Pooled data from more than 50 studies suggest that taking ACE-inhibitors and angiotensin receptor blockers (ARBs) has not led to worse outcomes in patients with Covid-19 and may be beneficial.
The systematic review and meta-analysis involving more than 100,000 patients suggested a protective benefit in patients who remained on the heart drugs while battling Covid-19, especially among patients taking the drugs for high blood pressure.
Compared to patients with hypertension who did not take the drugs, those who did had a significantly lower risk of death and severe adverse events.
The findings, published online March 31 in JAMA Network Open, are consistent with those of an earlier meta-analysis involving roughly 29,000 patients, and they extend the data to include patients with multiple comorbidities.
Early in the Covid-19 pandemic it was suggested that taking ACE-inhibitors, ARBs and other renin-angiotensin-aldosterone system (RAAS) inhibitors, may be contraindicated in patients with Covid-19, based on the observation that angiotensin-converting enzyme 2 acts as a binding site for the virus to gain entry into the cells, wrote researcher Vassilios Vassiliou, PhD, of the University of East Anglia, Norwich, United Kingdom, and colleagues.
Several observational studies have since evaluated the association of ACE inhibitors and ARBs with clinical outcomes in patients with Covid-19.
“Although a few studies have reported an increased risk of severe disease, most have found no association or even beneficial associations with the receipt of these drugs,” the researchers wrote.
They noted that since the publication of the earlier meta-analysis, additional studies have expanded the data, “allowing increased statistical power to further investigate specific subgroups.”
“Given the increasing number of Covid-19 cases and an evolving second wave of infections, it is important to summarize the data thus far to provide an updated perspective and an understanding of the association between ACEIs/ARBs and clinical Covid-19 outcomes,” they wrote.
Their meta-analysis identified 52 eligible studies (40 cohort studies, 6 case series, 4 case-control studies, 1 randomized clinical trial and 1 cross sectional study) with a total of 101,949 patients, including 26,545 (26%) taking ACE inhibitors or ARBs.
Most of the studies were conducted in China or Europe, with 5 studies conducted in the United States. Two of the studies included a subgroup of patients taking ACE inhibitors and/or ARBs that were explicitly discontinued at the time of hospital admission.
Among 11,696 patients with confirmed hypertension, 4,813 (41.2%) were taking ACE-inhibitors and/or ARBs.
A total of 41 studies (69,577 participants) that compared mortality rates of patients receiving vs not receiving ACEIs/ARBs were included in the meta-analysis.
Overall, the results of the pooled unadjusted meta-analysis indicated no increases in the risk of death among those who received ACEIs/ARBs (unadjusted OR, 1.05; 95% CI, 0.86-1.29; P=0.61; I2=85.0%) compared with those who did not.
Subgroup analysis revealed significant reductions in mortality among patients in the hypertension subgroup who were receiving ACEIs/ARBs (unadjusted OR, 0.66; 95% CI, 0.49-0.91; P=0.01).
The mixed subgroup comprising patients with multiple comorbidities indicated significant increases in mortality among those receiving ACEIs/ARBs (unadjusted OR, 1.46; 95% CI, 1.15-1.85; P=0.002), however, a pooled analysis of 17 studies (17,392 total participants) using an adjusted analysis of mortality found reductions in the risk of death among patients receiving vs not receiving ACEIs/ ARBs (adjusted OR [aOR], 0.57; 95% CI, 0.43-0.76; P<0.001; I2=54.0%).
A significant decrease in the risk of death was observed in both subgroups (for the hypertension subgroup, aOR, 0.51 [95 % CI, 0.32-0.84]; P=0.008; for the mixed subgroup, aOR, 0.64 [95% CI, 0.46-0.88]; P=0.006).
A total of 23 studies (23,129 total participants) reported an adjusted risk of severe adverse events associated with the receipt of ACEIs/ARBs in a COVID-19 cohort. A significant decrease in severe adverse events was found in patients who received ACEIs/ARBs compared with those who did not (aOR, 0.68; 95% CI, 0.53-0.88; P=0.003; I2=67.0%)
This reduced risk remained significant among the hypertension subgroup in 12 studies (aOR, 0.55; 95% CI, 0.36-0.85; P=0.007), however, in the mixed subgroup, the decreased risk was not statistically significant (OR, 0.79; 95% CI, 0.59-1.07; P=0.12).
Vassiliou and colleagues noted that the potential mechanisms associated with possible beneficial consequences of ACE inhibitors and ARBs are unknown.
“Our results suggest that these benefits are not solely associated with better blood pressure control, as patients receiving anti-hypertensive medications that were not ACE inhibitors/ARBs had comparably inferior clinical outcomes in the adjusted subgroup analysis.”
-
Pooled data from more than 50 studies suggest that taking ACE-inhibitors and angiotensin receptor blockers has not led to worse outcomes in patients with Covid-19 and may be beneficial.
-
The systematic review and meta-analysis involving more than 100,000 patients suggested a protective benefit in patients who remained on the heart drugs while battling Covid-19, especially among patients taking the drugs for high blood pressure.
Salynn Boyles, Contributing Writer, BreakingMED™
Vassiliou reported receiving grants from the Norfolk Heart Trust and personal fees from Daiichi Sankyo and Novartis outside the submitted work. No other disclosures were reported.
Cat ID: 190
Topic ID: 79,190,730,933,914,190,926,192,927,151,928,925,934
