Rivaroxaban in Rheumatic Heart Disease-Associated Atrial Fibrillation.

BACKGROUND: Testing of factor Xa inhibitors for the prevention of cardiovascular events in patients with rheumatic heart disease-associated atrial fibrillation has been limited. METHODS: We enrolled patients with atrial fibrillation and echocardiographically documented rheumatic heart disease who had any of the following: a CHA2DS2VASc score of at least 2 (on a scale from 0 to 9, with higher scores indicating a higher risk of stroke), a mitral-valve area of no more than 2 cm2, left atrial spontaneous echo contrast, or left atrial thrombus. Patients were randomly assigned to receive standard doses of rivaroxaban or dose-adjusted vitamin K antagonist. The primary efficacy outcome was a composite of stroke, systemic embolism, myocardial infarction, or death from vascular (cardiac or noncardiac) or unknown causes. We hypothesized that rivaroxaban therapy would be noninferior to vitamin K antagonist therapy. The primary safety outcome was major bleeding according to the International Society of Thrombosis and Hemostasis. RESULTS: Of 4565 enrolled patients, 4531 were included in the final analysis. The mean age of the patients was 50.5 years, and 72.3% were women. Permanent discontinuation of trial medication was more common with rivaroxaban than with vitamin K antagonist therapy at all visits. In the intention-to-treat analysis, 560 patients in the rivaroxaban group and 446 in the vitamin K antagonist group had a primary-outcome event. Survival curves were nonproportional. The restricted mean survival time was 1599 days in the rivaroxaban group and 1675 days in the vitamin K antagonist group (difference, -76 days; 95% confidence interval [CI], -121 to -31; P<0.001). A higher incidence of death occurred in the rivaroxaban group than in the vitamin K antagonist group (restricted mean survival time, 1608 days vs. 1680 days; difference, -72 days; 95% CI, -117 to -28). No significant between-group difference in the rate of major bleeding was noted. CONCLUSIONS: Among patients with rheumatic heart disease-associated atrial fibrillation, vitamin K antagonist therapy led to a lower rate of a composite of cardiovascular events or death than rivaroxaban therapy, without a higher rate of bleeding. (Funded by Bayer; INVICTUS ClinicalTrials.gov number, NCT02832544.).

Pre-morbid sleep disturbance and its association with stroke severity: results from the international INTERSTROKE study.

BACKGROUND AND PURPOSE: Whilst sleep disturbances are associated with stroke, their association with stroke severity is less certain. In the INTERSTROKE study, the association of pre-morbid sleep disturbance with stroke severity and functional outcome following stroke was evaluated. METHODS: INTERSTROKE is an international case-control study of first acute stroke. This analysis included cases who completed a standardized questionnaire concerning nine symptoms of sleep disturbance (sleep onset latency, duration, quality, nocturnal awakening, napping duration, whether a nap was planned, snoring, snorting and breathing cessation) in the month prior to stroke (n = 2361). Two indices were derived representing sleep disturbance (range 0-9) and obstructive sleep apnoea (range 0-3) symptoms. Logistic regression was used to estimate the magnitude of association between symptoms and stroke severity defined by the modified Rankin Score. RESULTS: The mean age of participants was 62.9 years, and 42% were female. On multivariable analysis, there was a graded association between increasing number of sleep disturbance symptoms and initially severe stroke (2-3, odds ratio [OR] 1.44, 95% confidence interval [CI] 1.07-1.94; 4-5, OR 1.66, 95% CI 1.23-2.25; >5, OR 2.58, 95% CI 1.83-3.66). Having >5 sleep disturbance symptoms was associated with significantly increased odds of functional deterioration at 1 month (OR 1.54, 95% CI 1.01-2.34). A higher obstructive sleep apnoea score was also associated with significantly increased odds of initially severe stroke (2-3, OR 1.48; 95% CI 1.20-1.83) but not functional deterioration at 1 month (OR 1.19, 95% CI 0.93-1.52). CONCLUSIONS: Sleep disturbance symptoms were common and associated with an increased odds of severe stroke and functional deterioration. Interventions to modify sleep disturbance may help prevent disabling stroke/improve functional outcomes and should be the subject of future research.

Anticoagulation control among patients on vitamin K antagonists in nine countries in Sub-Saharan Africa.

Vitamin K antagonists (VKA) is the primary anticoagulant in most settings of Sub-Saharan Africa. Understanding the quality of anticoagulation services in the continent is vital in optimising the intended benefits. This study assessed the quality of anticoagulation and associated factors among VKA-treated patients in nine SSA countries. We conducted a retrospective cohort study of randomly selected patients on anticoagulation from 20 clinics in Botswana, the Democratic Republic of Congo, Ethiopia, Gambia, Ghana, Mozambique, Nigeria, Tanzania, and South Africa. Eligible participants were those on VKAs for at least three months and with at least four international normalised ratios (INR) results in 2019-2021. We report the proportion of INR values in the therapeutic range, time-in-therapeutic range (TTR) using the Rosendaal method, and the proportion of patients with TTR ≥ 65% (optimal anticoagulation). The mean age was 51.1(16.1) years, and 64.2% were women. The most common indications for VKA included venous thromboembolism (29.6%), prosthetic valves (26.7%) and atrial fibrillation/flutter (30.1%). We analysed 6743 INR tests from 1011 participants, and of these, 48.5% were sub-therapeutic, 34.1% therapeutic, and 17.4% were supratherapeutic relative to disease-specific reference ranges. TTR was calculated for 660 patients using 4927 INR measurements. The median (interquartile range [IQR]) TTR was 35.8(15.9,57.2) %. Optimal anticoagulation control was evident in 19.2% of participants, varying from 2.7% in Tanzania to 23.1% in Ethiopia. The proportion of patients with TTR ≥ 65% was 15,4% for prosthetic heart valves, 21.1% for venous thromboembolism and 23.7% for atrial fibrillation or flutter. Countries with universal health coverage had higher odds of optimal anticoagulation control (adjusted odds ratio (aOR) 1.79, 95% confidence interval [CI], 1.15- 2.81, p = 0.01). Patients on VKAs for different therapeutic indications in SSA had suboptimal TTR. Universal health coverage increased the odds of achieving TTR by 79%. The evidence calls for more intensive warfarin management strategies in SSA, including providing VKA services without out-of-pocket payments.

Frailty and outcomes in heart failure patients from high-, middle-, and low-income countries.

BACKGROUND AND AIMS: There is little information on the incremental prognostic importance of frailty beyond conventional prognostic variables in heart failure (HF) populations from different country income levels. METHODS: A total of 3429 adults with HF (age 61 ± 14 years, 33% women) from 27 high-, middle- and low-income countries were prospectively studied. Baseline frailty was evaluated by the Fried index, incorporating handgrip strength, gait speed, physical activity, unintended weight loss, and self-reported exhaustion. Mean left ventricular ejection fraction was 39 ± 14% and 26% had New York Heart Association Class III/IV symptoms. Participants were followed for a median (25th to 75th percentile) of 3.1 (2.0-4.3) years. Cox proportional hazard models for death and HF hospitalization adjusted for country income level; age; sex; education; HF aetiology; left ventricular ejection fraction; diabetes; tobacco and alcohol use; New York Heart Association functional class; HF medication use; blood pressure; and haemoglobin, sodium, and creatinine concentrations were performed. The incremental discriminatory value of frailty over and above the MAGGIC risk score was evaluated by the area under the receiver-operating characteristic curve. RESULTS: At baseline, 18% of participants were robust, 61% pre-frail, and 21% frail. During follow-up, 565 (16%) participants died and 471 (14%) were hospitalized for HF. Respective adjusted hazard ratios (95% confidence interval) for death among the pre-frail and frail were 1.59 (1.12-2.26) and 2.92 (1.99-4.27). Respective adjusted hazard ratios (95% confidence interval) for HF hospitalization were 1.32 (0.93-1.87) and 1.97 (1.33-2.91). Findings were consistent among different country income levels and by most subgroups. Adding frailty to the MAGGIC risk score improved the discrimination of future death and HF hospitalization. CONCLUSIONS: Frailty confers substantial incremental prognostic information to prognostic variables for predicting death and HF hospitalization. The relationship between frailty and these outcomes is consistent across countries at all income levels.

Mortality and Morbidity in Adults With Rheumatic Heart Disease.

Importance: Rheumatic heart disease (RHD) remains a public health issue in low- and middle-income countries (LMICs). However, there are few large studies enrolling individuals from multiple endemic countries. Objective: To assess the risk and predictors of major patient-important clinical outcomes in patients with clinical RHD. Design, Setting, and Participants: Multicenter, hospital-based, prospective observational study including 138 sites in 24 RHD-endemic LMICs. Main Outcomes and Measures: The primary outcome was all-cause mortality. Secondary outcomes were cause-specific mortality, heart failure (HF) hospitalization, stroke, recurrent rheumatic fever, and infective endocarditis. This study analyzed event rates by World Bank country income groups and determined the predictors of mortality using multivariable Cox models. Results: Between August 2016 and May 2022, a total of 13 696 patients were enrolled. The mean age was 43.2 years and 72% were women. Data on vital status were available for 12 967 participants (94.7%) at the end of follow-up. Over a median duration of 3.2 years (41 478 patient-years), 1943 patients died (15% overall; 4.7% per patient-year). Most deaths were due to vascular causes (1312 [67.5%]), mainly HF or sudden cardiac death. The number of patients undergoing valve surgery (604 [4.4%]) and HF hospitalization (2% per year) was low. Strokes were infrequent (0.6% per year) and recurrent rheumatic fever was rare. Markers of severe valve disease, such as congestive HF (HR, 1.58 [95% CI, 1.50-1.87]; P < .001), pulmonary hypertension (HR, 1.52 [95% CI, 1.37-1.69]; P < .001), and atrial fibrillation (HR, 1.30 [95% CI, 1.15-1.46]; P < .001) were associated with increased mortality. Treatment with surgery (HR, 0.23 [95% CI, 0.12-0.44]; P < .001) or valvuloplasty (HR, 0.24 [95% CI, 0.06-0.95]; P = .042) were associated with lower mortality. Higher country income level was associated with lower mortality after adjustment for patient-level factors. Conclusions and Relevance: Mortality in RHD is high and is correlated with the severity of valve disease. Valve surgery and valvuloplasty were associated with substantially lower mortality. Study findings suggest a greater need to improve access to surgical and interventional care, in addition to the current approaches focused on antibiotic prophylaxis and anticoagulation.

The Pandemic of Coronary Artery Disease in the Sub-Saharan Africa: What Clinicians Need to Know.

PURPOSE OF REVIEW: Cardiovascular diseases (CVDs) are a leading cause of morbidity and mortality globally with an accelerated increase in CVD­related death in Africa and other low­middle­income countries. This review is aimed at highlighting the burden of coronary artery disease CAD, its peculiarities as well as challenges of management in sub-Saharan Africa. RECENT FINDINGS: Recent data revealed a shift from high incidence of CVDs associated with poverty and malnutrition (such as rheumatic heart disease) initially, which are now falling, to rising incidence of other non-communicable CVDs (such as hypertension, coronary artery disease (CAD), and heart failure). Africa disproportionately bears the brunt of CVD burden and has one of the highest risks of dying from non-communicable diseases (NCDs) worldwide, which is projected to supersede communicable diseases in the future. Previous studies have shown that CAD was rare among Africans. Those studies conducted in Africa in the 1940s-1960s reported that Black Africans were almost immune to developing CAD and were even thought to have specific genetic make-up protecting them from CAD. However, the continent is now experiencing a steady rise in the prevalence of CAD associated with severe disease burden, compared to other regions of the world. The changes seen have been attributed to the current epidemiological transition with increase in CVD risk factors that are poorly controlled, lack of awareness as well as the poor health facilities to tackle the menace of the disease. The Global Burden of Disease (GBD) estimates have also shown that over the past three decades the highest contribution to CVD burden in Africa is attributed to atherosclerotic diseases, with 71.4, 37.7, and 154% increases in the burden of ischemic heart disease, stroke, and peripheral artery disease respectively. There is a steady increase of CAD prevalence in Africa as a result of increase in CV risk factors. Hypertension, obesity, diabetes, dyslipidemia, and cigarette smoking are the rapidly rising risk factors for CAD on the continent. Africa also faces challenges in diagnosis and management of CAD. There is need for increased public and health personnel awareness on prevention and control of commonly identifiable risk factors, provision of prehospital emergency services, and provision of modern therapeutic facilities for treatment of CAD including reperfusion therapy. These are priority areas where efforts could be intensified in the future with potential to improve the current rate of progress of the disease on the continent.

Are there differences in perceptions, preferences and attitudes towards disclosure of genetic testing for Stroke? A qualitative study among stroke-free SIREN-SIBS genomics study participants.

OBJECTIVE: This study explored perceptions, preferences and attitudes towards disclosure of genetic testing results for stroke among stroke-free controls (and their family members) in the SIREN-SIBS Genomics Study, healthcare providers and policymakers. MATERIALS AND METHODS: We conducted a qualitative thematic analysis of key informant interviews with 61 participants recruited from community advisory boards (30) and health care providers (31) across seven sites in Nigeria and Ghana. RESULTS: Major findings illustrate differences in the knowledge of genetic testing with superior knowledge among health care professionals. Relatives and religious leaders were opined as the best to receive the disclosure as they would be able to break the news to the patient in a culturally sensitive manner to reduce the likely resultant emotional outburst. Poor level of awareness of national guidelines for disclosing genetic results exist. Key facilitating factors for disclosure are education, enabling environment, involvement of religious and community leaders, campaigns, and possible treatment options. Disclosure inhibitors include inadequate information, fear of marital break-up or family displacement, fear of stigmatization, fear of isolation, religious beliefs, health worker attitude, and lack of preparedness to accept results. CONCLUSIONS: These necessitate culturally sensitive interventions for continuing education, increased awareness and sustained engagement to equip all stakeholders in genetic testing disclosure process.

Comparison of Dual Therapies for Lowering Blood Pressure in Black Africans.

BACKGROUND: The prevalence of hypertension among black African patients is high, and these patients usually need two or more medications for blood-pressure control. However, the most effective two-drug combination that is currently available for blood-pressure control in these patients has not been established. METHODS: In this randomized, single-blind, three-group trial conducted in six countries in sub-Saharan Africa, we randomly assigned 728 black patients with uncontrolled hypertension (≥140/90 mm Hg while the patient was not being treated or was taking only one antihypertensive drug) to receive a daily regimen of 5 mg of amlodipine plus 12.5 mg of hydrochlorothiazide, 5 mg of amlodipine plus 4 mg of perindopril, or 4 mg of perindopril plus 12.5 mg of hydrochlorothiazide for 2 months. Doses were then doubled (10 and 25 mg, 10 and 8 mg, and 8 and 25 mg, respectively) for an additional 4 months. The primary end point was the change in the 24-hour ambulatory systolic blood pressure between baseline and 6 months. RESULTS: The mean age of the patients was 51 years, and 63% were women. Among the 621 patients who underwent 24-hour blood-pressure monitoring at baseline and at 6 months, those receiving amlodipine plus hydrochlorothiazide and those receiving amlodipine plus perindopril had a lower 24-hour ambulatory systolic blood pressure than those receiving perindopril plus hydrochlorothiazide (between-group difference in the change from baseline, -3.14 mm Hg; 95% confidence interval [CI], -5.90 to -0.38; P = 0.03; and -3.00 mm Hg; 95% CI, -5.8 to -0.20; P = 0.04, respectively). The difference between the group receiving amlodipine plus hydrochlorothiazide and the group receiving amlodipine plus perindopril was -0.14 mm Hg (95% CI, -2.90 to 2.61; P=0.92). Similar differential effects on office and ambulatory diastolic blood pressures, along with blood-pressure control and response rates, were apparent among the three groups. CONCLUSIONS: These findings suggest that in black patients in sub-Saharan Africa, amlodipine plus either hydrochlorothiazide or perindopril was more effective than perindopril plus hydrochlorothiazide at lowering blood pressure at 6 months. (Funded by GlaxoSmithKline Africa Noncommunicable Disease Open Lab; CREOLE ClinicalTrials.gov number, NCT02742467.).

Differential associations between pre-diabetes, diabetes and stroke occurrence among West Africans.

BACKGROUND: There are limited data from Africa on the burden and associations between pre-diabetes (pre-DM), diabetes mellitus (DM) and stroke occurrence in a region experiencing a profound rise in stroke burden. PURPOSE: To characterize the associations between stroke and dysglycemic status among West Africans. METHODS: The Stroke Investigative Research and Educational Network (SIREN) is a multicenter, case-control study involving 15 sites in Ghana and Nigeria. Cases include adults aged ≥18 years with clinical and radiological evidence of an acute stroke. Controls were age-and-gender matched stroke-free adults. Detailed evaluations for vascular factors were performed. Pre-diabetes was defined as HBA1c of 5.7%-6.4% or Fasting blood glucose (FBG) 5.6-7.0 mmol/L and DM as HBA1c >6.5% or FBG>7.0 mmol/L. We used conditional logistic regression to estimate adjusted odds ratios (aOR) with 95% Confidence Interval. RESULTS: Among 2,935 stroke cases the mean age was 60.0 ± 14.2 years with 55.2% being males. By glycemic status, 931 (31.7%) were euglycemic, 633 (21.6%) had Pre-diabetes and 1371 (46.7%) had DM. Of the age- and sex-matched stroke-free controls 69.2% were euglycemic, 13.3% had pre-DM and 17.5% had DM. Pre-DM [aOR (95% CI): 3.68(2.61-5.21)] and DM [4.29 (3.19-5.74)] were independently associated with stroke. The aOR of Pre-DM for ischemic stroke 3.06 (2.01-4.64)] was lower than 4.82 (3.37-6.89) for DM. However, the aOR of Pre-DM for hemorrhagic stroke 6.81 (95% CI: 3.29 - 14.08)] was higher than 3.36 (1.94-5.86) for DM. Furthermore, the aOR of pre-DM for ischemic stroke subtypes were 9.64 (1.30-71.57) for cardio-embolic stroke, 3.64 (1.80-7.34) for small-vessel occlusive disease and 4.63 (0.80-26.65) for large-vessel disease. CONCLUSION: Pre-DM is strongly and independently associated with stroke in Africans. Improving glycemic control through screening, healthy lifestyle and pharmacotherapy at a population level may be strategic in reducing the rising burden of stroke in Africa.

High prevalence of non-dipping patterns among Black Africans with uncontrolled hypertension: a secondary analysis of the CREOLE trial.

BACKGROUND: Dipping of blood pressure (BP) at night is a normal physiological phenomenon. However, a non-dipping pattern is associated with hypertension mediated organ damage, secondary forms of hypertension and poorer long-term outcome. Identifying a non-dipping pattern may be useful in assessing risk, aiding the decision to investigate for secondary causes, initiating treatment, assisting decisions on choice and timing of antihypertensive therapy, and intensifying salt restriction. OBJECTIVES: To estimate the prevalence and factors associated with non-dipping pattern and determine the effect of 6 months of three antihypertensive regimens on the dipping pattern among Black African hypertensive patients. METHODS: This was a secondary analysis of the CREOLE Study which was a randomized, single blind, three-group trial conducted in 10 sites in 6 Sub-Saharan African countries. The participants were 721 Black African patients, aged between 30 and 79 years, with uncontrolled hypertension and a baseline 24-h ambulatory blood pressure monitoring (ABPM). Dipping was calculated from the average day and average night systolic blood pressure measures. RESULTS: The prevalence of non-dipping pattern was 78% (564 of 721). Factors that were independently associated with non-dipping were: serum sodium > 140 mmol/l (OR = 1.72, 95% CI 1.17-2.51, p-value 0.005), a higher office systolic BP (OR = 1.03, 95% CI 1.01-1.05, p-value 0.003) and a lower office diastolic BP (OR = 0.97, 95% CI 0.95-0.99, p-value 0.03). Treatment allocation did not change dipping status at 6 months (McNemar's Chi2 0.71, p-value 0.40). CONCLUSION: There was a high prevalence of non-dipping among Black Africans with uncontrolled hypertension. ABPM should be considered more routinely in Black Africans with uncontrolled hypertension, if resources permit, to help personalise therapy. Further research is needed to understand the mechanisms and causes of non-dipping pattern and if targeting night-time BP improves clinical outcomes. Trial registration ClinicalTrials.gov (NCT02742467).

A Novel Afrocentric Stroke Risk Assessment Score: Models from the Siren Study.

BACKGROUND: Stroke risk can be quantified using risk factors whose effect sizes vary by geography and race. No stroke risk assessment tool exists to estimate aggregate stroke risk for indigenous African. OBJECTIVES: To develop Afrocentric risk-scoring models for stroke occurrence. MATERIALS AND METHODS: We evaluated 3533 radiologically confirmed West African stroke cases paired 1:1 with age-, and sex-matched stroke-free controls in the SIREN study. The 7,066 subjects were randomly split into a training and testing set at the ratio of 85:15. Conditional logistic regression models were constructed by including 17 putative factors linked to stroke occurrence using the training set. Significant risk factors were assigned constant and standardized statistical weights based on regression coefficients (ß) to develop an additive risk scoring system on a scale of 0-100%. Using the testing set, Receiver Operating Characteristics (ROC) curves were constructed to obtain a total score to serve as cut-off to discriminate between cases and controls. We calculated sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) at this cut-off. RESULTS: For stroke occurrence, we identified 15 traditional vascular factors. Cohen's kappa for validity was maximal at a total risk score of 56% using both statistical weighting approaches to risk quantification and in both datasets. The risk score had a predictive accuracy of 76% (95%CI: 74-79%), sensitivity of 80.3%, specificity of 63.0%, PPV of 68.5% and NPV of 76.2% in the test dataset. For ischemic strokes, 12 risk factors had predictive accuracy of 78% (95%CI: 74-81%). For hemorrhagic strokes, 7 factors had a predictive accuracy of 79% (95%CI: 73-84%). CONCLUSIONS: The SIREN models quantify aggregate stroke risk in indigenous West Africans with good accuracy. Prospective studies are needed to validate this instrument for stroke prevention.

The INVICTUS rheumatic heart disease research program: Rationale, design and baseline characteristics of a randomized trial of rivaroxaban compared to vitamin K antagonists in rheumatic valvular disease and atrial fibrillation.

BACKGROUND: Rheumatic heart disease (RHD) is a neglected disease affecting 33 million people, mainly in low and middle income countries. Yet very few large trials or registries have been conducted in this population. The INVICTUS program of research in RHD consists of a randomized-controlled trial (RCT) of 4500 patients comparing rivaroxaban with vitamin K antagonists (VKA) in patients with RHD and atrial fibrillation (AF), a registry of 17,000 patients to document the contemporary clinical course of patients with RHD, including a focused sub-study on pregnant women with RHD within the registry. This paper describes the rationale, design, organization and baseline characteristics of the RCT and a summary of the design of the registry and its sub-study. Patients with RHD and AF are considered to be at high risk of embolic strokes, and oral anticoagulation with VKAs is recommended for stroke prevention. But the quality of anticoagulation with VKA is poor in developing countries. A drug which does not require monitoring, and which is safe and effective for preventing stroke in patients with valvular AF, would fulfill a major unmet need. METHODS: The INVestIgation of rheumatiC AF Treatment Using VKAs, rivaroxaban or aspirin Studies (INVICTUS-VKA) trial is an international, multicentre, randomized, open-label, parallel group trial, testing whether rivaroxaban 20 mg given once daily is non-inferior (or superior) to VKA in patients with RHD, AF, and an elevated risk of stroke (mitral stenosis with valve area ≤2 cm2, left atrial spontaneous echo-contrast or thrombus, or a CHA2DS2VASc score ≥2). The primary efficacy outcome is a composite of stroke or systemic embolism and the primary safety outcome is the occurrence of major bleeding. The trial has enrolled 4565 patients from 138 sites in 23 countries from Africa, Asia and South America. The Registry plans to enroll an additional 17,000 patients with RHD and document their treatments, and their clinical course for at least 2 years. The pregnancy sub-study will document the clinical course of pregnant women with RHD. CONCLUSION: INVICTUS is the largest program of clinical research focused on a neglected cardiovascular disease and will provide new information on the clinical course of patients with RHD, and approaches to anticoagulation in those with concomitant AF.

Practice patterns and outcomes after stroke across countries at different economic levels (INTERSTROKE): an international observational study.

BACKGROUND: Stroke disproportionately affects people in low-income and middle-income countries. Although improvements in stroke care and outcomes have been reported in high-income countries, little is known about practice and outcomes in low and middle-income countries. We aimed to compare patterns of care available and their association with patient outcomes across countries at different economic levels. METHODS: We studied the patterns and effect of practice variations (ie, treatments used and access to services) among participants in the INTERSTROKE study, an international observational study that enrolled 13 447 stroke patients from 142 clinical sites in 32 countries between Jan 11, 2007, and Aug 8, 2015. We supplemented patient data with a questionnaire about health-care and stroke service facilities at all participating hospitals. Using univariate and multivariate regression analyses to account for patient casemix and service clustering, we estimated the association between services available, treatments given, and patient outcomes (death or dependency) at 1 month. FINDINGS: We obtained full information for 12 342 (92%) of 13 447 INTERSTROKE patients, from 108 hospitals in 28 countries; 2576 from 38 hospitals in ten high-income countries and 9766 from 70 hospitals in 18 low and middle-income countries. Patients in low-income and middle-income countries more often had severe strokes, intracerebral haemorrhage, poorer access to services, and used fewer investigations and treatments (p<0·0001) than those in high-income countries, although only differences in patient characteristics explained the poorer clinical outcomes in low and middle-income countries. However across all countries, irrespective of economic level, access to a stroke unit was associated with improved use of investigations and treatments, access to other rehabilitation services, and improved survival without severe dependency (odds ratio [OR] 1·29; 95% CI 1·14-1·44; all p<0·0001), which was independent of patient casemix characteristics and other measures of care. Use of acute antiplatelet treatment was associated with improved survival (1·39; 1·12-1·72) irrespective of other patient and service characteristics. INTERPRETATION: Evidence-based treatments, diagnostics, and stroke units were less commonly available or used in low and middle-income countries. Access to stroke units and appropriate use of antiplatelet treatment were associated with improved recovery. Improved care and facilities in low-income and middle-income countries are essential to improve outcomes. FUNDING: Chest, Heart and Stroke Scotland.

May Measurement Month 2017: screening for hypertension in Nigeria-Sub-Saharan Africa.

Hypertension and its complications are now responsible for about a quarter of emergency medical admissions in urban hospitals in Nigeria. It is the commonest risk factor for stroke, heart failure, chronic kidney disease, and dementia. Furthermore, high blood pressure is the commonest cause of sudden unexpected natural death in the country. Regrettably, the rate of awareness, treatment, and control is abysmally low in the country and in many parts of the world. May Measurement Month (MMM) is a global initiative of the International Society of Hypertension aimed at raising awareness of high blood pressure (BP) and to act as a temporary solution to the lack of screening programs worldwide. An opportunistic cross-sectional survey of volunteers aged ≥18 years was carried out in May 2017. Blood pressure measurement, the definition of hypertension and statistical analysis followed the standard MMM protocol. A total of 19 904 individuals with a mean age of 40.9 years, were screened during MMM17. After multiple imputation, 6709 (36.2%) had hypertension. Of individuals not receiving anti-hypertensive medication, 4140 (25.9%) were found to have hypertension. Of individuals receiving anti-hypertensive medication, 1449 (58.8%) had uncontrolled BP. MMM17 was one of the largest BP screening campaigns undertaken in Nigeria. A significant number of the participants were identified with hypertension (but not on any treatment) and uncontrolled BP despite being treated. These results suggest that opportunistic screening can identify significant numbers with raised BP.

Rationale and design of the comparison of 3 combination therapies in lowering blood pressure in black Africans (CREOLE study): 2 × 3 factorial randomized single-blind multicenter trial.

BACKGROUND: Current hypertension guidelines recommend the use of combination therapy as first-line treatment or early in the management of hypertensive patients. Although there are many possible combinations of blood pressure(BP)-lowering therapies, the best combination for the black population is still a subject of debate because no large randomized controlled trials have been conducted in this group to compare the efficacy of different combination therapies to address this issue. METHODS: The comparison of 3 combination therapies in lowering BP in the black Africans (CREOLE) study is a randomized single-blind trial that will compare the efficacy of amlodipine plus hydrochlorothiazide versus amlodipine plus perindopril and versus perindopril plus hydrochlorothiazide in blacks residing in sub-Saharan Africa (SSA). Seven hundred two patients aged 30-79 years with a sitting systolic BP of 140 mm Hg and above, and less than 160 mm Hg on antihypertensive monotherapy, or sitting systolic BP of 150 mm Hg and above, and less than 180 mm Hg on no treatment, will be centrally randomized into any of the 3 arms (234 into each arm). The CREOLE study is taking place in 10 sites in SSA, and the primary outcome measure is change in ambulatory systolic BP from baseline to 6 months. The first patient was randomized in June 2017, and the trial will be concluded by 2019. CONCLUSIONS: The CREOLE trial will provide unique information as to the most efficacious 2-drug combination in blacks residing in SSA and thereby inform the development of clinical guidelines for the treatment of hypertension in this subregion.

Clinical Outcomes in 3343 Children and Adults With Rheumatic Heart Disease From 14 Low- and Middle-Income Countries: Two-Year Follow-Up of the Global Rheumatic Heart Disease Registry (the REMEDY Study).

BACKGROUND: There are few contemporary data on the mortality and morbidity associated with rheumatic heart disease or information on their predictors. We report the 2-year follow-up of individuals with rheumatic heart disease from 14 low- and middle-income countries in Africa and Asia. METHODS: Between January 2010 and November 2012, we enrolled 3343 patients from 25 centers in 14 countries and followed them for 2 years to assess mortality, congestive heart failure, stroke or transient ischemic attack, recurrent acute rheumatic fever, and infective endocarditis. RESULTS: Vital status at 24 months was known for 2960 (88.5%) patients. Two-thirds were female. Although patients were young (median age, 28 years; interquartile range, 18-40), the 2-year case fatality rate was high (500 deaths, 16.9%). Mortality rate was 116.3/1000 patient-years in the first year and 65.4/1000 patient-years in the second year. Median age at death was 28.7 years. Independent predictors of death were severe valve disease (hazard ratio [HR], 2.36; 95% confidence interval [CI], 1.80-3.11), congestive heart failure (HR, 2.16; 95% CI, 1.70-2.72), New York Heart Association functional class III/IV (HR, 1.67; 95% CI, 1.32-2.10), atrial fibrillation (HR, 1.40; 95% CI, 1.10-1.78), and older age (HR, 1.02; 95% CI, 1.01-1.02 per year increase) at enrollment. Postprimary education (HR, 0.67; 95% CI, 0.54-0.85) and female sex (HR, 0.65; 95% CI, 0.52-0.80) were associated with lower risk of death. Two hundred and four (6.9%) patients had new congestive heart failure (incidence, 38.42/1000 patient-years), 46 (1.6%) had a stroke or transient ischemic attack (8.45/1000 patient-years), 19 (0.6%) had recurrent acute rheumatic fever (3.49/1000 patient-years), and 20 (0.7%) had infective endocarditis (3.65/1000 patient-years). Previous stroke and older age were independent predictors of stroke/transient ischemic attack or systemic embolism. Patients from low- and lower-middle-income countries had significantly higher age- and sex-adjusted mortality than patients from upper-middle-income countries. Valve surgery was significantly more common in upper-middle-income than in lower-middle- or low-income countries. CONCLUSIONS: Patients with clinical rheumatic heart disease have high mortality and morbidity despite being young; those from low- and lower-middle-income countries had a poorer prognosis associated with advanced disease and low education. Programs focused on early detection and the treatment of clinical rheumatic heart disease are required to improve outcomes.

Global and regional effects of potentially modifiable risk factors associated with acute stroke in 32 countries (INTERSTROKE): a case-control study.

BACKGROUND: Stroke is a leading cause of death and disability, especially in low-income and middle-income countries. We sought to quantify the importance of potentially modifiable risk factors for stroke in different regions of the world, and in key populations and primary pathological subtypes of stroke. METHODS: We completed a standardised international case-control study in 32 countries in Asia, America, Europe, Australia, the Middle East, and Africa. Cases were patients with acute first stroke (within 5 days of symptom onset and 72 h of hospital admission). Controls were hospital-based or community-based individuals with no history of stroke, and were matched with cases, recruited in a 1:1 ratio, for age and sex. All participants completed a clinical assessment and were requested to provide blood and urine samples. Odds ratios (OR) and their population attributable risks (PARs) were calculated, with 99% confidence intervals. FINDINGS: Between Jan 11, 2007, and Aug 8, 2015, 26 919 participants were recruited from 32 countries (13 447 cases [10 388 with ischaemic stroke and 3059 intracerebral haemorrhage] and 13 472 controls). Previous history of hypertension or blood pressure of 140/90 mm Hg or higher (OR 2·98, 99% CI 2·72-3·28; PAR 47·9%, 99% CI 45·1-50·6), regular physical activity (0·60, 0·52-0·70; 35·8%, 27·7-44·7), apolipoprotein (Apo)B/ApoA1 ratio (1·84, 1·65-2·06 for highest vs lowest tertile; 26·8%, 22·2-31·9 for top two tertiles vs lowest tertile), diet (0·60, 0·53-0·67 for highest vs lowest tertile of modified Alternative Healthy Eating Index [mAHEI]; 23·2%, 18·2-28·9 for lowest two tertiles vs highest tertile of mAHEI), waist-to-hip ratio (1·44, 1·27-1·64 for highest vs lowest tertile; 18·6%, 13·3-25·3 for top two tertiles vs lowest), psychosocial factors (2·20, 1·78-2·72; 17·4%, 13·1-22·6), current smoking (1·67, 1·49-1·87; 12·4%, 10·2-14·9), cardiac causes (3·17, 2·68-3·75; 9·1%, 8·0-10·2), alcohol consumption (2·09, 1·64-2·67 for high or heavy episodic intake vs never or former drinker; 5·8%, 3·4-9·7 for current alcohol drinker vs never or former drinker), and diabetes mellitus (1·16, 1·05-1·30; 3·9%, 1·9-7·6) were associated with all stroke. Collectively, these risk factors accounted for 90·7% of the PAR for all stroke worldwide (91·5% for ischaemic stroke, 87·1% for intracerebral haemorrhage), and were consistent across regions (ranging from 82·7% in Africa to 97·4% in southeast Asia), sex (90·6% in men and in women), and age groups (92·2% in patients aged ≤55 years, 90·0% in patients aged >55 years). We observed regional variations in the importance of individual risk factors, which were related to variations in the magnitude of ORs (rather than direction, which we observed for diet) and differences in prevalence of risk factors among regions. Hypertension was more associated with intracerebral haemorrhage than with ischaemic stroke, whereas current smoking, diabetes, apolipoproteins, and cardiac causes were more associated with ischaemic stroke (p<0·0001). INTERPRETATION: Ten potentially modifiable risk factors are collectively associated with about 90% of the PAR of stroke in each major region of the world, among ethnic groups, in men and women, and in all ages. However, we found important regional variations in the relative importance of most individual risk factors for stroke, which could contribute to worldwide variations in frequency and case-mix of stroke. Our findings support developing both global and region-specific programmes to prevent stroke. FUNDING: Canadian Institutes of Health Research, Heart and Stroke Foundation of Canada, Canadian Stroke Network, Health Research Board Ireland, Swedish Research Council, Swedish Heart and Lung Foundation, The Health & Medical Care Committee of the Regional Executive Board, Region Västra Götaland (Sweden), AstraZeneca, Boehringer Ingelheim (Canada), Pfizer (Canada), MSD, Chest, Heart and Stroke Scotland, and The Stroke Association, with support from The UK Stroke Research Network.

Prednisolone and Mycobacterium indicus pranii in tuberculous pericarditis.

BACKGROUND: Tuberculous pericarditis is associated with high morbidity and mortality even if antituberculosis therapy is administered. We evaluated the effects of adjunctive glucocorticoid therapy and Mycobacterium indicus pranii immunotherapy in patients with tuberculous pericarditis. METHODS: Using a 2-by-2 factorial design, we randomly assigned 1400 adults with definite or probable tuberculous pericarditis to either prednisolone or placebo for 6 weeks and to either M. indicus pranii or placebo, administered in five injections over the course of 3 months. Two thirds of the participants had concomitant human immunodeficiency virus (HIV) infection. The primary efficacy outcome was a composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. RESULTS: There was no significant difference in the primary outcome between patients who received prednisolone and those who received placebo (23.8% and 24.5%, respectively; hazard ratio, 0.95; 95% confidence interval [CI], 0.77 to 1.18; P=0.66) or between those who received M. indicus pranii immunotherapy and those who received placebo (25.0% and 24.3%, respectively; hazard ratio, 1.03; 95% CI, 0.82 to 1.29; P=0.81). Prednisolone therapy, as compared with placebo, was associated with significant reductions in the incidence of constrictive pericarditis (4.4% vs. 7.8%; hazard ratio, 0.56; 95% CI, 0.36 to 0.87; P=0.009) and hospitalization (20.7% vs. 25.2%; hazard ratio, 0.79; 95% CI, 0.63 to 0.99; P=0.04). Both prednisolone and M. indicus pranii, each as compared with placebo, were associated with a significant increase in the incidence of cancer (1.8% vs. 0.6%; hazard ratio, 3.27; 95% CI, 1.07 to 10.03; P=0.03, and 1.8% vs. 0.5%; hazard ratio, 3.69; 95% CI, 1.03 to 13.24; P=0.03, respectively), owing mainly to an increase in HIV-associated cancer. CONCLUSIONS: In patients with tuberculous pericarditis, neither prednisolone nor M. indicus pranii had a significant effect on the composite of death, cardiac tamponade requiring pericardiocentesis, or constrictive pericarditis. (Funded by the Canadian Institutes of Health Research and others; IMPI ClinicalTrials.gov number, NCT00810849.).

Symptoms and Signs of Heart Failure at Admission and Discharge and Outcomes in the Sub-Saharan Acute Heart Failure (THESUS-HF) Registry.

BACKGROUND: Symptoms and signs of heart failure (HF) are the most common reasons for admission to hospital for acute HF (AHF) and are used routinely throughout admission to assess the severity of disease and response to therapy. METHODS AND RESULTS: The data were collected in The Sub-Saharan Africa Survey on Heart Failure (THESUS-HF) study, a prospective, multicenter, observational survey of AHF from 9 countries in sub-Saharan Africa. A total of 1006 patients, ≥12 years of age, hospitalized for AHF were recruited. Symptoms and signs of HF and changes in dyspnea and well-being, relative to admission, were assessed at entry and on days 1, 2, and 7 (or on discharge if earlier) and included oxygen saturation, degree of edema and rales, body weight, and level of orthopnea. The patient determined dyspnea and general well-being, whereas the physician determined symptoms and signs of HF, as well as improvements in vital sign measurement, throughout the admission. After multivariable adjustment, baseline rales and changes to day 7 or discharge in general well-being predicted death or HF hospitalization through day 60, and baseline orthopnea, edema, rales, oxygen saturation, and changes to day 7 or on discharge in respiratory rate and general well-being were predictive of death through day 180. CONCLUSIONS: In AHF patients in sub-Saharan Africa, symptoms and signs of HF improve throughout admission, and simple assessments, including edema, rales, oxygen saturation, respiratory rate, and asking the patient about general well-being, are valuable tools in patients' clinical assessment.