SPRINT trial: Intensive blood pressure control reduces atrial fibrillation risk

At a glance

  • Aggressive blood pressure lowering may reduce the risk of developing atrial fibrillation (AF)

  • There is currently no definitive evidence to support the discontinuation of prescribed angiotensin-converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs) in the COVID-19 setting

New SPRINT trial findings

New research findings by scientists at the Wake Forest School of Medicine suggest that intensive blood pressure (BP) control has the potential to reduce the risk of AF, a common heart rhythm disorder characterised by irregular heartbeats with serious potential downstream complications [1]. The study, published in the American Heart Association (AHA) Journal, Hypertension analysed the data of 8,022 participants from the National Institutes of Health Systolic Blood Pressure (SPRINT) trial [1]. Participants were randomised into an intensive BP lowering group where the target systolic BP (SBP) was <120mmHg and a standard BP lowering group with a target SBP of <140mmHg [1]. In a 5 year follow-up period, a total of 206 cases of AF were recorded; 88 in the intensive BP lowering arm and 118 in the standard BP lowering arm [1]. This represented a 26% risk reduction of AF in those with a SBP <120mmHg compared to those with a SBP <140mmHg, a benefit that was consistent across age, gender, race and levels of SBP [1]. The findings are the first from a large randomised controlled trial (RCT) in support of AF risk reduction as a result of aggressive SBP control <120mmHg compared with the standard <140 mmHg [1]. However, authors noted that the findings may not be applicable to the types of hypertensive patients not enrolled in the SPRINT study such as those with diabetes mellitus and lower risk of cardiovascular disease [1]. An estimated 1.39 billion adults suffered from hypertension in 2010 [2]. According to the Population Health Survey 2014/15 conducted in Hong Kong, 27.7% of respondents aged 15-84 had hypertension [3]. An astonishing 47.5% were not diagnosed prior to the survey, implying that many are unaware that they have this condition. Furthermore, prevalence increased with age from 4.5% in the 15-24 age group to 64.8% in the 65-84 age group [3]. The main results of the landmark SPRINT study found that intensive BP lowering significantly reduced the rates of death and cardiovascular disease and were first published in 2015 [4]. These results helped to inform the 2017 AHA and American College of Cardiology (ACC) clinical guidelines for high BP which included redefining hypertension to 130/80mmHg (previously ≥140/90mmHg) and a new treatment goal of <130/80mmHg [5]. The Hong Kong Reference Framework for Hypertension Care currently recommends an initial BP goal of <140/90mmHg for individuals with uncomplicated hypertension and 130/80mmHg for those who can tolerate it [6]. Although there is clear evidence that demonstrates the benefits of lowering BP, there is also an increased risk of treatment noncompliance and serious adverse events as previously observed in the SPRINT trial [5]. As advised in the Hong Kong Reference Framework, BP treatment goals should be individualised based on age, underlying cardiovascular risk factors and patient tolerability [6]. The new study data provide some additional insight on the positive effects of lowering BP which physicians may take into consideration for the management of their hypertensive patients, particularly those at higher risk of cardiovascular diseases. Future long-term studies may also investigate whether AF is actually prevented or just delayed as a result of stringent BP control.

Antihypertensive medication in the COVID-19 setting

As one of the most common comorbidities observed with severe cases of SARS-CoV-2 (COVID-19), there is widespread concern about the effects of hypertension and medication used to treat hypertension on the risk and outcomes of COVID-19 infection [7–9]. Much attention has been given to ACE inhibitors and ARBs, antihypertensive drugs that target the renin-angiotensin-aldosterone system (RAAS). There is some evidence that suggests ACE inhibitors and ARBs can potentially increase the number of ACE2 receptors, the receptor that facilitates entry of COVID-19 into lung cells [10,11]. Therefore, individuals taking these drugs could be at risk for more severe COVID-19 outcomes due to increased viral entry. Conversely, some studies have also suggested that ACE2 is protective against lung injury and therefore, ACE inhibitors and ARBs could contribute to reducing the severity of COVID-19 outcomes [10,11]. Organisations such as the AHA and the European Society of Cardiology (ESC) recommend the continuation of prescribed ACE inhibitors or ARBs in COVID-19 patients due to lack of definitive evidence from clinical trials to conclude that these agents influence the infection in any way [12,13]. In support of current guidelines, four recent observational studies published in the New England Journal of Medicine and JAMA Cardiology have suggested that ACE inhibitors and ARBs are not associated with an increased risk of COVID-19 infection, severe COVID-19 illness or in-hospital death among patients with COVID-19 [14–17]. Given the global prevalence of hypertension, its impact on the clinical course of COVID-19 remains a critical public concern. Additional data collected over the course of the ongoing pandemic as well as RCTs will be fundamental to researchers in understanding the true risk of hypertension on the outcomes of COVID-19 illness and any implications on the management of this patient group.

References [1] Soliman, E. Z. et al. Effect of Intensive Blood Pressure Lowering on the Risk of Atrial Fibrillation. Hypertension 75, 1491–1496 (2020).

[2] Mills, K. T., Stefanescu, A. & He, J. The global epidemiology of hypertension. Nat. Rev. Nephrol. 16, 223–237 (2020).

[3] Centre for Health Protection, Department of Health - Hypertension. https://www.chp.gov.hk/en/healthtopics/content/25/35390.html.

[4] SPRINT Research Group et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N. Engl. J. Med. 373, 2103–2116 (2015).

[5] Whelton Paul K. 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. Hypertension 71, e13–e115 (2018).

[6] Primary Care Office, Department of Health, Hong Kong et al. Update on the Hong Kong Reference Framework for Hypertension Care for Adults in Primary Care Settings—review of evidence on the definition of high blood pressure and goal of therapy. Hong Kong Med. J. (2019).

[7] Huang, C. et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China. The Lancet 395, 497–506 (2020).

[8] Wu, C. et al. Risk Factors Associated With Acute Respiratory Distress Syndrome and Death in Patients With Coronavirus Disease 2019 Pneumonia in Wuhan, China. JAMA Intern. Med. (2020).

[9] Zhou, F. et al. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: a retrospective cohort study. The Lancet 395, 1054–1062 (2020).

[10] Vaduganathan, M. et al. Renin–Angiotensin–Aldosterone System Inhibitors in Patients with Covid-19. N. Engl. J. Med. 382, 1653–1659 (2020).

[11] Kai, H. & Kai, M. Interactions of coronaviruses with ACE2, angiotensin II, and RAS inhibitors—lessons from available evidence and insights into COVID-19. Hypertens. Res. 1–7 (2020).

[12] HFSA/ACC/AHA Statement Addresses Concerns Re: Using RAAS Antagonists in COVID-19. American College of Cardiology. https://www.acc.org/latest-in-cardiology/articles/2020/03/17/08/59/hfsa-acc-aha-statement-addresses-concerns-re-using-raas-antagonists-in-covid-19 (2020).

[13] Position Statement of the ESC Council on Hypertension on ACE-Inhibitors and Angiotensin Receptor Blockers. European Society of Cardiology. https://www.escardio.org/Councils/Council-on-Hypertension-(CHT)/News/position-statement-of-the-esc-council-on-hypertension-on-ace-inhibitors-and-ang (2020).

[14] Reynolds, H. R. et al. Renin–Angiotensin–Aldosterone System Inhibitors and Risk of Covid-19. N. Engl. J. Med. (2020).

[15] Mehra, M. R., Desai, S. S., Kuy, S., Henry, T. D. & Patel, A. N. Cardiovascular Disease, Drug Therapy, and Mortality in Covid-19. N. Engl. J. Med. (2020).

[16] Mancia, G., Rea, F., Ludergnani, M., Apolone, G. & Corrao, G. Renin–Angiotensin–Aldosterone System Blockers and the Risk of Covid-19. N. Engl. J. Med. (2020).

[17] Mehta, N. et al. Association of Use of Angiotensin-Converting Enzyme Inhibitors and Angiotensin II Receptor Blockers With Testing Positive for Coronavirus Disease 2019 (COVID-19). JAMA Cardiol. (2020).