Blood pressure targets

Blood pressure targets in the Systolic Blood Pressure Intervention Trial (SPRINT) are discussed and appraised In a 2010 investigation conducted by the Global Burden of Disease Study Group, high blood pressure (BP) was the most important of 67 risk factors analysed.1 It seemed to account for more deaths (approximately 9.4 million, worldwide) than any of the other risk factors and was responsible for about 7% of global disability-adjusted life years (DALYs) and more than half of the mortality due to ischaemic heart disease. High BP was the only risk factor that seemed to cause more deaths and DALYs than tobacco smoking (including second hand smoking). Even if one restricts ‘high BP’ to those who meet the current definition for hypertension (average systolic BP ≥140 mm Hg, diastolic BP ≥90 mm Hg, or use of antihypertensive medication) it is very common.2 A recent report based on 135 population-based surveys, including 968 419 adults from 90 countries, estimated a worldwide prevalence of 31.1%.3 Based on application of the prevalence estimates to census data, about 1.4 billion adults had hypertension, approximately 400 million more than reported using similar methods ten years earlier.4 During the 10-year interval (2000–10), prevalence decreased by 2.6% in high income countries to 349 million but increased by 7.7% to 1.04 billion in the more populated low and middle income countries. However, defined, high BP is common and consequential. As a result, prevention and management of high BP is a high priority for multilateral organizations such as the World Health Organization and the World Bank.5,6 The optimal response to the challenge of high BP is prevention. Nonpharmacological approaches including weight loss, reduced intake of sodium, increased intake of potassium, physical activity, moderation in alcohol consumption and a variety of ‘heart healthy’ diets including the DASH diet are effective in prevention and management of hypertension.7,8 Low dose antihypertensive drug therapy is also effective for prevention of hypertension9,10 and was recently shown to beneficially impact left ventricular mass.11 Whether and to what extent BP-lowering medications should be used for prevention of hypertension is unclear and nonpharmacological interventions that require a change in behaviour are difficult to implement and maintain.2 Currently, most clinicians rely heavily on BP lowering medication to prevent the consequences of hypertension. Randomized controlled trials have repeatedly demonstrated that antihypertensive drug therapy reduces the risk of cardiovascular disease (CVD),12 especially in the context of higher underlying CVD risk.13,14 Beginning with the 5th report of the Joint National Committee on detection, evaluation, and treatment of high blood pressure in 1993, the systolic BP (SBP) goal during treatment of hypertension has been <140 mm Hg15. Most patients with hypertension require more than one BP-lowering medication to achieve this goal.16,17 Whether the SBP target should be lower than 140 mm Hg has been unclear. Observational studies have identified a continuous relationship between BP and the likelihood of future CVD, with no threshold for risk.18 The systolic blood pressure intervention trial (SPRINT) was a two-arm parallel trial designed to evaluate whether adults with hypertension who were at high risk for CVD would derive greater benefit from treatment to a SBP goal <120 mm Hg compared to a goal of <140 mm Hg.19 It was conducted in 9361 US adults ≥50 years, who had hypertension and at least one other indicator for increased CVD risk, but did not have diabetes mellitus or history of a prior stroke. The trial was stopped after a median of only 3.26 years due to substantial benefits in the group randomized to the SBP goal <120 mm Hg.20 These benefits included not only a 25% reduction in the primary outcome (CVD composite) but a 27% reduction in all-cause mortality. Surprisingly, hypotension was more common in the group assigned to a SBP <140 mm Hg. As expected, hyponatremia, hypokalaemia, and hyperkalaemia, and modest reductions in glomerular filtration rate (GFR) were more common in the more intensively treated group. There was no overall difference in serious adverse events (SAEs) between the two treatment groups but SAEs associated with hypotension, syncope, electrolyte abnormalities, and acute kidney injury or failure were more common in the intensively treated group. The benefits of intensive therapy seemed to apply to all six subgroups that the SPRINT investigators had pre-specified as being of special interest (defined on the basis of age, gender, race, presence or absence of CVD, presence or absence of chronic kidney disease, and baseline level of BP). In participants who were ≥75 years at baseline, a subgroup where one might have the greatest concern for complications during intensive treatment, those assigned to the SBP <120 mm Hg group seemed to derive great health benefits.21 This was true even in the seniors who were most frail and in those with the slowest gait speed. To what extent are the SPRINT findings relevant to clinical practice? Some have claimed that SPRINT is an outlier trial.22 However, the SPRINT findings are consistent with experience in other trials that have studied the effects of more compared to less intensive BP treatment on CVD outcomes, independent of whether the analyses were confined to trials that randomized to different BP targets23 or additionally included trials that compared different intensities of treatment.24 Systolic blood pressure intervention trial had far more statistical power to answer the question of ‘how low to go’ compared to previous trials, but the pattern of treatment effect has been similar in most other trials.23,24 In addition, the findings in SPRINT are consistent with what would be expected on the basis of observational experience.25 Others have expressed concern with the SPRINT methods for BP measurement.26 Landmark BP treatment trials, including SPRINT, have tended to be efficacy studies that selected volunteers who were at higher than average risk for CVD and used methods, including those for measurement of BP, that were more in keeping with recommended approaches than is common in routine clinical practice. This was the case even in trials conducted three to four decades ago. For example, in the Medical Research Council Trial of Treatment in Mild Hypertension systematic errors in estimation of BP were managed by having study participants sit in a quiet room for 10 min, paying attention to patient positioning, choice of correct cuff size, use of a Hawksley Random-Zero sphygmomanometer, and ensuring a slow deflation rate.27 Random errors were minimized by basing the estimate on an average of four BP readings (two measurements at each of two visits).27 Expert panels16,17 and professional societies28 have repeatedly emphasized the importance of care in measuring BP but there is reason to believe that ‘sloppy’ BP readings are commonplace in routine practice. Evidence-based medicine is predicated on the assumption that clinicians identify the best evidence, determine how well it applies to the individual patient and arrive at a plan of therapy following a discussion between the clinician and patient. Systolic blood pressure intervention trial and the other landmark trials provide strong evidence in support of the ‘lower is better’ approach during management of hypertension but choice of a specific BP target has to take into account the patient characteristics, underlying CVD risk and general well-being or frailty, and patient wishes based on cost, inconvenience and potential for adverse consequences of the treatment. If a SPRINT-like goal is chosen, it is important to recognize that the BPs in SPRINT were obtained using methods that sought to minimize systematic and random error. In addition, the evaluation in SPRINT and other similar trials has been based on comparison of experience in groups assigned to different intensities of treatment. The average SBP during intensive therapy in SPRINT was 121.5 mm Hg, with some being above and others below this average. The SPRINT findings should not be interpreted as supporting rigid application of a SBP <120 mm performance indicator but rather that treating to a SBP target of <120 mm Hg in selected patients with hypertension who are at high risk for CVD is likely to yield substantial health benefits while concurrently exposing the patient to some potential for adverse effects of the treatment. An independent analysis of the SPRINT results concluded that ‘Intensive blood pressure management is cost-effective at typical thresholds for value in health care and remains so even with substantially higher adverse event rates’.29 The SPRINT experience applies most directly to patients with a profile similar to those enrolled in the trial and in a setting where clinicians are mindful of the methods used in the trial. As with any of the landmark BP treatment trials, greater caution has to be applied when patient characteristics or management methods deviate from the evidence base. During the past year, BP practice guidelines in Canada and Australia have responded to the SPRINT results by recommending consideration of SPRINT-like BP goals in selected patients with hypertension who are ≥50 years and at high risk for CVD.30,31 Publication of a new US BP guideline, sponsored by the American College of Cardiology/American Heart Association and nine other professional societies is expected later this year. In summary, clinical trial experience generally suggests that the ‘lower is better than higher’ approach to BP management is appropriate for many patients. Landmark trials, including SPRINT, provide the scientific underpinning for practice of evidence-based medicine. However, clinicians are in the best position to determine the extent to which findings in landmark trials apply to an individual patient. Careful follow-up and monitoring for adverse effects is essential when intensive BP lowering is instituted. Electrolyte abnormalities and a modest reduction in GFR are the most likely adverse effects and can usually be addressed by careful monitoring and/or modification of the treatment regimen. References are available as supplementary material at European Heart Journal online.

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