Hot Line 9: The latest in lowering levels of triglycerides or blood pressure

SHASTA-3 and SHASTA-4

Professor Gerald Watts (University of Western Australia - Perth, Australia) presented results from two trials with the APOC3-targeting RNA interference agent, plozasiran, in patients with severe hypertriglyceridaemia. In the SHASTA-3 and SHASTA-4 trials, participants with triglyceride levels of 500 mg/dL or greater received either four quarterly subcutaneous injections of plozasiran 25 mg or placebo. Plozasiran treatment led to median triglyceride reductions at month 12 of 79% and 81%, in SHASTA-3 and SHASTA-4, respectively, vs. a placebo reduction of approximately 27% in each trial. Across the trial populations, cumulative acute pancreatitis events were reduced by 78% in patients treated with plozasiran vs. placebo. Prof. Watts concluded, “These findings highlight the potential of plozasiran as a promising therapy for patients across the spectrum of severe hypertriglyceridaemia.”

CRHCP

The China Rural Hypertension Control Program (CRHCP) is a cluster-randomised trial studying an intensive BP intervention led by non-physician community healthcare providers. Doctor Shanshan Zhong (The First Affiliated Hospital of China Medical University - Shenyang, China) noted that in addition to evaluating the effect of the intervention on cardiovascular outcomes, another important aim was to assess whether intensive BP lowering can reduce the incidence of all-cause dementia. In total, 326 rural Chinese villages were randomised and almost 34,000 participants were included who had untreated SBP ≥140 mmHg or DBP ≥90 mmHg (≥130 mmHg and 80 mmHg for those at high risk of CVD or if treated). In the intervention group, trained non-physician community healthcare providers initiated and titrated antihypertensive medications according to a simple stepped-care protocol to achieve SBP <130 mmHg and DBP <80 mmHg with supervision from primary-care physicians. The active trial phase lasted for 4 years, followed by 3 additional years of observation only. Greater BP reductions from baseline were observed with the intervention vs. usual care after 7 years (SBP reductions of 17.6 mmHg vs. 2.4 mmHg).

Of note, the intervention group had a 15% lower risk of dementia than the usual-care group (8.85% vs. 10.55%; adjusted risk ratio 0.85; 95% CI 0.78 to 0.91; p<0.001). The intervention group also had a 13% lower risk of cognitive impairment and no dementia (p<0.001). “These results support the long-term sustainability of integrating structured BP management into routine primary care for dementia prevention at the population level,” concluded Dr. Zhong. 

Meta-analysis of BP trials

Next, Professor Kazem Rahimi (University of Oxford - Oxford, UK) described an individual-participant-data meta-analysis of randomised controlled trials comparing antihypertensive treatment (single or multiple agents, or intensive regimens) vs. a comparator (placebo, active comparators, or less intensive regimens) to assess whether the benefits of BP-lowering treatment extend across the spectrum of cardiovascular risk. A total of 357,440 randomised participants from 51 trials were included. Participants were classified into 10 categories defined by deciles of predicted 5-year CV risk at randomisation. Over a median follow-up of 4.2 years, the HR for major cardiovascular disease was 0.90 per 5 mm Hg reduction in SBP, with homogeneous effects across all risk categories (p for interaction >0.99). In absolute terms, risk reductions increased progressively with baseline predicted risk, from 0.4 percentage points in the lowest decile to 2.6 percentage points in the highest (p for trend <0.001). It was concluded that risk-guided management could prevent cardiovascular events missed under conventional strategies while avoiding unnecessary treatment in those least likely to benefit.

ECLIPSE-CKD

To end the session, Doctor Dong Shui (Harbin - China) presented the ECLIPSE-CKD trial, which assessed the efficacy and safety of salt substitutes in patients with CKD. A total of 640 participants with hypertension and an eGFR of 45 to 89 mL/min/1.73 m² were randomised to receive a salt substitute (75% sodium chloride and 25% potassium chloride) or regular salt (100% sodium chloride). At 3 months, SBP decreased by 6.6 mmHg with the salt substitute vs. 2.0 mmHg with regular salt (p<0.001). Serum potassium was higher in the salt substitute group (0.2 mmol/L vs. 0 mmol/L; p<0.001) but no episodes of hyperkalaemia were observed. It was concluded that further trials are required to establish the long-term effects of salt substitution on cardiovascular and kidney outcomes, and safety.