ACE INHIBITORS IN PATIENTS WITH COVID?

Hospitalized COVID-19 patients with high blood pressure who continue on angiotensin-converting enzyme (ACE) inhibitors and angiotensin-receptor blockers (ARBs) fare better than those who discontinue the drugs, according to a retrospective study.

Several professional societies have released statements recommending that ACE inhibitors/ARBs should be continued in hypertensive patients with COVID-19, and studies have shown that their use is not associated with worse COVID-19 disease severity or mortality.

Dr. Tim Q. Duong and colleagues from Renaissance School of Medicine, Stony Brook University, in New York, investigated the effects of in-hospital continuation or discontinuation of ACE inhibitors/ARBs on the clinical outcomes of 614 hypertensive COVID-19 patients, controlling for newly developed hypotension or acute kidney injury (AKI) during hospitalization.

Among 279 patients who did not take ACE inhibitors/ARBs prior to admission, 55 required intensive-care unit (ICU) admission and 62 died. Forty-five of 171 patients who discontinued their home ACE inhibitors/ARBs in the hospital required ICU care and 48 died. Of the 164 patients who continued taking their home ACE inhibitors/ARBs in the hospital, 20 required ICU care and 10 died.

Mortality did not differ significantly between the ACE inhibitor/ARB groups and the non-ACE inhibitor/ARB group. But among patients who had been taking ACE inhibitors/ARBs at home, the mortality rate was significantly lower in those who continued their medications than in those who discontinued them (6.09% vs. 28.07%, adjusted P=0.001).

Hospital-onset hypotension and AKI rates were significantly higher in the group that discontinued ACE inhibitors/ARBs. There was no significant difference in mortality between continuing or discontinuing ACE inhibitors/ARBs among patients who developed in-hospital hypotension or AKI.

In contrast, among patients who did not develop hypotension or AKI, continued ACE inhibitor/ARB use was associated with significantly lower mortality compared with discontinuation, the researchers report in the Journal of Infectious Diseases.

ICU admission rates did not differ overall between the groups that were or were not receiving ACE inhibitors/ARBs before hospitalization, but the ICU admission rate was twice as high in the group that discontinued their medications (26.3%) as in the group that continued them (12.2%).

"These findings not only confirm that ACE inhibitor/ARB use does not worsen clinical outcomes in COVID-19 patients with a history of hypertension, but also suggest that COVID-19 patients who are on ACE inhibitors/ARBs should continue these medications in the hospital as they may have beneficial effects, as long as these patients do not develop hypotension or acute kidney injury," the authors conclude.

Dr. Andrew M. South of Brenner Children's Hospital, Wake Forest School of Medicine, in Winston Salem, North Carolina, has addressed ACE inhibitor/ARB use during the pandemic in several papers. He told Reuters Health by email, "Though limited, the study's findings do support the current recommendation for patients to continue to take their angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker medication if they test positive for SARS-CoV-2 or develop COVID-19, unless there is a clear and previously established indication for stopping the medication, such as low blood pressure."

"It will be very interesting to see the results of ongoing observational studies and clinical trials that will further address these important questions," said Dr. South, who was not involved in the new research.

Dr. Matthias Barton of the University of Zurich, Switzerland, who recently wrote about the potential harmful effects of discontinuing ACE inhibitors and ARBs in COVID-19 patients, told Reuters Health by email, "One has to be careful about interpreting/over-interpreting the data and about drawing conclusions based on the findings reported. At this point we do not know whether any protective effects are (equally) present for ACEI and ARBs, or whether one has advantages over the other."

"ACE inhibitors block ACE-1 (which is identical to kininase-2 which inactivates bradykinin) but not ACE-2, the receptor of SARS-CoV-2, and we still know very little about the potential mechanisms that may provide protection in COVID-19 patients," he said. "Since SARS-CoV-2 is not simply a respiratory disease but rather a systemic illness, vascular effects of RAAS inhibitors, particularly on endothelial cells and on coagulation, may contribute to their protective effects."

"But we do not have the corresponding evidence yet," cautioned Dr. Barton, who also was not involved in the new study. "Again, robust prospective clinical trials are needed to answer such questions."

Dr. Duong did not respond to a request for comments.

SOURCE: https://bit.ly/311F69h Journal of Infectious Diseases, online July 23, 2020.