Drilling Down into ACCORD Yields Slim Stroke Results
A closer look at the stroke reduction observed in the ACCORD blood pressure trial revealed subgroups for which intensive treatment may be beneficial, although it is too early to draw firm conclusions, a researcher reported here.
As reported in March by William Cushman, MD, of the Memphis VA Medical Center, patients with type 2 diabetes who were treated aggressively to a target systolic blood pressure of less than 120 mm Hg did not have a significant reduction in composite cardiovascular events compared with standard treatment to below 140 mm Hg.
Serious adverse events were more frequent in the intensive group (3.3% versus 1.3%, P<0.0001).
But one of the secondary endpoints, total stroke, was significantly reduced by intensive lowering of blood pressure (HR 0.59, 95% CI 0.39 to 0.89). The number needed to treat to prevent one stroke over five years was 89.
At the American Society of Hypertension meeting here, Cushman noted that some researchers have attributed the stroke reduction to chance, considering the low number of strokes during the trial – 36 in the intensive group and 62 in the standard group.
“Most of us, probably, in hypertension feel that, no, it’s probably real,” Cushman said. “Then the issue is how do you decide how to apply that.”
Franz Messerli, MD, director of the hypertension program at St. Luke’s-Roosevelt Hospital Center in New York City, agreed that the stroke finding was probably real.
“We know that stroke is the most blood pressure-dependent risk factor,” said Messerli, an ASH officer. “So, therefore, it has to be expected, if anything would show, then you would have a stroke reduction. And indeed there is a 41% reduction in the stroke rate by lowering blood pressure more. So I think this is extremely important.”
Cushman and his colleagues looked at stroke rates among the predefined subgroups in the 4,733-patient blood pressure portion of the trial – by age, gender, ethnicity, cardiovascular disease history, intensity of glycemia management, hemoglobin A1c levels, and baseline systolic blood pressure.
In general, Cushman said, groups that would be expected to have higher stroke rates – black patients, older patients, and those with a history of cardiovascular disease – did, in fact, have elevated rates.
The interaction between subgroup and either intensive or standard blood pressure lowering was statistically significant only for baseline hemoglobin A1c (P=0.008).
Patients with a baseline level of less than 8.1% had a significant reduction in risk with intensive treatment (HR 0.20, P=0.001), whereas those with higher hemoglobin A1c values did not (P=0.55).
The interaction with the intensity of glycemia treatment was not significant (P=0.24), although there was a significant reduction in stroke rates for patients in the standard target group (7% to 7.9%) (HR 0.47, P=0.01) but not in those in the intensive (less than 6%) glycemia treatment group.
“Among diabetics, those with easier to control disease and perhaps those treated less intensively may benefit more from intensive blood pressure reduction, but we really can’t conclude much on that right now,” said Cushman, who noted that there is a forthcoming paper that will look at these interactions.
Among some of the other subgroups, there were hints at benefits in some patients – those older than 65, women, and those with a baseline diastolic pressure less than 72 – and not in others, but none of the interactions were statistically significant.
Cushman stressed the need for further study before concluding that any of these subgroups would benefit from an aggressive treatment strategy to lower systolic blood pressure to less than 120 mm Hg, both because of the small number of strokes overall and because the primary outcome of the study was not met.
“We’re not talking about a large number of strokes here,” he said. “And that’s one of the reasons that we have to be cautious about how to interpret it.”
Although Messerli said the overall stroke reduction was important, he put less weight into the subgroup findings.
“I was not very convinced about these possible interactions or lack thereof,” he said. “Some of it is probably more by chance than anything else.”
When asked if he would consider aggressively lowering blood pressure in any of his diabetic patients, Messerli responded, “If I’m sure the diastolic is not too low and if I’m certain that the patient’s coronaries are relatively okay, yes, I would, but if the patient had manifest coronary artery disease I would be careful.”
Primary source: American Society of Hypertension
Source reference: Cushman W, et al “Effects of intensive blood pressure control on stroke and other cardiovascular events in type 2 diabetes mellitus: the Action to Control Cardiovascular Risk in Diabetes (ACCORD) blood pressure trial” ASH 2010; Abstract LB-OR-09.