This is a summary of Kopczak A, Stringer MS, van den Brink H, Kerkhofs D, Blair GW, van Dinther M, (…) Dichgans M; TREAT-SVDs collaborators. Effect of blood pressure-lowering agents on microvascular function in people with small vessel diseases (TREAT-SVDs): a multicentre, open-label, randomised, crossover trial. The Lancet Neurology, 2023 https://doi.org/10.1016/S1474-4422(23)00293-4
The challenge
Small vessel disease is an umbrella term for conditions in which the walls of the small vessels are damaged, reducing blood flow and thus oxygen supply. It accounts for up to 30% of stroke and contributes to at least 40% of dementia cases. CADASIL is a rare hereditary form of small vessel disease.
High blood pressure is the most important risk factor for the disease and controlling blood pressure is therefore important. This is typically achieved by administering antihypertensive drugs. However, the effects of different types of antihypertensive drugs in patients who have had lacunar stroke or other manifestations of small vessel disease might differ. Comparing the effects of different drugs is important because drugs that improve vascular function at the level of cerebral microvessels might not only improve blood pressure but also positively affect the course of the disease. Therefore, we initiated a clinical trial.
Our approach
We conducted a randomized trial at five specialist centers in Europe. To account for the heterogeneity of small vessel diseases, we included people with both sporadic small vessel disease and CADASIL. We kept these two groups separated to analyze the effect of the drugs. After a two-week washout period to ensure that all traces of previous drugs were out of the system, the participants were randomly assigned to a 4-week treatment with one of the following three antihypertensive drugs: amlodipine, losartan, and atenolol. To measure the function of blood vessels, we quantified the cerebrovascular reactivity as assessed by brain magnetic resonance imaging (MRI).
Our findings
We found no difference in the effect of the three different drug classes on cerebrovascular reactivity in patients with sporadic small vessel disease. However, we did find that the cerebrovascular reactivity in patients with CADASIL improved with both amlodipine and losartan compared with atenolol.
The implications
Our findings in patients with CADASIL highlight the need for further research on different antihypertensive drug classes in people with small vessel disease. They also highlight the importance of including patients with rare hereditary subtypes of common diseases in clinical trials.
Creating SyNergies
This research in SyNergy was led by the Dichgans team at LMU and involved collaborators from both the UK (Edinburgh and Oxford) and the Netherlands (Utrecht and Maastricht). It was funded by a grant from the European Commission and further supported by the SyNergy cluster.
