Consensus Statement from India on the Renal Benefits of ARNi, SGLT-2i, and Bisoprolol in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a major contributor to morbidity and mortality in India. CKD often coexists with heart failure (HF), diabetes, and hypertension. All these comorbidities are risk factors for renal impairment. HF and CKD are pathophysiologically intertwined, and the deterioration of one can worsen the prognosis of the other. There is a need for safe renal pharmacological therapies that target both CKD and HF and are also useful in hypertension and diabetes. Neurohormonal activation achieved through the activation of the sympathetic nervous system (SNS), the renin-angiotensin-aldosterone system (RAAS), and the natriuretic peptide system (NPS) is fundamental in the pathogenesis and progression of CKD and HF. Angiotensin receptor neprilysin inhibitor (ARNi), sodium-glucose cotransporter 2 inhibitors (SGLT-2i), and selective ß1-blocker (B1B) bisoprolol suppress this neurohormonal activation. They also have many other cardiorenal benefits across a wide range of CKD patients with or without concomitant HF, diabetes, or hypertension. This consensus statement from India explores the place of ARNi, SGLT-2i, and bisoprolol in the management of CKD patients with or without HF and other comorbidities.

Current Place of SGLT2i in the Management of Heart Failure: An Expert Opinion from India.

Heart failure (HF) is a global health concern that is prevalent in India as well. HF is reported at a younger age in Indian patients with comorbidity of type 2 diabetes (T2DM) in approximately 50% of patients. Sodium-glucose cotransporter-2 inhibitors (SGLT2i), originally approved for T2DM, are new guideline-recommended and approved treatment strategies for HF. Extensive evidence highlights that SGLT2i exhibits profound cardiovascular (CV) benefits beyond glycemic control. SGLT2i, in conjunction with other guideline-directed medical therapies (GMDT), has additive effects in improving heart function and reducing adverse HF outcomes. The benefits of SGLT2i are across a spectrum of patients, with and without diabetes, suggesting their potential place in broader HF populations irrespective of ejection fraction (EF). This consensus builds on the updated evidence of the efficacy and safety of SGLT2i in HF and recommends its place in therapy with a focus on Indian patients with HF.

The Promise of Cilnidipine in Hypertension with Comorbidities: National Consensus Statement: National Consensus Group Comprises Cardiologists, Nephrologists, and Diabetologists from India in a National Meet at New Delhi held on 22nd May 2022.

The rapidly increasing burden of hypertension is responsible for premature deaths from cardiovascular disease (CVD), renal disease, and stroke, with a tremendous public health and financial burden. Hypertension detection, treatment, and control vary worldwide; it is still low, particularly in low- and middle-income countries (LMICs). High blood pressure (BP) and CVD risk have a strong, linear, and independent association. They contribute to alarming numbers of all-cause and CVD deaths. A major culprit for increased hypertension is sympathetic activity, and further complications of hypertension are heart failure, ischemic heart disease (IHD), stroke, and renal failure. Now, antihypertensive interventions have emerged as a global public health priority to reduce BP-related morbidity and mortality. Calcium channel blockers (CCB) are highly effective vasodilators. and the most common drugs used for managing hypertension and CVD. Cilnidipine, with both L- and N-type calcium channel blocking activity, is a promising 4th generation CCB. It causes vasodilation via L-type calcium channel blockade and inhibits the sympathetic nervous system (SNS) via N-type calcium channel blockade. Cilnidipine, which acts as a dual L/N-type CCB, is linked to a reduced occurrence of pedal edema compared to amlodipine, which solely blocks L-type calcium channels. The antihypertensive properties of cilnidipine are very substantial, with low BP variability and long-acting properties. It is beneficial for hypertensive patients to deal with morning hypertension and for patients with abnormal nocturnal BP due to exaggerated sympathetic nerve activation. Besides its BP-lowering effect, it also exhibits organ protection via sympathetic nerve inhibition and renin-angiotensin-aldosterone system inhibition; it controls heart rate and proteinuria. Reno-protective, neuroprotective, and cardioprotective effects of cilnidipine have been well-documented and demonstrated.

Critical Appraisal on the Role of Warfarin in the Current Era.

Warfarin has been the most extensively used oral anticoagulant (OAC) in medical settings for over 60 years. Its uses, potential adverse effects, and methods for reversing its effects have been firmly established, rendering it a routine medication in medical settings where most professionals feel at ease employing it. Compared to other vitamin K antagonists (VKAs), such as acenocoumarol, warfarin offers benefits like diminished prothrombin time (PT) assays leading to enhanced oral anticoagulation. Observations over the past few years have seen the inclusion of novel/direct OACs (NOACs/DOACs) in the anticoagulant armamentarium. Although DOACs have several advantages, warfarin still has an important role in subsets of patients where DOACs are contraindicated, not well-tolerated, or cannot afford DOACs due to higher costs. Moreover, there are patient profiles where warfarin is still considered a superior choice compared to DOACs, such as age group of >75 years, kidney failure with creatinine clearance (CrCl) below 30 mL/minute, and prosthetic mechanical valve replacement. Precise management of the international normalized ratio (INR) is crucial for the effectiveness of warfarin treatment. INR monitoring is the major concern in the Indian context due to the lack of laboratories for standardized measurement. Adopting strategies such as point-of-care INR monitoring devices and anticoagulation clinics can help to improve clinical outcomes with warfarin therapy. The present review provides a critical overview of the role of warfarin therapy in the current OAC arsenal and strategies for improving therapeutic control and patient adherence. How to cite this article: Nair T. Critical Appraisal on the Role of Warfarin in the Current Era. J Assoc Physicians India 2023;71(10):31-36.

Role of Iron Therapy in Heart Failure: A Consensus Statement from India.

Iron deficiency (ID) with or without anemia is frequently observed in patients with heart failure (HF). Uncorrected ID is associated with higher hospitalization and mortality in patients with acute HF (AHF) and chronic HF (CHF). Hence, in addition to chronic renal insufficiency, anemia, and diabetes, ID appears as a novel comorbidity and a treatment target of CHF. Intravenous (IV) ferric carboxymaltose (FCM) reduces the hospitalization risk due to HF worsening and improves functional capacity and quality of life (QOL) in HF patients. The current consensus document provides criteria, an expert opinion on the diagnosis of ID in HF, patient profiles for IV FCM, and correct administration and monitoring of such patients.

Angiotensin Receptor-Neprilysin Inhibitor Therapy and Cardiac Remodeling in Heart Failure: Consensus Statement from India.

Adverse cardiac remodeling refers to progressive structural and functional modifications in the heart because of increased wall stress in the myocardium, loss of viable myocardium, and neurohormonal stimulation. The guideline-directed medical therapy for Heart failure (HF) includes Angiotensin receptor-neprilysin inhibitor (ARNI) (sacubitril/valsartan), ß-blockers, sodium-glucose co-transporter 2 (SGLT2) inhibitors, and mineralocorticoid receptor antagonists (MRA). ARNI is under-prescribed in India despite its attractive safety and efficacy profile. Therefore, the consensus discusses objectives and topics related to ARNI in the management of cardiac remodeling, and experts shared their views on the early timely intervention of effective dosage of ARNI to improve the diagnosis and enhance mortality and morbidity benefits in cardiac reverse remodeling (CRR).

The Power and Promise of Angiotensin Receptor Neprilysin Inhibitor (ARNI) in Heart Failure Management: National Consensus Statement.

;Heart failure (HF) is a huge global public health task due to morbidity, mortality, disturbed quality of life, and major economic burden. It is an area of active research and newer treatment strategies are evolving. Recently angiotensin receptor-neprilysin inhibitor (ARNI), a class of drugs (the first agent in this class, Sacubitril-Valsartan), reduces cardiovascular mortality and morbidity in chronic HF patients with reduced left ventricular ejection fraction (LVEF). Positive therapeutic effects have led to a decrease in cardiovascular mortality and HF hospitalizations (HFH), with a favorable safety profile, and have been documented in several clinical studies with an unquestionable survival benefit with ARNI, Sacubitril-Valsartan. This consensus statement of the Indian group of experts in cardiology, nephrology, and diabetes provides a comprehensive review of the power and promise of ARNI in HF management and an evidence-based appraisal of the use of ARNI as an essential treatment strategy for HF patients in clinical practice. Consensus in this review favors an early utility of Sacubitril-Valsartan in patients with HF with reduced EF (HFrEF), regardless of the previous therapy being given. A lower rate of hospitalizations for HF with Sacubitril-Valsartan in HF patients with preserved EF who are phenotypically heterogeneous suggests possible benefits of ARNI in patients having 40-50% of LVEF, frequent subtle systolic dysfunction, and higher hospitalization risk.

Role of Bisoprolol in Heart Failure Management: A Consensus Statement from India.

In India, heart failure (HF) is an important health concern affecting younger age groups than the western population. A limited number of Indian patients receive guideline-directed medical therapy (GDMT). Selective ß-1 blockers (BB) are one of the GDMTs in HF and play an important role by decreasing the sympathetic overdrive. The BB reduces heart rate (HR) reverse the adverse cardiac (both ventricular and atrial), vascular, and renovascular remodeling seen in HF. Bisoprolol, a ß-1 blocker, has several advantages and can be used across a wide spectrum of HF presentations and in patients with HF and comorbid conditions such as coronary artery disease (CAD), atrial fibrillation (AF), post-myocardial infarction (MI), uncontrolled diabetes, uncontrolled hypertension, and renal impairment. Despite its advantages, bisoprolol is not optimally utilized for managing HF in India. This consensus builds on updated evidence on the efficacy and safety of bisoprolol in HF and recommends its place in therapy with a focus on Indian patients with HF.

Experts' Consensus on Use of Long-Acting Nitroglycerine in the Management of Angina and Chronic Coronary Syndrome in India.

AIM: To address the existing gaps in knowledge about long-acting nitroglycerine (LA-NTG) and provide recommendations to address these issues. METHODOLOGY: Approved LA-NTG questionnaire that included 17 questions related to the role of LA-NTG in the management of angina and chronic coronary syndrome (CCS) was shared with 150 expert cardiologists from different regions from India. Results of these survey questionnaires were further discussed in 12 regional level meetings. The opinions and suggestions from all the meetings were compiled and analyzed. Further, recommendations were made with the help of attending national cardiology experts and a consensus statement was derived. RESULTS: This is the first consensus on LA-NTG, summarizing the clinical evidence from India and suggesting recommendations based on these data. The experts recommended early use of LA-NTG as a first-line antianginal therapy in combination with beta-blocker since it improves exercise tolerance in patients with CCS. A strong consensus was observed for using LA-NTG in patients with co-morbid hypertension, diabetes, chronic kidney disease and post-percutaneous coronary intervention angina. As a part of cardiac rehabilitation, LA-NTG allows patients with angina to exercise to a greater functional capacity. CONCLUSIONS: A national consensus was observed for several aspects of LA-NTG in the management of angina and CCS. The clinical experience of the experts confirmed an extremely satisfied patient perception about the efficacy of LA-NTG.

COVID-Inflicted Coagulopathy: Expert Consensus on Management with Novel Oral Anticoagulants in India.

Coronavirus disease 2019 (COVID-19) is a highly hypercoagulable viral infection complicated as COVID-inflicted coagulopathy (CIC), that is associated with increased risk of morbidity and mortality. International guidelines recommend low molecular weight heparin (LMWH) to treat CIC in both in-hospital and in-home settings. However, in India, using subcutaneous LMWH may not be a feasible option for a vast majority of patients under home management. Additionally, while some evidence advocates the use of novel oral anticoagulants (NOACs), in hospitalized settings, most guidelines find no role of NOACs in hospital settings. On the other hand, the resource crunch faced in recent COVID-19 pandemic in India forced physicians to treat many patients in home settings. These patients had been usually prescribed NOACs for ease of administration and adherence. Therefore, there is a need to form a consensus on the use of NOACs to manage CIC in India.

Do we need to change the Patient Indications for Trimetazidine after ATPCI?

The results of the ATPCI (efficAcy and safety of Trimetazidine in patients with angina pectoris treated by Percutaneous Coronary Intervention) study showed no significant difference in the incidence of primary endpoint events between trimetazidine and the placebo group in angina patients who recently underwent percutaneous coronary intervention. The study had limitations specific to the design and selection of the target patient population. However, safety outcomes for trimetazidine were reconfirmed in this study. In this article, we discuss the limitations of study design, patient inclusion criteria and their implications in routine practice. We have also dissected the evidence to tweeze out patient groups who are likely to benefit from trimetazidine treatment.

Validation of the OPtimal Treatment of Angina (OPTA) Questionnaire in Indian Patients with Chronic Stable Angina.

BACKGROUND: A rising burden of coronary artery disease (CAD) in India is a major cause of concern, with angina being the leading manifestation. Hence a questionnaire to sensitize the clinicians about stable angina management and to assist in risk stratification is imperative. OBJECTIVE: To evaluate the content and face validity of a modified questionnaire adapted from the 7-item Seattle Angina Questionnaire (SAQ). MATERIALS AND METHODS: A panel of six experts in the field of evidence-based practice reviewed and rated the modified instrument for content clarity and relevance based on the 4-point ordinal scale. Face validity was assessed based on the trichotomous rating of "disagreed", "agree" or "neutral". Items on which ≥75% of patients "disagreed" were subjected to further review and revision. RESULTS: A total of six experts and 51 patients participated in the content and face validity, respectively. As no question received a score ≤2 by two or more experts for either content clarity or relevance, no modification in the questionnaire was required post content validation. During face validation, all patients agreed that the questions correctly measured the specific area of cardiovascular health status and response options correctly captured the answers provided. Demographic and baseline data of the patients were collected. CONCLUSION: The newly developed 5-item questionnaire demonstrated content and face validity, suggesting it to be a potential instrument to improve management decision and care of angina patients in India.

Consensus Statement on Holistic Management of Angina.

Worldwide, coronary heart disease (CHD), have assumed epidemic proportions. Increasing use of interventional therapy and a higher adherence to medical therapy have led to a 33% reduction in cardiac deaths at 5 years after hospital discharge. Angina pectoris is a common symptom of ischemic heart disease. The goals of anti-ischemia therapy in patients with stable coronary artery disease (CAD) include relieving angina symptoms, improving duration of exercise and quality of life, improving prognosis and preventing cardiovascular (CV) events. The consensus statement was devised with the help of multiple meetings held across India. Ten regional advisory board e-meetings were held in Mumbai, Delhi, Chennai, Kolkata, Ahmedabad, Cochin, Trivandrum, Lucknow, Bhopal and Varanasi. These meetings were attended by ten eminent experts from the field of cardiology from each region. Extensive literature review, intense discussions, and feedback from the cardiologists led to the development of the following consensus statements on definition, diagnosis, and management of angina, which have been reported in this article.

Cardiovascular Safety of Gla-100: Reflections From the ORIGIN and ORIGINALE Trials.

Cardiovascular diseases (CVD) risk in people with type 2 diabetes mellitus (T2DM) is two to four folds higher than in individuals without T2DM. Insulin therapy was speculated to be atherogenic- thereby aggravating CVD risk years ago. However, cardiovascular outcome trials (CVOTs) such as the Outcome Reduction with Initial Glargine Intervention (ORIGIN), and its extended follow-up study - ORIGIN and Legacy Effects (ORIGINALE) conclusively established the long-term cardiovascular (CV) safety of basal insulin, such as insulin glargine 100 U/mL (Gla-100). Moreover, these studies hinted at the possible benefits of early insulin therapy-including stalling the progression of diabetes with minimal weight gain and hypoglycemia risk. This review highlights the background developments which led to the ORIGIN trial. Additionally, it also dwells on the critical insights to emerge from this trial pertaining to the CV safety of basal insulin Gla-100 in high CV risk individuals with T2DM.

Cardiovigilance.

Cardiovascular disease (CVD) is a major cause of morbidity and mortality across the globe. Prevention and management of the CVD pandemic calls for concerted action on part of all health care professionals, as well as other concerned stakeholders. We call for cardiovigilance in healthcare and define it as "the action or state of keeping careful watch, to prevent, screen, diagnose and manage cardiovascular disease (CVD) in a timely and appropriate manner". We expand upon the concept of cardiovigilance, describe its utility, and suggest various taxonomic rubrics to simplify its practice.

Appropriate use of PCSK9 Inhibitors in India.

The burden of atherosclerotic cardiovascular (CV) disease is alarmingly high and increasing in our country. Dyslipidemia is one of the major modifiable risk factors, and INTERHEART study showed that dyslipidemia had the highest population attributable risk for myocardial infarction. In the management of dyslipidemia, low-density lipoprotein cholesterol (LDL-C) is the primary therapeutic target. In addition to therapeutic lifestyle changes, statins and ezetimibe effectively lower LDL-C and consequently improve CV outcomes. However, there are situations where these drugs fall short of achieving the target or they may not be well tolerated.

In-Hospital and Three-Year Outcomes of Heart Failure Patients in South India: The Trivandrum Heart Failure Registry.

BACKGROUND: Long-term data on outcomes of participants hospitalized with heart failure (HF) from low- and middle-income countries are limited. METHODS AND RESULTS: In the Trivandrum Heart Failure Registry (THFR) in 2013, 1205 participants from 18 hospitals in Trivandrum, India, were enrolled. Data were collected on demographics, clinical presentation, treatment, and outcomes. We performed survival analyses, compared groups and evaluated the association between heart failure (HF) type and mortality, adjusting for covariates that predicted mortality in a global HF risk score. The mean (standard deviation) age of participants was 61.2 (13.7) years. Ischemic heart disease was the most common cause (72%). The in-hospital mortality rate was higher for participants with HF with reduced ejection fraction (HFrEF; 9.7%) compared with those with HF with preserved ejection fraction (HFpEF; 4.8%; P = .003). After 3 years, 540 (44.8%) participants had died. The all-cause mortality rate was lower for participants with HFpEF (40.8%) compared with HFrEF (46.2%; P = .049). In multivariable models, older age (hazard ratio [HR] 1.24 per decade, 95% confidence interval [CI] 1.15-1.33), New York Heart Association functional class IV symptoms (HR 2.80, 95% CI 1.43-5.48), and higher serum creatinine (HR 1.12 per mg/dL, 95% CI 1.04-1.22) were associated with all-cause mortality. CONCLUSIONS: Participants with HF in the THFR have high 3-year all-cause mortality. Targeted hospital-based quality improvement initiatives are needed to improve survival during and after hospitalization for HF.

Expert Consensus Document on Management of ST-Elevation Myocardial Infarction: Adaptation of 2012 ESC Guidelines.

In 2012, the European Society of Cardiology (ESC) guidelines provided recommendations on the management of ST-elevation myocardial infarction (STEMI). The recommendation from these guidelines is restricted to the European subcontinent. To adapt the updated recommendations for Indian subset of STEMI patients, a panel of experts in the management of STEMI provided their expert opinions. This document provides expert consensus on adapting 2012 ESC STEMI guidelines recommendations in Indian setting. Document also discussed "India-specific" relevant literature to support the consensus opinions provided in the management of STEMI.

One-year mortality outcomes and hospital readmissions of patients admitted with acute heart failure: Data from the Trivandrum Heart Failure Registry in Kerala, India.

BACKGROUND: There are sparse data on outcomes of patients with heart failure (HF) from India. The objective was to evaluate hospital readmissions and 1-year mortality outcomes of patients with HF in Kerala, India. METHODS: We followed 1,205 patients enrolled in the Trivandrum Heart Failure Registry for 1 year. A trained research nurse contacted each participant every 3 months using a structured questionnaire which included hospital readmission and mortality information. RESULTS: The mean (SD) age was 61.2 (13.7) years, and 31% were women. One out of 4 (26%) participants had HF with preserved ejection fraction. Only 25% of patients with HF with reduced ejection fraction received guideline-directed medical therapy at discharge. Cumulative all-cause mortality at 1 year was 30.8% (n = 371), but the greatest risk of mortality was in the first 3 months (18.1%). Most deaths (61%) occurred in patients younger than 70 years. One out of every 3 (30.2%) patients was readmitted at least once over 1 year. The hospital readmission rates were similar between HF with preserved ejection fraction and HF with reduced ejection fraction patients. New York Heart Association functional class IV status and lack of guideline-directed medical treatment after index hospitalization were associated with increased likelihood of readmission. Similarly, older age, lower education status, nonischemic etiology, history of stroke, higher serum creatinine, lack of adherence to guideline-directed medical therapy, and hospital readmissions were associated with increased 1-year mortality. CONCLUSIONS: In the Trivandrum Heart Failure Registry, 1 of 3 HF patients died within 1 year of follow-up during their productive life years. Suboptimal adherence to guideline-directed treatment is associated with increased propensity of readmission and death. Quality improvement programs aiming to improve adherence to guideline-based therapy and reducing readmission may result in significant survival benefits in the relatively younger cohort of HF patients in India.

Pharmacological Reperfusion Therapy with Tenecteplase in 7,668 Indian Patients with ST Elevation Myocardial Infarction - A Real World Indian Experience.

OBJECTIVE: This real-world, observational, prescription event monitoring study was conducted to evaluate safety and efficacy of indigenous tenecteplase (TNK-tPA) in Indian patients presenting with ST elevation myocardial infarction (STEMI). METHODS: This is a multi-centric, observational, prescription event monitoring study. Data was collected for 7,668 patients from 1,307 investigator sites across India from January 2011 to February 2016. RESULTS: Overall, 76.71% patients were hypertensive, 47.97% patients were diabetic, 42.01% had dyslipidemia, 24.35% had ischemic heart disease and 40.82% patients were smokers. The overall rate for achieving clinically successful thrombolysis by TNK was 93.34%. Delayed administration of tenecteplase yielded lower success rate (84.66%) as against those patients who received tenecteplase within 3 hours of symptoms (94.34%). 93.2% patients had chest pain resolution after pharmacological fibrinolysis. Overall 91.1% patients had 50% resolution of ST elevation at 90 minutes and mean time for 50% ST resolution was 72.06 minutes. Overall 53 patients died (mortality of 0.69%) before discharge. The incidence of bleeding (excluding stroke) was 1.77%, any stroke without ICH was 0.18% and any ICH was 0.38%. CONCLUSION: The findings of this study further reinforce the safety and efficacy of indigenous TNK-tPA in Indian patients presenting with STEMI, including high-risk sub-groups. The study also highlights the importance of early reperfusion therapy.