STEP Towards Better Blood Pressure Control: The Prime Time for a Universal Target of < 130/80 mmHg

It is well established that a higher blood pressure is associated with a higher cardiovascular event. From the observational studies done in the South Korean population and people in the United Kingdom,^1,2 the positive correlation between blood pressures and cardiovascular events is continuous since the level of < 100/60 mmHg. The so-called J-curve phenomenon has not been observed in observational studies. However, the J curve phenomenon was seen in the post-hoc analyses of several blood pressure-lowering pharmacological intervention trials.^3,4 These observations led to the contrasting recommendations between hypertension management guidelines from the American Hypertension Association/American College of Cardiology and the European Society of Cardiology/European Society of Hypertension.^4,5 In the former guideline, a universal target of < 130/80 mmHg was recommended based on the SPRINT trial,⁶ whereas a target range of 120/70 to 139/79 was recommended in the European guideline. In this context, what blood pressure targets should be recommended for people in Taiwan are debatable.^7,8 In the annual conference of the European Society of Cardiology 2021, the announcement of the Strategy of Blood Pressure Intervention in the Elderly Hypertensive Patients (STEP) trial results provides important information for hypertension management in Asia regarding which blood pressure target should be recommended.⁹ In this multicenter, randomized controlled trial, Chinese patients 60 to 80 years of age with hypertension from both mainland China and Taiwan were assigned to a systolic blood pressure target of 110 to < 130 mmHg (intensive-treatment) or a target of 130 to < 150 mmHg (standard-treatment). The primary outcome was a composite of stroke, acute coronary syndrome (acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. Among the 8511 patients enrolled, 4243 were randomly assigned to the intensive-treatment group and 4268 to the standard-treatment group. During a median follow-up period of 3.34 years, the mean systolic blood pressure was 126.7 mmHg in the intensive-treatment group and 135.9 mmHg in the standard-treatment group; the mean diastolic blood pressure was 76.4 mmHg and 79.2 mmHg, respectively. The mean number of antihypertensive medications administered per patient was 1.9 in the intensive-treatment group and 1.5 in the standard-treatment group. The primary outcome events occurred in 147 patients (3.5%) in the intensive-treatment group, as compared with 196 patients (4.6%) in the standard-treatment group [hazard ratio, 0.74; 95% confidence interval (CI), 0.60 to 0.92; p = 0.007]. The hazard ratio for stroke was 0.67 (95% CI, 0.47 to 0.97), acute coronary syndrome 0.67 (95% CI, 0.47 to 0.94), acute decompensated heart failure 0.27 (95% CI, 0.08 to 0.98), coronary revascularization 0.69 (95% CI, 0.40 to 1.18), atrial fibrillation 0.96 (95% CI, 0.55 to 1.68), and death from cardiovascular causes 0.72 (95% CI, 0.39 to 1.32). The relative risk reduction divided by the between-group systolic blood pressure difference is 2.8%/mmHg (26%/9.2 mmHg). The results for safety and renal outcomes did not differ significantly between the two groups, except for the incidence of hypotension, which was higher in the intensive-treatment group. Therefore, in older patients with hypertension, intensive treatment with a systolic blood pressure target of 110 to < 130 mmHg resulted in a lower incidence of cardiovascular events than standard treatment with a target of 130 to < 150 mmHg.

There are five points worth mentioning regarding the STEP trial. First, the STEP trial is the only trial which replicated the SPRINT finding, by applying a conventional office blood pressure measurement setting. It is of importance since the office blood pressure measurement conducted in the SPRINT trial, the so-called "complete" automated blood pressure monitoring, is different from all the other large-scale blood pressure target-driven or pharmacological intervention trials.^9,10 Some experts even considered that the blood pressure levels obtained in the SPRINT was underestimated and should not be interpreted at face value.¹⁰ However, the almost identical findings observed in the STEP, by using a conventional, "semi-automated" blood pressure measurement, reinforce what were observed in the SPRINT. Further, it reconfirms that < 130/80 mmHg, no matter by "complete (unattended)" automated blood pressure measurement or conventional "semi-automated" blood pressure measurement, is associated with lower cardiovascular events, compared to the traditional systolic blood pressure target of 130 to < 140 or < 150 mmHg. Second, the incidence rate in the standard-treatment group of the STEP trial is low [1.4% per year for the composite primary endpoint, approximately 0.7% per year for atherosclerotic cardiovascular disease events (stroke, myocardial infarction, and cardiovascular death)]. The average incidence rate in the standard-treatment group in the SPRINT is 2.2% per year.⁶ Therefore, findings from the STEP fill the evidence gap in the low-risk (annual atherosclerotic cardiovascular event rate < 1%) population. In the HOPE-3 trial, blood pressure reduction by a single pill comprised of angiotensin receptor blocker and thiazide-type diuretic was not associated with a lower cardiovascular risk in patients with pre-treatment systolic blood pressure of < 144 mmHg and an annual atherosclerotic cardiovascular disease event rate of < 1%.¹¹ The STEP trial refutes the HOPE-3 findings and provides insights regarding the blood pressure targets for hypertensive patients in Taiwan. Third, it should be emphasized that the STEP not only demonstrates the clinical benefits with a systolic blood pressure target of < 130 mmHg, compared to a target of ≥ 130 mmHg, but also a lower range of 110 mmHg. The clinical implication of a lower range of systolic blood pressure target is that drug de-escalation strategy could be started once the average systolic blood pressure is below the lower range. However, this interpretation should be validated by more prospectively designed studies. Fourth, the relative risk reduction for a given systolic blood pressure reduction in the STEP, 2.8%/mmHg, is higher than that (approximately 2%/mmHg) observed from the individual participant data-based meta-analysis by the BPLTTC consortium.¹² This finding is consistent with the phenomenon that Asian population is more sensitive to blood pressure-related cardiovascular events. For Asian populations, aggressive blood pressure control could provide greater clinical benefits, as compared to that in Caucasian populations. Finally, since home blood pressure monitoring had been required to be performed at least once per week in the STEP, the corresponding home blood pressure target could be obtained in the subsequent STEP analyses. According to the average office and home blood pressure levels in both treatment groups, both levels are comparable. In other words, the target values based on office blood pressures might be directly converted to home blood pressures.^8,13 The direct conversion between office and home blood pressures could greatly facilitate the implementation of home blood pressure-based targets.

In the recent 3 years, several articles related to hypertension were published in the Journal.^14-25 Together with the STEP trial, these publications make the management of hypertension step forwards. It seems that a universal target of < 130/80 mmHg is beneficial not only for Caucasian populations, but also for Asian populations. On the other hand, we should pay close attention to each individual treated with more aggressive blood pressure-lowering medications to pursue a lower target. The first priority of blood pressure management is to ensure the tolerability of each individual. The tolerable lowest blood pressure is the best blood pressure from the organ-protection perspective.

CONFLICT OF INTEREST

The author declare no conflicts of interest.