describe important racial/ethnic differences between and within ethnic groups in the prevalence, risk factors, haemostatic factors, anti-inflammatory and endothelial markers, recurrence, and outcomes of CVD. We discuss important differences in the selection, doses, and response [efficacy and adverse drug reactions (ADRs)] in ethnically diverse patients treated with antithrombotics or lipid-lowering drugs. Differences in drug response are mainly related to racial/ethnic differences in the frequency of polymorphisms in genes encoding drug-metabolizing enzymes (DMEs) and drug transporters. These polymorphisms markedly influence the pharmacokinetics, dose requirements, and safety of warfarin, clopidogrel, and statins. This review aims to support a better understanding of the genetic differences between and among populations to identify patients who may experience an ADR or a lack of drug response, thus optimizing therapy and improving outcomes. The greater the understanding of the differences in the genetic variants of DMEs and transporters that determine the differences in the exposure, efficacy, and safety of cardiovascular drugs between races/ethnicities, the greater the probability that personalized medicine will become a reality.

RAAS inhibition and beyond-cardiovascular medications in patients at risk of or affected by COVID-19.

The COVID-19 pandemic led to an enormous burden on healthcare systems worldwide. Causal therapy is still in its infancy. Contrary to initial views that the use of angiotensin-converting enzyme inhibitors (ACEi)/angiotensin II receptor blockers (ARBs) may increase the risk for a deleterious disease course, it has been shown that these agents may actually be beneficial for patients affected by COVID-19. In this article, we provide an overview of the three most commonly used classes of drugs in cardiovascular disease (ACEi/ARB, statins, beta-blockers) and their potential role in COVID-19 therapy. More results from randomized clinical trials are necessary to identify patients that can benefit most from the use of the respective drugs.

Impact of the COVID-19 pandemic on cardiovascular heart disease medication use: time-series analysis of England's prescription data during the COVID-19 pandemic (January 2019 to October 2020).

BACKGROUND: Management of high blood pressure (BP) typically requires adherence to medication regimes. However, it is known that the COVID-19 pandemic both interrupted access to some routine prescriptions and changed some patient health behaviours. AIM: This study, therefore, retrospectively investigated prescription reimbursement of cardiovascular (CVD) medicines as a proxy measure for patient adherence and access to medicines during the pandemic. METHODS: A cohort study of all primary care patients in England prescribed CVD medicines. The exposure was to the global pandemic. Prescriptions were compared before and after the pandemic's onset. Statistical variation was the outcome of interest. RESULTS: Descriptive statistics show changes to monthly prescriptions, with wide confidence intervals indicating varying underlying practice. Analysis of variance reveals statistically significant differences for bendroflumethiazide, potassium-sparing diuretics, nicorandil, ezetimibe, ivabradine, ranolazine, colesevelam and midodrine. After the pandemic began (March-October 2020), negative parameters are observed for ACE inhibitors, beta-blockers, calcium channel blockers, statins, antiplatelet, antithrombotics, ARBs, loop diuretics, doxazosin, bendroflumethiazide, nitrates and indapamide, indicating decelerating monthly prescription items (statistically significant declines of calcium channel blockers, antithrombotic, adrenoreceptor blockers and diuretics) of CVD medicines within the general population. Many data points are not statistically significant, but fluctuations remain clinically important for the large population of patients taking these medications. CONCLUSION: A concerning decline in uptake of CVD therapies for chronic heart disease was observed. Accessible screening and treatment alongside financial relief on prescription levies are needed. A video abstract is (4 min 51 s) available: https://bit.ly/39gvEHi.

Cardiovascular Drug Interactions With Nirmatrelvir/Ritonavir in Patients With COVID-19: JACC Review Topic of the Week.

Nirmatrelvir-ritonavir (NMVr) is used to treat symptomatic, nonhospitalized patients with coronavirus disease-2019 (COVID-19) who are at high risk of progression to severe disease. Patients with cardiovascular risk factors and cardiovascular disease are at a high risk of developing adverse events from COVID-19 and as a result have a higher likelihood of receiving NMVr. Ritonavir, the pharmaceutical enhancer used in NMVr, is an inhibitor of the enzymes of CYP450 pathway, particularly CYP3A4 and to a lesser degree CYP2D6, and affects the P-glycoprotein pump. Co-administration of NMVr with medications commonly used to manage cardiovascular conditions can potentially cause significant drug-drug interactions and may lead to severe adverse effects. It is crucial to be aware of such interactions and take appropriate measures to avoid them. In this review, we discuss potential drug-drug interactions between NMVr and commonly used cardiovascular medications based on their pharmacokinetics and pharmacodynamic properties.

A Cross-Sectional Study on Hypertension Medication Adherence in a High-Burden Region in Namibia: Exploring Hypertension Interventions and Validation of the Namibia Hill-Bone Compliance Scale.

In Namibia, the prevalence of hypertension among women and men aged 35-64 years is high, ranging from 44% to 57%. In this study, we aimed to determine adherence and predictors to antihypertensive therapy in Khomas region, Namibia. A cross-sectional study was performed to consecutively sample 400 patients from urban and peri-urban settings in Namibia. Results were validated using the Hill-Bone Compliance to High Blood Pressure Therapy Scale. Crude associations between predictors of adherence and compliance were tested using the Pearson chi-square test. A multivariable logistic regression analysis was then performed on adherence variables found to be significant to adjust for confounders, and the results are presented as adjusted odds ratios (aOR) with 95% confidence intervals. A total of 400 patients participated in this study. The participants' mean age and standard deviation were Mean ± SD = 48.9 ± 12.5. In this study, 351 (87.7%) patients were estimated to have good adherence. Education, employment, and the presence of other chronic diseases were associated with adherence. Following multivariate adjustment, the following factors were significantly associated and are therefore predictors of adherence (95%CI, p < 0.005): receiving enough medication at last check-up until next one (OR = 5.44, CI 1.76-16.85), lack of encouragement from family and friends (OR = 0.11 (0.03-0.42)), and attendance of follow-ups on schedule (OR = 8.49, CI = 3.82-18.85). The success of hypertension therapy is dependent on the healthcare systems and healthcare professionals in supplying enough medication, support of friends/family, and maintaining scheduled follow-ups. A combination of interventions using low-cost mobile technology led by healthcare professionals could be endorsed. To fully practice universal access to medication, public and private hospitals in Namibia should collaborate.

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.

Cardiovascular drugs and analysis of potential risk factors associated with mortality in severe coronavirus disease 2019 patients.

OBJECTIVES: Cardiovascular diseases are also considered to increase the risk of death in COVID-19 patients. However, real-world data concerning the risk factors for death in patients with severe COVID-19 still remain vague. This study aimed to identify the potential risk factors associated with mortality in severe COVID-19 patients. METHODS: All consecutive patients admitted to the intensive care unit (ICU) of our institute for COVID-19 for severe COVID-19 pneumonia from April 1, 2020 to July 20, 2020 were included in the analysis. Patient characteristics, including complete medical history and comorbid diseases, blood test results during admission and on day 7, and clinical characteristics were compared between survivors and nonsurvivors. RESULTS: There was no significant difference between survivors and nonsurvivors regarding age, gender, and preexisting cardiovascular diseases. Moreover, the rate of the medications including angiotensin-converting enzyme (ACE) inhibitor and angiotensin receptor blockers did not differ between survivors and nonsurvivors. The peak C-reactive protein (CRP), procalcitonin, fibrinogen, and d-dimer levels and the rate for chronic renal failure were significantly higher in nonsurvivors compared with survivors. Intubated patients had a higher risk of death than the others had. CONCLUSIONS: This study failed to demonstrate a significant difference in preexisting cardiovascular diseases and cardiovascular medications between survivors and nonsurvivors who were admitted to ICU for severe COVID-19. Our findings indicate that the presence of chronic renal failure, a high peak ferritin concentration, and the need for invasive mechanical ventilation appear predictive for mortality. We propose that these risk factors should be taken into account in defining the risk status of severe COVID-19 patients admitted to the ICU.

Therapeutic potential of colchicine in cardiovascular medicine: a pharmacological review.

Colchicine is an ancient herbal drug derived from Colchicum autumnale. It was first used to treat familial Mediterranean fever and gout. Based on its unique efficacy as an anti-inflammatory agent, colchicine has been used in the therapy of cardiovascular diseases including coronary artery disease, atherosclerosis, recurrent pericarditis, vascular restenosis, heart failure, and myocardial infarction. More recently, colchicine has also shown therapeutic efficacy in alleviating cardiovascular complications of COVID-19. COLCOT and LoDoCo2 are two milestone clinical trials that confirm the curative effect of long-term administration of colchicine in reducing the incidence of cardiovascular events in patients with coronary artery disease. There is growing interest in studying the anti-inflammatory mechanisms of colchicine. The anti-inflammatory action of colchicine is mediated mainly through inhibiting the assembly of microtubules. At the cellular level, colchicine inhibits the following: (1) endothelial cell dysfunction and inflammation; (2) smooth muscle cell proliferation and migration; (3) macrophage chemotaxis, migration, and adhesion; (4) platelet activation. At the molecular level, colchicine reduces proinflammatory cytokine release and inhibits NF-κB signaling and NLRP3 inflammasome activation. In this review, we summarize the current clinical trials with proven curative effect of colchicine in treating cardiovascular diseases. We also systematically discuss the mechanisms of colchicine action in cardiovascular therapeutics. Altogether, colchicine, a bioactive constituent from an ancient medicinal herb, exerts unique anti-inflammatory effects and prominent cardiovascular actions, and will charter a new page in cardiovascular medicine.

Endothelial Dysfunction in Atherosclerotic Cardiovascular Diseases and Beyond: From Mechanism to Pharmacotherapies.

The endothelium, a cellular monolayer lining the blood vessel wall, plays a critical role in maintaining multiorgan health and homeostasis. Endothelial functions in health include dynamic maintenance of vascular tone, angiogenesis, hemostasis, and the provision of an antioxidant, anti-inflammatory, and antithrombotic interface. Dysfunction of the vascular endothelium presents with impaired endothelium-dependent vasodilation, heightened oxidative stress, chronic inflammation, leukocyte adhesion and hyperpermeability, and endothelial cell senescence. Recent studies have implicated altered endothelial cell metabolism and endothelial-to-mesenchymal transition as new features of endothelial dysfunction. Endothelial dysfunction is regarded as a hallmark of many diverse human panvascular diseases, including atherosclerosis, hypertension, and diabetes. Endothelial dysfunction has also been implicated in severe coronavirus disease 2019. Many clinically used pharmacotherapies, ranging from traditional lipid-lowering drugs, antihypertensive drugs, and antidiabetic drugs to proprotein convertase subtilisin/kexin type 9 inhibitors and interleukin 1ß monoclonal antibodies, counter endothelial dysfunction as part of their clinical benefits. The regulation of endothelial dysfunction by noncoding RNAs has provided novel insights into these newly described regulators of endothelial dysfunction, thus yielding potential new therapeutic approaches. Altogether, a better understanding of the versatile (dys)functions of endothelial cells will not only deepen our comprehension of human diseases but also accelerate effective therapeutic drug discovery. In this review, we provide a timely overview of the multiple layers of endothelial function, describe the consequences and mechanisms of endothelial dysfunction, and identify pathways to effective targeted therapies. SIGNIFICANCE STATEMENT: The endothelium was initially considered to be a semipermeable biomechanical barrier and gatekeeper of vascular health. In recent decades, a deepened understanding of the biological functions of the endothelium has led to its recognition as a ubiquitous tissue regulating vascular tone, cell behavior, innate immunity, cell-cell interactions, and cell metabolism in the vessel wall. Endothelial dysfunction is the hallmark of cardiovascular, metabolic, and emerging infectious diseases. Pharmacotherapies targeting endothelial dysfunction have potential for treatment of cardiovascular and many other diseases.

Association between cardiovascular disease, cardiovascular drug therapy, and in-hospital outcomes in patients with COVID-19: data from a large single-center registry in Poland.

BACKGROUND: The coronavirus disease 19 (COVID-19) recently became one of the leading causes of death worldwide, similar to cardiovascular disease (CVD). Coexisting CVD may influence the prognosis of patients with COVID-19. AIMS: We analyzed the impact of CVD and the use of cardiovascular drugs on the in-hospital course and mortality of patients with COVID-19. METHODS: We retrospectively studied data for consecutive patients admitted to our hospital, with COVID-19 between March 6th and October 15th, 2020. RESULTS: 1729 patients (median interquartile range age 63 [50-75] years; women 48.8%) were included. Overall, in-hospital mortality was 12.9%. The most prevalent CVD was arterial hypertension (56.1%), followed by hyperlipidemia (27.4%), diabetes mellitus (DM) (25.7%), coronary artery disease (16.8%), heart failure (HF) (10.3%), atrial fibrillation (13.5%), and stroke (8%). Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers (ACEIs/ARBs) were used in 25.0% of patients, ß-blockers in 40.7%, statins in 15.6%, and antiplatelet therapy in 19.9%. Age over 65 years (odds ratio [OR], 6.4; 95% CI, 4.3-9.6), male sex (OR, 1.4; 95% CI, 1.1-2.0), pre-existing DM (OR, 1.5; 95% CI, 1.1-2.1), and HF (OR, 2.3; 95% CI, 1.5-3.5) were independent predictors of in-hospital death, whereas treatment with ACEIs/ARBs (OR, 0.4; 95% CI, 0.3-0.6), ß-blockers (OR, 0.6; 95% CI, 0.4-0.9), statins (OR, 0.5; 95% CI, 0.3-0.8), or antiplatelet therapy (OR, 0.6; 95% CI: 0.4-0.9) was associated with lower risk of death. CONCLUSIONS: Among cardiovascular risk factors and diseases, HF and DM appeared to increase in-hospital COVID-19 mortality, whereas the use of cardiovascular drugs was associated with lower mortality.

Changes in Purchases for Intensive Care Medicines During the COVID-19 Pandemic: A Global Time Series Study.

BACKGROUND: Drug supply disruptions have increased during the COVID-19 pandemic, especially for medicines used in the ICU. Despite reported shortages in wealthy countries, global analyses of ICU drug purchasing during COVID-19 are limited. RESEARCH QUESTION: Has COVID-19 impacted global drug purchases of first-, second-, and third-choice agents used in intensive care? STUDY DESIGN AND METHODS: We conducted a cross-sectional time series study in a global pharmacy sales dataset comprising approximately 60% of the world's population. We analyzed pandemic-related changes in units purchased per 1,000 population for 69 ICU agents. Interventional autoregressive integrated moving average models tested for significant changes when the pandemic was declared (March 2020) and during its first stage from April through August 2020, globally and by development status. RESULTS: Relative to 2019, ICU drug purchases increased by 23.6% (95% CI, 7.9%-37.9%) in March 2020 (P < .001) and then decreased by 10.3% (95% CI, -16.9% to -3.5%) from April through August (P = .006). Purchases for second-choice medicines changed the most, especially in developing countries (eg, 29.3% increase in March 2020). Despite similar relative changes (P = .88), absolute purchasing rates in developing nations remained low. The observed decrease from April through August 2020 was significant only in developed countries (-13.1%; 95% CI, -17.4% to -4.4%; P < .001). Country-level variation seemed unrelated to expected demand and health care infrastructure. INTERPRETATION: Purchases for intensive care medicines increased globally in the month of the COVID-19 pandemic declaration, but before peak infection rates. These changes were most pronounced for second-choice agents, suggesting that inexpensive, generic medicines may be purchased more easily in anticipation of pandemic-related ICU surges. Nevertheless, disparities in access persisted. Trends seemed unrelated to expected demand, and decreased purchasing from April through August 2020 may suggest overbuying. National and international policies are needed to ensure equitable drug purchasing during future pandemics.