By Dr. Jonathan Shurlock
On the second day of the BCS centenary conference, the cardiac society of Australia and New Zealand presented a series of talks focussing on recent research demonstrating potential new or updated treatment strategies for hypertension.
The Salt Substitute and Stroke Study
The session was opened by Professor Bruce Neal of the George Institute, Sydney, presenting the Salt Substitute and Stroke Study (SSaSS). The study was performed on the basis that salt substitutes with reduced sodium and increased potassium levels have previously been shown to reduce blood pressure, but with an uncertain effect on cardiovascular and safety outcomes. The authors enrolled 20,995 participants into their open-label cluster-randomised trial and followed them up for a mean of 4.74 years. The mean age at enrolment was 65.4 years, 49.5% of participants were female, and 88.4% of participants had a history of hypertension.
The participant clusters were randomly assigned in a 1:1 ratio to the salt substitute group (75% sodium chloride and 25% potassium chloride by mass), or to the regular salt group (100% sodium chloride).
The authors found a lower rate of stroke in the salt substitute group compared with regular salt users (29.14 events vs. 33.65 events per 1000 person-years; rate ratio [RR], 0.86; 95% confidence interval [CI], 0.77 to 0.96; P=0.006). There was also a lower rate of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; RR, 0.87; 95% CI, 0.80 to 0.94; P<0.001) and death (39.28 events vs. 44.61 events per 1000 person-years; RR, 0.88; 95% CI, 0.82 to 0.95; P<0.001) in the salt substitute group. Importantly, the authors also found that the rate of serious adverse events related to hyperkalaemia were not significantly higher in the salt substitute group (3.35 events vs. 3.30 events per 1000 person-years; RR, 1.04; 95% CI, 0.80 to 1.37; P=0.76).
Professor Clara Chow of the University of Sydney then presented work exploring the role of an anti-hypertensive poly-pill for the medical management of hypertension. QUARTET was a multicentre, double-blind, randomised, phase 3 trial. The authors enrolled Australian adults with hypertension who were either untreated or receiving monotherapy. Participants were randomised to either the intervention group (receiving a ‘quad-pill’ containing 37.5mg irbesartan, 1.25mg amlodipine, 0.625mg indapamide, and 2.5mg bisoprolol) or the control group (receiving irbesartan 150mg). Treatment group allocation was blinded to all participants and members of the study team including the outcome assessors.
The authors recruited 591 participants. Mean age at recruitment was 59 years. 40% of participants were female. Baseline mean blood pressure of participants was 141/85mmHg.
At follow-up systolic blood pressure (SBP) was lower by 6·9mmHg (95% CI 4.9–8.9; p<0.0001) in the intervention group. In addition rates of adequate blood pressure control were higher in the intervention group (76%) versus control group (58%; RR 1.30, 95% CI 1.15–1.47; p<0·=.0001). At longer term follow-up (52 weeks) mean SBP remained 7.7mmHg lower in the intervention group (95% CI 5·2–10·3). There was no difference in treatment withdrawal secondary to adverse events at 12 weeks follow-up (intervention 4.0% vs control 2.4%; p=0.27).
The authors propose that early treatment with a set dose ‘quad-pill’ improved blood pressure control over the standard use of starting monotherapy, while remaining tolerable and safe.
The role of renal denervation in blood pressure control
Professor Markus Schlaich of the University of Western Australia presented multiple research studies exploring the potential role of renal denervation in hypertension. Initial discussion focussed on research which has shown adherence to antihypertensive medication as being generally poor, as identified by direct quantification of metabolites in the blood or urine. Professor Schalch proposed renal denervation as a strategy for effective and sustained blood pressure lowering and discussed multiple sham-controlled trials which demonstrated blood pressure lowering effects.
A recent study by Professor Schlaich in the Journal of Hypertension explored the effect of renal denervation on salt-sensitivity in patients with uncontrolled hypertension. Salt-sensitivity was derived from an index based on ambulatory blood pressure monitoring. The authors found that the proportion of participants in the intermediate and high-salt sensitivity risk groups increased after renal denervation and that the odds of being in a higher salt sensitivity risk group increased significantly during 12 months of follow up. These findings have important implications for the role of salt moderation post-renal denervation due to potential renal compensatory mechanisms post-procedure.
Professor Schlaich further discussed the difficulties with performing a renal denervation trial that can adequately assess clinically important outcomes, such as mortality and major cardiovascular events, but that this would be the ideal way of attempting to demonstrate the role and efficacy of renal denervation.
- Video summary of the SSaSS trial: https://www.nejm.org/do/10.1056/NEJMdo006159/full/
- QUARTET study: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(21)01922-X/fulltext
- Renal denervation trial: https://journals.lww.com/jhypertension/Fulltext/2022/03000/Renal_denervation_alters_ambulatory_blood.19.aspx?casa_token=x2P1_lJswd4AAAAA:lce9H-isNKN2M_vwa016cfolaco8TqjHZ_sB2G5ZyjdOgfL_UEJ98rGXURVJRkof4RRFTK56s7FCb5EaQBEfeH7fR_Bl