Blood pressure (BP) control is of enormous clinical and public health importance, owing to the high prevalence of hypertension and the proven benefits of treatment. Incontrovertible evidence has shown that the treatment of hypertension reduces the risk of major cardiovascular events and death.
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, 2
, 3
Even so, optimal treatment targets remain uncertain and continue to be the subject of ongoing debate. In the last year, a controversial shift towards adopting a systolic BP (SBP) target <130 mm Hg was made by the American College of Cardiology and American Heart Association,4
, - Whelton P.K.
- Carey R.M.
- Aronow W.S.
- et al.
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines.
J Am Coll Cardiol. 2018; 71: e127-e248
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a change that was mostly driven by the results of a landmark study, the Systolic Blood Pressure Intervention Trial (SPRINT),6
which reported a significant reduction in major cardiovascular events with an intensive SBP target of <120 mm Hg compared with <140 mm Hg.Ongoing difficulty in identifying an optimal SBP target stems from concerns related to the generalizability of the results from SPRINT to populations at large with hypertension, the seemingly discordant results from other major clinical trials examining intensive vs less-intensive treatment goals, and the risk of adverse effects.
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In this issue of the Canadian Journal of Cardiology, Fei et al.8
present a high-quality network meta-analysis of 14 randomized controlled trials, comprising nearly 45,000 participants, examining the relationship between achieved SBP and the risk of cardiovascular morbidity and mortality. Overall, the authors found that lowering SBP to <130 mm Hg, compared with 130-139 mm Hg, resulted in a reduced odds of stroke (odds ratio [OR], 0.83; 95% confidence interval [CI], 0.69 to 0.99) and major adverse cardiovascular events (OR, 0.84; 95% CI, 0.73 to 0.96). More intensive SBP lowering to <120 mm Hg led to further reductions in stroke (OR, 0.58; 95% CI, 0.38 to 0.87). In light of these findings, the authors suggested implementing an SBP target of <130 mm Hg for older hypertensive individuals at high cardiovascular risk (reflecting the general demographics of the clinical trials included in the study), and considering a lower SBP target of <120 mm Hg for stroke prevention in selected cases, if tolerated.The strength of this network meta-analysis is that it allowed for a much larger number of comparisons to be made between mean achieved SBP levels on clinical outcomes, in contrast to traditional meta-analyses, because both direct and indirect comparisons could be incorporated.
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The findings of the study by Fei et al. are highly consistent with reports from other recent network meta-analyses,10
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traditional meta-analyses of clinical trials,1
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and observational studies,13
all broadly showing a linear association between SBP and clinical outcomes, and generally favouring SBP lowering to around 120 to 129 mm Hg for patients with and without diabetes. When considered together, the collective evidence suggests that the treatment of SBP below the traditional target of 140 mm Hg reduces the risk of stroke, major adverse cardiovascular events, and possibly mortality.2
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How should clinicians go about applying this evidence and where should the “optimal” SBP target be assigned? An intensive SBP treatment target of <130 mm Hg (or even <120 mm Hg in some cases) makes sense for selected high-risk patients, as this is consistent with the trials studied,
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and aligns with current guideline recommendations (Table 1).6
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The more difficult question to answer is whether these findings can be safely extrapolated to lower risk groups or those who are highly vulnerable to adverse drug events. Addressing this, we suggest a few guiding principles to help weigh the expected benefits of intensive BP reduction against the foreseeable harms related to treatment.Table 1Criteria used to identify high-risk patients for intensive blood pressure lowering according to major clinical practice guidelines
| Guideline (y) | Suggested intensive BP target | Criteria for possible intensive BP lowering | Cautions and contraindications to intensive BP lowering |
|---|---|---|---|
| Hypertension Canada (2018) 14 | < 120/90 mm Hg |
|
|
| American College of Cardiology/American Heart Association (2017) 4
2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines. J Am Coll Cardiol. 2018; 71: e127-e248 | < 130/80 mm Hg |
|
|
| European Society of Hypertension/European Society of Hypertension (2018) 23 | < 130/80 mm Hg |
|
|
BP, blood pressure; eGFR, estimated glomerular filtration rate; SBP, systolic BP.
∗ Hypertension Canada recommends a diastolic blood pressure target of < 80 mm Hg for persons with diabetes mellitus, and a diastolic blood pressure target of < 90 mm Hg for all other individuals.
† Estimated using the Framingham Risk Score.
‡ Estimated using the American College of Cardiology/American Heart Association Pooled Cohort Equations.
First, treatment effects are best contextualized in absolute terms according to an individual’s baseline risk. An important limitation of the study by Fei et al.
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(and most meta-analyses) was their exclusive focus on relative treatment effects in their analyses. In contrast to relative risk measures (eg, OR), measures of absolute risk (eg, absolute risk reduction and the number needed to treat) vary with baseline risk. Measures of absolute risk are particularly useful because they can be used to discriminate between large and small treatment effects to guide therapeutic decisions.15
For example, accepting that the relative odds reduction in major cardiovascular events with an SBP target of <130 mm Hg vs 130-139 mm Hg is constant across different risk strata (16%),8
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the absolute number of events prevented per 1000 patients treated over 10 years ranges from 8 events in low-risk patients to 26 events in those at high cardiovascular risk (assuming a baseline 10-year risk of cardiovascular disease of 5% and 20%, respectively).17
As shown, interventions applied to lower risk groups tend to be less favourable when conveyed as an absolute measure, but this fact is often obscured if the treatment effect is only expressed in relative terms.Second, a decision for intensive BP lowering should always take into consideration the potential risk of treatment-related harms, particularly for people who are elderly and frail, as well as those who have complex comorbidity or limited life expectancy. Further caution should be exercised in lowering diastolic BP ≤60 mm Hg in those with coronary artery disease because of the possible risk of decreased coronary perfusion.
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Most of the evidence informing risks related to intensive BP lowering derives from SPRINT. In that clinical trial, intensive BP lowering to an SBP target of <120 mm Hg compared with <140 mm Hg led to an increase in hypotension (2.4% vs 1.4%), syncope (2.3% vs 1.7%), electrolyte abnormalities (3.1% vs 2.3%), and acute kidney injury (4.1% vs 2.5%).6
Subsequent data from the SPRINT trial indicated that the treatment benefit was similar when stratified by frailty status.19
However, in actual practice, the risk of treatment-related adverse events is likely far greater, as the frequencies of injurious falls and syncope in elderly cohorts have been reported to be 5-fold higher than those observed in the control arm of SPRINT.20
Indeed, it should be remembered that, as a general rule, the benefits of treatment are often overestimated and harms underestimated in clinical trials compared with real-world settings.21
Clinical trials tend to enroll healthy and motivated individuals who are able to tolerate run-in periods. Participants are more likely to be adherent to treatment protocols and less prone to experiencing serious side effects compared with unselected patients encountered in routine clinical practice. This latter point is crucial to considering the trade-off of benefit and harm associated with implementing an intensive SBP target.Finally, amidst all the controversy and debate related to optimal SBP targets, clinicians should be reminded to not allow this debate to detract them from the treatment of hypertension altogether. Indisputable data from a myriad of sources have demonstrated the benefits of SBP lowering to <140 mm Hg in preventing cardiovascular disease in both the young and old.
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At the same time, clinicians should recognize that there may not be a single overriding treatment recommendation that applies to all patients. Taken in context, the findings from Fei et al.’s study help to clarify the potential added benefits related to a more intensive SBP reduction of <130 mm Hg in high-risk individuals with hypertension. An “optimal” BP goal is ideally guided by reliable information about benefits and harms for a given individual, and informed by patient preferences. Given that patients are often less likely than physicians to favour drug therapy for a given cardiovascular risk threshold, decision aids may be useful to ensure informed decision making.22
There may be specific patient profiles (eg, established atherosclerotic disease at high risk of stroke) for which the potential benefits of intensive SBP lowering to <120 mm Hg may be justified, even in light of the recognized risk of serious adverse events. These elements underscore the critical importance of appropriate patient selection in determining BP targets and treatment goals.Funding Sources
A.A. Leung is supported by the Hypertension Canada New Investigator Award.
Disclosures
A.A. Leung is a member of Hypertension Canada’s Central Review Committee. R.S. Padwal is on the Board of Directors for Hypertension Canada and also serves as the Co-Chair of Hypertension Canada’s Operations Committee.
References
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- 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults: a report of the American College of Cardiology/American Heart Association Task Force on clinical practice guidelines.J Am Coll Cardiol. 2018; 71: e127-e248
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- Combination of direct and indirect evidence in mixed treatment comparisons.Stat Med. 2004; 23: 3105-3124
- Optimal systolic blood pressure target after SPRINT: insights from a network meta-analysis of randomized trials.Am J Med. 2017; 130: 707-719.e708
- Systolic blood pressure reduction and risk of cardiovascular disease and mortality: a systematic review and network meta-analysis.JAMA Cardiol. 2017; 2: 775-781
- Use of blood pressure lowering drugs in the prevention of cardiovascular disease: meta-analysis of 147 randomised trials in the context of expectations from prospective epidemiological studies.BMJ. 2009; 338: b1665
- Prospective Studies Collaboration. Age-specific relevance of usual blood pressure to vascular mortality: a meta-analysis of individual data for one million adults in 61 prospective studies.Lancet. 2002; 360: 1903-1913
- Hypertension Canada’s 2018 guidelines for diagnosis, risk assessment, prevention, and treatment of hypertension in adults and children.Can J Cardiol. 2018; 34: 506-525
- Assessing and reporting heterogeneity in treatment effects in clinical trials: a proposal.Trials. 2010; 11: 85
- Commentary: relative treatment effects are consistent across the spectrum of underlying risks.usually. Int J Epidemiol. 2002; 31: 76-77
- Using numerical results from systematic reviews in clinical practice.Ann Intern Med. 1997; 126: 712-720
- Are we endangering hypertensive patients by overzealous treatment that induces diastolic hypotension? A SPRINT to the answer?.Can J Cardiol. 2016; 32: 607-608
- Intensive vs standard blood pressure control and cardiovascular disease outcomes in adults aged ≥75 years: a randomized clinical trial.JAMA. 2016; 315: 2673-2682
- Injurious falls and syncope in older community-dwelling adults meeting inclusion criteria for SPRINT.JAMA Intern Med. 2017; 177: 1385-1387
- Why clinical trial outcomes fail to translate into benefits for patients.Trials. 2017; 18: 122
- When should hypertension be treated? The different perspectives of Canadian family physicians and patients.CMAJ. 2000; 163: 403-408
- 2018 ESC/ESH Guidelines for the management of arterial hypertension.Eur Heart J. 2018; 39: 3021-3104
Article info
Publication history
Published online: August 30, 2018
Accepted:
August 28,
2018
Received:
August 25,
2018
Footnotes
See article by Fei et al., pages 1581–1589 of this issue.
See page 1545 for disclosure information.
Identification
Copyright
© 2018 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.
