Impact of COVID-19 epidemic on antihypertensive drug treatment disruptions: results from a nationwide interrupted time-series analysis.

Background: The COVID-19 epidemic has disrupted care and access to care in many ways. It was accompanied by an excess of cardiovascular drug treatment discontinuations. We sought to investigate a deeper potential impact of the COVID-19 epidemic on antihypertensive drug treatment disruptions by assessing whether the epidemic induced some changes in the characteristics of disruptions in terms of duration, treatment outcome, and patient characteristics. Methods: From March 2018 to February 2021, a repeated cohort analysis was performed using French national health insurance databases. The impact of the epidemic on treatment discontinuations and resumption of antihypertensive medications was assessed using preformed interrupted time series analyses either on a quarterly basis. Results: Among all adult patients on antihypertensive medication, we identified 2,318,844 (18.7%) who discontinued their antihypertensive treatment during the first blocking period in France. No differences were observed between periods in the characteristics of patients who interrupted their treatment or in the duration of treatment disruptions. The COVID-19 epidemic was not accompanied by a change in the proportion of patients who fully resumed treatment after a disruption, neither in level nor in trend/slope [change in level: 2.66 (-0.11; 5.42); change in slope: -0.67 (-1.54; 0.20)]. Results were similar for the proportion of patients who permanently discontinued treatment within 1 year of disruption [level change: -0.21 (-2.08; 1.65); slope change: 0.24 (-0.40; 0.87)]. Conclusion: This study showed that, although it led to an increase in cardiovascular drug disruptions, the COVID-19 epidemic did not change the characteristics of these. First, disruptions were not prolonged, and post-disruption treatment outcomes remained unchanged. Second, patients who experienced antihypertensive drug disruptions during the COVID-19 outbreak were essentially similar to those who experienced disruptions before it.

Sex differences in adverse drug reactions: Are women more impacted?

Pharmacovigilance and pharmacoepidemiology studies regarding the sex difference in adverse drug reactions are numerous, and it is now a challenge to take them into account in order to increase drug safety. Here, we present an overview of this topic through data on epidemiology, mechanisms, and methods used for assessing sex differences in drug safety. Because the literature is extensive, we choose to expose a few examples of studies for cardiovascular drugs, anti-infectious, psychotropics, antidiabetics, anticancer drugs and some specific drugs to illustrate our purpose. Many studies show a higher risk in women for most of drugs involving in sex differences. However, physiological, methodological and subjective points have to be taken into account to interpret these results. Clinical trials must also enroll more women to better evaluate sex differences both in efficacy and pharmacovigilance. Nevertheless, when there is a pharmacological rationale underlying the observed association between sex and drug safety profile, it is now unavoidable to think about its consideration for a personalized prescription.

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.

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.

Cardiovascular drugs and COVID-19 clinical outcomes: A living systematic review and meta-analysis.

AIMS: The aim of this study was to continually evaluate the association between cardiovascular drug exposure and COVID-19 clinical outcomes (susceptibility to infection, disease severity, hospitalization, hospitalization length, and all-cause mortality) in patients at risk of/with confirmed COVID-19. METHODS: Eligible publications were identified from more than 500 databases on 1 November 2020. One reviewer extracted data with 20% of the records independently extracted/evaluated by a second reviewer. RESULTS: Of 52 735 screened records, 429 and 390 studies were included in the qualitative and quantitative syntheses, respectively. The most-reported drugs were angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin receptor blockers (ARBs) with ACEI/ARB exposure having borderline association with confirmed COVID-19 infection (OR 1.14, 95% CI 1.00-1.31). Among COVID-19 patients, unadjusted estimates showed that ACEI/ARB exposure was associated with hospitalization (OR 1.76, 95% CI 1.34-2.32), disease severity (OR 1.40, 95% CI 1.26-1.55) and all-cause mortality (OR 1.22, 95% CI 1.12-1.33) but not hospitalization length (mean difference -0.27, 95% CI -1.36-0.82 days). After adjustment, ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.92, 95% CI 0.71-1.19), hospitalization (OR 0.93, 95% CI 0.70-1.24), disease severity (OR 1.05, 95% CI 0.81-1.38) or all-cause mortality (OR 0.84, 95% CI 0.70-1.00). Similarly, subgroup analyses involving only hypertensive patients revealed that ACEI/ARB exposure was not associated with confirmed COVID-19 infection (OR 0.93, 95% CI 0.79-1.09), hospitalization (OR 0.84, 95% CI 0.58-1.22), hospitalization length (mean difference -0.14, 95% CI -1.65-1.36 days), disease severity (OR 0.92, 95% CI 0.76-1.11) while it decreased the odds of dying (OR 0.76, 95% CI 0.65-0.88). A similar trend was observed for other cardiovascular drugs. However, the validity of these findings is limited by a high level of heterogeneity and serious risk of bias. CONCLUSION: Cardiovascular drugs are not associated with poor COVID-19 outcomes in adjusted analyses. Patients should continue taking these drugs as prescribed.

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.

Cardiovascular involvement during COVID-19 and clinical implications in elderly patients. A review.

SARS-CoV-2 betacoronavirus is responsible for the Corona Virus Disease 2019 (COVID-19) which has relevant pathogenic implications for the cardiovascular system. Incidence and severity of COVID-19 are higher in the elderly population (65 years and older). This may be due to higher frequency of comorbidities, but increased frailty and immunosenescence linked with aging may also contribute. Moreover, in elderly individuals, SARS-CoV-2 may adopt different molecular strategies to strongly impact on cardiac aging that culminate in exacerbating a pro-inflammatory state (cytokine storm activation), which, in turn, may lead to pulmonary vascular endothelialitis, microangiopathy, diffuse thrombosis, myocarditis, heart failure, cardiac arrhythmias, and acute coronary syndromes. All these events are particularly relevant in elderly patients, and deserve targeted cardiovascular treatments and specific management of repurposed drugs against COVID-19. We discuss current evidence about the cardiovascular involvement during COVID-19, and elaborate on clinical implications in elderly patients.