Vericiguat and Cardiovascular Outcomes in Heart Failure by Baseline Diabetes Status: Insights From the VICTORIA Trial.

BACKGROUND: Type 2 diabetes mellitus (T2DM) significantly worsens heart failure (HF) prognosis. OBJECTIVES: This study sought to investigate the impact of T2DM on outcomes in patients enrolled in VICTORIA and assess the efficacy of vericiguat in patients with and without T2DM. METHODS: Patients with HF with reduced ejection fraction were randomized to receive vericiguat or placebo in addition to standard therapy. The primary outcome was a composite of cardiovascular death or first heart failure hospitalization (HFH). A Cox proportional hazards model was used to calculate HRs and 95% CIs to assess if the effect of vericiguat differed by history of T2DM. RESULTS: Of 5,050 patients enrolled, 3,683 (72.9%) had glycosylated hemoglobin (HbA1c) measured at baseline. Of these, 2,270 (61.6%) had T2DM, 741 (20.1%) had pre-T2DM, 449 (12.2%) did not have T2DM, and 178 (4.8%) had undiagnosed T2DM. The risks of the primary outcome, HFH, and all-cause and cardiovascular mortality were high across all categories. The efficacy of vericiguat on the primary outcome did not differ in patients stratified by T2DM by history (HR: 0.92; 95% CI: 0.81-1.04), T2DM measured by HbA1c (HR: 0.77; 95% CI: 0.49-1.20), and pre-T2DM measured by HbA1c (HR: 0.88; 95% CI: 0.68-1.13) and in those with normoglycemia (HR: 1.02: 95% CI: 0.75-1.39; P for interaction = 0.752). No significant differences were observed in subgroups with respect to the efficacy of vericiguat on HFH and all-cause or cardiovascular death. CONCLUSIONS: In this post hoc analysis of VICTORIA, vericiguat compared with placebo significantly reduced the risk of cardiovascular death or HFH in patients with worsening HF with reduced ejection fraction regardless of T2DM status. (A Study of Vericiguat in Participants With Heart Failure With Reduced Ejection Fraction [HFrEF] [Mk-1242-001] [VICTORIA]; NCT02861534).

Role of ß-blockers in the cardiovascular disease continuum: a collaborative Delphi survey-based consensus from Asia-Pacific.

OBJECTIVE: This Delphi method of consensus was designed to develop scientific statements for ß-blockers in the continuum of cardiovascular diseases with a special focus on the role of bisoprolol. METHODS: Eleven experienced cardiologists from across the Asia-Pacific countries participated in two rounds of the survey. In the first round, experts were asked to rate agreement/disagreement with 35 statements across seven domains regarding the use of ß-blockers for treating hypertension, heart failure, coronary artery diseases, co-morbidities, as well as their safety profile, usage pattern, and pharmacokinetic variability. A consensus for a statement could be reached with >70% agreement. RESULTS: Except for seven statements, all attained consensus in the first round. In the second round that was conducted virtually, the experts re-appraised their ratings for the seven statements along with a critical appraisal of two additional statements that were suggested by experts in the preceding round. At the end of the second round, the final version included 36 statements (34 original statements, two statements suggested by experts, and the omission of one statement that did not attain consensus). The final version of statements in the second round was disseminated among experts for their approval followed by manuscript development. CONCLUSION: Attainment of consensus for almost all statements reconfirms the clinical benefits of ß-blockers, particularly ß1-selective blockers for the entire spectrum of cardiovascular diseases.

Renal function and the effects of vericiguat in patients with worsening heart failure with reduced ejection fraction: insights from the VICTORIA (Vericiguat Global Study in Subjects with HFrEF) trial.

AIMS: Vericiguat reduced the primary composite outcome of cardiovascular death or heart failure (HF) hospitalization in patients with worsening HF with reduced ejection fraction (HFrEF) and a lower limit of baseline estimated glomerular filtration rate (eGFR) of 15 mL/min/1.73 m2 . We evaluated the relationship between the efficacy of vericiguat and baseline and subsequent changes in renal function. METHODS AND RESULTS: In VICTORIA, core laboratory serum creatinine was measured at baseline (n = 4956) and weeks 16, 32, and 48. Worsening renal function (WRF), defined as an increase ≥0.3 mg/dL in creatinine from baseline to week 16, was assessed via a Cox model with respect to subsequent primary events. Mean age was 69 years, 24% were female, and mean baseline eGFR was 61 mL/min/1.73 m2 . During 48 weeks of treatment, the trajectories in eGFR and creatinine with vericiguat were similar to placebo (P = 0.50 and 0.18). The beneficial effects of vericiguat on the primary outcome were not influenced by baseline eGFR (interaction P = 0.48). WRF occurred in 15% of patients and was associated with worse outcomes (adjusted hazard ratio 1.28, 95% confidence interval 1.11-1.47; P < 0.001), but the beneficial effects of vericiguat on the primary outcome were similar in patients with or without WRF (interaction P = 0.76). CONCLUSION: Renal function trajectories were similar between vericiguat- and placebo-treated patients and the beneficial effects of vericiguat on the primary outcome were consistent across the full range of eGFR and irrespective of WRF.

Heart failure with preserved ejection fraction in Asia.

BACKGROUND: Heart failure with preserved ejection fraction (HFpEF) is a global public health problem. Unfortunately, little is known about HFpEF across Asia. METHODS AND RESULTS: We prospectively studied clinical characteristics, echocardiographic parameters and outcomes in 1204 patients with HFpEF (left ventricular ejection fraction ≥50%) from 11 Asian regions, grouped as Northeast Asia (Hong Kong, Taiwan, China, Japan, Korea, n = 543), South Asia (India, n = 252), and Southeast Asia (Malaysia, Thailand, Singapore, Indonesia, Philippines, n = 409). Mean age was 68 ±12 years (37% were < 65 years) and 50% were women. Seventy per cent of patients had ≥2 co-morbidities, most commonly hypertension (71%), followed by anaemia (57%), chronic kidney disease (50%), diabetes (45%), coronary artery disease (29%), atrial fibrillation (29%) and obesity (26%). Southeast Asian patients had the highest prevalence of all co-morbidities except atrial fibrillation, South Asians had the lowest prevalence of all co-morbidities except anaemia and obesity, and Northeast Asians had more atrial fibrillation. Left ventricular hypertrophy and concentric remodelling were most prominent among Southeast and South Asians, respectively (P < 0.001). Overall, 12.1% of patients died or were hospitalized for heart failure within 1 year. Southeast Asians were at higher risk for adverse outcomes, independent of co-morbidity burden and cardiac geometry. CONCLUSION: These first prospective multinational data from Asia show that HFpEF affects relatively young patients with a high burden of co-morbidities. Regional differences in types of co-morbidities, cardiac remodelling and outcomes of HFpEF across Asia have important implications for public health measures and global HFpEF trial design.

Disparity Between Indications for and Utilization of Implantable Cardioverter Defibrillators in Asian Patients With Heart Failure.

BACKGROUND: Implantable cardioverter defibrillators (ICDs) are lifesaving devices for patients with heart failure (HF) and reduced ejection fraction. However, utilization and determinants of ICD insertion in Asia are poorly defined. We determined the utilization, associations of ICD uptake, patient-perceived barriers to device therapy and, impact of ICDs on mortality in Asian patients with HF. METHODS AND RESULTS: Using the prospective ASIAN-HF (Asian Sudden Cardiac Death in Heart Failure) registry, 5276 patients with symptomatic HF and reduced ejection fraction (HFrEF) from 11 Asian regions and across 3 income regions (high: Hong Kong, Japan, Korea, Singapore, and Taiwan; middle: China, Malaysia, and Thailand; and low: India, Indonesia, and Philippines) were studied. ICD utilization, clinical characteristics, as well as device perception and knowledge, were assessed at baseline among ICD-eligible patients (EF ≤35% and New York Heart Association Class II-III). Patients were followed for the primary outcome of all-cause mortality. Among 3240 ICD-eligible patients (mean age 58.9±12.9 years, 79.1% men), 389 (12%) were ICD recipients. Utilization varied across Asia (from 1.5% in Indonesia to 52.5% in Japan) with a trend toward greater uptake in regions with government reimbursement for ICDs and lower out-of-pocket healthcare expenditure. ICD (versus non-ICD) recipients were more likely to be older (63±11 versus 58±13 year; P<0.001), have tertiary (versus ≤primary) education (34.9% versus 18.1%; P<0.001) and be residing in a high (versus low) income region (64.5% versus 36.5%; P<0.001). Among 2000 ICD nonrecipients surveyed, 55% were either unaware of the benefits of, or needed more information on, device therapy. ICD implantation reduced risks of all-cause mortality (hazard ratio, 0.71; 95% confidence interval, 0.52-0.97) and sudden cardiac deaths (hazard ratio, 0.33; 95% confidence interval, 0.14-0.79) over a median follow-up of 417 days. CONCLUSIONS: ICDs reduce mortality risk, yet utilization in Asia is low; with disparity across geographic regions and socioeconomic status. Better patient education and targeted healthcare reforms in extending ICD reimbursement may improve access. CLINICAL TRIAL REGISTRATION: URL: https://clinicaltrials.gov/ct2/show/NCT01633398. Unique identifier: NCT01633398.

Regional and ethnic differences among patients with heart failure in Asia: the Asian sudden cardiac death in heart failure registry.

AIMS: To characterize regional and ethnic differences in heart failure (HF) across Asia. METHODS AND RESULTS: We prospectively studied 5276 patients with stable HF and reduced ejection fraction (≤40%) from 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan, and Thailand). Mean age was 59.6 ± 13.1 years, 78.2% were men, and mean body mass index was 24.9 ± 5.1 kg/m2. Majority (64%) of patients had two or more comorbid conditions such as hypertension (51.9%), coronary artery disease (CAD, 50.2%), or diabetes (40.4%). The prevalence of CAD was highest in Southeast Asians (58.8 vs. 38.2% in Northeast Asians). Compared with Chinese ethnicity, Malays (adjusted odds ratio [OR] 1.97, 95% CI 1.63-2.38) and Indians (OR 1.44, 95% CI 1.24-1.68) had higher odds of CAD, whereas Koreans (OR 0.38, 95% CI 0.29-0.50) and Japanese (OR 0.44, 95% CI 0.36-0.55) had lower odds. The prevalence of hypertension and diabetes was highest in Southeast Asians (64.2 and 49.3%, respectively) and high-income regions (59.7 and 46.2%, respectively). There was significant interaction between ethnicity and region, where the adjusted odds were 3.95 (95% CI 2.51-6.21) for hypertension and 4.91 (95% CI 3.07-7.87) for diabetes among Indians from high- vs. low-income regions; and 2.60 (95% CI 1.66-4.06) for hypertension and 2.62 (95% CI 1.73-3.97) for diabetes among Malays from high- vs. low-income regions. CONCLUSIONS: These first prospective multi-national data from Asia highlight the significant heterogeneity among Asian patients with stable HF, and the important influence of both ethnicity and regional income level on patient characteristics. CLINICALTRIALSGOV IDENTIFIER: NCT01633398.

The UP-Philippine General Hospital acute coronary events at the emergency room registry (UP PGH-ACER)

OBJECTIVES: This study pilots the creation of a clinical registry for all patients admitted for Acute Coronary Syndromes(ACS) at the Philippine General Hospital (PGH) Emergency Room (ER). METHODS: This is a single-institution prospective observational study including all patients >18 years old admitted from September to October 2011 with suspected acute coronary syndromes. Abstraction of chart information using a data collection form was done. Patient's clinical data, medications received, and quality of care indicators were noted. The primary study outcome measure is the completeness of chart data, quality indicators such as door-to-ECG time and door-to-needle time, and the clinical profile of patients with ACS. RESULTS: Thirty patients were included, with equal numbers of males females, and a mean age of 59 years old. There were equal numbers of patients with STEMI (43%) and NSTEMI (43%). The most common risk factor was hypertension (72.4%) followed by smoking (34.48%). Around 20% are diabetics, and 31% have known lipid abnormalities or are on lipid-lowering agents. Around one third of the patients have had previous admissions for acute coronary events. Only two patients had angiographically confirmed CAD. The majority of patients assessed to have acute coronary syndromes (26 patients) were Killip Class I. Only one was cardiogenic shock upon admission. Temporal information such as time of first physician contact and time of drug administration was not available in more than half of the cases. While there is a high rate of physician compliance to guideline recommended therapies, temporal quality indicators sch as door-to-ECG time (2 hours) and door-to-needle time (3.5 hours) remain substandard. The rest of the patients presented beyond 12 hours of chest pain onset and were already chest pain free. Among those who were eligible for thrombolysis, 67% received thrombolytic therapy with streptokinase. No patient was given thrombolytic agent within 30 minutes upon admission to the emergency department. No patient underwent cardiac catheterization as the primary means of revascularization. Hence, door-to-balloon time could not be determined. CONCLUSION: A standardized ACS pathway for adequate documentation of information is necessary for a complete and effective clinical registry for ACS must be set in place. Establishment of an efficient clinical registry must be a joint effort of all services involved in the care for these patients. Proper documentation in clinical charts of patients admitted at the PGH-ER needs to be improved. The quality indicators such as door-to-ECG and door-to-needle time were remarkably above the guideline recommended targets. The compliance for class 1 medications among patients admitted for ACS during the time of the study was optimal.

Asian Sudden Cardiac Death in Heart Failure (ASIAN-HF) registry.

AIMS: Our aim is to determine mortality and morbidity in Asian patients under clinical management for heart failure (HF). Specifically, we will define the incidence of, and risk factors for, sudden cardiac death, as well as the socio-cultural factors influencing therapeutic choices in these patients. Methods This is a prospective observational multinational Asian registry of 5000 patients with symptomatic HF (stage C) and LV systolic dysfunction (EF ≤ 40%) involving 44 centres across 11 Asian regions (China, Hong Kong, India, Indonesia, Japan, Korea, Malaysia, Philippines, Singapore, Taiwan and Thailand). Data collection includes demographic variables, clinical symptoms, functional status, date of HF diagnosis and prior cardiovascular investigations, clinical risk factors, lifestyle factors, socio-economic status, and survey of cultural beliefs, health practices, and attitudes towards device therapy. Centre-level characteristics (case load, referral pattern, specialization, and infrastructure) are also obtained. Patients uniformly undergo standard 12-lead ECG and transthoracic echocardiography at baseline, and are followed over 3 years for outcomes of death or hospitalization. The mode of death and cause of hospitalization are adjudicated by a central event adjudication committee using pre-specified criteria. Perspective By providing prospective data regarding the demographics, risk factors, and outcomes of Asian patients under treatment for HF, the ASIAN-HF registry is expected to advance fundamental understanding of the burden and predictors of death and hospitalization among these patients. The knowledge gained will be important for guiding resource allocation and planning preventive strategies to address the unmet and growing clinical needs of patients with cardiovascular disease in Asia. Trial registration NCT01633398.

Clinical and echocardiographic profile and outcomes of peripartum cardiomyopathy: the Philippine General Hospital experience.

BACKGROUND: Peripartum cardiomyopathy (PPCM) is a rare disease entity of unknown aetiology. High rates of mortality or poor overall clinical outcome are reported in women with this condition. Certain characteristics are risk factors for this disease. In Asia, there are limited data, especially in the Southeast Asian region. In the Philippines, no data exist regarding the prevalence or risk factors. OBJECTIVES: To determine the prevalence, profile and outcomes of PPCM in Philippine General Hospital and to describe their echocardiographic findings. METHODS: All patients diagnosed with PPCM in the period of 1 January 2009-31 December 2010 were seen and examined. Demographic data and echocardiogram of the patients were reviewed. RESULTS: 9 were diagnosed with PPCM during the study period. The prevalence is 1 in 1270 live births. Mean age was 29. 78% presented with moderate to severe heart failure symptoms in the prepartum period. Among purported risk factors for PPCM, obesity, multiparity and pre-eclampsia were seen in most. Conversely, only one patient admitted to having more than a single sexual partner. Only one patient had multifetal pregnancy. None were smokers. 44% underwent caesarean section for maternal indication. No mortality was seen. Fetal outcomes were good with all resulting in live births and most were appropriate for gestational age. Echocardiographic findings showed global wall motion abnormalities in the majority, mean ejection fraction of 34% and mean fractional shortening of 20%. CONCLUSIONS: PPCM is rare in the Philippines. Compared with international data, our patients are younger with low percentages of promiscuity, multifetal pregnancy, smoking history and tocolytic use. Similar to previous studies, obesity, multiparity and pre-eclampsia were also present in our PPCM patients. Immediate maternal and fetal outcomes were generally good. Adherence to standard heart failure management is high.

Smoking burden in the Philippines

BACKGROUND: The 2nd National Nutrition and Health Survey (NNHeS II) was conducted in 2008 to measure the prevalence of lifestyle-related diseases and risk factors among adult Filipinos 20 years or older. One of the risk factors measured was smoking. METHODS: The survey used a stratified multi-stage sampling design and covered the 17 regions of the country. The clinical component included Filipino adults 20 years or older. Data was collected using health questionaires; anthropometric measurements were made, and blood examinations performed on all participants. The prevalence of smoking was determined. RESULTS: A total of 7,700 subjects were included in the survey. The over-all prevalence of current smokers was 31% (53.2% and 12.5% for men and women, respectively). 14% were former smokers (20.9% of men and 9.5% of women) while 25.9% of men and 78.1% of women were never smokers.Among current male smokers, the highest prevalence (57.7%) belonged to the 20-29 age group. While among current female smokers, the highest prevalence (23.2%) belonged to the greater than 70-year-old category.There were more current smokers in the rural areas (33.1%) than the urban areas (28.9%) and there were more current and former smokers among respondents whose educational attainment was at least tertiary level (62.7%). CONCLUSION: Tobacco use in the Philippines is still prevalent at 31% and is predominantly composed of males in the 20-29 age group. Current smoking is highest among rural dwellers and among individuals with elementary education, while majority of women and college level respondents are never smokers.