Heart Failure With Reduced Ejection Fraction Polypill Implementation Strategy in India: A Convergent Parallel Mixed Methods Study.

Introduction: A polypill-based implementation strategy has been proposed to increase rates of guideline-directed medical therapy (GDMT) in patients with heart failure with reduced ejection fraction. This has the potential to improve mortality and morbidity in India and undertreated populations globally. Methods: We conducted a convergent parallel mixed methods study integrating quantitative data from stakeholder surveys using modified implementation science outcome measures and qualitative data from key informant in-depth interviews. Our objective was to explore physician, nurse, pharmacist, and patient perspectives on a HFrEF polypill implementation strategy in India from January 2021 to April 2021. Quantitative and qualitative data were integrated to develop an Implementation Research Logic Model. Results: Among 69 respondents to the stakeholder survey, there was moderate acceptability (mean [SD] 3.8 [1.0]), appropriateness (3.6 [1.0]), and feasibility (3.7 [1.0]) of HFrEF polypill implementation strategy. Participants in the key-informant in-depth interviews (n = 20) highlighted numerous relative advantages of the HFrEF polypill innovation including potential to simplify medication regimens and improve patient adherence. Key relative disadvantages elucidated, include concerns about side effects and interruption of multiple GDMT medications due to polypill discontinuation for side effects or hospitalizations. Based on this data, the proposed implementation strategies in the Implementation Research Logic Model include 1) HFrEF polypills, 2) HFrEF polypill initiation, titration, and maintenance protocols, and 3) HFrEF polypill laboratory monitoring protocols for safety which we postulate will lead to desired clinical and implementation outcomes through multiple mechanisms including increased medication adherence to a single pill. Conclusion: This study demonstrates that a HFrEF polypill-based implementation strategy is considered acceptable, feasible, and appropriate among healthcare providers in India. We identified contextually relevant determinants, strategies, mechanism, and outcomes outlined in an Implementation Research Logic Model to inform future research to improve heart failure care in South Asia.

Effect of a multicomponent quality improvement strategy on sustained achievement of diabetes care goals and macrovascular and microvascular complications in South Asia at 6.5 years follow-up: Post hoc analyses of the CARRS randomized clinical trial.

BACKGROUND: Diabetes control is poor globally and leads to burdensome microvascular and macrovascular complications. We aimed to assess post hoc between-group differences in sustained risk factor control and macrovascular and microvascular endpoints at 6.5 years in the Center for cArdiovascular Risk Reduction in South Asia (CARRS) randomized trial. METHODS AND FINDINGS: This parallel group individual randomized clinical trial was performed at 10 outpatient diabetes clinics in India and Pakistan from January 2011 through September 2019. A total of 1,146 patients with poorly controlled type 2 diabetes (HbA1c ≥8% and systolic BP ≥140 mm Hg and/or LDL-cholesterol ≥130 mg/dL) were randomized to a multicomponent quality improvement (QI) strategy (trained nonphysician care coordinator to facilitate care for patients and clinical decision support system for physicians) or usual care. At 2.5 years, compared to usual care, those receiving the QI strategy were significantly more likely to achieve multiple risk factor control. Six clinics continued, while 4 clinics discontinued implementing the QI strategy for an additional 4-year follow-up (overall median 6.5 years follow-up). In this post hoc analysis, using intention-to-treat, we examined between-group differences in multiple risk factor control (HbA1c <7% plus BP <130/80 mm Hg and/or LDL-cholesterol <100 mg/dL) and first macrovascular endpoints (nonfatal myocardial infarction, nonfatal stroke, death, revascularization [angioplasty or coronary artery bypass graft]), which were co-primary outcomes. We also examined secondary outcomes, namely, single risk factor control, first microvascular endpoints (retinopathy, nephropathy, neuropathy), and composite first macrovascular plus microvascular events (which also included amputation and all-cause mortality) by treatment group and whether QI strategy implementation was continued over 6.5 years. At 6.5 years, assessment data were available for 854 participants (74.5%; n = 417 [intervention]; n = 437 [usual care]). In terms of sociodemographic and clinical characteristics, participants in the intervention and usual care groups were similar and participants at sites that continued were no different to participants at sites that discontinued intervention implementation. Patients in the intervention arm were more likely to exhibit sustained multiple risk factor control than usual care (relative risk: 1.77; 95% confidence interval [CI], 1.45, 2.16), p < 0.001. Cumulatively, there were 233 (40.5%) first microvascular and macrovascular events in intervention and 274 (48.0%) in usual care patients (absolute risk reduction: 7.5% [95% CI: -13.2, -1.7], p = 0.01; hazard ratio [HR] = 0.72 [95% CI: 0.61, 0.86]), p < 0.001. Patients in the intervention arm experienced lower incidence of first microvascular endpoints (HR = 0.68 [95% CI: 0.56, 0.83), p < 0.001, but there was no evidence of between-group differences in first macrovascular events. Beneficial effects on microvascular and composite vascular outcomes were observed in sites that continued, but not sites that discontinued the intervention. CONCLUSIONS: In urban South Asian clinics, a multicomponent QI strategy led to sustained multiple risk factor control and between-group differences in microvascular, but not macrovascular, endpoints. Between-group reductions in vascular outcomes at 6.5 years were observed only at sites that continued the QI intervention, suggesting that practice change needs to be maintained for better population health of people with diabetes. TRIAL REGISTRATION: ClinicalTrials.gov NCT01212328.

Presentation, Management, and In-Hospital Outcomes of Patients with Acute Heart Failure in South India by Sex: A Secondary Analysis of a Prospective, Interrupted Time Series Study.

Background: Sex differences in presentation, management, and outcomes of heart failure (HF) have been observed, but it is uncertain whether these differences exist in South India. Objective: We describe sex differences in presentation, management, and in-hospital outcomes in patients hospitalized with HF in South India and explore sex-based differences in the effect of the quality improvement intervention in a secondary analysis of a prospective, interrupted time series study. Methods: The Heart Failure Quality Improvement in Kerala (HF QUIK) study evaluated the effect of a quality improvement toolkit on process of care measures and clinical outcomes in patients hospitalized with HF in eight hospitals in Kerala using an interrupted time series design from February 2018 to August 2018. The primary outcome was guideline-directed medical therapy (GDMT) at hospital discharge for patients with HF with reduced ejection fraction (HFrEF). We performed sex-stratified analyses using mixed effect logistic regression models. Results: Among 1,400 patients, 536 (38.3%) were female. Female patients were older (69.6 vs. 65 years, p < 0.001), were less likely to have an ischemic etiology of HF (control period: 78.2% vs. 87.5%; intervention period: 83.6% vs. 91.5%; p < 0.05 for both) and were less likely to undergo coronary angiography or percutaneous coronary intervention. The quality improvement intervention had similar effects on the odds of GDMT at discharge in females with HFrEF (adjusted OR 1.79, 95% CI 0.92, 3.47) and males with HFrEF (adjusted OR 1.68, 95% CI 1.07, 2.64, pinteraction = 0.69). Conclusions: We observed sex-specific differences in presentation and procedural management of patients with HF but no differences in the effect of the quality improvement intervention on discharge GDMT rates. Both male and female patients with HFrEF remained undertreated in the study intervention period, demonstrating the need for implementation strategies to close the HFrEF treatment gap in South India.

Effect of a quality improvement intervention for acute heart failure in South India: An interrupted time series study.

BACKGROUND: Although quality improvement interventions for acute heart failure have been studied in high-income countries, none have been studied in low- or middle-income country settings where quality of care can be lower. We evaluated the effect of a quality improvement toolkit on process of care measures and clinical outcomes in patients hospitalized for acute heart failure in 8 hospitals in Kerala, India utilizing an interrupted time series design from February 2018 to August 2018. METHODS: The quality improvement toolkit included checklists, audit-and-feedback reports, and patient education materials. The primary outcome was rate of discharge guideline-directed medical therapy for patients with heart failure with reduced ejection fraction. We used mixed effect logistic regression and interrupted time series models for analysis. RESULTS: Among 1400 participants, mean (SD) age was 66.6 (12.2) years, and 38% were female. Mean (SD) left ventricular ejection fraction was 35.2% (9.7%). The primary outcome was observed in 41.3% of participants in the intervention period and 28.1% of participants in the control period (difference 13.2%; 95% CI 6.8, 19.0; adjusted OR = 1.70; 95% CI 1.17, 2.48). Interrupted time series model demonstrated highest rate of guideline-directed medical therapy at discharge in the initial weeks following intervention delivery with a concomitant decline over time. Improvements were observed in discharge process of care measures, including diet counseling, weight monitoring instructions, and scheduling of outpatient clinic follow-up but not hospital length of stay nor inpatient mortality. CONCLUSIONS: Higher rates of guideline-directed medical therapy at discharge were observed in Kerala. Broader implementation of this quality improvement intervention may improve heart failure care in low- and middle-income countries.

Factors affecting achievement of glycemic targets among type 2 diabetes patients in South Asia: Analysis of the CARRS trial.

OBJECTIVE: To assess the predictors of achieving and maintaining guideline-recommended glycemic control in people with poorly controlled type 2 diabetes. METHODS: We analyzed data from the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) Trial (n = 1146), to identify groups that achieved guideline-recommended glycemic control (HbA1c < 7%) and those that remained persistently poorly controlled (HbA1c > 9%) over a median of 28 months of follow-up. We used generalized estimation equations (GEE) analysis for each outcome i.e. achieving guideline-recommended control and persistently poorly controlled and constructed four regression models (demographics, disease-related, self-care, and other risk factors) separately to identify predictors of HbA1c < 7% and HbA1c > 9% at the end of the trial, adjusting for trial group assignment and site. RESULTS: In the final multivariate model, adherence to prescribed medications (RR: 1.46, 95%CI: 1.09, 1.95), adherence to diet plans (RR: 1.79, 95% CI: 1.43, 2.23) and middle-aged: 50-64 years (RR: 1.32; 95% CI: 1.02-1.71) were associated with achieving guideline-recommended control (HbA1c < 7%). Presence of microvascular complications (RR: 0.70; 95%CI: 0.53-0.92) reduced the probability of achieving guideline-recommended glycemic control (HbA1c 7%). Further, longer duration of diabetes (>15 years), RR: 1.41; 95% CI: 1.15, 1.72, hyperlipidemia, RR: 1.19; 95% CI: 1.06, 1.34 and younger age group (35-49 years vs. >64 years: RR: 0.61; 95% CI: 0.47-0.79) were associated with persistently poor glycemic control (HbA1c > 9%). CONCLUSION: To achieve and maintain guideline-recommended glycemic control, care delivery models must put additional emphasis and effort on patients with longer disease duration, younger people and those having microvascular complications and hyperlipidemia.

Yoga-Based Cardiac Rehabilitation After Acute Myocardial Infarction: A Randomized Trial.

BACKGROUND: Given the shortage of cardiac rehabilitation (CR) programs in India and poor uptake worldwide, there is an urgent need to find alternative models of CR that are inexpensive and may offer choice to subgroups with poor uptake (e.g., women and elderly). OBJECTIVES: This study sought to evaluate the effects of yoga-based CR (Yoga-CaRe) on major cardiovascular events and self-rated health in a multicenter randomized controlled trial. METHODS: The trial was conducted in 24 medical centers across India. This study recruited 3,959 patients with acute myocardial infarction with a median and minimum follow-up of 22 and 6 months. Patients were individually randomized to receive either a Yoga-CaRe program (n = 1,970) or enhanced standard care involving educational advice (n = 1,989). The co-primary outcomes were: 1) first occurrence of major adverse cardiovascular events (MACE) (composite of all-cause mortality, myocardial infarction, stroke, or emergency cardiovascular hospitalization); and 2) self-rated health on the European Quality of Life-5 Dimensions-5 Level visual analogue scale at 12 weeks. RESULTS: MACE occurred in 131 (6.7%) patients in the Yoga-CaRe group and 146 (7.4%) patients in the enhanced standard care group (hazard ratio with Yoga-CaRe: 0.90; 95% confidence interval [CI]: 0.71 to 1.15; p = 0.41). Self-rated health was 77 in Yoga-CaRe and 75.7 in the enhanced standard care group (baseline-adjusted mean difference in favor of Yoga-CaRe: 1.5; 95% CI: 0.5 to 2.5; p = 0.002). The Yoga-CaRe group had greater return to pre-infarct activities, but there was no difference in tobacco cessation or medication adherence between the treatment groups (secondary outcomes). CONCLUSIONS: Yoga-CaRe improved self-rated health and return to pre-infarct activities after acute myocardial infarction, but the trial lacked statistical power to show a difference in MACE. Yoga-CaRe may be an option when conventional CR is unavailable or unacceptable to individuals. (A study on effectiveness of YOGA based cardiac rehabilitation programme in India and United Kingdom; CTRI/2012/02/002408).

Built environment for physical activity-An urban barometer, surveillance, and monitoring.

The Lancet Commission on Obesity (LCO), also known as the "syndemic commission," states that radical changes are required to harness the common drivers of "obesity, undernutrition, and climate change." Urban design, land use, and the built environment are few such drivers. Holding individuals responsible for obesity detracts from the obesogenic built environments. Pedestrian priority and dignity, wide pavements with tree canopies, water fountains with potable water, benches for the elderly at regular intervals, access to open-green spaces within 0.5-km radius and playgrounds in schools are required. Facilities for physical activity at worksite, prioritization of staircases and ramps in building construction, redistribution of land use, and access to quality, adequate capacity, comfortable, and well-networked public transport, which are elderly and differently abled sensitive with universal design are some of the interventions that require urgent implementation and monitoring. An urban barometer consisting of valid relevant indicators aligned to the sustainable development goals (SDGs), UN-Habitat-3 and healthy cities, should be considered a basic human right and ought to be mounted for purposes of surveillance and monitoring. A "Framework Convention on Built Environment and Physical Activity" needs to be taken up by WHO and the UN for uptake and implementation by member countries.

Hospital-Level Cardiovascular Management Practices in Kerala, India.

Background Hospital management practices are associated with cardiovascular process of care measures and patient outcomes. However, management practices related to acute cardiac care in India has not been studied. Methods and Results We measured management practices through semistructured, in-person interviews with hospital administrators, physician managers, and nurse managers in Kerala, India between October and November 2017 using the adapted World Management Survey. Trained interviewers independently scored management interview responses (range: 1-5) to capture management practices ranging from performance data tracking to setting targets. We performed univariate regression analyses to assess the relationship between hospital-level factors and management practices. Using Pearson correlation coefficients and mixed-effect logistic regression models, we explored the relationship between management practices and 30-day major adverse cardiovascular events defined as all-cause mortality, reinfarction, stroke, or major bleeding. Ninety managers from 37 hospitals participated. We found suboptimal management practices across 3 management levels (mean [SD]: 2.1 [0.5], 2.0 [0.3], and 1.9 [0.3] for hospital administrators, physician managers, and nurse managers, respectively [ P=0.08]) with lowest scores related to setting organizational targets. Hospitals with existing healthcare quality accreditation, more cardiologists, and private ownership were associated with higher management scores. In our exploratory analysis, higher physician management practice scores related to operation, performance, and target management were correlated with lower 30-day major adverse cardiovascular event. Conclusions Management practices related to acute cardiac care in participating Kerala hospitals were suboptimal but were correlated with clinical outcomes. We identified opportunities to strengthen nonclinical practices to improve patient care.

Microeconomic Costs, Insurance, and Catastrophic Health Spending Among Patients With Acute Myocardial Infarction in India: Substudy of a Randomized Clinical Trial.

Importance: Ischemic heart disease is the leading cause of death in India, and treatment can be costly. Objective: To evaluate individual- and household-level costs and impoverishing effects of acute myocardial infarction among patients in Kerala, India. Design, Setting, and Participants: This investigation was a prespecified substudy of the Acute Coronary Syndrome Quality Improvement in Kerala study, a stepped-wedge, cluster randomized clinical trial conducted between November 2014 and November 2016 across 63 hospitals in Kerala, India. In this cross-sectional substudy, individual- and household-level cost data were collected 30 days after hospital discharge from a sample of 2114 respondents from November 2014 to July 2016. Data were analyzed from July through October 2018 and in March 2019. Exposures: Health insurance status. Main Outcomes and Measures: The primary outcomes were detailed direct and indirect cost data associated with acute myocardial infarction and respondent ability to pay as well as catastrophic health spending and distress financing. Catastrophic health spending was defined as 40% or more of household expenditures minus food costs spent on health, and distress financing was defined as borrowing money or selling assets to cover health costs. Hierarchical regression models were used to evaluate the association between health insurance and measures of financial risk. Costs were converted from Indian rupees to international dollars (represented herein as "$"). Results: Among 2114 respondents, the mean (SD) age was 62.3 (12.7) years, 1521 (71.9%) were men, 1144 (54.1%) presented with an ST-segment elevation myocardial infarction, and 1600 (75.7%) had no health insurance. The median (interquartile range) expenditure among respondents was $480.4 ($112.5-$1733.0) per acute myocardial infarction encounter, largely driven by in-hospital expenditures. There was greater than 15-fold variability between the 25th and 75th percentiles. Individuals with or without health insurance had similar monthly incomes and annual household expenditures, yet individuals without health insurance had approximately $400 higher out-of-pocket cardiovascular health care costs (median [interquartile range] total cardiovascular expenditures among uninsured, $560.3 [$134.1-$1733.6] vs insured, $161.4 [$23.2-$1726.9]; P < .001). Individuals without health insurance also had a 24% higher risk of catastrophic health spending (adjusted risk ratio, 1.24; 95% CI, 1.07-1.43) and 3-fold higher risk of distress financing (adjusted risk ratio; 3.05; 95% CI, 1.45-6.44). Conclusions and Relevance: The results of this study indicate that acute myocardial infarction carries substantial financial risk for patients in Kerala. Expansion of health insurance may be an important strategy for financial risk protection to disrupt the poverty cycle associated with cardiovascular diseases in India.

Rationale and protocol for estimating the economic value of a multicomponent quality improvement strategy for diabetes care in South Asia.

BACKGROUND: Economic dimensions of implementing quality improvement for diabetes care are understudied worldwide. We describe the economic evaluation protocol within a randomised controlled trial that tested a multi-component quality improvement (QI) strategy for individuals with poorly-controlled type 2 diabetes in South Asia. METHODS/DESIGN: This economic evaluation of the Centre for Cardiometabolic Risk Reduction in South Asia (CARRS) randomised trial involved 1146 people with poorly-controlled type 2 diabetes receiving care at 10 diverse diabetes clinics across India and Pakistan. The economic evaluation comprises both a within-trial cost-effectiveness analysis (mean 2.5 years follow up) and a microsimulation model-based cost-utility analysis (life-time horizon). Effectiveness measures include multiple risk factor control (achieving HbA1c < 7% and blood pressure < 130/80 mmHg and/or LDL-cholesterol< 100 mg/dl), and patient reported outcomes including quality adjusted life years (QALYs) measured by EQ-5D-3 L, hospitalizations, and diabetes related complications at the trial end. Cost measures include direct medical and non-medical costs relevant to outpatient care (consultation fee, medicines, laboratory tests, supplies, food, and escort/accompanying person costs, transport) and inpatient care (hospitalization, transport, and accompanying person costs) of the intervention compared to usual diabetes care. Patient, healthcare system, and societal perspectives will be applied for costing. Both cost and health effects will be discounted at 3% per year for within trial cost-effectiveness analysis over 2.5 years and decision modelling analysis over a lifetime horizon. Outcomes will be reported as the incremental cost-effectiveness ratios (ICER) to achieve multiple risk factor control, avoid diabetes-related complications, or QALYs gained against varying levels of willingness to pay threshold values. Sensitivity analyses will be performed to assess uncertainties around ICER estimates by varying costs (95% CIs) across public vs. private settings and using conservative estimates of effect size (95% CIs) for multiple risk factor control. Costs will be reported in US$ 2018. DISCUSSION: We hypothesize that the additional upfront costs of delivering the intervention will be counterbalanced by improvements in clinical outcomes and patient-reported outcomes, thereby rendering this multi-component QI intervention cost-effective in resource constrained South Asian settings. TRIAL REGISTRATION: ClinicalTrials.gov: NCT01212328.

Implementation and acceptability of a heart attack quality improvement intervention in India: a mixed methods analysis of the ACS QUIK trial.

BACKGROUND: The ACS QUIK trial showed that a multicomponent quality improvement toolkit intervention resulted in improvements in processes of care for patients with acute myocardial infarction in Kerala but did not improve clinical outcomes in the context of background improvements in care. We describe the development of the ACS QUIK intervention and evaluate its implementation, acceptability, and sustainability. METHODS: We performed a mixed methods process evaluation alongside a cluster randomized, stepped-wedge trial in Kerala, India. The ACS QUIK intervention aimed to reduce the rate of major adverse cardiovascular events at 30 days compared with usual care across 63 hospitals (n = 21,374 patients). The ACS QUIK toolkit intervention, consisting of audit and feedback report, admission and discharge checklists, patient education materials, and guidelines for the development of code and rapid response teams, was developed based on formative qualitative research in Kerala and from systematic reviews. After four or more months of the center's participation in the toolkit intervention phase of the trial, an online survey and physician interviews were administered. Physician interviews focused on evaluating the implementation and acceptability of the toolkit intervention. A framework analysis of transcripts incorporated context and intervening mechanisms. RESULTS: Among 63 participating hospitals, 22 physicians (35%) completed online surveys. Of these, 17 (77%) respondents reported that their hospital had a cardiovascular quality improvement team, 18 (82%) respondents reported having read an audit report, admission checklist, or discharge checklist, and 19 (86%) respondents reported using patient education materials. Among the 28 interviewees (44%), facilitators of toolkit intervention implementation were physicians' support and leadership, hospital administrators' support, ease-of-use of checklists and patient education materials, and availability of training opportunities for staff. Barriers that influenced the implementation or acceptability of the toolkit intervention for physicians included time and staff constraints, Internet access, patient volume, and inadequate understanding of the quality improvement toolkit intervention. CONCLUSIONS: Implementation and acceptability of the ACS QUIK toolkit intervention were enhanced by hospital-level management support, physician and team support, and usefulness of checklists and patient education materials. Wider and longer-term use of the toolkit intervention and its expansion to potentially other cardiovascular conditions or other locations where the quality of care is not as high as in the ACS QUIK trial may be useful for improving acute cardiovascular care in Kerala and beyond. TRIAL REGISTRATION: NCT02256657.

Health-Related Quality of Life at 30 Days Among Indian Patients With Acute Myocardial Infarction.

BACKGROUND: Despite a high cardiovascular disease burden, data on patient-reported health status outcomes among individuals with cardiovascular disease in India are limited. METHODS AND RESULTS: Between November 2014 and November 2016, we collected health-related quality of life data among 1261 participants in the ACS QUIK trial (Acute Coronary Syndrome Quality Improvement in Kerala). We used a translated, validated version of the Seattle Angina Questionnaire administered 30 days after discharge for acute myocardial infarction, wherein higher scores represent better health status. We compared results across sex, myocardial infarction type, and randomization status using regression models that account for clustering and temporal trends. Mean (SD) age was 60.8 (13.7) years, 62% were men, and 63% presented with ST-segment-elevation myocardial infarction. More than 2 out of 5 respondents (44%) experienced angina 30 days after hospitalization, but most (68% of respondents with angina; 27% of the total sample) experienced it less than once per week (Seattle Angina Questionnaire angina frequency score 60). Respondents rated high median (interquartile range [IQR]) scores for angina frequency (100.0 [80.0-100.0]) overall with similar unadjusted scores by sex, but between-hospitality variability was high. Median (IQR) physical limitation scale response was 58.3 (41.7-77.8), which is consistent with limitations in moderate- and high-intensity activities at 30-day follow-up. Older respondents had more angina frequency and physical limitations and lower treatment satisfaction and quality of life. Women had greater physical limitations (median [IQR], 52.8 [38.9-72.2] for women versus median [IQR], 61.1 [44.4-80.6] for men; P<0.01). Overall treatment satisfaction was high with median (IQR) score, 81.3 (75.0-93.8), but overall quality of life was lower with median (IQR) score, 66.7 (50.0-83.3). Allocation to the quality improvement intervention group had the strongest direct association with higher quality of life (difference, 4.2; P=0.03), but overall effects were modest. CONCLUSIONS: This study represents the largest report of quality of life among myocardial infarction survivors in India with variability across age, sex, and quality improvement intervention status. Wide variability demonstrated across hospitals warrants further study. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov . Unique identifier: NCT02256657.

Effectiveness and cost-effectiveness of a Yoga-based Cardiac Rehabilitation (Yoga-CaRe) program following acute myocardial infarction: Study rationale and design of a multi-center randomized controlled trial.

BACKGROUND: Cardiac rehabilitation (CR) is a standard treatment for secondary prevention of acute myocardial infarction (AMI) in high income countries (HICs), but it is inaccessible to most patients in India due to high costs and skills required for multidisciplinary CR teams. We developed a low-cost and scalable CR program based on culturally-acceptable practice of yoga (Yoga-CaRe). In this paper, we report the rationale and design for evaluation of its effectiveness and cost-effectiveness. METHODS: This is a multi-center, single-blind, two-arm parallel-group randomized controlled trial across 22 cardiac care hospitals in India. Four thousand patients aged 18-80 years with AMI will be recruited and randomized 1:1 to receive Yoga-CaRe program (13 sessions supervised by an instructor and encouragement to self-practice daily) or enhanced standard care (3 sessions of health education) delivered over a period of three months. Participants will be followed 3-monthly till the end of the trial. The co-primary outcomes are a) time to occurrence of first cardiovascular event (composite of all-cause mortality, non-fatal myocardial infarction, non-fatal stroke and emergency cardiovascular hospitalization), and b) quality of life (Euro-QoL-5L) at 12 weeks. Secondary outcomes include need for revascularization procedures, return to pre-infarct activities, tobacco cessation, medication adherence, and cost-effectiveness of the intervention. CONCLUSION: This trial will alone contribute >20% participants to existing meta-analyses of randomized trials of CR worldwide. If Yoga-CaRe is found to be effective, it has the potential to save millions of lives and transform care of AMI patients in India and other low and middle income country settings.

Effect of a Quality Improvement Intervention on Clinical Outcomes in Patients in India With Acute Myocardial Infarction: The ACS QUIK Randomized Clinical Trial.

Importance: Wide heterogeneity exists in acute myocardial infarction treatment and outcomes in India. Objective: To evaluate the effect of a locally adapted quality improvement tool kit on clinical outcomes and process measures in Kerala, a southern Indian state. Design, Setting, and Participants: Cluster randomized, stepped-wedge clinical trial conducted between November 10, 2014, and November 9, 2016, in 63 hospitals in Kerala, India, with a last date of follow-up of December 31, 2016. During 5 predefined steps over the study period, hospitals were randomly selected to move in a 1-way crossover from the control group to the intervention group. Consecutively presenting patients with acute myocardial infarction were offered participation. Interventions: Hospitals provided either usual care (control group; n = 10 066 participants [step 0: n = 2915; step 1: n = 2649; step 2: n = 2251; step 3: n = 1422; step 4; n = 829; step 5: n = 0]) or care using a quality improvement tool kit (intervention group; n = 11 308 participants [step 0: n = 0; step 1: n = 662; step 2: n = 1265; step 3: n = 2432; step 4: n = 3214; step 5: n = 3735]) that consisted of audit and feedback, checklists, patient education materials, and linkage to emergency cardiovascular care and quality improvement training. Main Outcomes and Measures: The primary outcome was the composite of all-cause death, reinfarction, stroke, or major bleeding using standardized definitions at 30 days. Secondary outcomes included the primary outcome's individual components, 30-day cardiovascular death, medication use, and tobacco cessation counseling. Mixed-effects logistic regression models were used to account for clustering and temporal trends. Results: Among 21 374 eligible randomized participants (mean age, 60.6 [SD, 12.0] years; n = 16 183 men [76%] ; n = 13 689 [64%] with ST-segment elevation myocardial infarction), 21 079 (99%) completed the trial. The primary composite outcome was observed in 5.3% of the intervention participants and 6.4% of the control participants. The observed difference in 30-day major adverse cardiovascular event rates between the groups was not statistically significant after adjustment (adjusted risk difference, -0.09% [95% CI, -1.32% to 1.14%]; adjusted odds ratio, 0.98 [95% CI, 0.80-1.21]). The intervention group had a higher rate of medication use including reperfusion but no effect on tobacco cessation counseling. There were no unexpected adverse events reported. Conclusions and Relevance: Among patients with acute myocardial infarction in Kerala, India, use of a quality improvement intervention compared with usual care did not decrease a composite of 30-day major adverse cardiovascular events. Further research is needed to understand the lack of efficacy. Trial Registration: clinicaltrials.gov Identifier: NCT02256657.

Availability, Sales, and Affordability of Tobacco Cessation Medicines in Kerala, India.

BACKGROUND: India is the world's second largest consumer of tobacco, but tobacco cessation remains uncommon due, at least in part, to underutilization of cessation pharmacotherapy. We evaluated the availability, sales, and affordability of nicotine replacement therapy, bupropion, and varenicline in the South Indian state of Kerala to understand potential reasons for underutilization. METHODS AND RESULTS: From November 2016 to April 2017, we collected data on availability, inventory, and pricing of cessation medication through a cross-sectional survey of 199 public, semiprivate (Karunya), and private pharmacies across 5 districts in Kerala using World Health Organization/Health Action International methodology. Revenue and sales data were obtained from the latest Pharmatrac medication database. We assessed affordability using individual- and household-level income and expenditure data collected from November 2014 to November 2016 through the Acute Coronary Syndrome Quality Improvement in Kerala randomized trial. Cessation medications were not available in public hospitals (0%, n=58) nor in public specialty centers (0%, n=10) including those designated to provide cessation services. At least 1 cessation medicine was available at 63% of private pharmacies (n=109) and 27% of Karunya (semiprivate) pharmacies (n=22). Among the 75 pharmacies that stocked cessation medications, 96% had nicotine replacement therapy, 28% had bupropion, and 1% had varenicline. No outlets had sufficient inventory for a patient to purchase a 12-week treatment regimen. There were an estimated 253 270 treatment regimens sold throughout India and 14 092 in Kerala in 2013 to 2014. Treatment regimens cost 1.9 to 13.0× the median amount spent on smoked tobacco and between 8% and 52% of nonsubsistence income. CONCLUSIONS: Tobacco cessation medications are unavailable in the Kerala public sector and have limited availability in the private and semiprivate sectors. When available, medications are unaffordable for most patients. Addition of tobacco cessation medication onto national and state essential medicines lists may help increase access. CLINICAL TRIAL REGISTRATION: URL: https://www.clinicaltrials.gov. Unique identifier: NCT02256657.

Acute coronary syndrome quality improvement in Kerala (ACS QUIK): Rationale and design for a cluster-randomized stepped-wedge trial.

Ischemic heart disease is the leading cause of death in India, and there are likely more myocardial infarctions in India than in any other country in the world. We have previously reported heterogeneous care for patients with myocardial infarction in Kerala, a state in southern India, including both gaps in optimal care and inappropriate care. Based on that prior work, limitations from previous nonrandomized quality improvement studies and promising gains in process of care measures demonstrated from previous randomized trials, we and the Cardiological Society of India-Kerala chapter sought to develop, implement, and evaluate a quality improvement intervention to improve process of care measures and clinical outcomes for these patients. In this article, we report the rationale and study design for the ACS QUIK cluster-randomized stepped-wedge clinical trial (NCT02256657) in which we aim to enroll 15,750 participants with acute coronary syndromes across 63 hospitals. To date, most participants are men (76%) and have ST-segment elevation myocardial infarction (63%). The primary outcome is 30-day major adverse cardiovascular events defined as death, recurrent infarction, stroke, or major bleeding. Our secondary outcomes include health-related quality of life and individual- and household-level costs. We also describe the principal features and limitations of the stepped-wedge study design, which may be important for other investigators or sponsors considering cluster-randomized stepped-wedge trials.

Effectiveness of a Multicomponent Quality Improvement Strategy to Improve Achievement of Diabetes Care Goals: A Randomized, Controlled Trial.

BACKGROUND: Achievement of diabetes care goals is suboptimal globally. Diabetes-focused quality improvement (QI) is effective but remains untested in South Asia. OBJECTIVE: To compare the effect of a multicomponent QI strategy versus usual care on cardiometabolic profiles in patients with poorly controlled diabetes. DESIGN: Parallel, open-label, pragmatic randomized, controlled trial. (ClinicalTrials.gov: NCT01212328). SETTING: Diabetes clinics in India and Pakistan. PATIENTS: 1146 patients (575 in the intervention group and 571 in the usual care group) with type 2 diabetes and poor cardiometabolic profiles (glycated hemoglobin [HbA1c] level ≥8% plus systolic blood pressure [BP] ≥140 mm Hg and/or low-density lipoprotein cholesterol [LDLc] level ≥130 mg/dL). INTERVENTION: Multicomponent QI strategy comprising nonphysician care coordinators and decision-support electronic health records. MEASUREMENTS: Proportions achieving HbA1c level less than 7% plus BP less than 130/80 mm Hg and/or LDLc level less than 100 mg/dL (primary outcome); mean risk factor reductions, health-related quality of life (HRQL), and treatment satisfaction (secondary outcomes). RESULTS: Baseline characteristics were similar between groups. Median diabetes duration was 7.0 years; 6.8% and 39.4% of participants had preexisting cardiovascular and microvascular disease, respectively; mean HbA1c level was 9.9%; mean BP was 143.3/81.7 mm Hg; and mean LDLc level was 122.4 mg/dL. Over a median of 28 months, a greater percentage of intervention participants achieved the primary outcome (18.2% vs. 8.1%; relative risk, 2.24 [95% CI, 1.71 to 2.92]). Compared with usual care, intervention participants achieved larger reductions in HbA1c level (-0.50% [CI, -0.69% to -0.32%]), systolic BP (-4.04 mm Hg [CI, -5.85 to -2.22 mm Hg]), diastolic BP (-2.03 mm Hg [CI, -3.00 to -1.05 mm Hg]), and LDLc level (-7.86 mg/dL [CI, -10.90 to -4.81 mg/dL]) and reported higher HRQL and treatment satisfaction. LIMITATION: Findings were confined to urban specialist diabetes clinics. CONCLUSION: Multicomponent QI improves achievement of diabetes care goals, even in resource-challenged clinics. PRIMARY FUNDING SOURCE: National Heart, Lung, and Blood Institute and UnitedHealth Group.