Effects of discontinuation of antihypertensive medications on outcome of hospitalised patients with SARS-CoV-2 infection
Discontinuation of at-home angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARB), or β-blockers (BB) in patients hospitalised for a severe acute respiratory syndrome-coronavirus 2 (SARS-CoV-2) infection was associated with an increased mortality risk, whereas discontinuation of calcium channel blockers (CCBs) and diuretics was not associated with an increased mortality risk, according to a study published in Hypertension.
In this retrospective cohort study, researchers led by Sandeep Singh, Academic Medical Center Amsterdam, Amsterdam, the Netherlands, analysed data of 1,584 (mean age, 68.77 years; 59.2% were male) hospitalised patients with SARS-CoV-2 infection from 10 participating hospitals in the Netherlands.
Of the 1,584 patients, 914 (57.70%) reported use of antihypertensive medications at home, of whom 241 (26.37%) were on ARBs, 309 (33.81%) were on ACE inhibitors, 524 (57.33%) were on BB, 305 (33.37%) were on CCBs, and 437 (47.81%) were on diuretics. Of the 914 patients who were on at-home antihypertensive medication, 270 discontinued their antihypertensive medication during hospitalisation.
Of the 1,584 patients, 418 (26.39%) had mild disease, 791 (49.94%) had severe disease, and 375 (23.67%) patients died. Meanwhile, among the 914 patients who were on antihypertensive medications, 248 (27.13%) had mild disease, 408 (44.64%) had severe disease and 258 (28.23%) died. A higher proportion of the patients who died were reported to have discontinued use of ACE inhibitors (46.93% vs 24.0% vs 27.91%; P < 0.05) and BB (11.33% vs 4.85% vs 3.40%; P < 0.05) compared with patients who developed severe disease and mild disease, respectively.
After adjusting for confounders such as age, sex, and modified early warning score at admission, the researchers observed that discontinuation of ARBs (odds ratio [OR] 2.65, 95% confidence interval [CI] 1.17–6.04, P< 0.05), ACE inhibitors (OR 2.28, 95% CI 1.15–4.54, P< 0.05) and BB (OR 3.60, 95% CI 1.10–10.27, P< 0.05) was associated with an increased risk of dying from a SARS-CoV-2 infection. Meanwhile, discontinuation of CCBs or diuretics was not associated with an increased mortality risk.
“RAASi (renin-angiotensin-aldosterone system inhibitors) are suggested as possible treatment option in the early phase of SARS-CoV-2 infection. A meta-analysis investigating the possible detrimental effects of RAASi on the severity of SARS-CoV-2 infection showed that ambulatory use of RAASi, by hospitalised patients, has a neutral effect. It is, however, conceivable that this observation is biased by the fact that antihypertensive medications are often discontinued at or during admission in hospitalised patients with SARS-CoV-2,” the authors wrote.
“In the present study, we show that discontinuation of ARBs, ACE inhibitor, and BB during hospitalisation for a SARS-CoV-2 infection is associated with a [2 to 4 times] increased risk of death, independent of the severity of disease at admission,” the authors concluded.
“One could speculate that discontinuation of ACE inhibitor, ARBs, and BB among patients who died of SARSCoV-2, could be due to the fact that these patients were already on the verge of dying and for that reason antihypertensive medication was not deemed necessary and therefore discontinued. On the contrary, if this was the case, then this would also hold true for CCB and diuretics, which was not the case,” the authors explained.
With regard to the lack of information on when or for what reason medication was discontinued during hospitalisation, the authors noted that “although medications will often be discontinued because of more severe disease, we tried to control for that by correcting our data for the modified early warning score score, which did not change the results.”
“Therefore, we speculate that higher risk of mortality is related to the discontinuation of RAAS and β-blockers themselves, although this analysis cannot confirm this because of its cross-sectional nature,” the authors remarked.
Nonetheless, the authors further noted that “whether these medications might protect against a SARS-CoV-2 infection cannot be concluded from this observational study.”