Jay Thakkar

Effect of Lifestyle-Focused Text Messaging on Risk Factor Modification in Patients With Coronary Heart Disease: A Randomized Clinical Trial

IMPORTANCE Cardiovascular disease prevention, including lifestyle modification, is important but underutilized. Mobile health strategies could address this gap but lack evidence of therapeutic benefit. OBJECTIVE To examine the effect of a lifestyle-focused semipersonalized support program delivered by mobile phone text message on cardiovascular risk factors. DESIGN AND SETTING The Tobacco, Exercise and Diet Messages (TEXT ME) trial was a parallel-group, single-blind, randomized clinical trial that recruited 710 patients (mean age, 58 [SD, 9.2] years; 82% men; 53% current smokers) with proven coronary heart disease (prior myocardial infarction or proven angiographically) between September 2011 and November 2013 from a large tertiary hospital in Sydney, Australia. INTERVENTIONS Patients in the intervention group (n = 352) received 4 text messages per week for 6 months in addition to usual care. Text messages provided advice, motivational reminders, and support to change lifestyle behaviors. Patients in the control group (n=358) received usual care. Messages for each participant were selected from a bank of messages according to baseline characteristics (eg, smoking) and delivered via an automated computerized message management system. The program was not interactive. MAIN OUTCOMES AND MEASURES The primary end point was low-density lipoprotein cholesterol (LDL-C) level at 6 months. Secondary end points included systolic blood pressure, body mass index (BMI), physical activity, and smoking status. RESULTS At 6 months, levels of LDL-C were significantly lower in intervention participants, with concurrent reductions in systolic blood pressure and BMI, significant increases in physical activity, and a significant reduction in smoking. The majority reported the text messages to be useful (91%), easy to understand (97%), and appropriate in frequency (86%). [table: see text]. CONCLUSIONS AND RELEVANCE Among patients with coronary heart disease, the use of a lifestyle-focused text messaging service compared with usual care resulted in a modest improvement in LDL-C level and greater improvement in other cardiovascular disease risk factors. The duration of these effects and hence whether they result in improved clinical outcomes remain to be determined. TRIAL REGISTRATION anzctr.org.au Identifier: ACTRN12611000161921.

Mobile Telephone Text Messaging for Medication Adherence in Chronic Disease: A Meta-analysis

IMPORTANCE Adherence to long-term therapies in chronic disease is poor. Traditional interventions to improve adherence are complex and not widely effective. Mobile telephone text messaging may be a scalable means to support medication adherence. OBJECTIVES To conduct a meta-analysis of randomized clinical trials to assess the effect of mobile telephone text messaging on medication adherence in chronic disease. DATA SOURCES MEDLINE, EMBASE, Cochrane Central Register of Controlled Trials, PsycINFO, and CINAHL (from database inception to January 15, 2015), as well as reference lists of the articles identified. The data were analyzed in March 2015. STUDY SELECTION Randomized clinical trials evaluating a mobile telephone text message intervention to promote medication adherence in adults with chronic disease. DATA EXTRACTION Two authors independently extracted information on study characteristics, text message characteristics, and outcome measures as per the predefined protocol. MAIN OUTCOMES AND MEASURES Odds ratios and pooled data were calculated using random-effects models. Risk of bias and study quality were assessed as per Cochrane guidelines. Disagreement was resolved by consensus. RESULTS Sixteen randomized clinical trials were included, with 5 of 16 using personalization, 8 of 16 using 2-way communication, and 8 of 16 using a daily text message frequency. The median intervention duration was 12 weeks, and self-report was the most commonly used method to assess medication adherence. In the pooled analysis of 2742 patients (median age, 39 years and 50.3% [1380 of 2742] female), text messaging significantly improved medication adherence (odds ratio, 2.11; 95% CI, 1.52-2.93; P < .001). The effect was not sensitive to study characteristics (intervention duration or type of disease) or text message characteristics (personalization, 2-way communication, or daily text message frequency). In a sensitivity analysis, our findings remained robust to change in inclusion criteria based on study quality (odds ratio, 1.67; 95% CI, 1.21-2.29; P = .002). There was moderate heterogeneity (I2 = 62%) across clinical trials. After adjustment for publication bias, the point estimate was reduced but remained positive for an intervention effect (odds ratio, 1.68; 95% CI, 1.18-2.39). CONCLUSIONS AND RELEVANCE Mobile phone text messaging approximately doubles the odds of medication adherence. This increase translates into adherence rates improving from 50% (assuming this baseline rate in patients with chronic disease) to 67.8%, or an absolute increase of 17.8%. While promising, these results should be interpreted with caution given the short duration of trials and reliance on self-reported medication adherence measures. Future studies need to determine the features of text message interventions that improve success, as well as appropriate patient populations, sustained effects, and influences on clinical outcomes.

Quarter-dose quadruple combination therapy for initial treatment of hypertension: placebo-controlled, crossover, randomised trial and systematic review.

BACKGROUND Globally, most patients with hypertension are treated with monotherapy, and control rates are poor because monotherapy only reduces blood pressure by around 9/5 mm Hg on average. There is a pressing need for blood pressure-control strategies with improved efficacy and tolerability. We aimed to assess whether ultra-low-dose combination therapy could meet these needs. METHODS We did a randomised, placebo-controlled, double-blind, crossover trial of a quadpill-a single capsule containing four blood pressure-lowering drugs each at quarter-dose (irbesartan 37·5 mg, amlodipine 1·25 mg, hydrochlorothiazide 6·25 mg, and atenolol 12·5 mg). Participants with untreated hypertension were enrolled from four centres in the community of western Sydney, NSW, Australia, mainly by general practitioners. Participants were randomly allocated by computer to either the quadpill or matching placebo for 4 weeks; this treatment was followed by a 2-week washout, then the other study treatment was administered for 4 weeks. Study staff and participants were unaware of treatment allocations, and masking was achieved by use of identical opaque capsules. The primary outcome was placebo-corrected 24-h systolic ambulatory blood pressure reduction after 4 weeks and analysis was by intention to treat. We also did a systematic review of trials evaluating the efficacy and safety of quarter-standard-dose blood pressure-lowering therapy against placebo. This trial is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12614001057673. The trial ended after 1 year and this report presents the final analysis. FINDINGS Between November, 2014, and December, 2015, 55 patients were screened for our randomised trial, of whom 21 underwent randomisation. Mean age of participants was 58 years (SD 11) and mean baseline office and 24-h systolic and diastolic blood pressure levels were 154 (14)/90 (11) mm Hg and 140 (9)/87 (8) mm Hg, respectively. One individual declined participation after randomisation and two patients dropped out for administrative reasons. The placebo-corrected reduction in systolic 24-h blood pressure with the quadpill was 19 mm Hg (95% CI 14-23), and office blood pressure was reduced by 22/13 mm Hg (p<0·0001). During quadpill treatment, 18 (100%) of 18 participants achieved office blood pressure less than 140/90 mm Hg, compared with six (33%) of 18 during placebo treatment (p=0·0013). There were no serious adverse events and all patients reported that the quadpill was easy to swallow. Our systematic review identified 36 trials (n=4721 participants) of one drug at quarter-dose and six trials (n=312) of two drugs at quarter-dose, against placebo. The pooled placebo-corrected blood pressure-lowering effects were 5/2 mm Hg and 7/5 mm Hg, respectively (both p<0·0001), and there were no side-effects from either regimen. INTERPRETATION The findings of our small trial in the context of previous randomised evidence suggest that the benefits of quarter-dose therapy could be additive across classes and might confer a clinically important reduction in blood pressure. Further examination of the quadpill concept is needed to investigate effectiveness against usual treatment options and longer term tolerability. FUNDING National Heart Foundation, Australia; University of Sydney; and National Health and Medical Research Council of Australia.

Sedation for Electrophysiological Procedures

Administration of intravenous sedation (IVS) has become an integral component of procedural cardiac electrophysiology. IVS is employed in diagnostic and ablation procedures for transcutaneous treatment of cardiac arrhythmias, electrical cardioversion of arrhythmias, and the insertion of implantable electronic devices including pacemakers, defibrillators, and loop recorders. Sedation is frequently performed by nursing staff under the supervision of the proceduralist and in the absence of specialist anesthesiologists. The sedation requirements vary depending on the nature of the procedure. A wide range of sedation techniques have been reported with sedation from the near fully conscious to levels approaching that of general anesthesia. This review examines the methods employed and outcomes associated with reported sedation techniques. There is a large experience with the combination of benzodiazepines and narcotics. These drugs have a broad therapeutic range and the advantage of readily available reversal agents. More recently, the use of propofol without serious adverse events has been reported. The results provide a guide regarding the expected outcomes of these approaches. The complication rate and need for emergency assistance is low in reported series where sedation is administered by nonspecialist anesthesiology staff.

Interventions to improve medication adherence in coronary disease patients: A systematic review and meta-analysis of randomised controlled trials

Background Adherence to multiple cardiovascular (CV) medications is a cornerstone of coronary heart disease (CHD) management and prevention, but it is sub-optimal worldwide. This review aimed to examine whether interventions improve adherence to multiple CV medications in a CHD population. Design This study was based on a systematic review and meta-analysis according to Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines. Methods Randomised controlled trials were identified by searching multiple databases and reference lists. Studies were selected if they evaluated interventions aiming to improve adherence to multiple CV medications targeting a CHD population and if they provided an appropriate measure of adherence. Interventions were classified as complex or simple interventions. Odds ratios (ORs) were calculated and pooled for a meta-analysis. Risk of bias, heterogeneity and publication bias were also assessed. Results Sixteen studies (10,706 patients) were included. The mean age was 62 years (standard deviation (SD) 3.6) and 72% were male. In a pooled analysis, the interventions significantly improved medication adherence (OR 1.52; 95% confidence interval (CI) 1.25–1.86; p < 0.001) and there were no significant differences based on intervention type (complex vs simple), components categories and adherence method. There was moderate heterogeneity (I2 = 61%) across the studies. After adjusting for publication bias, the effect size was attenuated but remained significant (OR 1.35; 95% CI 1.09–1.68). Conclusion Interventions to improve adherence to multiple CV medication in a CHD population significantly improved the odds of being adherent. Simple one-component interventions might be a promising way to improve medication adherence in a CHD population, as they would be easier to replicate in different settings and on a large scale.

Factors Influencing Engagement, Perceived Usefulness and Behavioral Mechanisms Associated with a Text Message Support Program

Introduction Many studies have now demonstrated the efficacy of text messaging in positively changing behaviours. We aimed to identify features and factors that explain the effectiveness of a successful text messaging program in terms of user engagement, perceived usefulness, behavior change and program delivery preferences. Methods Mixed methods qualitative design combining four data sources; (i) analytic data extracted directly from the software system, (ii) participant survey, (iii) focus groups to identify barriers and enablers to implementation and mechanisms of effect and (iv) recruitment screening logs and text message responses to examine engagement. This evaluation was conducted within the TEXT ME trial—a parallel design, single-blind randomized controlled trial (RCT) of 710 patients with coronary heart disease (CHD). Qualitative data were interpreted using inductive thematic analysis. Results 307/352 (87% response rate) of recruited patients with CHD completed the program evaluation survey at six months and 25 participated in a focus group. Factors increasing engagement included (i) ability to save and share messages, (ii) having the support of providers and family, (iii) a feeling of support through participation in the program, (iv) the program being initiated close to the time of a cardiovascular event, (v) personalization of the messages, (vi) opportunity for initial face-to-face contact with a provider and (vii) that program and content was perceived to be from a credible source. Clear themes relating to program delivery were that diet and physical activity messages were most valued, four messages per week was ideal and most participants felt program duration should be provided for at least for six months or longer. Conclusions This study provides context and insight into the factors influencing consumer engagement with a text message program aimed at improving health-related behavior. The study suggests program components that may enhance potential success but will require integration at the development stage to optimize up-scaling. Trial Registration Australia and New Zealand Clinical Trials Registry, ACTRN12611000161921.

Patterns, predictors and effects of texting intervention on physical activity in CHD – insights from the TEXT ME randomized clinical trial

Background Mobile phone text message interventions are used to support behaviour change including physical activity, but we have less insight into how these interventions work and what factors predict response. Aims To study the effect of TEXT ME (Tobacco EXercise and dieT Messages) text message intervention on physical activity domains, consistency of effects across sub-groups and its additive value in patients that received traditional cardiac rehabilitation programme. Methods This is a secondary analysis of the TEXT ME, a randomized clinical trial of lifestyle-focused text message intervention compared with usual care in patients with coronary heart disease. A quarter of the messages were designed specifically to encourage physical activity. Sedentary time and physical activity were assessed using the Global Physical Activity Questionnaire. Results At baseline, 85% of the 710 participants reported low physical activity levels. At six months, compared with controls, the intervention arm reported higher recreational physical activity (471 vs. 307 metabolic equivalent-min/week, p = 0.001) and travel physical activity (230 vs. 128 MET-min/week, p = 0.002), similar work-related physical activity and lower sedentary times (494 vs. 587 min, p < 0.001). Male gender, high baseline physical activity, cardiac rehabilitation participation and text message intervention predicted physically active status at six months. Subjects that received both cardiac rehabilitation and text messaging intervention were more likely to achieve target physical activity levels compared with cardiac rehabilitation alone (odds ratio 7.07 vs. 1.80, p < 0.001). Conclusions The TEXT ME intervention improved recreational and travel physical activity, reduced sedentary times but had no effects on work-related physical activity. It had incremental benefits at achieving target physical activity levels even in patients participating in the traditional cardiac rehabilitation programme.

Adherence to secondary prevention therapies in acute coronary syndrome.

Despite overwhelming evidence of the effectiveness of secondary prevention therapies, surveys indicate poor adherence to medical treatments and lifestyle recommendations after an acute coronary syndrome. The term adherence is preferred over compliance, as the former suggests a therapeutic alliance, whereas the latter reflects passive patient obedience. Poor adherence results from a complex interplay of multiple factors at patient, practitioner and system levels. Poor adherence among patients with stable coronary artery disease is associated with increased risk of cardiovascular admissions (10%–40%), coronary interventions (10%–30%) and cardiovascular mortality (50%–80%). Improving adherence is a complex process. A range of interventions that target modifiable factors influencing adherence have been explored, but there are no guidelines to guide the choice, and multidisciplinary efforts may be needed. Future research in the area should focus on comparative efficacy of interventions to enhance adherence.

Efficacy and Safety of Quarter-Dose Blood Pressure-Lowering Agents: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

There is a critical need for blood pressure–lowering strategies that have greater efficacy and minimal side effects. Low-dose combinations hold promise in this regard, but there are few data on very-low-dose therapy. We, therefore, conducted a systematic review and meta-analysis of randomized controlled trials with at least one quarter-dose and one placebo and standard-dose monotherapy arm. A search was conducted of Medline, Embase, Cochrane Registry, Food and Drug Administration, and European Medicinal Agency websites. Data on blood pressure and adverse events were pooled using a fixed-effect model, and bias was assessed using Cochrane risk of bias. The review included 42 trials involving 20 284 participants. Thirty-six comparisons evaluated quarter-dose with placebo and indicated a blood pressure reduction of −4.7/−2.4 mm Hg (P<0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a −6.7/ −4.4 mm Hg (P<0.001) blood pressure reduction. There were no trials of triple quarter-dose combination versus placebo, but one quadruple quarter-dose study observed a blood pressure reduction of −22.4/−13.1 mm Hg versus placebo (P<0.001). Compared with standard-dose monotherapy, the blood pressure differences achieved by single (37 comparisons), dual (7 comparisons), and quadruple (1 trial) quarter-dose combinations were +3.7/+2.6 (P<0.001), +1.3/−0.3 (NS), and −13.1/−7.9 (P<0.001) mm Hg, respectively. In terms of adverse events, single and dual quarter-dose therapy was not significantly different from placebo and had significantly fewer adverse events compared with standard-dose monotherapy. Quarter-dose combinations could provide improvements in efficacy and tolerability of blood pressure–lowering therapy.

Efficacy and Safety of Quarter-Dose Blood Pressure–Lowering Agents

There is a critical need for blood pressure–lowering strategies that have greater efficacy and minimal side effects. Low-dose combinations hold promise in this regard, but there are few data on very-low-dose therapy. We, therefore, conducted a systematic review and meta-analysis of randomized controlled trials with at least one quarter-dose and one placebo and standard-dose monotherapy arm. A search was conducted of Medline, Embase, Cochrane Registry, Food and Drug Administration, and European Medicinal Agency websites. Data on blood pressure and adverse events were pooled using a fixed-effect model, and bias was assessed using Cochrane risk of bias. The review included 42 trials involving 20 284 participants. Thirty-six comparisons evaluated quarter-dose with placebo and indicated a blood pressure reduction of −4.7/−2.4 mm Hg (P<0.001). Six comparisons were of dual quarter-dose therapy versus placebo, observing a −6.7/ −4.4 mm Hg (P<0.001) blood pressure reduction. There were no trials of triple quarter-dose combination versus placebo, but one quadruple quarter-dose study observed a blood pressure reduction of −22.4/−13.1 mm Hg versus placebo (P<0.001). Compared with standard-dose monotherapy, the blood pressure differences achieved by single (37 comparisons), dual (7 comparisons), and quadruple (1 trial) quarter-dose combinations were +3.7/+2.6 (P<0.001), +1.3/−0.3 (NS), and −13.1/−7.9 (P<0.001) mm Hg, respectively. In terms of adverse events, single and dual quarter-dose therapy was not significantly different from placebo and had significantly fewer adverse events compared with standard-dose monotherapy. Quarter-dose combinations could provide improvements in efficacy and tolerability of blood pressure–lowering therapy.