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.

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.

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.

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.

COVID-19 and cardiovascular system-a comprehensive review.

Coronavirus disease 2019 (COVID-19), a mystified cryptic virus has challenged the mankind that has brought life to a standstill. Catastrophic loss of life, perplexed healthcare system and the downfall of global economy are some of the outcomes of this pandemic. Humans are raging a war with an unknown enemy. Infections, irrespective of age and gender, and more so in comorbidities are escalating at an alarming rate. Cardiovascular diseases, are the leading cause of death globally with an estimate of 31% of deaths worldwide out of which nearly 85% are due to heart attacks and stroke. Theoretically and practically, researchers have observed that persons with pre-existing cardiovascular conditions are comparatively more vulnerable to the COVID-19 infection. Moreover, they have studied the data between less severe and more severe cases, survivors and non survivors, intensive care unit (ICU) patients and non ICU patients, to analyse the relationship and the influence of COVID-19 on cardiovascular health of an individual, further the risk of susceptibility to submit to the virus. This review aims to provide a comprehensive particular on the possible effects, either direct or indirect, of COVID-19 on the cardiovascular heath of an individual.

Increased pharmacy purchases of cardiovascular drugs from wholesalers prior to the first and second COVID-19 lockdowns.

AIM: The aim of this study was to examine the development of drug purchases over the course of the coronavirus crisis in Germany in 2020. MATERIALS AND METHODS: The evaluations in this retrospective cross-sectional study are based on the IMS RPM (Regional Pharmaceutical Market) weekly database, which shows weekly purchases by public pharmacies from full-service wholesalers at the time the pharmacy purchase is made in Germany. The outcome of this investigation was the development of cardiovascular drug sales by packing unit over all 52 weeks of 2020. RESULTS: We found an increase of 68% in week 12 compared to the average sales for weeks 2 - 11, 2020 (vs. -2% in week 12, 2019), while the increase in week 51 was 61%, compared to the average sales for weeks 13 - 50, 2020 (vs. 35% in week 51, 2019). The largest increases in week 12 were for calcium channel blockers (64%), and the largest increases in week 51 were for lipid-lowering drugs (67%). CONCLUSION: The results of this retrospective cross-sectional study suggest that the COVID-19 lockdown in Germany was associated with a significant surge in pharmacy purchases of cardiovascular drugs, indicating panic buying. Although there were no drug shortages during the first lockdown, this panic buying recurred shortly before the second lockdown, albeit to a lesser extent.

Trends and concerns of potentially inappropriate medication use in patients with cardiovascular diseases.

Introduction: The use of potentially inappropriate medications (PIM) is an alarming social risk factor in cardiovascular patients. PIM administration may result in iatrogenic disorders and adverse consequences may be attenuated by limiting PIM intake.Areas covered: The goal of this review article is to discuss the trends, risks, and concerns regarding PIM administration with focus on cardiovascular patients. To find data, we searched literature using electronic databases (Pubmed/Medline 1966-2021 and Web of Science 1975-2021). The data search terms were cardiovascular diseases, potentially inappropriate medication, potentially harmful drug-drug combination, potentially harmful drug-disease combination, drug interaction, deprescribing, and electronic health record.Expert opinion: Drugs for heart diseases are the most commonly prescribed medications in older individuals. Despite the availability of explicit and implicit PIM criteria, the incidence of PIM use in cardiovascular patients remains high ranging from 7 to 85% in different patient categories. Physician-induced disorders often occur when PIM is administered and adverse effects may be reduced by limiting PIM intake. Main strategies promising for addressing PIM use include deprescribing, implementation of systematic electronic records, pharmacist medication review, and collaboration among cardiologists, internists, geriatricians, clinical pharmacologists, pharmacists, and other healthcare professionals as basis of multidisciplinary assessment teams.

Impact of the presence of heart disease, cardiovascular medications and cardiac events on outcome in COVID-19.

BACKGROUND: Cardiovascular risk factors and usage of cardiovascular medication are prevalent among coronavirus disease 2019 (COVID-19) patients. Little is known about the cardiovascular implications of COVID-19. The goal herein, was to evaluate the prognostic impact of having heart disease (HD) and taking cardiovascular medications in a population diagnosed of COVID-19 who required hospitalization. Also, we studied the development of cardiovascular events during hospitalization. METHODS: Consecutive patients with definitive diagnosis of COVID-19 made by a positive real time- -polymerase chain reaction of nasopharyngeal swabs who were admitted to the hospital from March 15 to April 14 were included in a retrospective registry. The association of HD with mortality and with mortality or respiratory failure were the primary and secondary objectives, respectively. RESULTS: A total of 859 patients were included in the present analysis. Cardiovascular risk factors were related to death, particularly diabetes mellitus (hazard ratio in the multivariate analysis: 1.810 [1.159- -2.827], p = 0.009). A total of 113 (13.1%) patients had HD. The presence of HD identified a group of patients with higher mortality (35.4% vs. 18.2%, p < 0.001) but HD was not independently related to prognosis; renin-angiotensin-aldosterone system inhibitors, calcium channel blockers, diuretics and beta-blockers did not worsen prognosis. Statins were independently associated with decreased mortality (0.551 [0.329-0.921], p = 0.023). Cardiovascular events during hospitalization identified a group of patients with poor outcome (mortality 31.8% vs. 19.3% without cardiovascular events, p = 0.007). CONCLUSIONS: The presence of HD is related to higher mortality. Cardiovascular medications taken before admission are not harmful, statins being protective. The development of cardiovascular events during the course of the disease is related to poor outcome.

Potential mechanisms of cerebrovascular diseases in COVID-19 patients.

Since the outbreak of coronavirus disease 2019 (COVID-19) in 2019, it is gaining worldwide attention at the moment. Apart from respiratory manifestations, neurological dysfunction in COVID-19 patients, especially the occurrence of cerebrovascular diseases (CVD), has been intensively investigated. In this review, the effects of COVID-19 infection on CVD were summarized as follows: (I) angiotensin-converting enzyme 2 (ACE2) may be involved in the attack on vascular endothelial cells by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), leading to endothelial damage and increased subintimal inflammation, which are followed by hemorrhage or thrombosis; (II) SARS-CoV-2 could alter the expression/activity of ACE2, consequently resulting in the disruption of renin-angiotensin system which is associated with the occurrence and progression of atherosclerosis; (III) upregulation of neutrophil extracellular traps has been detected in COVID-19 patients, which is closely associated with immunothrombosis; (IV) the inflammatory cascade induced by SARS-CoV-2 often leads to hypercoagulability and promotes the formation and progress of atherosclerosis; (V) antiphospholipid antibodies are also detected in plasma of some severe cases, which aggravate the thrombosis through the formation of immune complexes; (VI) hyperglycemia in COVID-19 patients may trigger CVD by increasing oxidative stress and blood viscosity; (VII) the COVID-19 outbreak is a global emergency and causes psychological stress, which could be a potential risk factor of CVD as coagulation, and fibrinolysis may be affected. In this review, we aimed to further our understanding of CVD-associated COVID-19 infection, which could improve the therapeutic outcomes of patients. Personalized treatments should be offered to COVID-19 patients at greater risk for stroke in future clinical practice.

Worsening of heart failure by coronavirus disease 2019 is associated with high mortality.

AIMS: Patients with advanced heart failure (HF) with reduced left ventricular ejection fraction (HFrEF) and concurrent coronavirus disease 2019 (COVID-19) might have a higher risk of severe events. METHODS AND RESULTS: We retrospectively studied 16 patients with advanced HFrEF who developed COVID-19 between 1 March and 29 May 2020. Follow-up lasted until 30 September. Ten patients previously hospitalized with decompensated HFrEF were infected with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) during hospitalization. Six patients undergoing ambulatory care at initiation of COVID-19 symptoms were hospitalized because of advanced HFrEF. All patients who experienced worsening of HFrEF due to COVID-19 required higher doses or introduction of additional inotropic drugs or intra-aortic balloon pump in the intensive care unit. The mean intravenous dobutamine dose before SARS-CoV-2 infection in previously hospitalized patients (n = 10) and the median (inter-quartile range) peak intravenous dobutamine dose during SARS-CoV-2 infection in all patients (n = 16) were 2 (0-7) µg/kg/min and 20 (14-20) (P < 0.001), respectively. During follow-up, 56% underwent heart transplantation (n = 2) or died (n = 7). Four patients died during hospitalization from mixed shock consequent to severe acute respiratory syndrome with inflammatory storm syndrome associated with septic and cardiogenic shock during COVID-19. After COVID-19 recovery, two patients died from mixed septic and cardiogenic shock and one from sustained ventricular tachycardia and cardiogenic shock. Five patients were discharged from hospital to ambulatory care. Four were awaiting heart transplantation. CONCLUSION: Worsening of advanced HF by COVID-19 is associated with high mortality. This report highlights the importance of preventing COVID-19 in patients with advanced HF.

Adverse effects, pharmacological interactions, and cardiovascular drugs in COVID-19 treatment.

In severe coronavirus disease (COVID)-19 patients, an extraordinary systemic inflammatory response is seen. It could impact in multiple organ disorders, specially a severe myocardial injury, an acute myocarditis results in focal or global myocardial inflammation and necrosis. Those events can be present in healthy subjects or cardiovascular (CV) patients. It is clinically associated with ventricular dysfunction exacerbation or worsening and tachyarrhythmias. It is also related to a poor outcome for CV patients with ischemic heart disease, hypertensión, and heart failure. COVID-19 patients require multiple and complex treatment that alleviates symptoms, the vast variety of agents interacts with diseases and CV drugs. Our purpose is to correlate in guidance synopsis: Adverse effects, pharmacological interactions, and CV drugs in COVID-19 treatment.

En pacientes con COVID-19 grave se ha observado una extraordinaria respuesta inflamatoria sistémica. Este impacto se traduce en múltiples trastornos de órganos, especialmente cardíacos, por lesión miocárdica grave, miocarditis aguda que resulta en inflamación focal o miocárdica global, necrosis cardiaca. Estos tremendos eventos son observados en sujetos sanos como pacientes cardiovasculares. Clínicamente asociados con nueva presentación o empeoramiento de la disfunción ventricular y taquiarritmias. Relacionado a un predictor principal de malos resultado en pacientes cardiovasculares (CV), especialmente en aquellos con cardiopatía isquémica, hipertensión e insuficiencia cardíaca. Los enfermos con COVID-19 requieren múltiples y complejos tratamientos que alivien los síntomas, esta gran variedad de agentes interactúa con enfermedades y medicamentos CV. Nuestro propósito es correlacionar, en una guía sinóptica: efectos adversos, interacciones farmacológicas y fármacos cardiovasculares en el tratamiento del COVID-19.

Clinical Features and Outcomes of Acute Kidney Injury in Patients Infected with COVID-19 in Xiangyang, China.

BACKGROUND: In December 2019, pneumonia associated with COVID-19 has spread from Wuhan to other areas in China. In the present study, we aimed to further clarify the clinical features and outcomes of acute kidney injury (AKI) in patients infected with COVID-19 in Xiangyang, Hubei, China. METHODS: All confirmed cases of COVID-19 with AKI in Xiangyang Central Hospital from January 22 to May 31, 2020, were included in this retrospective study. Data of epidemiological, clinical, laboratory, radiological tests, treatment, complication, and outcomes were collected and analyzed. Patients were divided into intensive care unit (ICU) group and isolation ward (non-ICU) group. RESULTS: Of the total patients, 33.3% in the non-ICU group and 85.7% in the ICU group had chronic diseases. In addition, 85.7% of patients in the ICU group died. The most common symptoms were fever, cough, and fatigue. The lymphocyte count in the ICU group was significantly reduced compared with the non-ICU group. The chest computed tomography (CT) images appeared showed multiple mottles and ground-glass opacity. Strip shadow could be found in chest CT images of some recovered patients. All patients received antiviral treatment. Most patients in the ICU group were given methylprednisolone, immunoglobulin, antibiotics, and mechanical ventilation and 35.7% of patients in the ICU group received continuous renal replacement therapy. CONCLUSIONS: Elderly with chronic comorbidities were more susceptible to COVID-19, showing a higher mortality rate due to multiple organ damage, and 35.7% of patients with AKI in ICU received renal replacement therapy. Moreover, part of the cured patients might need additional time to recover for poor lung function.