Is the lower the better in finding the best practical blood pressure goal under antihypertensive treatment?

Abstract

Hypertension is a common and treatable cardiovascular risk factor of global importance, even if unmet needs still exist [1]. Over time, better antihypertensive drugs and treatment algorithms have been developed, as reflected in recent international guidelines [2, 3]. The combination of effective antihypertensive drugs, often in fixed drug combinations, has made it possible to achieve more intensive blood pressure (BP) goals in many patients, even if still a large proportion of patients on treatment for hypertension do not reach BP goals set in guidelines [4]. A need, therefore, exists to find more solid evidence to motivate even further search for and definition of BP goals, as has been a continuous development over the last few decades based on numerous clinical trials. It is also challenging that the number of patients with elevated BP in need of treatment and follow-up is ever increasing, in developed countries mostly due to ageing populations and in the global south due to societal transformation affecting how people live, eat, work and travel [1]. Thus, there is a need to develop sustainable hypertension care [5, 6] when integrating scientific evidence with practical and cost-effective methods to guide patients and support the responsible staff, mostly in primary care, where most hypertensive patients are diagnosed, treated and followed.

In the most recent European Guidelines from the European Society of Cardiology 2024 [3], the systolic BP (SBP) goal for most hypertensive patients was set to a target range of 120–129 mmHg, and the diastolic BP should be lower than 80 mmHg but not less than 70 mmHg, provided that the treatment was well tolerated. In fact, this treatment recommendation was also stated for elderly patients up to an age range of 80–85 years if tolerated. During the review process, however, even tighter SBP control targets were proposed [3], but this did not end up in the official guidelines, mostly due to lack of evidence.

In this issue of the Journal of Internal Medicine, a group of authors from Austria has published a well-conducted systematic review and meta-analysis of all available evidence derived from the outcome of randomized clinical trials through November 2024 to search for an updated evidence-based SBP goal in hypertension, comparing a goal of <120 mmHg with a goal of <140 mmHg [7]. Five randomized controlled trials comprising 39,434 hypertensive patients were included. Of particular interest is that this systematic review includes two new studies from China that were not included in the ESC Guidelines 2024 [3] because they were published very late in the process or even after the launch of the ESC Guidelines. The two studies [8, 9] were designed to compare composite MACE outcomes and mortality of a treatment strategy for lowering SBP <120 versus <140 mmHg in a large group of mixed hypertensive patients [8] or in hypertensive patients with Type 2 diabetes [9]. The analysis was based on intention-to-treat principles of the studies included.

The outcome of these two intervention trials was that both total mortality and MACE were significantly reduced in the <120 mmHg SBP group [8, 9], a finding much influenced by a reduction of stroke, both fatal and non-fatal. This was not unexpected, as stroke is relatively more common than other components of MACE in East Asian populations as compared to Western populations, where coronary heart disease (CHD) events are relatively more common. In addition, the two studies [8, 9] were not blinded, probably due to practical reasons, but still a matter of some concern. These findings substantially influenced the meta-analysis [7] and its conclusion in general. The authors thus concluded that in patients at increased cardiovascular risk, an intensive BP target below 120 mmHg compared with a standard BP target below 140 mmHg was associated with a reduction in all-cause mortality, relative risk 0.87 (95% CI, 0.76–0.99, p = 0.03), cardiovascular death and a reduced incidence of MACE, myocardial infarction, stroke and heart failure [7]. The strength of evidence was rated as low by the authors themselves, mostly because of the open design of the studies. Among side effects, there was a significant increase in the incidence of hypotension, syncope, acute kidney injury and electrolyte abnormalities in the intensive control group [7]. Especially hypotension and syncope could reduce tolerability to reach such ambitious SBP targets in some patients, especially in the elderly and frail. No change of results was found in subgroup analyses of younger versus elderly patients or related to diabetes or previous cardiovascular disease.

From a European perspective, it is reasonable to argue that before these impressive findings can be incorporated in future European guidelines, the findings from the two Chinese studies, as dominated by stroke as an endpoint [8, 9], should be repeated in corresponding European populations of hypertensive patients, with or without Type 2 diabetes. Ideally, also a third treatment arm should then be added when patients could also be randomized to an SBP goal of <130 mmHg, so far lacking in the five trials of the systematic review, including the two new available studies, comparing only <120 and <140 mmHg as SBP treatment goals [8, 9].

In summary, new evidence for the benefits versus risks associated with intensified antihypertensive treatment should be welcomed, in particular from non-European populations relevant to the majority of people with hypertension on a global scale. The current meta-analysis adds interesting and important information [7], and so does a corresponding recent meta-analysis of the benefits of treating hypertension in patients over 60 years to lower than 130 mmHg SBP and in patients over 70 years to lower than 140 mmHg [10]. In China, even simplified methods for screening and treatment of hypertension have been successfully shown based on activities of non-physicians [11]. Even if these health providers were reimbursed related to the number of their patients achieving tight BP control and thus prone to reporting bias in an open-label study, it is of great importance to find new ways to handle hypertension as a major public health problem in large populations. Whether a very tight goal for SBP control <120 mmHg should be a part of this solution also in Western populations of hypertensive patients at relatively higher risk of CHD or not takes further studies in both high-risk and middle/low-risk populations for cardiovascular disease.

A most important aspect to consider is also the consequences for the health care system in general that new recommendations might lead to, with an even higher number of patients in need of guidance, tailored antihypertensive drug therapy, and frequent as well as time-consuming regular visits to primary health care units. In addition, the number of referrals to secondary and tertiary health care will increase as primary care physicians will encounter numerous problems in difficult-to-treat patients not reaching their ambitious SBP targets. The only solution to this is to support new models of sustainable hypertension care aiming for a realistic care model integrating best evidence from studies and systematic reviews with cost-effective drug treatment, lifestyle advice, digital health solutions, home-BP measurements and a wider role for trained non-physicians, with GP support in the background, for treatment titration and medical guidance.

Peter M. Nilsson: Conceptualization; writing—original draft.

The author has received modest honoraria for lectures on drug treatment of diabetes and lipid disorders from Amgen, AstraZeneca, Boehringer Ingelheim, Novartis and Novo Nordisk. He was one of the reviewers for the European Society of Cardiology Guidelines on hypertension 2024.