The effect of ACE inhibitors on inflammation and clinical end-points in COVID-19 patients Relationship of ACE inhibitors to COVID-19 patients

Aim: COVID-19 infection has affected the whole world. It has been speculated that the virus might hold on to angiotensin-converting enzyme 2 (ACE 2) surfaces of type 2 alveolar cells. ACE inhibitors and angiotensin receptor antagonists (ARBs) are essential antihypertensive and cardiac failure drugs in the guidelines. In this study, we aimed to find the effect of these drugs on clinical, laboratory courses, and outcomes of COVID-19 patients. Material(s) and Method(s): We included 109 patients in this study. There were 43 patients in the ACE/ARB group and 66 patients in the non-ACE/ARB group. The mean age was 60 years in the ACE/ARB group and 52 years old in the non-ACE/ARB group. Basal symptoms, hemogram, CRP, D-dimer, LDH, Ferritin, AST, duration of hospitalization, percentage of intensive care unit (ICU) need, length of stay in ICU were compared between the groups. Result(s): The mean age in the ACE/ARB group was higher than in the other group and was statistically significant (p=.027). The initial symptoms were not different. There were no differences between the laboratory results of the groups. The ICU need was higher in the patients who do not use the drug than in the users (p<.020). Discussion(s): ACE/ARB usage in COVID-19 patients did not worsen the course of the disease. However, ACE/ARB users before COVID-19 pandemic were taken to ICU at a low rate.Copyright © 2022, Derman Medical Publishing. All rights reserved.

Oral anticoagulants, dementia . . . and other stories

Anticoagulants conferred a small increase in life expectancy—but at the price of an increase in bleeding complications. Since the primary goal of treatment for patients with advanced dementia should surely be comfort, this may not be optimal care (J Am Ger Soc doi:10.1111/jgs.18108). Intravenous antihypertensives Rapid treatment may do more harm than good, according to a retrospective study of 20 000 adults who developed a systolic blood pressure of greater than 180 mm Hg or a diastolic pressure greater than 110 mm Hg while in hospital for a reason other than hypertension. Vitamin D supplementation and dementia A recent meta-analysis concluded that vitamin D supplementation had no useful protective effect on cognitive function.

Stroke, diabetes, . . . and other stories

In Denmark, time trends of ischaemic stroke in people with type 2 diabetes are showing a striking decline. Between 1996 and 2015, the incidence of stroke dropped by around 50%. The fall coincided with an increase in the use of prophylactic cardiovascular medications, especially statins (where the prevalence of use increased from 5% to 50%) and multiple antihypertensive drugs (where the prevalence of use increased from 18% to 33%) (Diabetes Care doi:10.2337/dc22-0440).

Initiation of antihypertensive drugs to patients with confirmed COVID-19-A population-based cohort study in Sweden.

PURPOSE: Hypertension is an important risk factor for severe outcomes in patients with COVID-19, and antihypertensive drugs may have a protective effect. However, the pandemic may have negatively impacted health care services for chronic diseases. The aim of this study was to assess initiations of antihypertensive medicines in patients infected by COVID-19. METHODS: A cohort study including all Swedish residents 20-80 years old with a COVID-19 positive test compared with an unexposed group without COVID-19 matched for age, sex, and index date (date of confirmed COVID-19). Data were collected within SCIFI-PEARL, a study including linked data on COVID tests, hospital diagnoses, dispensed prescriptions, and socioeconomic data from Swedish national registers. Initiations of different antihypertensive drugs were studied from March 2020 until October 2020. Associations between COVID-19 and initiation of antihypertensives were assessed by a multivariable Cox proportional hazards model. RESULTS: A total of 224 582 patients (exposed and unexposed) were included. After adjusting for cardiovascular comorbidities and education level, ACEi was the most commonly initiated antihypertensive agent to patients with COVID-19. Hazard ratio and 95% confidence interval for initiation of drug therapy was 1.83 [1.53-2.19] for ACEi, followed by beta-blockers 1.74 [1.55-1.95], calcium channel blockers 1.61 [1.41-1.83], angiotensin receptor blockers 1.61 [1.40-1.86], and diuretics 1.53 [1.32-1.77]. CONCLUSION: All antihypertensive medicines were initiated more frequently in COVID-19 patients. This can either be associated with hypertension caused by the COVID-19 infection, more frequent diagnosis of hypertension among people with COVID-19 since they consult health care, or residual confounding factors not adjusted for in the study.

This Week in the Journal

Antihypertensive agents and magnesium sulfate can help control the systemic manifestations of preeclampsia, which is usually resolved by delivery of the placenta. see Review Article, N Engl J Med 2022;386:1817-1832 Emphysematous Aortitis A 74-year-old man with end-stage kidney disease and coronary artery disease presented with decreased responsiveness, anorexia, and generalized weakness. [...]its struggles to enact a broader reform agenda reflect the daunting political constraints that limit U.S. health policy. see Perspective, N Engl J Med 2022;386:1773-1775 Supporting Innovation in Medicaid Policy Randomized, controlled trials remain underutilized within the Medicaid program, even though state Medicaid programs regularly implement new policies that require evaluation. What are the key barriers to implementing RCTs in Medicaid, and how can we increase their use? see Perspective, N Engl J Med 2022;386:1775-1777 Unmute Early in the Covid pandemic, the lead staffer on a state ventilator allocation committee follows the group’s virtual deliberations, while attending to the constant needs of her children and trying to avert exposure from her husband who’s caring for patients in the ICU. see Perspective, N Engl J Med 2022;386:1777-1779 Protection from Covid-19 after Third Vaccine Dose In a cohort of frontline health care workers, a third dose of an mRNA vaccine provided 91% protection against SARS-CoV-2 infection with the delta variant and 60% against the omicron variant. see Correspondence, N Engl J Med 2022;386:1855-1857 Pulse Oximetry in Covid-19 Pulse oximetry is frequently used to monitor the respiratory status of outpatients with Covid-19.

Latest hypertension research to inform clinical practice in Asia.

Despite the challenges associated with the coronavirus pandemic, the last 2 years have been active periods for hypertension research and initiatives in Asia. There are new hypertension guidelines from the World Health Organization that can be interpreted and applied locally. This is also the case for data from the latest Blood Pressure Lowering Treatment Trialists' Collaboration meta-analysis, which showed that greater reductions in systolic blood pressure (BP) are associated with lower risks of cardiovascular events. The randomized controlled Strategy of Blood Pressure Intervention in the Elderly Hypertensive study and the Salt Substitute and Stroke Study provide local data to inform practice. Other initiatives to help reduce high salt intake in Asia are also underway. Both drug-resistant and nocturnal hypertension are appropriate areas of focus in Asia, and there are an increasing number of pharmacological and non-pharmacological treatment options for these conditions. Digital therapeutics to promote uptake and implementation of lifestyle interventions are showing promise, and other digital-based strategies such as telemedicine, wearable BP monitors to detect beat-by-beat BP and artificial intelligence will no doubt become integral parts of future strategies to reduce the burden of hypertension and hypertension-related disease. A number of initiatives from the Hypertension Cardiovascular Outcome Prevention and Evidence in Asia Network and Japanese Society of hypertension are underway, and there is good reason for optimism regarding the ongoing and future management of hypertension in Asia based on these and the active research activities in the region.

Preventive Oral Treatment of Episodic Migraine: An Overview.

BACKGROUND: Migraine is a common primary headache disorder and Episodic migraine is characterized by the occurrence of up to 14 headache days in a month. The preventive treatment of migraine is useful in patients with frequent migraine attacks, impaired activities of daily living, failure of acute pain management, disabling aura and limitations in the use of acute treatment. It is aimed at reducing headache frequency and intensity, improve response to acute treatment of migraine and improve the quality of life. AIM: To analyze the evidence for the efficacy and tolerability of preventive oral drugs used in the management of episodic migraine. METHODS: A narrative review of the references were reviewed by searching the literature for the articles published in PubMed in English language using all the following MeSH keywords "preventive treatment", "preventive oral treatment", AND "episodic migraine", "migraine". RESULTS: Out of articles identified in the search, 38 articles were reviewed for evidence and summarized. The various oral drugs used in the prevention of episodic migraine are antihypertensives (beta-blockers, calcium channel blockers and Angiotensin-converting enzyme inhibitors/Angiotensin receptor blockers), antidepressants (tricyclic antidepressants, selective serotonin reuptake inhibitors, serotonin-norepinephrine reuptake inhibitors), antiepileptic drugs (valproic acid, topiramate, lamotrigine) and other miscellaneous agents. HURT questionnaire and HALT 30 index are useful in assessing response to treatment in the follow up of migraine patients. CONCLUSION: An appropriately chosen oral drug is useful in the preventive treatment of episodic migraine. In patients, who fail to respond to the preventive treatment, it is essential to review the diagnosis of migraine, titrate the dosage and duration of preventive treatment and ensure patient compliance. In those patients who fail to respond to monotherapy, polytherapy is a useful option to be considered.

Experimental data using candesartan and captopril indicate no double-edged sword effect in COVID-19.

The key link between renin-angiotensin system (RAS) and COVID-19 is ACE2 (angiotensin-converting enzyme 2), which acts as a double-edged sword, because ACE2 increases the tissue anti-inflammatory response but it is also the entry receptor for the virus. There is an important controversy on several drugs that regulate RAS activity and possibly ACE2, and are widely used, particularly by patients most vulnerable to severe COVID-19. In the lung of healthy rats, we observed that candesartan (an angiotensin type-1, AT1, receptor blocker; ARB) and captopril (an ACE inhibitor; ACEI) up-regulated expression of tissue ACE2 and RAS anti-inflammatory axis receptors (AT2 and Mas receptors). This effect was particularly pronounced in rats with metabolic syndrome (obesity, increased blood pressure and hyperglycemia) and aged rats. Treatment of cultures of human type-II pneumocytes with candesartan or captopril induced up-regulation of ACE2 expression in cells. Treatment with viral spike protein induced a decrease in full-length (i.e. transmembrane) ACE2, an increase in levels of a short intracellular ACE2 polypeptide and an increase in ADAM17 activity in cells, together with an increase in levels of soluble ACE2 and major proinflammatory cytokines in the culture medium. Spike protein-induced changes and levels of spike protein internalization in cells were inhibited by pretreatment with the above-mentioned drugs. The results suggest that these drugs increase ACE2 levels and promote the anti-inflammatory RAS axis in the lung. Furthermore, possible up-regulation of viral entry by the drug-induced increase in expression of transmembrane ACE2 is counteracted by additional mechanisms, particularly by drug-induced inhibition of ADAM17 activity.

Associations of Medications With Lower Odds of Typical COVID-19 Symptoms: Cross-Sectional Symptom Surveillance Study.

BACKGROUND: As the COVID-19 pandemic continues to spread across the globe, the search for an effective medication to treat the symptoms of COVID-19 continues as well. It would be desirable to identify a medication that is already in use for another condition and whose side effect profile and safety data are already known and approved. OBJECTIVE: The objective of this study was to evaluate the effect of different medications on typical COVID-19 symptoms by using data from an online surveillance survey. METHODS: Between early April and late-July 2020, a total of 3654 individuals in Lower Saxony, Germany, participated in an online symptom-tracking survey conducted through the app covid-nein-danke.de. The questionnaire comprised items on typical COVID-19 symptoms, age range, gender, employment in patient-facing healthcare, housing status, postal code, previous illnesses, permanent medication, vaccination status, results of reverse transcription polymerase chain reaction (RT-PCR) and antibody tests for COVID-19 diagnosis, and consequent COVID-19 treatment if applicable. Odds ratio estimates with corresponding 95% CIs were computed for each medication and symptom by using logistic regression models. RESULTS: Data analysis suggested a statistically significant inverse relationship between typical COVID-19 symptoms self-reported by the participants and self-reported statin therapy and, to a lesser extent, antihypertensive therapy. When COVID-19 diagnosis was based on restrictive symptom criteria (ie, presence of 4 out of 7 symptoms) or a positive RT-PCR test, a statistically significant association was found solely for statins (odds ratio 0.28, 95% CI 0.1-0.78). CONCLUSIONS: Individuals taking statin medication are more likely to have asymptomatic COVID-19, in which case they may be at an increased risk of transmitting the disease unknowingly. We suggest that the results of this study be incorporated into symptoms-based surveillance and decision-making protocols in regard to COVID-19 management. Whether statin therapy has a beneficial effect in combating COVID-19 cannot be deduced based on our findings and should be investigated by further study. TRIAL REGISTRATION: German Clinical Trials Register DRKS00022185; https://www.drks.de/drks_web/navigate.do?navigationId=trial.HTML&TRIAL_ID=DRKS00022185; World Health Organization International Clinical Trials Registry Platform U1111-1252-6946.