Key Points:
- The STEP Study was a multicenter, randomized, controlled trial which was conducted in 42 clinical centers in China. Patients aged 60 – 80 years with hypertension were randomized to a systolic blood-pressure target of 110 to less than 130 mm Hg (intensive treatment) or a target of 130 to less than 150 mm Hg (standard treatment).
- The results of the trial mostly favored intensive treatment, including better outcomes with respect to rates of stroke, acute coronary syndrome, acute decompensated heart failure, coronary revascularization, atrial fibrillation and death from cardiovascular causes in the intensive as compared to the control group.
- 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.
- The trial’s principal investigator, Dr. Jun Cai, wrote in an exclusive interview: “We suggested that in older patients treated for hypertension, the target of systolic blood pressure (SBP) should be below 130 mm Hg for better cardiovascular [outcomes]. The results of STEP could be generalized to and benefit more than 100 million persons in China, and we believe our result will provide important evidence for the development of future hypertension guidelines and bring progress in public health in the near future”.
The prevalence of arterial hypertension continues to rise worldwide, mainly due to arterial stiffening because of an aging global population. The impacts of chronic blood pressure elevation are enormous since hypertension is a major risk factor not only for cardiovascular morbidity and mortality but also for cognitive decline and autonomy loss later in life. The ideal targets for management of older adults with hypertension is increasingly discussed, and the STEP Study presented by Principal investigator Professor Jun Cai of the Chinese Academy of Medical Sciences, Beijing, China at today’s ESC Congress 2021 sought to provide additional evidence that would guide clinicians in optimal blood pressure management for elderly adults. Currently, optimal blood pressure targets are uncertain. During Dr. Cai’s presentation this morning he pointed out that several recent trials that focus on this topic have diverging findings regarding benefits of intensive blood pressure management as well as the risks. As a result, blood pressure target guidelines differ all over the world and by institution.
To clarify the optimal blood pressure target goals, Dr. Cai’s group launched the STEP trail – a prospective, multicenter, randomized, controlled trial which aimed to determine if intensive hypertension treatment (systolic blood-pressure [SBP] target, 110 to <130 mm Hg) would reduce cardiovascular risk to a greater extent than standard treatment (target, 130 to <150 mm Hg) in Chinese patients 60 to 80 years of age with hypertension over a planned 4-year period.
Beginning in January 2017, a total of 8,511 patients were enrolled in the study from 42 clinical sites in China. All participants had a SBP of 140–190 mmHg during three screening visits or were taking antihypertensive medication. Patients with prior stroke were excluded. After randomization, all patients were scheduled for follow up at 1, 2, and 3 months, and every 3 months thereafter until month 48 or until the end of study. Antihypertensive medications were provided to the patients. Office blood pressure monitoring was all conducted on a standardized, validated monitor, by a trained physician or nurse, measured three times with 1-minute intervals, and participants were required to rest for at least 5 minutes prior to measurement.
Though medication titrations were based off in-office blood pressure measurements, this trial was unique in that patients also received validated and automated home blood pressure monitors. The blood-pressure monitor was paired to the smartphone-based app with a Bluetooth function. The app was used to collect home blood-pressure readings obtained by the patient and then to upload the readings to a data-recording center. All the patients were required to obtain home blood- pressure readings at least 1 day per week during follow-up. Patients were not enrolled in the trial unless they could use the app or had a family member who could use it on their behalf. The details of the effects of the app-based management are not presented in the current study.
The primary outcome was a composite of stroke, acute coronary syndrome (which included acute myocardial infarction and hospitalization for unstable angina), acute decompensated heart failure, coronary revascularization, atrial fibrillation, or death from cardiovascular causes. Secondary outcomes included the components of the primary endpoint, death from any cause, major adverse cardiac events, and renal outcomes (a decrease in renal function or the development of end-stage renal disease).
The results of the study, published today in the New England Journal of Medicine, showed that baseline characteristics were evenly matched between the intensive and standard treatment groups, though importantly >75% of patients were aged 60-69 years in both groups. During the median follow up period of 3.34 years, the average decrease in SBP from baseline was 19.4 mmHg in the intensive treatment group and 10.1 mmHg in the standard treatment group. Average SBP reached 126.7 mmHg and 135.9 mmHg in the intensive and standard groups, respectively, with an average between-group difference of 9.2 mmHg. A total of 196 primary outcome events occurred in the standard treatment group (4.6%) compared to 147 events in the intensive treatment group (3.5%), with a relative risk reduction of 26% (hazard ratio with intensive treatment 0.74; 95% confidence interval [CI] 0.60–0.92). Dr. Cai wrote in an email interview, “The results showed that the risk of adverse cardiovascular events was reduced by 26% with intensive treatment, and the results for safety (except for hypotension) and renal outcomes did not differ significantly between the two groups.” The results for most of the secondary outcomes were also more favorable in the intensive-treatment group than in the standard-treatment group, including a 33% lower relative risk of stroke (95%CI 0.47–0.97) and a 33% lower relative risk of acute coronary syndrome (95%CI 0.47– 0.94) in the intensive as compared to standard blood pressure control groups.
During the ESC Congress live release this morning, commentator Dr. Bryan Williams (University College London – London, United Kingdom of Great Britain and Northern Ireland) points out that the study population was relatively low risk, with very few patients with cardiovascular or renal disease and none with prior stroke because of exclusion criteria. He notes the impressive findings of the study included reduction in several important cardiovascular outcomes in the intensive group, which was extremely well tolerated as indicated by the few adverse events in this study arm. He makes the point, however, that older adults are a rather heterogenous group due to wide spectrums of comorbidities, frailty, and cognitive function among the elderly. He therefore remarked that this study indicates that clinicians may need to be more aggressive with blood pressure targets in certain groups, though the risk versus benefit of intensive blood pressure lowering may differ according to each patient.