Does the choice of therapy for primary hypertension in patients with COVID-19 affect the severity of the disease?

Hypertension and COVID-19

Newly published guidelines from the European Society of Cardiology (ESC) indicate that the initial suspicion that hypertension might be an independent risk factor for severe COVID-19 complications or death has not been confirmed. As the authors of the guidelines explain, early observational studies were unable to separate the effects of age and common comorbidities of hypertension – diabetes and obesity, which later emerged as significantly more important risk factors. Nevertheless, proper antihypertensive treatment in patients hospitalized with COVID-19 remains an important tool for reducing mortality and morbidity.

These guidelines recommend following the current procedures of the European Society of Hypertension (ESH) and state that the existing recommendations do not need to be changed in the context of the pandemic. It is important to monitor potassium levels, as more frequent hypokalemia has been observed in patients hospitalized with COVID-19. Moreover, in patients with severe COVID-19, it may be advisable to temporarily discontinue antihypertensive medication if they develop hypotension or acute renal failure.

During the pandemic, some research teams have focused on the benefits and risks of individual antihypertensives (and other drugs) in patients hospitalized with COVID-19 in an effort to optimize the pharmacotherapy of these patients. The following clinical evaluation is an example of such research.

Study Course

In the period from April to June 2020, patients with COVID-19 (confirmed by PCR test) and primary hypertension (systolic blood pressure 130–140 mmHg, diastolic blood pressure 85–90 mmHg) without prior antihypertensive medication or newly diagnosed were enrolled in a monocentric study. Patients were randomized in a 1:1 ratio to at least a 2-week treatment with the AT₁ receptor antagonist for angiotensin II, losartan (25 mg 2× daily), or the calcium channel blocker amlodipine (5 mg/day). The average age of patients treated with losartan (n = 41) and amlodipine (n = 39) was 67.3 ± 14.8 years and 60.1 ± 17.3 years (p = 0.068). If patients required intubation, treatment continued via a nasogastric tube.

Results and Discussion

The administration of losartan and amlodipine significantly reduced blood pressure values. The length of hospitalization was 4.57 ± 2.59 days in the losartan group and 7.30 ± 8.70 days in the amlodipine group (p = 0.085). The length of stay in the intensive care unit (ICU) was 7.13 ± 5.99 days in the losartan group and 7.15 ± 9.95 days in the amlodipine group (p = 0.994). During the 30-day follow-up, there were 2 deaths in the losartan group and 5 in the amlodipine group (p = 0.241).

The differences in the monitored parameters between the groups did not reach statistical significance. However, the number of patients in both arms was relatively small, raising the question of whether the study was sufficiently powered to detect the hypothesized difference between the groups. Generally, larger differences can be detected more reliably in smaller populations, while subtle differences are more likely confirmed in larger populations. The authors did not provide details on sample size estimation or the final number of included patients, stating only that it was low. In addition to the unclear statistical reasoning, it should also be noted that the results were obtained in 2020, and thus for patients infected with a different variant of the SARS-CoV-2 virus than the one currently prevalent in the population.

Conclusion

The presented clinical study did not demonstrate that the length of hospitalization, ICU stay, and mortality of patients with COVID-19 were significantly influenced by the choice of antihypertensive for the treatment of primary hypertension. This aligns with the perspective of current European recommendations.

(eko)

Sources:
1. The Task Force for the management of COVID-19 of the European Society of Cardiology. ESC guidance for the diagnosis and management of cardiovascular disease during the COVID-19 pandemic: part 2 – care pathways, treatment, and follow-up. Eur Heart J 2022 Mar 14; 43 (11): 1059–1103, doi: 10.1093/eurheartj/ehab697..
2. Nouri-Vaskeh M., Kalami N., Zand R. et al. Comparison of losartan and amlodipine effects on the outcomes of patient with COVID-19 and primary hypertension: a randomised clinical trial. Int J Clin Pract 2021; 75 (6): e14124, doi: 10.1111/ijcp.14124.