Discontinuation of Antihypertensive Drug Use Compared to Continuation in COVID-19 Patients: A Systematic Review with Meta-analysis and Trial Sequential Analysis

Abstract

Introduction COVID-19 related mortality is about 2%, and it increases with comorbidities, like hypertension. Regarding management, there is debatable evidence about the benefits of continuation vs. discontinuation of angiotensin-converting enzyme inhibitors and angiotensin receptor blockers (ACEI/ARB). Aim We performed a systematic review to assess the effects and safety of in-hospital discontinuation compared to continuation of ACEI/ARB in COVID-19 patients. Methods We systematically searched on PubMed, Scopus, and EMBASE from inception to June 19, 2021. We included observational studies and trials that compared the effects and safety of continuing ACEI/ARB compared to discontinuing it in COVID-19 patients. Effects sizes for dichotomous variables were expressed as risk ratios (RR) and 95% confidence intervals. For continuous variables, effects were expressed as mean difference (MD). We used random effect models with the inverse variance method. We assessed certainty of evidence using the GRADE approach. Results We included three open-label randomized controlled trials and five cohort studies. We found that the continuation group had lower risk of death compared with the discontinuation group only in the cohort group (RR: 0.46, 95% CI: 0.24–0.90), but not in the RCT group (RR: 1.22, 95% CI: 0.75–2.00). The ICU admission rate was significantly lower in the continuation group (RR: 0.46, 95% CI: 0.31–0.68) in the cohort group, but not in RCT group (RR: 1.03, 95% CI: 0.67–1.59). We did not find significant differences between groups regarding hospitalization length, hypotension, AKI needing renal replacement therapy, mechanical ventilation, new or worsening heart failure, myocarditis, renal replacement therapy, arrhythmias, thromboembolic events and SOFA AUC. The GRADE approach revealed that the certainty ranged from moderate to high level. Conclusions There is no significant difference in mortality and other outcomes between continuation and discontinuation groups. Supplementary Information The online version contains supplementary material available at 10.1007/s40292-023-00579-0.

What is the quantity, quality and type of systematic review evidence available to inform the optimal prescribing of statins and antihypertensives? A systematic umbrella review and evidence and gap map

“…Medications of interest within the 80 reviews included in our umbrella review were: statins (n=10),25–34 antihypertensives (n=38),35–72 and statins and antihypertensives (n=34) 73–104. Nine of the reviews synthesised qualitative evidence,27 31 42 50 55 58 60 61 83 104 four of which also included quantitative evidence in a mixed evidence synthesis 42 50 58 61.…”

“…Nine of the reviews synthesised qualitative evidence,27 31 42 50 55 58 60 61 83 104 four of which also included quantitative evidence in a mixed evidence synthesis 42 50 58 61. Of the reviews synthesising quantitative evidence evaluating interventions, interventions focused on: enhancing patient adherence to medication as prescribed (n=57),25 30 32–35 37–41 43–46 48 49 51 53 54 56 57 59 62 63 65–71 73–81 86 87 89–96 98–103 105 deprescribing a prescribed medication (n=6)36 46 72 80 88 93 or optimising the prescribing of medication to meet the needs of the patient (n=13) 26 28 29 38 52 64 71 84 85 87 90 100 106. Three of these reviews were judged by reviewers to have dual aims 71 87 90.…”

“…Three reviews, one of ‘low’ quality,82 five of ‘critically low’ quality36 47 88 97 105 synthesised quantitative evidence evaluating interventions promote deprescribing.…”