Early hypertension in stroke often predicts undiagnosed or untreated chronic hypertension. However, the vast majority of stroke patients with early hypertension develop it in part as a result of a neuroendocrine response to physiological stress. This response is self-limiting, with most such hypertension developing within hours of the onset of cerebral ischemia and decreasing in blood pressure several days later. Most stroke patients have a spontaneous reduction in blood pressure of about 1/4 within 24 hours. One of the major unresolved issues in stroke treatment is how to manage hypertension in the early stages of cerebral ischemia. Both options, aggressive reduction of blood pressure and no intervention at all for early stroke hypertension, seem reasonable in a physiological sense. On the one hand, controlling blood pressure reduces cerebral edema and prevents cerebral infarction from developing into cerebral hemorrhage; on the other hand, lowering blood pressure early may affect the compensatory blood supply of the collateral circulation and further increase the area of cerebral infarction. Therefore, large clinical trials are needed to guide the development of an optimal management plan for early hypertension in ischemic stroke. Previous clinical studies have not been adequately guided. For 12 small randomized trials since 2008 enrolling only 1153 stroke patients, there was insufficient evidence to assess the impact of controlling early stroke hypertension on functional prognosis and mortality. In recent years, 2 large trials have provided further useful data, but the 2 trials included populations with a mix of hemorrhagic stroke in addition to ischemic stroke, rather than studying ischemic stroke alone. The COSSACS study randomized 763 patients with predominantly ischemic stroke (5% primary cerebral hemorrhage) to two groups: one group continued to be given antihypertensive medication two weeks after the stroke and the other group suspended antihypertensive medication. The SCAST study randomized 2029 patients with subacute stroke (approximately 85% ischemic stroke, 15% hemorrhagic stroke) to two groups: the ARB group and the placebo group, each given for 7 days. Antihypertensive drugs were also given empirically (unblinded), and more than a quarter of the patients received such drugs. At day 7, systolic blood pressure was reduced by 5 percentage points in the ARB group, but the effects on the co-primary endpoint events were very different, with no significant differences in death, heart attack or recurrent stroke between the two groups at 6 months, but after 6 months, ARB had a slight adverse effect on major functional prognosis, risk of death or major disability. Given the above state of research, the results of the CATIS study published in this issue of JAMA by He et al. make an important addition to the management of blood pressure in patients with acute ischemic stroke. The study has several important design features. the CATIS study was a large study (2038 in the intervention group and 2033 in the control group), the largest single study of subacute ischemic stroke to date, and included only patients with cerebral ischemia. Unlike the SCAST study, the CATIS study was more precise in its analysis of blood pressure reduction, unless control patients developed blood pressure values that caused hypertensive encephalopathy or active end-organ damage that further complicated the management of hypertension, and otherwise were not treated with blood pressure reduction. Unlike the COSSACS study, the CATIS study used an intensive BP-lowering regimen aimed at achieving targets, rather than simply continuing the BP-lowering medication that was used before the stroke occurred. In the CATIS study, the intervention group lowered blood pressure more effectively and rapidly in stroke patients, while the control group showed a natural decline in blood pressure. The absolute reduction in blood pressure at 24 hours was 8.2 mmHg in the intervention group compared with the control group, significantly greater than the 3.3 mmHg in the SCAST study, and the absolute reduction at 2 weeks was 8.5 mmHg, although less than the 13 mmHg in the COSSACS study, but still a significant reduction in blood pressure. These results were sufficient to expect that blood pressure control in the acute phase of ischemic stroke would have a significant impact on recurrent stroke and disability. However, this was not the case, as the CATIS study showed that BP control did not change the primary endpoint of death or severe disability at 2 weeks (both 33.6%) or the secondary endpoints of death or severe disability at 3 months (25.2% and 25.3%, respectively). The following points must be considered when summarizing the significance of CATIS study results.There are several limitations to CATIS study design and implementation. Non-blinded pharmacological interventions are prone to assessment bias. Ischemic stroke subtype classification does not use a standard approach. Stroke severity was relatively mild, with a median American Institutes of Health Stroke Scale score of 4. This stroke severity was comparable to the average severity of ischemic stroke in clinical practice, but less severe than in traditional stroke clinical trials, because stroke severity affects prognosis. Thus, 2/3 of control patients achieved the primary prognostic indicator (survival or soundness) and control of blood pressure was less likely to present a benefit. the CATIS study excluded patients with known cervicocerebral macrovascular disease, limiting the generalizability to these stroke-prone patients. Most importantly, the median time to randomization grouping was approximately 15 hours after stroke, which is really a subacute phase, rather than an acute phase within 1 to 10 hours after the onset of ischemic stroke. In addition, the CATIS trial responded to a Chinese population and clinical practice and may not be fully generalizable to other populations. For example, the included population is younger, smokes regularly, and is more likely to be treated with anticoagulation in the acute phase than in typical stroke studies in Western countries. Inclusion of population characteristics may not be measured in the trial but based on epidemiological investigations, including more intracranial small and large artery atherosclerosis and less carotid atherosclerosis. Two-thirds to three-quarters of patients with ischemic stroke have elevated blood pressure at the time of stroke onset. Nevertheless, the CATIS study confirms that blood pressure control during the subacute period of 12 hours to 2 weeks after the onset of ischemic stroke is of little significance. Failure to control hypertension during the first 2 weeks of stroke was associated with an approximately 3.0% reduction in the risk of a composite recurrent vascular event (vascular death, nonfatal stroke, nonfatal infarction, angina readmission, congestive heart failure, or peripheral arterial disease), suggesting that aggressive control of hypertension early on does little to improve prognosis. Conversely, aggressive control of blood pressure during the subacute phase was associated with little increase in infarct size due to poor collateral circulation, probably because progression of the region at risk to the infarct zone is largely dependent on the 10 hours of stroke. It is imperative to address blood pressure management in the acute phase of ischemic stroke, that is, in the hours after stroke onset when the penumbra-like danger zone is still visible. Physiologically, the best BP management within 12 hours of ischemic stroke onset is to avoid antihypertensive medications, as this period of collateral circulation compensation is beneficial for most patients, and to initiate antihypertensive therapy in the following 24 hours, between 12 and 36 hours of stroke onset, provided there is no early neurological damage, to prevent secondary injury and to ensure that the patient enters secondary long-term antihypertensive prophylaxis. A time-based randomized group analysis in the CATIS study suggests the advantages of this approach, as it showed that no blood pressure intervention within 12 hours of stroke and better prognosis at 6 months after starting blood pressure control at 24 hours. However, the results of a recent phase 2 clinical trial of nitroglycerin (which treated nitroglycerin in the hyperacute phase, a median time of 55 minutes after stroke onset) were contrasting: the possible benefit of lowering blood pressure in the hyperacute phase may be related to neuroprotection rather than hypotensive effects. Trials such as ENCHANTED, ENOS, and FAST-MAG may help to address this issue. Although the findings of these studies have not been published, the results of the CATIS study suggest that lowering blood pressure in the subacute phase of ischemic stroke is safe and that blood pressure control should be delayed until 2 weeks after stroke onset.