After Acute Stroke, No Rush to Continue Antihypertensive Therapy

A meta-analysis published in Hypertension¹ compared the effects of continuing prestroke antihypertensive therapy vs pausing prestroke antihypertensive therapy on hospital admission for acute stroke.

Lisa J. Woodhouse, a medical statistician from the University of Nottingham in the United Kingdom, and colleagues identified 2 randomized controlled trials to include in the meta-analysis: COSSACS (Continue or Stop Post-Stroke Antihypertensives Collaborative Study) and ENOS (Efficacy of Nitric Oxide in Stroke trial), which included individual patient data from 2860 patients with ≤48 hours of acute stroke.^2,3

The researchers found no significant association between continuation of prestroke antihypertensive therapy and risk for death, dependency, recurrent stroke, or neurological deterioration at follow-up vs stopping prestroke antihypertensive therapy (odds ratio, 0.96; 95% CI, 0.80-1.14).

There was also no significant association between continuing antihypertensive therapy and recurrent stroke or neurological deterioration, nor was there a significant benefit of continuing antihypertensive treatment in the acute stroke period, indicating that “[t]here is no urgency to administer preexisting antihypertensive therapy in the first few hours or days after stroke…unless indicated for other comorbid conditions.”

They continue, “Analyses for the effect of continuing versus stopping antihypertensives on death or dependency, by our predefined subgroups, including effect by drug class, baseline [blood pressure], and stroke subtype…showed no obvious effect, with the exception of the subgroup randomized within 12 hours of stroke onset, in which continuation (vs stopping) of antihypertensives was significantly associated with risk of worse outcome.”

It is unclear why continuation of antihypertensives was associated with worse outcomes in the subgroup randomized within 12 hours of stroke onset, especially given that previous studies found a benefit to continuing antihypertensives in this and earlier timeframes.^3-5

Some possible explanations include the effect of chance; the penumbral and potentially salvageable tissue may be vulnerable to lower blood pressure after stroke; early continuation of medications may cause aspiration pneumonia in patients who have or develop dysphagia early after stroke; some classes of antihypertensives may provide a beneficial effect, whereas others may provide a detrimental effect; some patients may not regularly take their medication, so suddenly taking it regularly after stroke might cause abrupt and potentially dangerous blood pressure declines; and finally, the effect of antihypertensives may differ depending on premorbid blood pressure levels.

“In the absence of any ongoing or planned studies further examining this question, the main implication for clinical practice is that in the acute stroke period, clinicians should not rush to administer preexisting antihypertensive therapy, unless indicated by other comorbid conditions,” the investigators concluded. “Indeed, a reasonable approach would be to withhold BP-lowering drugs until patients are medically and neurologically stable, and are either able to swallow safely or enteral access via feeding tube has been obtained.”

Limitations

• This analysis is underpowered. Future trials would need to recruit over 10,000 participants to detect a difference between the 2 groups in the primary outcome. Applying these conclusions to all subgroups may therefore not be appropriate.
• Selection bias may have been present in both trials due to their exclusion criteria.
• Residual confounding may have still occurred even though statistical models were adjusted for several covariables.
• Both trials were open label, and performance bias cannot be excluded.
• There are limited data on patients recruited early after stroke onset. This should be a focus of future acute stroke blood pressure research.

References

1. Woodhouse LJ, Manning L, Potter JF, et al. Continuing or temporarily stopping prestroke antihypertensive medication in acute stroke. Hypertension. 2017;69:00-00.  doi:10.1161/HYPERTENSIONAHA.116.07982

2. Robinson TG, Potter JF, Ford GA, Bulpitt CJ, Chernova J, Jagger C, James MA, Knight J, Markus HS, Mistri AK, Poulter NRet al; for the COSSACS Investigators. Effects of antihypertensive treatment after acute stroke in the Continue or Stop Post-Stroke Antihypertensives Collaborative Study (COSSACS): a prospective, randomised, open, blinded-endpoint trial. Lancet Neurol. 2010;9:767–775. doi:10.1016/S1474-4422(10)70163-0

3. The ENOS Trial Investigators. Efficacy of nitric oxide, with or without continuing antihypertensive treatment, for management of high blood pressure in acute stroke (ENOS): a partial-factorial randomised controlled trial. Lancet. 2015;385:617–628.

4. Ankolekar S, Fuller M, Cross I, Renton C, Cox P, Sprigg N, Siriwardena AN, Bath PMet al. Feasibility of an ambulance-based stroke trial, and safety of glyceryl trinitrate in ultra-acute stroke: the rapid intervention with glyceryl trinitrate in Hypertensive Stroke Trial (RIGHT, ISRCTN66434824). Stroke. 2013;44:3120–3128. doi: 10.1161/STROKEAHA.113.001301

5. Anderson CS, Heeley E, Huang Y, et al; for the INTERACT2 Investigators. Rapid blood-pressure lowering in patients with acute intracerebral hemorrhage. N Engl J Med. 2013;368:2355–2365. doi:10.1056/NEJMoa1214609