Recent studies about COVID-19 patients have reported that hypertension is associated with higher in-hospital complications and mortality. Also, worse results in angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) were hypothesized. There was uncertainty about initial clinical studies solidity. Most of cardiologic societies around the world, advise to continue ACEI and ARBs treatment, according to guidelines recommendations and proposed further clinical studies to assess safety in antihypertensive drugs use.
The use of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) is a major concern for clinicians treating coronavirus disease 2019 (COVID-19) in patients with hypertension. Comorbidities, drug safety, in-hospital mortality, and high-risk predictors in cardiovascular patients with COVID-19 were evaluated in two clinical studies.
Zhang et al, on 17 Apr 2020, ahead to print published in Circulation Research https://doi.org/10.1161/CIRCRESAHA.120.317134 an association between in-hospital use of ACEI/ARB and all-cause mortality in COVID-19 patients with hypertension.
A retrospective study, in nine hospitals in Hubei, China, from December 2019 to February 2020. They included 1128 adult hypertensive patients with COVID-19. Authors analyzed two groups: A taking ACEI/ARB (188 patients) group and 940 without treatment (non-ACEI/ARB group). Clinical characteristics were similar in both groups, but the non-ACEI/ARB group had higher prevalence of fever, dyspnea, and bilateral lung lesion at presentation. Unadjusted mortality rate was lower in the ACEI/ARB group versus the non- ACEI/ARB group (3.7% vs. 9.8%; P = 0.01). All- cause mortality risk was observed in age, gender, coronary heart disease and cerebrovascular disease.
In-hospital use of ACEI/ARB was associated with lower risk of all-cause mortality (adjusted HR, 0.29; 95%CI, 0.12-0.69; P = 0.005) due to COVID-19. After adjusting for age, gender, comorbidities, and in-hospital medications, risk for all-cause mortality was lower in the ACEI/ARB group
Mehra et al published in NEJM.org.DOI:10.1056/NEJMoa2007621, (May 1th, 2020) an observational study in 8,910 COVID-19 patients from 169 hospitals in Asia, Europe, and North America, between December 2019, and March 2020. They contrasted cardiovascular disease and drug therapy history with in-hospital mortality.
In this collaborative database, investigators described that in-hospital global mortality was 5.8%, factors associated with an increased mortality were: age greater than 65 years (10.0%, vs. 4.9%;) coronary artery disease (10.2%, vs. 5.2%)¸ heart failure (15.3%, vs. 5.6%); cardiac arrhythmia (11.5%, vs. 5.6%); chronic obstructive pulmonary disease (14.2%, vs. 5.6%).
No increased risk of in-hospital death was found to be associated with use of ACEI (2.1% vs. 6.1%); ARBs (6.8% vs. 5.7%) and female gender (5.0% vs 6.35)
As clinical data progresses, we can have a better guidance to address these research questions.
Both prospective and consecutive clinical studies revised had non comparable populations, but in common, the pair evaluate mortality, risks of the history of comorbidities and cardiovascular treatment. The impact on hypertensive patients and the use of ACEI/ARB was described by Zhang et al, instead comparisons based on survivors and non survivors were analyzed by Mehra et al.
In my consideration, both clinical studies are complementary because safety of antihypertensive drugs were analyzed, and high risk in cardiovascular history with COVID-19 patients was determined.
What do we learn from these studies?
- Beneficial effects observed with continued use of ACEI/ARB therapy.
- ACEI/ARB was associated with lower risk of all-cause mortality.
- Elderly, heart failure and coronary artery disease have high risk.
- Both are retrospective and consecutive studies.
- Antihypertensive drugs were not controlled.
- They could be biased by residual confounders.
- Studies were evaluated at different time periods.
Instituto Nacional de Cardiología