Hypertension
Corey Diamond, PharmD
Researchers of a recently published retrospective cohort analysis published in the February 2022 issue of The Journal of Clinical Hypertension looked at hypertensive urgency patients at several teaching hospitals within their health system. Perhaps surprisingly, their results suggest that treatment of end organ damage (i.e., hypertensive urgency)—when developed during an admission—in addition to intravenous antihypertensive medication may be more deleterious than oral antihypertensive medication or no treatment at all.
Results
In their retrospective cohort analysis, Ghazi and colleagues from Yale New Haven Health System looked at inpatient blood pressure (BP) measurements and antihypertensive medication administrations from 2016 to 2020 in over 300,000 patients in the health system with a length of stay of two to thirty days. The researchers defined severe hypertension as the first documented BP elevation of systolic BP (SBP) > 180 mm Hg or diastolic BP (DBP) > 110 mm Hg being reported after admission. Severe hypertension events resolving within an hour of the index event were excluded.
The researchers defined antihypertensive treatment as receiving any oral or I.V. antihypertensive medication class (angiotensin converting enzyme inhibitors/angiotensin receptor blockers, calcium channel blockers, beta blockers, diuretics, renin inhibitors, and vasodilators) within 6 hours of developing severe hypertension.
The primary outcome investigated was a mean arterial pressure (MAP) drop of ≥ 30% within 6 hours of a severe hypertension record. Of the over 20,000 severe hypertension events identified, the analysis compared the frequency of the primary outcome with respect to 3 different exposure comparisons: treatment with I.V. antihypertensives versus untreated, treatment with oral antihypertensives versus untreated, and treatment with I.V. antihypertensives versus oral antihypertensives.
After adjusting for a wide range of confounders, the analysis revealed that, overall, severe hypertension treatment with antihypertensive medication in general resulted in a statistically significant 11% relative lower rate of a > 30% MAP drop within 6 hours of the index event. Counter to this result, however, is that when restricting the analysis to patients treated with I.V. antihypertensives only there was a statistically significant increase in rates of a > 30% MAP drop in BP by 38%.
This result was also observed when comparing I.V. antihypertensive treatment to oral antihypertensive treatment, with a greater 100% relative rate increase of a ≥ 30% MAP reduction of the former over the latter.
Are aggressive reductions bad?
Patients presenting to the hospital with SBP/DBP greater than 180/110 mm Hg with acute end organ damage need to be treated quickly in the intensive care environment in order to prevent substantial morbidity and mortality. However, treatment guidance becomes murky if there is no evidence of end organ damage (also known as hypertensive urgency). This condition has not been associated with any negative short-term outcomes and it is often treated in the ambulatory setting; thus, there is very scarce information known about hypertensive urgency when it develops in the inpatient setting, let alone strong recommendations for its management.
The authors were interested in the rate of a > 30% reduction in MAP within 6 hours of the index severe hypertension event because current guidance on a very similar condition, hypertensive emergencies (i.e., elevations of BP > 180/110 mm Hg with evidence of end organ damage) recommend decreasing MAP 10% to 20% within the first hour, followed by an additional 55% to 15% over the next 23 hours.
This recommendation is intended to prevent ischemic damage and conserve cerebral perfusion. Thus, the authors believed a more than 30% drop in BP within 6 hours would, likewise, represent a negative surrogate outcome.
Evidence continues to grow that excessive antihypertensive treatment in hospitalized patients may not always be appropriate. A recent study by the Cleveland Clinic, published in JAMA Internal Medicine in March 2020, suggested that excessive BP reduction in inpatients with acute hypertension and no signs of end organ damage was associated with increased composite risk of acute kidney injury, myocardial injury, and stroke.
Implications
In this study, antihypertensive treatment in the inpatient setting with the exception of I.V. antihypertensive therapy resulted in lower rates of intense MAP drops within 6 hours compared to no treatment. However, the mechanism of this—if one exists—remains unclear.
“Even though there is no substantive evidence that antihypertensive medications improve outcomes of hospitalized patients who develop [hypertension], physicians believe it is important,” stated the authors.
The study suggests that oral antihypertensives may be a good compromise to inpatient hypertension urgency treatment by reducing BP more rapidly than no treatment, but not rapid enough to cause possible excess morbidity. However, this hypothesis would still need to be confirmed. ■