Intensive/guideline-directed BP-lowering after ischaemic stroke yield similar functional outcomes
Among patients with a recent acute ischaemic stroke treated with thrombolytic therapy, intensive blood pressure (BP)-lowering conferred no additional benefit in functional recovery compared with guideline-recommended BP-lowering, despite a reduced risk of intracranial haemorrhage with intensive therapy, according to results of the ENCHANTED* trial.
“In lysis-eligible patients with acute ischaemic stroke, more intensive BP-lowering [<140 mm Hg target] was not shown to be superior to guideline-recommended BP-lowering [<180 mm Hg] for the primary disability outcome,” said study author Professor Craig Anderson from The George Institute for Global Health, University of New South Wales, Sydney, Australia. However, there was evidence to support a lower risk of intracranial haemorrhage in patients who received intensive therapy, he added.
The multinational (110 sites in 15 countries), open-label trial involved adults with BP <185 mm Hg (mean age 66.9 years, 38 percent female, 73.7 percent Asian, mean systolic BP pre-treatment 165.3 mm Hg) who had experienced a mild-to-moderate acute ischaemic stroke <6 hours prior. They were randomized (median time between stroke and randomization, 3.3 hours) to receive intensive (target systolic BP 130–140 mm Hg within 1 hour of randomization; n=1,081) or guideline-recommended BP-lowering therapy (target systolic BP <180 mm Hg; n=1,115) over a 72-hour period following treatment with intravenous alteplase.
Over 24 hours, mean systolic BP was significantly lower among patients who received intensive vs guideline-recommended therapy (144.3 vs 149.8 mm Hg; p<0.0001).
Functional outcome at 90 days, measured by change in modified Rankin scale (mRS) score, was comparable between patients who received intensive or guideline-recommended therapy (odds ratio [OR], 1.01, 95 percent confidence interval [CI], 0.87–1.17; p=0.8702). [ISC 2019, abstract LB6; Lancet 2019;doi:10.1016/S0140-6736(19)30038-8]
The incidence of death or disability at 90 days (mRS score 2–6) was also similar between patients who received intensive or guideline-recommended therapy (OR, 0.94, 95 percent CI, 0.78–1.14; p=0.5508).
Incidence of intracranial haemorrhage was lower among patients who received intensive vs guideline-recommended therapy (14.8 percent vs 18.7 percent, OR, 0.75, 95 percent CI, 0.60–0.94; p=0.0137). While incidence of serious adverse events (AEs) was comparable between groups (19.4 percent vs 22.0 percent, OR, 0.86, 95 percent CI, 0.70–1.05; p=0.1412), patients on intensive therapy had fewer incidences of intracranial haemorrhage (6.1 percent vs 9.4 percent, OR, 0.63; p=0.0040) and intracerebral haemorrhage (5.5 percent vs 9.0 percent, OR, 0.59; p=0.0017) as serious AEs compared with those on guideline-recommended therapy.
“[T]he results indicate that intensive BP-lowering is safe in this patient group, with significantly decreased incidence of intracranial haemorrhage compared with that of the guideline group,” said the researchers.
However, there is no evidence to support a major change in the guidelines with uncertainty remaining regarding optimal BP levels and approaches for BP control, said Anderson. Further research is needed to identify why the reduced risk of intracerebral haemorrhage did not translate into improved recovery, he added.
One potential reason was that the 130–140 mm Hg target in the intensive therapy group may have been too low and as such, led to hypoperfusion and subsequently, “neutralizing favourable outcomes resulting from reduced intracranial haemorrhage”, suggested Dr Else Charlotte Sandset from Oslo University Hospital, Oslo, Norway, and Professor Urs Fischer from University Hospital Bern, Bern, Switzerland, in an editorial. [Lancet 2019;doi:10.1016/S0140-6736(19)30196-5]
Another reason for the neutral results could have been the “broad inclusion criteria”, they said, highlighting the need for individualized treatment strategies in this setting.