Effectiveness of bivalent COVID-19 boosters against COVID-19 mortality in people aged 65 years and older, Australia, November 2022 to May 2023.

We followed 4,081,257 Australian adults aged ≥ 65 years between November 2022 and May 2023 for COVID-19-specific mortality, when recombinant SARS-CoV-2 Omicron lineages (predominantly XB and XBB) as well as BA.2.75 were circulating. Compared with a COVID-19 booster targeting ancestral SARS-CoV-2 given > 180 days earlier, the relative vaccine effectiveness against COVID-19 death of a bivalent (ancestral/BA.1 or ancestral/BA.4-5) booster given 8 to 90 days earlier was 66.0% (95%CI: 57.6 to 72.2%) and that of a monovalent ancestral booster given 8 to 90 days earlier was 44.7% (95%CI: 23.9 to 59.7%).

Effectiveness of COVID-19 vaccination against COVID-19 specific and all-cause mortality in older Australians: a population based study.

Background: Few studies have examined effectiveness of COVID-19 vaccines against COVID-19 and all-cause mortality across different pandemic periods in 2022. Methods: We used linked whole-of-population data from the 2021 Australian Census, Australian Immunisation Register, death registrations and other national datasets including migration data. Among 3.8 million adults aged 65+ years and >170,000 aged care residents, we used survival analysis to estimate vaccine effectiveness (VE) against COVID-19 specific mortality and all-cause mortality, by vaccine dose and time since receipt, adjusted for age, sex and other factors. We also estimated absolute COVID-19 mortality rates. Findings: From January-May 2022 (Omicron BA.1/2), 3250 COVID-19 deaths occurred; from June-November (Omicron BA.4/5) 3185 COVID-19 deaths occurred. During January-May, VE of a 3rd COVID-19 vaccine dose within 3 months was 93% (95% CI 93-94%) whilst VE of a 2nd dose >6 months since receipt was 34% (26-42%). During June-November, VE of a 4th COVID-19 vaccine dose within 3 months was 84% (82-86%) whilst VE of a 3rd dose >6 months since receipt was 56% (50-62%). VE estimates for aged care residents were similar, but absolute risk reductions were substantially greater. During June-November 2022, for all-cause mortality, VE of a 4th dose within 3 months was 58% (56-59%) whilst VE of a 3rd dose >6 months since receipt was 19% (16-22%). Interpretations: COVID-19 vaccination is highly effective against COVID-19 mortality among older adults although effectiveness wanes with time since the last dose. Our findings emphasise the importance of continuing to administer booster doses, particularly to those at highest risk. Funding: This study was funded by the Health Economics Research Division in the Australian Government Department of Health and Aged Care.

Comparative effectiveness of four COVID-19 vaccines, BNT162b2 mRNA, mRNA-1273, ChAdOx1 nCov-19 and NVX-CoV2373 against SARS-CoV-2 B.1.1.529 (Omicron) infection.

BACKGROUND: There is limited data directly comparing the effectiveness of different COVID-19 vaccines. METHODS: We compared rates of SARS-CoV-2 Omicron BA.1/2 infection during March to May 2022 in Australian adults who had received one of four COVID-19 vaccines in the last 14-63 days as either a primary course or a booster dose using Cox proportional hazards models adjusting for age and other characteristics. RESULTS: As a primary course, over 2318 person-years and 1033 infections, compared to recipients of BNT162b2 mRNA vaccine, adjusted hazard ratios for SARS-CoV-2 infection were 1.03 (95%CI 0.82-1.30), 1.19 (0.95-1.49), 1.70 (1.46-1.97) for respectively mRNA-1273, ChAdOx-1 nCov-19 and NVX-CoV2373. For the booster dose, over 154,984 person-years and 93,580 infections the respective adjusted hazard ratios compared to BNT162b2 mRNA vaccine were 1.02 (95%CI 1.00-1.04), 1.20 (1.10-1.32), 1.39 (1.20-1.60). CONCLUSIONS: Our findings suggest relatively higher effectiveness of ancestral strain mRNA vaccines against SARS-CoV-2 Omicron infection than viral vector and protein subunit vaccines and provide clinical confirmation of immunological data on differences in COVID-19 vaccine performance.

COVID-19 Vaccine Uptake by Infection Status in New South Wales, Australia.

Using linked public health data from Australia to measure uptake of COVID-19 vaccination by infection status, we found coverage considerably lower among infected than uninfected persons for all ages. Increasing uptake of scheduled doses, including among previously infected persons after the recommended postinfection delay, is needed to reduce COVID-19 illness rates.

Relative effectiveness of COVID-19 vaccination with 3 compared to 2 doses against SARS-CoV-2 B.1.1.529 (Omicron) among an Australian population with low prior rates of SARS-CoV-2 infection.

BACKGROUND: We estimate effectiveness of 3 versus 2 vaccine doses against SARS-CoV-2 B.1.1.529 Omicron in a mostly infection-naiive but highly vaccinated Australian population. METHODS: Cohort study of adults aged 40+ years resident in Sydney followed from 1 January 2022 for SARS-CoV-2 infection and COVID-19 hospitalisation or death using linked immunisation, disease notification and hospitalisation registers. Adjusted hazard ratios (aHR) and corresponding relative vaccine effectiveness (rVE) were estimated comparing 3 to 2 vaccine dose recipients by time since dose receipt, vaccine brand, and prior infection. Absolute risk reductions and numbers needed to boost by age groups were calculated. RESULTS: 2,053,123 infection-naiive individuals (mean age 59 years) were followed for 327,272 person-years for infection and 224,269 person-years for severe outcomes (hospitalisation/death). There were 175,849 infections and 4113 hospitalisations/deaths. Compared to individuals receiving dose 2 within the last 3 months, rVE in dose 3 recipients was 7% (95% CI 5-9%) against infection and 65% (95%CI 61-69%) against hospitalisation/death. Almost all dose 3 recipients had an mRNA vaccine; there was little difference in dose 3 rVE by primary course vaccine brand (ChAdOx1 versus BNT162b2). Over the 6-week follow-up, we estimated one hospitalisation/death was avoided for every 192 adults aged ≥70 years boosted with dose 3 in the infection-naiive cohort. The aHR for hospitalisation/death from Omicron was 0.12 (95 %CI 0.07-0.23) for 2-dose recipients with a prior Delta infection compared with 2-dose recipients with no prior infection. CONCLUSIONS: Receipt of a third COVID-19 vaccine dose in adults aged 40 years and above significantly reduced hospitalisations and deaths from SARS-CoV-2 Omicron infections in a primarily infection-naiive population.

High Attack Rate of Severe Acute Respiratory Syndrome Coronavirus 2 B.1.1.529 Among 2-Dose Vaccinated Populations in 2 Indoor Entertainment Setting Outbreaks.

We estimated attack rates of severe acute respiratory syndrome coronavirus 2 Omicron (B.1.1.529) infection among people attending a nightclub and a graduation ball where >95% had at least 2 vaccine doses. Attack rates were 295 of 535 (55.1%) and 102 of 189 (54.0%), respectively (mean, 5 days postevent). At the ball, attack rates increased with time since vaccination: 12.5% among those vaccinated 1-2 months previously and 68.0% among those vaccinated ≥3 months previously; such differences were not found at the nightclub. Recent vaccination prevents Omicron infection, but is time and setting dependent, emphasizing the importance of nonpharmaceutical public health measures in addition to vaccine booster doses to maximize protection in high-risk contexts.

Text Messages to Improve Medication Adherence and Secondary Prevention After Acute Coronary Syndrome: The TEXTMEDS Randomized Clinical Trial.

BACKGROUND: TEXTMEDS (Text Messages to Improve Medication Adherence and Secondary Prevention After Acute Coronary Syndrome) examined the effects of text message-delivered cardiac education and support on medication adherence after an acute coronary syndrome. METHODS: TEXTMEDS was a single-blind, multicenter, randomized controlled trial of patients after acute coronary syndrome. The control group received usual care (secondary prevention as determined by the treating clinician); the intervention group also received multiple motivational and supportive weekly text messages on medications and healthy lifestyle with the opportunity for 2-way communication (text or telephone). The primary end point of self-reported medication adherence was the percentage of patients who were adherent, defined as >80% adherence to each of up to 5 indicated cardioprotective medications, at both 6 and 12 months. RESULTS: A total of 1424 patients (mean age, 58 years [SD, 11]; 79% male) were randomized from 18 Australian public teaching hospitals. There was no significant difference in the primary end point of self-reported medication adherence between the intervention and control groups (relative risk, 0.93 [95% CI, 0.84-1.03]; P=0.15). There was no difference between intervention and control groups at 12 months in adherence to individual medications (aspirin, 96% vs 96%; ß-blocker, 84% vs 84%; angiotensin-converting enzyme inhibitor/angiotensin receptor blocker, 77% vs 80%; statin, 95% vs 95%; second antiplatelet, 84% vs 84% [all P>0.05]), systolic blood pressure (130 vs 129 mm Hg; P=0.26), low-density lipoprotein cholesterol (2.0 vs 1.9 mmol/L; P=0.34), smoking (P=0.59), or exercising regularly (71% vs 68%; P=0.52). There were small differences in lifestyle risk factors in favor of intervention on body mass index <25 kg/m2 (21% vs 18%; P=0.01), eating ≥5 servings per day of vegetables (9% vs 5%; P=0.03), and eating ≥2 servings per day of fruit (44% vs 39%; P=0.01). CONCLUSIONS: A text message-based program had no effect on medical adherence but small effects on lifestyle risk factors. REGISTRATION: URL: https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=364448; Unique identifier: ANZCTR ACTRN12613000793718.

Effect of Oral Methylprednisolone on Decline in Kidney Function or Kidney Failure in Patients With IgA Nephropathy: The TESTING Randomized Clinical Trial.

Importance: The effect of glucocorticoids on major kidney outcomes and adverse events in IgA nephropathy has been uncertain. Objective: To evaluate the efficacy and adverse effects of methylprednisolone in patients with IgA nephropathy at high risk of kidney function decline. Design, Setting, and Participants: An international, multicenter, double-blind, randomized clinical trial that enrolled 503 participants with IgA nephropathy, proteinuria greater than or equal to 1 g per day, and estimated glomerular filtration rate (eGFR) of 20 to 120 mL/min/1.73 m2 after at least 3 months of optimized background care from 67 centers in Australia, Canada, China, India, and Malaysia between May 2012 and November 2019, with follow-up until June 2021. Interventions: Participants were randomized in a 1:1 ratio to receive oral methylprednisolone (initially 0.6-0.8 mg/kg/d, maximum 48 mg/d, weaning by 8 mg/d/mo; n = 136) or placebo (n = 126). After 262 participants were randomized, an excess of serious infections was identified, leading to dose reduction (0.4 mg/kg/d, maximum 32 mg/d, weaning by 4 mg/d/mo) and addition of antibiotic prophylaxis for pneumocystis pneumonia for subsequent participants (121 in the oral methylprednisolone group and 120 in the placebo group). Main Outcomes And Measures: The primary end point was a composite of 40% decline in eGFR, kidney failure (dialysis, transplant), or death due to kidney disease. There were 11 secondary outcomes, including kidney failure. Results: Among 503 randomized patients (mean age, 38 years; 198 [39%] women; mean eGFR, 61.5 mL/min/1.73 m2; mean proteinuria, 2.46 g/d), 493 (98%) completed the trial. Over a mean of 4.2 years of follow-up, the primary outcome occurred in 74 participants (28.8%) in the methylprednisolone group compared with 106 (43.1%) in the placebo group (hazard ratio [HR], 0.53 [95% CI, 0.39-0.72]; P < .001; absolute annual event rate difference, -4.8% per year [95% CI, -8.0% to -1.6%]). The effect on the primary outcome was seen across each dose compared with the relevant participants in the placebo group recruited to each regimen (P for heterogeneity = .11): full-dose HR, 0.58 (95% CI, 0.41-0.81); reduced-dose HR, 0.27 (95% CI, 0.11-0.65). Of the 11 prespecified secondary end points, 9 showed significant differences in favor of the intervention, including kidney failure (50 [19.5%] vs 67 [27.2%]; HR, 0.59 [95% CI, 0.40-0.87]; P = .008; annual event rate difference, -2.9% per year [95% CI, -5.4% to -0.3%]). Serious adverse events were more frequent with methylprednisolone vs placebo (28 [10.9%] vs 7 [2.8%] patients with serious adverse events), primarily with full-dose therapy compared with its matching placebo (22 [16.2%] vs 4 [3.2%]). Conclusions and Relevance: Among patients with IgA nephropathy at high risk of progression, treatment with oral methylprednisolone for 6 to 9 months, compared with placebo, significantly reduced the risk of the composite outcome of kidney function decline, kidney failure, or death due to kidney disease. However, the incidence of serious adverse events was increased with oral methylprednisolone, mainly with high-dose therapy. Trial Registration: ClinicalTrials.gov Identifier: NCT01560052.

Effect of Salt Substitution on Cardiovascular Events and Death.

BACKGROUND: Salt substitutes with reduced sodium levels and increased potassium levels have been shown to lower blood pressure, but their effects on cardiovascular and safety outcomes are uncertain. METHODS: We conducted an open-label, cluster-randomized trial involving persons from 600 villages in rural China. The participants had a history of stroke or were 60 years of age or older and had high blood pressure. The villages were randomly assigned in a 1:1 ratio to the intervention group, in which the participants used a salt substitute (75% sodium chloride and 25% potassium chloride by mass), or to the control group, in which the participants continued to use regular salt (100% sodium chloride). The primary outcome was stroke, the secondary outcomes were major adverse cardiovascular events and death from any cause, and the safety outcome was clinical hyperkalemia. RESULTS: A total of 20,995 persons were enrolled in the trial. The mean age of the participants was 65.4 years, and 49.5% were female, 72.6% had a history of stroke, and 88.4% a history of hypertension. The mean duration of follow-up was 4.74 years. The rate of stroke was lower with the salt substitute than with regular salt (29.14 events vs. 33.65 events per 1000 person-years; rate ratio, 0.86; 95% confidence interval [CI], 0.77 to 0.96; P = 0.006), as were the rates of major cardiovascular events (49.09 events vs. 56.29 events per 1000 person-years; rate ratio, 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; rate ratio, 0.88; 95% CI, 0.82 to 0.95; P<0.001). The rate of serious adverse events attributed to hyperkalemia was not significantly higher with the salt substitute than with regular salt (3.35 events vs. 3.30 events per 1000 person-years; rate ratio, 1.04; 95% CI, 0.80 to 1.37; P = 0.76). CONCLUSIONS: Among persons who had a history of stroke or were 60 years of age or older and had high blood pressure, the rates of stroke, major cardiovascular events, and death from any cause were lower with the salt substitute than with regular salt. (Funded by the National Health and Medical Research Council of Australia; SSaSS ClinicalTrials.gov number, NCT02092090.).

Association of Low-Dose Triple Combination Therapy With Therapeutic Inertia and Prescribing Patterns in Patients With Hypertension: A Secondary Analysis of the TRIUMPH Trial.

Importance: Fixed-dose combination (FDC) therapies are being increasingly recommended for initial or early management of patients with hypertension, as they reduce treatment complexity and potentially reduce therapeutic inertia. Objective: To investigate the association of antihypertensive triple drug FDC therapy with therapeutic inertia and prescribing patterns compared with usual care. Design, Setting, and Participants: A post hoc analysis of the Triple Pill vs Usual Care Management for Patients With Mild-to-Moderate Hypertension (TRIUMPH) study, a randomized clinical trial of 700 patients with hypertension, was conducted. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Data were analyzed from September to November 2019. Interventions: Once-daily FDC antihypertensive pill (telmisartan, 20 mg; amlodipine, 2.5 mg; and chlorthalidone, 12.5 mg) or usual care. Main Outcomes and Measures: Therapeutic inertia, defined as not intensifying therapy in those with blood pressure (BP) above target, was assessed at baseline and during follow-up visits. Prescribing patterns were characterized by BP-lowering drug class and treatment regimen potency. Predictors of therapeutic inertia were assessed with binomial logistic regression. Results: Of the 700 included patients, 403 (57.6%) were female, and the mean (SD) age was 56 (11) years. Among patients who did not reach the BP target, therapeutic inertia was more common in the triple pill group compared with the usual care group at the week 6 visit (92 of 106 [86.8%] vs 124 of 194 [63.9%]; P < .001) and week 12 visit (81 of 90 [90%] vs 116 of 179 [64.8%]; P < .001). At the end of the study, 221 of 318 patients in the triple pill group (69.5%) and 182 of 329 patients in the usual care group (55.3%) reached BP targets. Among those who received treatment intensification, the increase in estimated regimen potency was greater in the triple pill group compared with the usual care group at baseline (predicted mean [SD] increase in regimen potency: triple pill, 15 [6] mm Hg; usual care, 10 [5] mm Hg; P < .001), whereas there were no significant differences at the week 6 or at week 12 visit. Clinic systolic BP level was the only consistent predictor of treatment intensification during follow-up. During follow-up, there were 23 vs 54 unique treatment regimens per 100 treated patients in the triple pill vs usual care groups, respectively (P < .001). Conclusions and Relevance: Triple pill FDC therapy was associated with greater rates of therapeutic inertia compared with usual care. Despite this, triple pill FDC therapy substantially simplified prescribing patterns and improved 6-month BP control rates compared with usual care. Further improvements in hypertension control could be achieved by addressing therapeutic inertia among the minority of patients who do not achieve BP control after initial FDC therapy. Trial Registration: ANZCTR Identifier: ACTRN12612001120864.

Mobile phone text-messaging interventions aimed to prevent cardiovascular diseases (Text2PreventCVD): systematic review and individual patient data meta-analysis.

Background: A variety of small mobile phone text-messaging interventions have indicated improvement in risk factors for cardiovascular disease (CVD). Yet the extent of this improvement and whether it impacts multiple risk factors together is uncertain. We aimed to conduct a systematic review and individual patient data (IPD) meta-analysis to investigate the effects of text-messaging interventions for CVD prevention. Methods: Electronic databases were searched to identify trials investigating a text-messaging intervention focusing on CVD prevention with the potential to modify at least two CVD risk factors in adults. The main outcome was blood pressure (BP). We conducted standard and IPD meta-analysis on pooled data. We accounted for clustering of patients within studies and the primary analysis used random-effects models. Sensitivity and subgroup analyses were performed. Results: Nine trials were included in the systematic review involving 3779 participants and 5 (n=2612) contributed data to the IPD meta-analysis. Standard meta-analysis showed that the weighted mean differences are as follows: systolic blood pressure (SBP), -4.13 mm Hg (95% CI -11.07 to 2.81, p<0.0001); diastolic blood pressure (DBP), -1.11 mm Hg (-1.91 to -0.31, p=0.002); and body mass index (BMI), -0.32 (-0.49 to -0.16, p=0.000). In the IPD meta-analysis, the mean difference are as follows: SBP, -1.3 mm Hg (-5.4 to 2.7, p=0.5236); DBP, -0.8 mm Hg (-2.5 to 1.0, p=0.3912); and BMI, -0.2 (-0.8 to 0.4, p=0.5200) in the random-effects model. The impact on other risk factors is described, but there were insufficient data to conduct meta-analyses. Conclusion: Mobile phone text-messaging interventions have modest impacts on BP and BMI. Simultaneous but small impacts on multiple risk factors are likely to be clinically relevant and improve outcome, but there are currently insufficient data in pooled analyses to examine the extent to which simultaneous reduction in multiple risk factors occurs. PROSPERO registration number: CRD42016033236.

Fixed-combination, low-dose, triple-pill antihypertensive medication versus usual care in patients with mild-to-moderate hypertension in Sri Lanka: a within-trial and modelled economic evaluation of the TRIUMPH trial.

BACKGROUND: Elevated blood pressure incurs a major health and economic burden, particularly in low-income and middle-income countries. The Triple Pill versus Usual Care Management for Patients with Mild-to-Moderate Hypertension (TRIUMPH) trial showed a greater reduction in blood pressure in patients using fixed-combination, low-dose, triple-pill antihypertensive therapy (consisting of amlodipine, telmisartan, and chlorthalidone) than in those receiving usual care in Sri Lanka. We aimed to assess the cost-effectiveness of the triple-pill strategy. METHODS: We did a within-trial (6-month) and modelled (10-year) economic evaluation of the TRIUMPH trial, using the health system perspective. Health-care costs, reported in 2017 US dollars, were determined from trial records and published literature. A discrete-time simulation model was developed, extrapolating trial findings of reduced systolic blood pressure to 10-year health-care costs, cardiovascular disease events, and mortality. The primary outcomes were the proportion of people reaching blood pressure targets (at 6 months from baseline) and disability-adjusted life-years (DALYs) averted (at 10 years from baseline). Incremental cost-effectiveness ratios were calculated to estimate the cost per additional participant achieving target blood pressure at 6 months and cost per DALY averted over 10 years. FINDINGS: The triple-pill strategy, compared with usual care, cost an additional US$9·63 (95% CI 5·29 to 13·97) per person in the within-trial analysis and $347·75 (285·55 to 412·54) per person in the modelled analysis. Incremental cost-effectiveness ratios were estimated at $7·93 (95% CI 6·59 to 11·84) per participant reaching blood pressure targets at 6 months and $2842·79 (-28·67 to 5714·24) per DALY averted over a 10-year period. INTERPRETATION: Compared with usual care, the triple-pill strategy is cost-effective for patients with mild-to-moderate hypertension. Scaled up investment in the triple pill for hypertension management in Sri Lanka should be supported to address the high population burden of cardiovascular disease. FUNDING: Australian National Health and Medical Research Council.

Effect of text messaging on depression in patients with coronary heart disease: a substudy analysis from the TEXT ME randomised controlled trial.

OBJECTIVE: We aimed to evaluate the effects on depression scores of a lifestyle-focused cardiac support programme delivered via mobile phone text messaging among patients with coronary heart disease (CHD). DESIGN: Substudy and secondary analysis of a parallel-group, single-blind randomised controlled trial of patients with CHD. SETTING: A tertiary hospital in Sydney, Australia. INTERVENTION: The Tobacco, Exercise and dieT MEssages programme comprised four text messages per week for 6 months that provided education, motivation and support on diet, physical activity, general cardiac education and smoking, if relevant. The programme did not have any specific mental health component. OUTCOMES: Depression scores at 6 months measured using the Patient Health Questionnaire-9 (PHQ-9). Treatment effect across subgroups was measured using log-binomial regression model for the binary outcome (depressed/not depressed, where depressed is any score of PHQ-9 ≥5) with treatment, subgroup and treatment by subgroup interaction as fixed effects. RESULTS: Depression scores at 6 months were lower in the intervention group compared with the control group, mean difference 1.9 (95% CI 1.5 to 2.4, p<0.0001). The frequency of mild or greater depressive symptoms (PHQ-9 scores≥5) at 6 months was 21/333 (6.3%) in the intervention group and 86/350 (24.6%) in the control group (relative risk (RR) 0.26, 95% CI 0.16 to 0.40, p<0.001). This proportional reduction in depressive symptoms was similar across groups defined by age, sex, education, body mass index, physical activity, current smoking, current drinking and history of depression, diabetes and hypertension. In particular, the rates of PHQ-9 ≥5 among people with a history of depression were 4/44 (9.1%) vs 29/62 (46.8%) in intervention vs control (RR 0.19, 95% CI 0.07 to 0.51, p<0.001), and were 17/289 (5.9%) vs 57/288 (19.8%) among others (RR 0.30, 95% CI 0.18 to 0.50, p<0.001). CONCLUSIONS: Among people with CHD, a cardiac support programme delivered via mobile phone text messaging was associated with fewer symptoms of mild-to-moderate depression at 6 months in the treatment group compared with controls. TRIAL REGISTRATION NUMBER: ACTRN12611000161921.

Reaching cardiovascular prevention guideline targets with a polypill-based approach: a meta-analysis of randomised clinical trials.

OBJECTIVE: The aim of this study was to determine the effect of polypill-based care on the achievement of 2016 European Society of Cardiology (ESC) guideline targets for blood pressure (BP), low-density lipoprotein (LDL) cholesterol and antiplatelet therapy. METHODS: We conducted an individual participant data meta-analysis of three randomised clinical trials that compared a strategy using a polypill containing aspirin, statin and antihypertensive therapy with usual care in patients with a prior cardiovascular disease (CVD) event or who were at high risk of their first event. Overall, the trials included 3140 patients from Australia, England, India, Ireland, the Netherlands and New Zealand (75% male, mean age 62 years and 76% with a prior CVD event). The primary outcome for this study was the proportion of people achieving ESC guideline targets for BP, LDL and antiplatelet therapy. RESULTS: Those randomised to polypill-based care were more likely than those receiving usual care to achieve recommended targets for BP (62% vs 58%, risk ratio (RR) 1.08, 95% CI 1.02 to 1.15), LDL (39% vs 34%, RR 1.13, 95% CI 1.02 to 1.25) and all three targets for BP, LDL and adherence to antiplatelet therapy (the latter only applicable to those with a prior CVD event) simultaneously (24% vs 19%, RR 1.27, 95% CI 1.10 to 1.47) at 12 months. There was no difference between groups in antiplatelet adherence (96% vs 96%, RR 1.00, 95% CI 0.98 to 1.01). There was heterogeneity by baseline treatment intensity such that treatment effects increased with the fewer the number of treatments being taken at baseline: for patients taking 3, 2 and 0-1 treatment modalities the RRs for reaching all three guideline goals simultaneously were 1.10 (95% CI 0.94 to 1.30, 22% vs 20%), 1.62 (95% CI 1.09 to 2.42, 27% vs 17%) and 3.07 (95% CI 1.77 to 5.33, 35% vs 11%), respectively. CONCLUSIONS: Polypill-based therapy significantly improved the achievement of all three ESC targets for BP, LDL and antiplatelet therapy compared with usual care, particularly among those undertreated at baseline.

Spot urine samples compared with 24-h urine samples for estimating changes in urinary sodium and potassium excretion in the China Salt Substitute and Stroke Study.

Background: The capacity of spot urine samples for detecting changes in population sodium and potassium excretion is unclear. Methods: Changes in urinary sodium and potassium excretion, over a 6-month to 2-year interval, were measured from 24-h urine samples and estimated from spot urine samples using several published methods in 3270 Chinese. Additional estimates were made by multiplying individual spot sodium and potassium concentrations by a single estimated 24-h urine volume derived from external data. Results: The measured difference in 24-h urinary excretion between intervention and control groups was -0.35 g (95% CI: -0.68 to -0.02; P = 0.039) for sodium and 0.66 g (95% CI: 0.52 to 0.80; P < 0.001) for potassium, based upon 24-h urine samples. The corresponding estimates of sodium differences for the Tanaka (-0.06 g), Kawasaki (-0.09 g), Intersalt without potassium (-0.09 g) and Intersalt with potassium (-0.14 g) equations were all smaller and identified no reduction in sodium excretion (all P > 0.10). The estimates were -0.65 g for sodium and 1.11 g for potassium using individual spot urine concentrations and an externally derived standard urine volume (both P < 0.01). Conclusions: The published equations were unable to detect the differences in sodium excretion measured by 24-h urine samples. A method based upon spot urine electrolyte concentrations and a standard urine volume may offer an alternative approach to measuring differences in sodium and potassium excretion between population groups without requiring 24-h urine, but will need further investigation.

Fixed Low-Dose Triple Combination Antihypertensive Medication vs Usual Care for Blood Pressure Control in Patients With Mild to Moderate Hypertension in Sri Lanka: A Randomized Clinical Trial.

Importance: Poorly controlled hypertension is a leading global public health problem requiring new treatment strategies. Objective: To assess whether a low-dose triple combination antihypertensive medication would achieve better blood pressure (BP) control vs usual care. Design, Setting, and Participants: Randomized, open-label trial of a low-dose triple BP therapy vs usual care for adults with hypertension (systolic BP >140 mm Hg and/or diastolic BP >90 mm Hg; or in patients with diabetes or chronic kidney disease: >130 mm Hg and/or >80 mm Hg) requiring initiation (untreated patients) or escalation (patients receiving monotherapy) of antihypertensive therapy. Patients were enrolled from 11 urban hospital clinics in Sri Lanka from February 2016 to May 2017; follow-up ended in October 2017. Interventions: A once-daily fixed-dose triple combination pill (20 mg of telmisartan, 2.5 mg of amlodipine, and 12.5 mg of chlorthalidone) therapy (n = 349) or usual care (n = 351). Main Outcomes and Measures: The primary outcome was the proportion achieving target systolic/diastolic BP (<140/90 mm Hg or <130/80 mm Hg in patients with diabetes or chronic kidney disease) at 6 months. Secondary outcomes included mean systolic/diastolic BP difference during follow-up and withdrawal of BP medications due to an adverse event. Results: Among 700 randomized patients (mean age, 56 years; 58% women; 29% had diabetes; mean baseline systolic/diastolic BP, 154/90 mm Hg), 675 (96%) completed the trial. The triple combination pill increased the proportion achieving target BP vs usual care at 6 months (70% vs 55%, respectively; risk difference, 12.7% [95% CI, 3.2% to 22.0%]; P < .001). Mean systolic/diastolic BP at 6 months was 125/76 mm Hg for the triple combination pill vs 134/81 mm Hg for usual care (adjusted difference in postrandomization BP over the entire follow-up: systolic BP, -9.8 [95% CI, -7.9 to -11.6] mm Hg; diastolic BP, -5.0 [95% CI, -3.9 to -6.1] mm Hg; P < .001 for both comparisons). Overall, 419 adverse events were reported in 255 patients (38.1% for triple combination pill vs 34.8% for usual care) with the most common being musculoskeletal pain (6.0% and 8.0%, respectively) and dizziness, presyncope, or syncope (5.2% and 2.8%). There were no significant between-group differences in the proportion of patient withdrawal from BP-lowering therapy due to adverse events (6.6% for triple combination pill vs 6.8% for usual care). Conclusions and Relevance: Among patients with mild to moderate hypertension, treatment with a pill containing low doses of 3 antihypertensive drugs led to an increased proportion of patients achieving their target BP goal vs usual care. Use of such medication as initial therapy or to replace monotherapy may be an effective way to improve BP control. Trial Registration: anzctr.org.au Identifier: ACTRN12612001120864; slctr.lk Identifier: SLCTR/2015/020.

Contrasting Timing of Virological Relapse After Discontinuation of Tenofovir or Entecavir in Hepatitis B e Antigen-Negative Patients.

Stopping long-term nucleos(t)ide analogue therapy increases hepatitis B virus (HBV) surface antigen (HBsAg) loss rates in HBV e antigen (HBeAg)-negative patients. Viral rebound may induce immune responses facilitating functional cure. We analyzed which factors are associated with timing of virological relapse in 220 Asian HBeAg-negative patients from the prospective ABX203 vaccine study. Unexpectedly, only the type of antiviral therapy was significantly associated with early virological relapse, defined as an HBV DNA load of >2000 IU/mL until week 12, and relapse occurred earlier in patients treated with tenofovir versus those treated with entecavir (median time, 6 vs 24 weeks; P < .0001). This should be considered for future trials and monitoring of patients after treatment discontinuation.

TEXT messages to improve MEDication adherence and Secondary prevention (TEXTMEDS) after acute coronary syndrome: a randomised clinical trial protocol.

BACKGROUND: Identifying simple, low-cost and scalable means of supporting lifestyle change and medication adherence for patients following a cardiovascular (CV) event is important. OBJECTIVE: The TEXTMEDS (TEXT messages to improve MEDication adherence and Secondary prevention) study aims to investigate whether a cardiac education and support programme sent via mobile phone text message improves medication adherence and risk factor levels in patients following an acute coronary syndrome (ACS). STUDY DESIGN: A single-blind, multicentre, randomised clinical trial of 1400 patients after an ACS with 12 months follow-up. The intervention group will receive multiple weekly text messages that provide information, motivation, support to adhere to medications, quit smoking (if relevant) and recommendations for healthy diet and exercise. The primary endpoint is the percentage of patients who are adherent to cardioprotective medications and the key secondary outcomes are mean systolic blood pressure (BP) and low-density lipoprotein cholesterol. Secondary outcomes will also include total cholesterol, mean diastolic BP, the percentage of participants who are adherent to each cardioprotective medication class, the percentage of participants who achieve target levels of CV risk factors, major vascular events, hospital readmissions and all-cause mortality. The study will be augmented by formal economic and process evaluations to assess acceptability, utility and cost-effectiveness. SUMMARY: The study will provide multicentre randomised trial evidence of the effects of a text message-based programme on cardioprotective medication adherence and levels of CV risk factors. ETHICS AND DISSEMINATION: Primary ethics approval was received from Western Sydney Local Health District Human Research Ethics Committee (HREC2012/12/4.1 (3648) AU RED HREC/13/WMEAD/15). Results will be disseminated via peer-reviewed publications and presentations at international conferences. TRIAL REGISTRATION NUMBER: ACTRN12613000793718; Pre-results.

Impact of switching to polypill based therapy by baseline potency of medication: Post-hoc analysis of the SPACE Collaboration dataset.

BACKGROUND: Fixed dose combinations of cardiovascular therapy ('polypills') have now been launched in several dozen countries. There is considerable clinical interest in the effects of switching to polypill-based care from typical current treatment regimens, especially if polypills contain components at sub-maximal dosage. METHODS: The SPACE Collaboration includes three trials of polypill based care vs usual care in patients with established CVD or at high calculated risk. Individual patient data for 3140 trial participants were combined. Patients were categorized according to the potency of the statin and the number of BP lowering medications they were taking at baseline. Effects on adherence to anti-platelet medication, systolic blood pressure (SBP) and LDL cholesterol stratified by baseline potency of medication were determined using fixed effects models. RESULTS: Randomisation to the polypill group was associated with improved SBP at 12months, but this improvement varied according to baseline BP regimen: -3.3, -5.9, -2.5 and +1mmHg for patients taking 0, 1, 2 and 3+ BP lowering medications at baseline. For changes in LDL cholesterol at 12months, significant improvements in LDL cholesterol were seen for those taking no statin (-0.21mmol/L; 95% CI: -0.34 to -0.07), less potent statin (-0.16mmol/L; 95% CI: -0.29 to -0.04) and equipotent statins (-0.14mmol/L; 95% CI -0.26 to -0.02) at baseline. CONCLUSION: The adherence benefits of polypills tend to offset the loss of potency from use of individual components with lower dose potency, and to facilitate improvements in multiple risk factors.

Rationale, design, and baseline characteristics of the Salt Substitute and Stroke Study (SSaSS)-A large-scale cluster randomized controlled trial.

Lowering sodium intake with a reduced-sodium, added potassium salt substitute has been proved to lower blood pressure levels. Whether the same strategy will also reduce the risks of vascular outcomes is uncertain and controversial. The SSaSS has been designed to test whether sodium reduction achieved with a salt substitute can reduce the risk of vascular disease. The study is a large-scale, open, cluster-randomized controlled trial done in 600 villages across 5 provinces in China. Participants have either a history of stroke or an elevated risk of stroke based on age and blood pressure level at entry. Villages were randomized in a 1:1 ratio to intervention or continued usual care. Salt substitute is provided free of charge to participants in villages assigned to the intervention group. Follow-up is scheduled every 6months for 5years, and all potential endpoints are reviewed by a masked adjudication committee. The primary end point is fatal and nonfatal stroke, and the 2 secondary endpoints are total major cardiovascular events and total mortality. The study has been designed to provide 90% statistical power (with 2-sided α = .05) to detect a 13% or greater relative risk reduction for stroke. The power estimate assumes a primary outcome event rate of 3.5% per year and a systolic blood pressure difference of 3.0mm Hg between randomized groups. Recruitment is complete and there are 20,996 participants (about 35 per village) that have been enrolled. Mean age is 65years and 49% are female. There were 73% enrolled on the basis of a history of stroke. The trial is well placed to describe the effects of salt substitution on the risks of vascular disease and death and will provide important policy-relevant data.