‘No benefit’ of blood pressure pill for stroke

“A drug used to lower blood pressure could harm patients if given following a stroke,” reported The Daily Telegraph. It said a study of 2,000 stroke patients, who all had high blood pressure, found that the drug did not benefit the patients "and may actually be harmful".

This story is based on a large, well-conducted trial. The blood-pressure-lowering effect of a drug called candesartan was compared to a placebo in patients who had very recently had a stroke (in their first week of recovery). There were no significant differences between the effects of either treatment, and patients were slightly worse off when taking the drug than when taking the placebo.

Candesartan is used to lower blood pressure. High blood pressure is a major risk factor for stroke, and blood pressure commonly rises in the early days after a stroke. The researchers were surprised, therefore, when the drug did not benefit people who had recently had a stroke. It is not yet clear whether only candesartan is of no benefit to stroke patients, or if any blood-pressure-lowering medication will produce similar results. More trials into lowering blood pressure in the very early days after a stroke are clearly needed. The researchers say that until such trials take place, they “see no place for routine blood pressure lowering” in the period immediately after a stroke.

People who take candesartan for other reasons, for example to control blood pressure, should continue to do so.

Where did the story come from?

The study was carried out by researchers from several institutions across Europe. Funding was provided by the South-East Norway Regional Health Authority, Ulleval University Hospital in Oslo and the pharmaceutical companies AstraZeneca and Takeda. AstraZeneca manufactures candesartan, the drug studied here. The authors report that the manufacturer’s representatives had no role in data collection, analysis or write-up of the report or the decision to submit it for publication. The study was published in the peer-reviewed medical journal The Lancet.

The Daily Telegraph did not mention the fact that this study only applies to people in hospital within days of having had a stroke and that the drug has been proven as safe for other uses.

What kind of research was this?

This randomised controlled trial assessed the use of candesartan, an angiotensin-receptor blocker (ARB), in people who had just had a stroke and who had high blood pressure. A randomised controlled trial is the most robust and accepted way of determining the effectiveness of a treatment in a single study.

High blood pressure is not only one of the major risk factors/causes of stroke, but blood pressure also commonly rises in the early days after a stroke. However, the researchers say the best way of treating high blood pressure in this situation is unknown and current practice is not to treat it.

In this study, the researchers wanted to know the drug’s effect on a combined outcome that included death from vascular causes (related to the blood vessels), non-fatal heart attack or non-fatal stroke. Patients were treated for seven days after their stroke and were followed up for six months. The researchers also assessed the drug’s effects on a number of other outcomes, including death from all causes, risk of stroke, risk of heart attack, activities of daily living (normal everyday tasks) and neurological status (brain function) at day seven.

What did the research involve?

This placebo-controlled trial compared candesartan with no treatment. Stroke patients were recruited from a range of centres across Northern Europe. To be applicable, participants had to have a clinical diagnosis of stroke, have been to hospital within 30 hours of the onset of their symptoms, have systolic blood pressure higher than 140mmHg and be over 18 years of age. Patients were excluded from the trial if they had previously been treated with an ARB, had reduced consciousness or the doctor thought they needed to be given ARB treatment. Patients were also excluded if the doctors felt they urgently needed treatment to reduce their blood pressure.

The patients were randomly allocated to receive either candesartan or placebo. Those in the treatment group received escalating doses of the ARB according to a fixed schedule over the following week. At the same time, the placebo group received an identical tablet.

Blood pressure was assessed in both groups every morning and the dose of treatment was adjusted if blood pressure was returning to normal. All participants also received standard stroke treatment and any other medications they would have taken if they had not been in the study. Patients were followed up for a further six months, and visited the clinic on day seven and at one and six months. A telephone or postal interview was carried out at the third month.

What were the basic results?

The participants were on average 71 years old, and most of them had symptoms for 18 hours before being entered into the study. Average blood pressure was 171/90mmHg. Most of the patients had had an ischaemic stroke (85%), which occurs when the blood supply to a part of the brain is blocked by a blood clot.

Overall, blood pressure fell in both groups during treatment, but more so in the candesartan group than in the placebo group, with a 5mmHg difference in systolic blood pressure at day seven. After six months, this difference between the effects of the treatments was no longer significant. There was no difference between groups in the combined outcomes of vascular death, stroke or heart attack.

When the researchers measured brain function and the ability to do everyday tasks, there was a borderline significant increase in the risk of a poorer outcome with candesartan. They also note that for a number of other outcomes, the placebo had a small, non-significant benefit.

How did the researchers interpret the results?

While most of the comparisons between candesartan and placebo in this patient group were not significant, overall the results seemed to favour the placebo and demonstrated a slight increase in risk of negative outcomes with candesartan. The researchers say, “taken together, these findings might suggest that blood-pressure-lowering treatment in acute stroke confers risk”.

Conclusion

This well-conducted randomised controlled trial suggests that candesartan, a drug for lowering blood pressure, has no benefit for people who have recently had a stroke. The researchers note that further studies will help clarify whether this finding can be applied to the wider population or whether there are subgroups of stroke patients who might benefit from this treatment.

High blood pressure is a major risk factor for stroke, and blood pressure commonly rises in the early days after a stroke. As such, the researchers were surprised when the drug did not benefit people who had recently had a stroke. More trials into lowering blood pressure in the very early days after a stroke are clearly needed. As yet, it isn’t clear whether the results were due to the specific effects of candesartan or if any blood-pressure-lowering medication, including other ARBs, will produce a similar result. The researchers say that until further trials are carried out, they see no reason for routine blood pressure lowering in the period immediately after a stroke.

People who are taking candesartan for other reasons, for example to control blood pressure, should continue to do so.