Patients who have had a cerebral hemorrhage are at increased risk of having another stroke later in life. With a combination pill of three blood pressure-lowering medications, this risk decreases by almost 40 percent. This is evident from an international study in which hospitals from ten different countries participated. In the Netherlands, Radboudumc in Nijmegen provided the most patients. The results were published last week in The New England Journal of Medicine.
Every day, around 25 people in the Netherlands suffer a brain haemorrhage. About a third of them will have another stroke within five years, especially in the first three months after the hemorrhage. A stroke is the umbrella term for both a cerebral hemorrhage and a cerebral infarction. In a cerebral hemorrhage (about a quarter of all strokes), a blood vessel bursts in the brain; During a cerebral infarction, the blood vessel becomes blocked, often by a blood clot.
“We know a lot about the prevention of a second stroke in people who have experienced a infarction, but much less about people with a cerebral hemorrhage,” says Karin Klijn, professor of neurology at Radboud university medical center and involved in the study. “A brain haemorrhage is a serious condition and a third of people die. This means that two-thirds survive. In recent years, there has been increasing attention to how we can prevent this group from having a new stroke. We have suspected for some time that we have to monitor their blood pressure much more strictly than is currently stated in the guidelines, but no research has ever been conducted for brain haemorrhage patients that was large enough to demonstrate this. Until now.”
Adjust guidelines
The combination pill contains three blood pressure lowering medications in very low doses, each with a different mechanism of action. The drug telmisartan causes blood vessels to dilate and relax, amlodipine relaxes the muscles in the walls of blood vessels and indapamide is a water tablet. By keeping blood pressure low with this pill, the risk of a second stroke after a cerebral hemorrhage is significantly reduced by almost 40 percent, this study shows.
“The results of this study actually surprise me very little,” says Annemijn Algra, a neurologist at Erasmus MC, who said she read the study “with great interest.” “The mechanism behind it was already known: lowering and stabilizing blood pressure is extremely important for this group of patients. This study shows once again how important it is to properly apply the things we already know.”
That is also an important side note about these results, says Lorena Miquelañez, doctor in training as an internal medicine specialist: the existence of the combination pill has not yet solved the problem. “Reality shows that it is quite difficult to get and keep blood pressure low. Doctors must continue to monitor the patient closely, and for patients there is more to it than just medication. They also have to live a healthier life, such as eating less salt and quitting smoking.”
But the fact that the risk of a second stroke can decrease as much as this study shows is, according to neurologist Algra, “a great motivation for us doctors to really continue to pay closer attention to blood pressure in this patient group.”
Very low dosage
Nearly 1,700 people participated in the randomized, double-blind study, which lasted almost seven years, mainly from Sri Lanka, but also from various European and Australian hospitals. Half of the participants received the combination pill, and the other half a placebo. After 2.5 years, 38 people taking the combined pill had had another stroke, compared to 62 people in the group taking the placebo – the number of bleedings in particular decreased in the group taking the pill. The average blood pressure among the pill users during that period was also lower than in the placebo group.
Neurologist Algra warns that in the future we will have to look carefully at the question of for which patients this pill can be a solution. “In this study, the people who are in the so-called run-in phase those who responded poorly to the drug were excluded in advance from participating in the study. So we only know something about the effect on people who tolerate the drug.” Moreover, the average age in the study is 58. “But in vulnerable, older patients you also have to be careful that kidney function does not deteriorate and blood pressure does not become too low, because that increases the risk of falls.”
The combination pill is not yet available in the Netherlands, but the individual drugs are. According to Klijn, it is precisely the very low dosage of the drugs in the pill that is of great importance. “That contributes to how well the drug is tolerated. Patients now often receive a combination of medications to keep blood pressure low. At a lower dose, the chance of side effects is smaller.”
