Dear Sirs,
In the recent article ‘Drug therapies for stroke prevention’, under the heading entitled ‘Control of blood pressure’, the authors specified that “A systolic blood pressure (SBP) target of 120–129 mmHg should be routinely aimed for in those <65 years old….”.1 This ‘goal’ SBP does not take recognition of the fact that the goal SBP that optimally mitigates the risk of incident atrial fibrillation (AF) and, hence, cardioembolic stroke, is a SBP <120 mmHg.2
The latter study enrolled 9,361 participants, of whom 4,683 were randomised to a goal SBP of <140 mmHg, and 4,678 were randomised to a goal SBP of <120 mmHg, the latter defined as intensive blood-pressure lowering.
During 5.2 years of follow-up, intensive SBP lowering was associated with a 26% lower risk of developing new-onset AF (hazard ratio 0.74, 95% confidence interval 0.56 to 0.98, p<0.037). This effect was consistent among prespecified subgroups of participants stratified by age and sex.2
It is salutary to note that patients aged 60 years and older who have a life-expectancy of >3 years also benefit from intensive SBP lowering (i.e. goal SBP <120 mmHg).3 In the latter study, the authors evaluated the results of six trials that compared standard SBP lowering versus intensive SBP lowering, and enrolled subjects aged 60 years or more. They discovered that intensive SBP lowering was associated with a 21% reduction in major adverse cardiovascular events, such as stroke and myocardial infarction, for example. On average, 100 patients aged >60 needed to receive 34.4 months of intensive antihypertensive medication to prevent the occurrence of one major adverse cardiovascular event. In other words, a 60 year old with a life-expectancy of 34.4 months would derive significant benefit from intensive SBP lowering. Conversely, a frail elderly counterpart, with more limited life-expectancy, would not benefit from intensive SBP lowering.
Intensive SBP lowering imposes an obligation for the doctor to commit to titration of antihypertensive medication, so as to mitigate the risk of iatrogenic symptomatic hypotension. It also imposes an obligation for the patient to undertake home blood pressure monitoring and to alert their doctor when low SBP readings occur, so that drug treatment can be modified accordingly. These challenges can, however, be overcome if there is a shared understanding that the aim of treatment is to mitigate the risk of stroke.
Oscar M P Jolobe
Retired geriatrician
Manchester
([email protected])
Conflicts of interest
None declared.
Funding
None.
References
1. Shaji N, Storey RF, Parker WAE. Drug therapies for stroke prevention. Br J Cardiol 2023;30:139–43. https://doi.org/10.5837/bjc.2023.040
2. Soliman E, Rahman F, Zhang Z-M et al. Effect of intensive blood pressure lowering on the risk of atrial fibrillation. Hypertension 2020;75:1491–6. https://doi.org/10.1161/HYPERTENSIONAHA.120.14766
3. Chen T, Shao F, Chen K. Time to clinical benefit of intensive blood pressure lowering in patients 60 years and older with hypertension. A secondary analysis of randomised clinical trials. JAMA Intern Med 2022;182:660–7. https://doi.org/10.1001/jamainternmed.2022.1657
Authors’ reply
From Nimisha Shaji, Robert F Storey and William A E Parker
We thank the correspondent for raising these insightful points. We agree, and reiterate that achieving optimal blood pressure (BP) control is crucial to prevention of stroke. If this can also achieve a reduction in the incidence of atrial fibrillation (AF), this will likely contribute to the benefits of BP lowering on stroke prevention. With regards to BP targets for use in routine clinical practice, the results of the Systolic Blood Pressure Intervention Trial (SPRINT), to which the correspondent refers, have indeed been prominent in informing guideline recommendations.1 It should be noted that, while SPRINT showed a significant reduction in the primary composite end point of myocardial infarction, other acute coronary syndromes, stroke, heart failure, or death from cardiovascular causes when comparing intensive with standard BP control, though there was a numerical reduction in stroke events, this did not itself reach the threshold for statistical significance. Furthermore, it is important to consider how the results of SPRINT can be translated into conventional practice when BP measurements are made in different settings.2 In SPRINT, BP was measured using an unattended automated method that typically results in readings significantly lower than conventional office measurement, with a mean difference in systolic BP (SBP) between the methods suggested to be of the order of 16 mmHg.3 Other trials have studied intensive (SBP <120 mmHg) versus standard (<140 mmHg) lowering of BP using conventional office measurement, such as the Action to Control Cardiovascular Risk in Diabetes (ACCORD) study, and have failed to demonstrate a significant difference in composite major adverse cardiovascular events, though were likely underpowered, and, in fact, conversely, did demonstrate a significant reduction in incidence of non-fatal stroke.4 Any contribution to this of a reduction in the incidence of AF was not assessed. However, any benefits should be weighed against the fact that in both SPRINT and ACCORD, intensive BP control was associated with an increase in adverse events, such as syncope and acute kidney injury. Guideline recommendations for office BP targets, including those cited in our article, have, therefore, balanced these factors to arrive at consensus.
We agree that the benefits of good BP control appear to be present across a range of ages, but that this should be weighed against the context of an individual’s broader outlook and the likelihood of developing adverse effects from treatment.
Finally, we concur with the correspondent that a collaborative effort between physician and patient is key to setting and achieving goals in BP management. Though it is clearly important to determine the level of BP control that is most beneficial to an individual, it remains the case that in real-world practice, across different healthcare systems, BP targets are infrequently met, so improving this aspect of care is also of vital importance.5
Nimisha Shaji
Foundation Doctor
Robert F Storey
Professor of Cardiology
William A E Parker
Clinical Lecturer in Cardiology
([email protected])
Cardiovascular Research Unit, Division of Clinical Medicine, University of Sheffield, Northern General Hospital, Herries Road, Sheffield, S5 7AU
Conflicts of interest
NS: none declared. RFS reports institutional research grants from AstraZeneca, Cytosorbents and GlyCardial Diagnostics; and consultancy fees from AlfaSigma, Alnylam, Amgen, AstraZeneca, Bayer, Bristol Myers Squibb/Pfizer, Chiesi, CSL Behring, Cytosorbents, Daiichi Sankyo, GlyCardial Diagnostics, Hengrui, Idorsia, Novartis, PhaseBio, Sanofi Aventis and Thromboserin. WAEP reports institutional research grants and consultancy fees from AstraZeneca.
Funding
None.
References
1. Williams B, Mancia G, Spiering W et al. 2018 ESC/ESH guidelines for the management of arterial hypertension. Eur Heart J 2018;39:3021–104. https://doi.org/10.1093/eurheartj/ehy339
2. Kjeldsen SE, Lund-Johansen P, Nilsson PM, Mancia G. Unattended blood pressure measurements in the systolic blood pressure intervention trial. Hypertension 2016;67:808–12. https://doi.org/10.1161/HYPERTENSIONAHA.116.07257
3. Filipovský J, Seidlerová J, Kratochvíl Z, Karnosová P, Hronová M, Mayer Jr O. Automated compared to manual office blood pressure and to home blood pressure in hypertensive patients. Blood Pressure 2016;25:228–34. https://doi.org/10.3109/08037051.2015.1134086
4. ACCORD Investigators. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med 2010;362:1575–85. https://doi.org/10.1056/NEJMoa1001286
5. Chow CK, Teo KK, Rangarajan S et al. Prevalence, awareness, treatment, and control of hypertension in rural and urban communities in high-, middle-, and low-income countries. JAMA 2013;310:959–68. https://doi.org/10.1001/jama.2013.184182
Note from the Editors
We thank Dr Oscar Jolobe and the authors of the original paper for this interesting and balanced discussion. We expect further debate with the recent publication by Jiamin Liu et al, which supports the conclusions of systolic blood pressure intervention trial (SPRINT).1
Several questions are raised by this evidence. Should guidelines encourage lower targets for everyone or specific people? Are we treating individuals or populations? Are randomised controlled trials the best evidence to use in these instances, or would real-world data be more useful as it is includes people with multi-morbidity? Is clinical judgement valid in a system where the practitioners are increasingly from the non-physician workforce and forced to follow strict guidance? Is the likelihood of more polypharmacy safe and how do we enhance patient choice?
We welcome further correspondence on this issue.
References
1. Liu J, Li Y, Ge J, Yan X et al. Lowering systolic blood pressure to less than 120 mm Hg versus less than 140 mm Hg in patients with high cardiovascular risk with and without diabetes or previous stroke: an open-label, blinded-outcome, randomised trial. Lancet 2024;404:245–55. https://doi.org/10.1016/S0140-6736(24)01028-6
