SPS3: Systolic BP <130 beneficial in lacunar stroke

June 05, 2013

London, UK - Lowering systolic blood pressure to <130 mm Hg in patients with recent lacunar stroke is likely to be beneficial, results from the Secondary Prevention of Small Subcortical Strokes (SPS3) trial show [1].

Although the primary end point was not quite significant, it did suggest a reduction in stroke in the lower-BP group. In addition, the secondary end point of hemorrhagic stroke was significantly reduced.

"Our results are consistent with previous trials of blood-pressure lowering after stroke and support a treatment target of less than 130 mm Hg systolic for most patients with recent lacunar stroke," commented lead investigator Dr Oscar R Benaven te (University of British Columbia, Vancouver).

Their findings were presented here at the European Stroke Conference 2013 on May 29, 2013 and published simultaneously online in the Lancet. Preliminary results of the blood-pressure-lowering arm of SPS3 were presented earlier this year at the International Stroke Conference 2013 in February and reported at that time.

A second arm of the trial, published previously in the New England Journal of Medicine, looked at antiplatelet regimens and showed no benefit from combined aspirin and clopidogrel over aspirin alone in this same population [2].

Blood-pressure targets

In the trial, 3020 patients with a lacunar stroke within the previous 180 days were randomized to two systolic blood-pressure targets—130-149 mm Hg (higher group) or <130 mm Hg (lower group). Antihypertensive medication was chosen by the individual local study physician.

After one year, mean blood pressures were 138 mm Hg in the higher group and 127 mm Hg in the lower group, and this 11-mm-Hg difference was maintained throughout the 3.7 years of follow-up. Patients in the lower-target group used an average of 2.4 antihypertensive medications vs 1.8 in the higher-target group.

The primary end point, all recurrent stroke, was nonsignificantly reduced, as was disabling or fatal stroke. And intracerebral hemorrhage was significantly reduced by about two-thirds.

SPS-3: Key results

End point
Higher BP , n=1519 (% per p a t ient- year)
Lower BP , n=1501 (% per p a t ient- year)
Hazard ratio (95% CI)
p
All s t roke
2.77
2.25
0.81(0.64-1.03)
0.08
Ischemic s troke
2.4
2.0
0.84
(0.66-1.09)
0.19
Intracerebral h emorrhag e
0.29
0.11
0.37
(0.15-0.95)
0.03
Fatal or disabling s troke
0.89
0.72
0.81 (0.53-1.23)
0.32

Benavente said the benefits were consistent across major subgroups, including patients with diabetes and Hispanic patients, and were seen irrespective of blood pressure at study entry.

In terms of adverse events, there was a suggestion of a higher incidence of orthostatic syncope, which occurred in five patients in the higher-BP group vs 11 patients in the lower-BP group.

During the discussion of the trial at the conference, a member of the audience noted that the average age of patients in SPS3 was 63, which was "quite young," and that the number needed to treat to prevent one stroke was about 200. He asked whether the benefit would also apply to the elderly, who would have a risk higher than one in 200 of falling or syncope from hypotension.

Benavente replied that they were looking at this now and so far had not seen any reduction in tolerance in the older patients.

In the Lancet paper, the SPS3 investigators note that on the basis of previous studies, an 11-mm-Hg reduction in blood pressure should have resulted in about a 30% reduction in recurrent stroke, more than the 19% seen here. They say this may be due to chance or the specific population of patients assessed.

They point out that the PROGRESS trial found a 28% reduction in stroke by lowering blood pressure, but the mean achieved systolic blood pressure at the end of this study was 138 mm Hg, whereas in SPS3 they got down to 127 mm Hg.

Result "likely to be real"

In an associated comment [3], Dr Graeme J Hankey (University of Western Australia, Perth), who was also the cochair of the session at which SPS3 was presented, suggests that the association between systolic blood pressure and stroke risk might be weaker as lower systolic pressures are achieved.

 
C linicians should endeavo r to achieve and maintain systolic blood pressures lower than 130 mm Hg in patients who have survived two wee ks or more after subcortical lacunar ischemic stroke.
 

But he also points out that the 63% reduction in hemorrhagic stroke with the 11-mm-Hg BP difference in SPS3 is consistent with the 50% reduction in hemorrhagic stroke with the 9-mm-Hg BP difference in PROGRESS.

Hankey says that when the SPS3 results are viewed in the context of other evidence for lowering of blood pressure in individuals with previous stroke, the 19% rate reduction for all recurrent stroke "seems likely to be real rather than a chance observation." He believes the failure to reach significance was probably because the trial was underpowered due to a rate of recurrent stroke that was actually half of what was anticipated. But he also notes that the trial was also underpowered with regard to hypotensive adverse effects.

With this in mind, he concludes that "clinicians should endeavor to achieve and maintain systolic blood pressures lower than 130 mm Hg in patients who have survived two weeks or more after subcortical lacunar ischemic stroke" but that blood pressure should be lowered gradually and cautiously, in view of the potential for serious complications related to hypotension.

The study was supported by the US National Institutes of Health-National Institute o f Neurological Disorders and Stroke (NIH-NINDS).The authors declare no conflicts of interest.

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