6 minute read
CARDIOLOGY
Untreated hypertension + Covid-19 = increased risk of mortality
Since the outbreak of the Covid-19 pandemic globally, concerns have been raised about the possibility that renin–angiotensin–aldosterone system (RAAS) blockers could predispose individuals to severe Covid-19. 1,2 Some studies show that patients treated with RAAS inhibitors have a lower risk of mortality compared to those treated with non-RAAS inhibitors
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However, several subsequent studies found that RAAS inhibitors, which include angiotensin-converting enzyme inhibitors (ACEi), angiotensin-receptor blockers (ARBs) and direct renin inhibitors, are in fact not associated with an increased risk of infection, nor with an increased risk of severe disease, or in-hospital death among patients with Covid-19. 1,2
In fact, some studies show that patients treated with RAAS inhibitors have a lower risk of mortality compared to those treated with non-RAAS inhibitors (eg beta blockers, calcium channel blockers [CCBs]and diuretics). 1,2
Reviews published the prestigious journals the New England Journal of Medicine, Lancet, Journal of the American Medical Association (JAMA) Cardiology and Nature, all concur that there is no link between treatment with antihypertensive drugs (including ACEi inhibitors and ARBs) was not associated with either a higher likelihood of infection or a higher risk of severe Covid-19 or morbidity. 1
An Italian study (n=6272) showed that although the use of ACEi and ARBs was more frequent among patients with Covid-19 than among control individuals (n=30 759), there was no association between these drug classes and an increased risk of infection or the severity of the disease. 1
Two American studies also showed that previous treatment with antihypertensive drugs (including ACEi and ARBs) was not
associated with either a higher likelihood of infection or a higher risk of severe Covid-19. And finally, a Spanish study showed that the use of RAAS inhibitors was not associated with a higher risk of Covid-19 requiring hospital admission compared with the use of other antihypertensive drugs. Fernadez-Ruiz pointed out that in this study, patients with diabetes who were treated with RAAS inhibitors in fact had a lower risk of Covid-19 requiring hospital admission. 1
Risk factors
In a study published in the June issue of the Gao et al also found that hypertensive patients with Covid-19 have a two-fold increase in the relative risk of mortality compared to those who do not have hypertension (4.0% vs. 1.1%). 2
One of the studies Fernandes-Ruiz used to base her review on, found that age >65 years, coronary artery disease, congestive heart failure (HF), cardiac arrhythmia, chronic obstructive pulmonary disease and current smoking were independently associated with an increased risk of in-hospital death. 1
Gao et al also explore the potential risk factors for mortality, they performed a multivariable Cox regression analysis with backwards-stepwise selection to identify the predictors of mortality.
A total of seven variables were identified, namely fatigue, age, hypertension, myocardial infarction, renal failure (RF), respiratory rate and chronic HF. ACEIs and ARBs are widely used for treating hypertension and RF or HF. 2
Data compiled by the Western Cape government and released on 9 June 2020 showed that 65% of patients who died following Covid-19 infection had one or more comorbidity. Diabetes and hypertension topped the list. In the age groups 50-59, diabetes, and in people >60, hypertension, were the main comorbidities associated with mortality. 4
Gao et al found that hypertensive patients who did not receive treatment had a significantly higher risk of mortality compared to those on treatment (7.9% vs 3.2%), underlining the importance of continuing treatment. 2
The aim of their study was to test the hypothesis that treatment of hypertension, especially with RAAS inhibitors, might have an impact on the mortality of patients with Covid-19. 2 The primary endpoint was all-cause mortality during hospitalisation. Other endpoints included the time elapsed between onset of symptoms and discharge, the rates of use of invasive mechanical ventilation, and the severity of Covid-19. 2
Covid-19 severity was categorised as mild (non-pneumonia and mild pneumonia cases), severe (dyspnoea, respiratory frequency ≥30/ min, blood oxygen saturation ≤93%, PaO 2 /FiO 2 ratio <300, and/or lung infiltrates >50% within 24–48 hours), or critical (respiratory failure requiring mechanic ventilation, septic shock and/or multiple organ dysfunction/failure). 2
The data of 2877 patients were analysed. Of this number, 29.5% had a confirmed medical history of hypertension and 83.5% were on antihypertensive treatment. When compared with patients without hypertension (<140/90mmHg), those with hypertension were older, more often had a prior history of diabetes, angina, stroke, renal failure or previous revascularisation and were receiving more medication for diabetes and hypertension. 2
The antihypertensive regimens were in principle unchanged during hospitalisation. Discontinuation or alteration of the antihypertensive treatment during hospitalisation was at the physician’s discretion. Those who required antihypertensive medication during hospitalisation with no prior prescription, or those who had discontinued the medications prior to admission, were treated with calcium channel blockers (CCBs) or diuretics. 2
The cohorts of without antihypertensive and with antihypertensive treatments, as well as the cohorts of RAAS inhibitors (ACEi/ARBs) and non-RAAS inhibitors, were stratified at the time of their admission and according to their preadmission medications. 2
A total of 25.7% patients were treated with RAAS inhibitors, 74.2% treated with nonRAAS inhibitors. Compared with those treated with non-RAAS inhibitors, RAAS inhibitors were associated with a lower risk of mortality (3.6% vs 2.2%).The time from symptom onset to discharge, the severity of the Covid-19, and percentage of ventilation were all similar between the two cohorts. 2
They concluded that while hypertension and the discontinuation of antihypertensive treatment may be related to increased risk of mortality, they detected no harm associated with RAAS inhibitors in patients infected with Covid-19. 2
The 2020 International Society of Hypertension guideline defines hypertension as systolic blood pressure (SBP) in the office or clinic is ≥140mmHg and/or their diastolic blood pressure (DBP) is ≥90mmHg following repeated examination. 5
In a strongly worded consensus statement, the Council on Hypertension of the European Society of Cardiology (ESC) blamed ‘social media-related amplification’ of a possible link between the use of RAAS inhibitors and the risk of Covid-19 infection, severity and mortality. In some cases, these reports prompted both clinicians and patients to stop prescribing and taking their ACEi or ARB medication. 3
“This speculation about the safety of ACEi or ARB treatment in relation to Covid-19 does not have a sound scientific basis or evidence to support it. Indeed, there is evidence from studies in animals suggesting that these medications might be rather protective against serious lung complications in patients with Covid-19 infection, but to date there is no data in humans.” 3
The ESC Council on Hypertension strongly recommend that physicians and patients should continue treatment with their usual anti-hypertensive therapy because there is no clinical or scientific evidence to suggest that treatment with ACEi or ARBs should be discontinued because of the Covid-19 infection. 3
The World Hypertension League also strongly urged that hypertensive patients with Covid-19 should continue taking their antihypertensive medications as recommended by their clinicians. 6
Furthermore, they recommend that if possible, patients should monitor their BP at home. Patients should be advised that if their BP is lower or higher than usual, they should not change or stop taking their medication without consulting their clinicians. Other nonmedication causes (eg dehydration) might be the culprit and warrant investigation.
References
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6. Fernandez-Ruiz. RAAS inhibitors do not increase
the risk of COVID-19. Nature Reviews Cardiology,
2020.
Gao C, Cai Y, Zhang K et al. Association of hypertension and antihypertensive treatment with COVID-19 mortality: a retrospective observational study. European Heart Journal, 2020. De Simone G. Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers. https://www.escardio.org/ Councils/Council-on-Hypertension-(CHT)/ News/position-statement-of-the-esc-council-onhypertension-on-ace-inhibitors-and-ang. Western Cape government. Covid-19: Diabetes, hypertension and HIV – what Western Cape’s death data shows. https://www.news24.com/news24/ southafrica/news/infographics-covid-19-diabeteshypertension-and-hiv-what-western-capes-deathsdata-shows-by-age-20200609. Unger T, Borghi C, Charchar F et al. 2020 International Society of Hypertension Global Hypertension Practice Guidelines. Hypertension,
2020.
World Hypertension League. Covid-19 hypertension guidance. https://www.whleague.org/index. php/2014-07-09-22-47-11/covid-19-hypertensionguidance. SF
