SPS3: Systolic BP < 130 Beneficial in Lacunar Stroke

June 04, 2013

LONDON, United Kingdom — Lowering systolic blood pressure to below 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.

Although the primary endpoint was not quite significant, it did suggest a reduction in stroke in the lower blood pressure group. In addition, the secondary endpoint 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 Oscar R. Benavente, MD, University of British Columbia, Vancouver, Canada.

Their findings were presented here at the XXII European Stroke Conference (ESC) on May 29 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 by Medscape Medical News 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.

Blood Pressure Targets

In the trial, 3020 patients with a lacunar stroke within the previous 180 days were randomly assigned to 2 different systolic blood pressure targets: 130 to 149 mmHg (higher group) or below 130 mmHg (lower group). Antihypertensive medication was chosen by the individual local study physician.

After 1 year, mean blood pressures were 138 mmHg in the higher group and 127 mmHg in the lower group, and this 11–mmHg 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 endpoint, all recurrent stroke, was nonsignificantly reduced, as was disabling or fatal stroke. And intracerebral hemorrhagic stroke was significantly reduced by about two thirds.

Table. SPS3: Key Results

Endpoint Higher BP (n = 1519) Lower BP (n = 1501) Hazard Ratio (95% Confidence Interval) P Value
All stroke (% per patient-year) 2.77 2.25 0.81 (0.64 -  1.03) .08
Ischemic stroke (% per patient-year) 2.4 2.0 0.84 (0.66 - 1.09) .19
Intracerebral hemorrhagic stroke (% per patient-year) 0.29 0.11 0.37 (0.15 -  0.95) .03
Fatal or disabling stroke (% per patient-year) 0.89 0.72 0.81 (0.53 -  1.23) .32


Dr. 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 5 patients in the higher blood pressure group vs 11 patients in the lower blood pressure 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 1 stroke was about 200. He asked whether the benefit would also apply to the elderly, who would have a risk higher than 1 in 200 of falling or syncope from hypotension.

Dr. 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 SPS investigators note on the basis of previous studies, an 11-mmHg 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 remind 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 mmHg, whereas in SPS3 they got down to 127 mmHg.

Result "Likely to be Real"

In an associated Comment, Graeme J. Hankey, MD, University of Western Australia, Perth, who was also the co-chair 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.

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

Professor 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 probably occurred because the trial was underpowered due to a rate of recurrent stroke that was actually half that anticipated. But he also notes that the trial was also underpowered with regard to hypotensive adverse effects.

… clinicians should endeavor to achieve and maintain systolic blood pressures lower than 130 mm Hg in patients who have survived 2 weeks or more after subcortical lacunar ischemic stroke … Dr. Graeme J. Hankey

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 2 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 National Institutes of Health/National Institute of Neurological Disorders and Stroke (NIH/NINDS).The authors have disclosed no relevant financial relationships.

Lancet. Published online May 29, 2013. Abstract Comment


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