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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.
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Antagonistas de Receptores de Angiotensina , Bisoprolol , Insuficiencia Renal Crónica , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Insuficiencia Renal Crónica/complicaciones , Insuficiencia Renal Crónica/tratamiento farmacológico , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , India/epidemiología , Bisoprolol/uso terapéutico , Antagonistas de Receptores de Angiotensina/uso terapéutico , Consenso , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéuticoRESUMEN
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.
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Diabetes Mellitus Tipo 2 , Insuficiencia Cardíaca , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , India , Diabetes Mellitus Tipo 2/tratamiento farmacológico , Diabetes Mellitus Tipo 2/complicacionesRESUMEN
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).
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Insuficiencia Cardíaca , Neprilisina , Humanos , Neprilisina/farmacología , Remodelación Ventricular , Tetrazoles/farmacología , Resultado del Tratamiento , Antagonistas de Receptores de Angiotensina/uso terapéutico , Volumen Sistólico , Insuficiencia Cardíaca/tratamiento farmacológico , Insuficiencia Cardíaca/diagnóstico , AntihipertensivosRESUMEN
;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.
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Insuficiencia Cardíaca , Humanos , Insuficiencia Cardíaca/tratamiento farmacológico , Neprilisina/farmacología , Volumen Sistólico/fisiología , Tetrazoles/uso terapéutico , Tetrazoles/farmacología , Calidad de Vida , Función Ventricular Izquierda , Antagonistas de Receptores de Angiotensina/uso terapéutico , Antagonistas de Receptores de Angiotensina/farmacología , Resultado del Tratamiento , Antihipertensivos/uso terapéutico , Combinación de MedicamentosRESUMEN
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.
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Anemia Ferropénica , Insuficiencia Cardíaca , Deficiencias de Hierro , Humanos , Anemia Ferropénica/etiología , Anemia Ferropénica/complicaciones , Calidad de Vida , Hierro/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Insuficiencia Cardíaca/tratamiento farmacológicoRESUMEN
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.
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Antagonistas de Receptores Adrenérgicos beta 1 , Bisoprolol , Insuficiencia Cardíaca , Humanos , Bisoprolol/uso terapéutico , Insuficiencia Cardíaca/tratamiento farmacológico , India , Antagonistas de Receptores Adrenérgicos beta 1/uso terapéutico , ConsensoRESUMEN
Heart failure with preserved ejection fraction (HFpEF) accounts for 15-20% of patients with heart failure (HF) in India. Diagnosis is by clinical features supported by biomarkers and echocardiography. Lifestyle modifications, control of risk factors to optimum levels, and treatment of comorbidities are essential in the management of HFpEF. Spironolactone and sacubitril-valsartan [angiotensin receptor neprilysin inhibitor (ARNI)] are beneficial in subsets of HFpEF, especially with lower range of ejection fraction (EF). Sodium-glucose co-transporter-2 inhibitors (SGLT2i)-empagliflozin and dapagliflozin and probably sotagliflozin are the only currently available drugs which have shown benefits in HFpEF, mostly by reducing hospitalizations. The benefit of SGLT2i is evident in both diabetic and nondiabetic subsets.
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Insuficiencia Cardíaca , Médicos , Inhibidores del Cotransportador de Sodio-Glucosa 2 , Aminobutiratos , Antagonistas de Receptores de Angiotensina/uso terapéutico , Compuestos de Bifenilo , Combinación de Medicamentos , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Humanos , Inhibidores del Cotransportador de Sodio-Glucosa 2/uso terapéutico , Volumen Sistólico , Tetrazoles/efectos adversosRESUMEN
BACKGROUND: Clinical experience on details of CRRT initiation and outcomes in cardiac intensive care unit (CICU) patients is not available from developing countries like India. This study shares the 5-year clinical experience of managing CICU patients requiring CRRT in a tertiary care cardiac center of North India. MATERIALS AND METHODS: Medical records of all CICU patients with acute kidney injury (AKI) managed by CRRT from October 2011 to September 2016 at tertiary referral center in North India were retrospectively reviewed. Multiple logistic regression analysis was used to identify predictors of post-CRRT mortality. RESULTS: A total of 630 patients received CRRT during the study period. Most commonly AKI developed in patients with acute coronary syndrome (30.2 %) with cardiogenic shock. 55.9 % of the CRRT patients were >60 years of age, and/or on multiple supports in ICU including, mechanical ventilation, high doses of inotropes & vasopressors and other cardiovascular support. Of those on CRRT, 130 (20.6 %) patients had died, 215 (34.1 %) were discharged and 285 (45.2 %) could not complete the desired course. Multivariate regression analysis showed independent association of mortality with high vasoactive-inotropic score, single CRRT cycle and low mean arterial pressure in CRRT patients. CONCLUSION: About 34.1 % of patients receiving CRRT were alive at discharge, emphasizing the feasibility and utility of CRRT as a promising modality in this population for improving outcomes.
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Lesión Renal Aguda , Terapia de Reemplazo Renal Continuo , Lesión Renal Aguda/epidemiología , Lesión Renal Aguda/terapia , Humanos , Unidades de Cuidados Intensivos , Terapia de Reemplazo Renal , Estudios Retrospectivos , Atención Terciaria de SaludRESUMEN
Healthcare workers (HCW's) are at increased risk of corona virus disease (COVID-19) infection during aerosol generating activities. The aerosol box has been used during intubation and extubation to prevent transmission of infection to HCWs. Isolation room with negative pressure has been advocated for COVID-19 patients. The described containment box has been designed to be useful in COVID intensive care unit (ICU) as a multipurpose box which is a cost effective and readily available resource. This innovation combines the containment box with negative pressure generation using central vacuum.
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The COVID-19 pandemic has affected human life significantly. In spite of significant advancement of medical technology, management is still focused on preventive strategies due to non availability of vaccine or any definitive treatment. The preventive strategies include hand hygiene, social distancing, isolation/quarantine along with the methods for boosting immunity. The ancient literature and several traditional practices of our country guide a hygienic life style and address several preventive aspects of transmission of infection across the society. Furthermore, healthy eating habits and use of various herbs and spices as regular food ingredients has been proven for boosting the immunity. In this review, we have tried to correlate the traditional practices with the available scientific evidences.
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The unprecedented and rapidly spreading Coronavirus Disease-19 (COVID-19) pandemic has challenged public health care systems globally. Based on worldwide experience, India has initiated a nationwide lockdown to prevent the exponential surge of cases. During COVID-19, management of cardiovascular emergencies like acute Myocardial Infarction (MI) may be compromised. Cardiological Society of India (CSI) has ventured in this moment of crisis to evolve a consensus document for care of acute MI. However, this care should be individualized, based on local expertise and governmental advisories.
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Control de Enfermedades Transmisibles/organización & administración , Infecciones por Coronavirus/prevención & control , Infarto del Miocardio/terapia , Evaluación de Resultado en la Atención de Salud , Pandemias/prevención & control , Neumonía Viral/prevención & control , Guías de Práctica Clínica como Asunto/normas , COVID-19 , Cardiología , Infecciones por Coronavirus/epidemiología , Manejo de la Enfermedad , Femenino , Humanos , India , Masculino , Infarto del Miocardio/diagnóstico , Pandemias/estadística & datos numéricos , Selección de Paciente , Neumonía Viral/epidemiología , Sociedades Médicas/organización & administración , Resultado del TratamientoRESUMEN
OBJECTIVE: India Heart Study (IHS) is aimed at investigating the agreement between office blood pressure measurement (OBPM) and self (S)BPM in a hypertension-naive population. METHODS: A total of 18â918 individuals (aged 42.6â±â11.7 years, 62.7% men), visiting 1237 primary care physicians across India, underwent OBPM. They performed SBPM for a period of 1 week using a validated oscillometric BP monitor that was preprogrammed to adhere to a guideline-based SBPM-schedule and blinded to the results. Thereafter, individuals underwent a second OBPM. Available laboratory results were obtained. Thresholds for elevated OBPM and SBPM were 140/90 and 135/85âmmHg, respectively. RESULTS: On the basis of first-visit OBPM and SBPM, there were 5787 (30.6%) individuals with normotension; 5208 (27.5%) with hypertension; 4485 (23.7%) with white-coat hypertension (WCH) and 3438 (18.2%) with masked hypertension. Thus, a diagnosis contradiction between SBPM and first-visit OBPM was seen in 9870 (41.9%) individuals. On the basis of second-visit OBPM, the normotension, hypertension, WCH and masked hypertension prevalence values were 7875 (41.6%); 4857 (25.7%); 2397 (12.7%) and 3789 (20.0%). There was poor agreement (kappa value 0.37) between OBPM of visit 1 and 2 with a diagnosis difference in 6027 (31.8%) individuals. The majority of masked hypertension and WCH individuals had BP values close to thresholds. CONCLUSION: There was a poor agreement between OBPM of visit1 and visit 2. Likewise, the agreement between OBPM at both visits and SBPM was poor. SBPM being considered to have a better correlation with patient prognosis should be the preferred method for diagnosing hypertension.
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Determinación de la Presión Sanguínea/métodos , Presión Sanguínea , Hipertensión/diagnóstico , Autocuidado , Adulto , Femenino , Humanos , Hipertensión/fisiopatología , India/epidemiología , Masculino , Hipertensión Enmascarada/diagnóstico , Persona de Mediana Edad , Visita a Consultorio Médico , Oscilometría , Prevalencia , Atención Primaria de Salud , Reproducibilidad de los Resultados , Hipertensión de la Bata Blanca/diagnósticoRESUMEN
BACKGROUND: The impact of the 2017 American College of Cardiology (ACC)/American Heart Association (AHA) guidelines for diagnosis and management of hypertension on the prevalence of hypertension in India is unknown. METHODS: We analyzed data from the Cardiac Prevent 2015 survey to estimate the change in the prevalence of hypertension. The JNC8 guidelines defined hypertension as a systolic blood pressure of ≥140 âmmHg or diastolic blood pressure of ≥90 âmmHg. The 2017 ACC/AHA guidelines define hypertension as a systolic blood pressure of ≥130 âmmHg or diastolic blood pressure of ≥80 âmmHg. We standardized the prevalence as per the 2011 census population of India. We also calculated the prevalence as per the World Health Organization (WHO) World Standard Population (2000-2025). RESULTS: Among 180,335 participants (33.2% women), the mean age was 40.6 â± â14.9 years (41.1 â± â15.0 and 39.7 â± â14.7 years in men and women, respectively). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%) and 2,878 (1.6%) participants belonged to age group 18-19, 20-44, 45-54, 55-64, 65-74 and â≥ â75 years respectively. The prevalence of hypertension according to the JNC8 and 2017 ACC/AHA guidelines was 29.7% and 63.8%, respectively- an increase of 115%. With the 2011 census population of India, this suggests that currently, 486 million Indian adults have hypertension according to the 2017 ACC/AHA guidelines, an addition of 260 million as compared to the JNC8 guidelines. CONCLUSION: According to the 2017 ACC/AHA guidelines, 3 in every 5 Indian adults have hypertension.
RESUMEN
OBJECTIVE: Hypertension is the most important risk factor for cardiovascular morbidity and mortality. There is limited data on hypertension prevalence in India. This study was conducted to estimate the prevalence of hypertension among Indian adults. METHODS: A national level survey was conducted with fixed one-day blood pressure measurement camps across 24 states and union territories of India. Hypertension was defined as systolic blood pressure (BP) ≥140 mmHg or a diastolic BP ≥90 mmHg or on treatment for hypertension. The prevalence was age- and gender-standardized according to the 2011 census population of India. RESULTS: Blood pressure was recorded for 180,335 participants (33.2% women; mean age 40.6 ± 14.9 years). Among them, 8,898 (4.9%), 99,791 (55.3%), 35,694 (11.9%), 23,084 (12.8%), 9,989 (5.5%), and 2,878 (1.6%) participants were of the age group 18-19, 20-44, 45-54, 55-64, 65-74, and ≥ 75 years, respectively. Overall prevalence of hypertension was 30.7% (95% confidence interval [CI]: 30.5, 30.9) and the prevalence among women was 23.7% (95% CI: 23.3, 24). Prevalence adjusted for 2011 census population and the WHO reference population was 29.7% and 32.8%, respectively. CONCLUSION: There is a high prevalence of hypertension, with almost one in every three Indian adult affected.
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Hipertensión/epidemiología , Adulto , Anciano , Determinación de la Presión Sanguínea , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , PrevalenciaRESUMEN
BACKGROUND: The PANARrhythMia and Heart Failure Registry (PANARM HF) characterized demographic, clinical and interventional therapy indication profiles of cardiac arrhythmia (CA) and heart failure (HF) patients in India. METHODS: Consulting Physicians (CP) who medically manage CA and HF patients enrolled patients with one or more of the following: syncope, pre-syncope, dyspnea, palpitation, fatigue and LV dysfunction. The CPs were trained by interventional cardiologists (IC) to identify CA/HF patients indicated for implantable device/radiofrequency ablation (RFA). 59 CP's, 16 IC's & 2205 patients from 12 cities participated. Demographic, clinical, device/RFA indication and referral-consultation profiles were created. IC's provided device/RFA recommendations based on these profiles. RESULTS: The CA/HF distribution of patients was: HF - 58%, bradyarrhythmia - 15%, atrial fibrillation - 15%, other supraventricular tachyarrhythmia - 10% and ventricular tachycardia/fibrillation - 4.5%. 62% of the CA/HF population was male and 45% were below age 60. Coronary artery disease (52%), hypertension (44%), diabetes (30%) & myocardial infarction (20%) were prominent. 1011 (46%) of the CA/HF population were potential device/RFA candidates according to the IC's. However, only 700 (69%) of these patients were referred to the IC by the CP. Of referred patients, only 177 (25%) consulted the IC and were recommended therapy. Thus, 824 (83%) of patients indicated for interventional therapy were not advised therapy or did not opt for it. CONCLUSION: The India PANARM HF study provides new information and insights into the demographic, clinical, interventional therapy, referral and consultation pattern profiles of CA/HF patients in India.
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Arritmias Cardíacas/epidemiología , Insuficiencia Cardíaca/epidemiología , Medición de Riesgo , Femenino , Humanos , India/epidemiología , Masculino , Persona de Mediana Edad , Morbilidad/tendencias , Sistema de Registros , Estudios Retrospectivos , Tasa de Supervivencia/tendenciasRESUMEN
INTRODUCTION: Hypertension is directly responsible for 57% of all stroke deaths and 24% of all coronary heart disease deaths in India. Appropriate blood pressure measurement techniques are the cornerstone of clinical acumen. Despite the clear guidelines on BP measurement technique, there seems to be large inter-observer variations. AIM & METHODS: A prospective, observational study was done to assess the knowledge and to study the current practices of office BP measurement among the 400 medical and paramedical staff working in various hospitals of a northern district of India. A single observer under the supervision of investigators observed all the participants and a proforma was filled based on AHA guidelines. After observing BP measurement technique scoring was done (≤ 8 question correct = inaccurate practices, >9 questions correct = accurate practices). Similarly, the knowledge was assessed by giving a pretested questionnaire. RESULTS: 5.85 % of the medical staff had excellent knowledge and 80% of the doctors and 62% of the paramedical staff had good knowledge about BPM. Only 1.47% (3 doctors) and 0.5% (1 nurse) had accurate practices. There was no correlation between knowledge and practices. CONCLUSIONS: We conclude that the right technique and knowledge of blood pressure measurement among community health providers is inadequate and warrants further interventions to improve.
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Determinación de la Presión Sanguínea/normas , Conocimientos, Actitudes y Práctica en Salud , Consultorios Médicos , Pautas de la Práctica en Medicina/estadística & datos numéricos , Adhesión a Directriz , Humanos , India , Estudios Prospectivos , Encuestas y CuestionariosRESUMEN
UNLABELLED: In India, the prevalence of ST elevation myocardial infarction (STEMI) is rising exponentially leading to cardiovascular morbidity and mortality. Despite advancement in reperfusion therapy (pharmacologic and interventional), the overall utilization, system of care and timely reperfusion remains suboptimal. JUSTIFICATION AND PURPOSE: Alarming treatment delays exist in patients presenting with chest pain observed in real-world and published evidences. Time to diagnose STEMI and initiation of reperfusion therapy at various first medical contacts in India is variable mandating immediate attention. We intend to provide evidence based explicit recommendations for practicing clinicians about time-dependent early management and the concept of pharmaco-invasive (PI) approach, contextualized to the situation in India. PROCESS: Pre-prepared guidance document by expert steering committee was discussed and commented by over 150 experts representing from 16 states in India at regional level. The moderators of these meetings arrived at a consensus on the evaluation and management of STEMI patients by PI approach to improve clinical outcomes. RECOMMENDATIONS: In addition to patient awareness and education for early symptom identification, education is required for general practitioners and physicians/intensivists to implement early time dependent STEMI management. Percutaneous Coronary Intervention (PCI) is the gold standard, yet it remains inaccessible to majority of patients, hence early reperfusion by initial use of fibrinolytics is recommended followed by coronary intervention. Fibrinolytics are easily available, economical and evaluated in several clinical studies and hence we recommend a PI approach (early fibrinolysis followed by PCI 3-24 hours later). We recommend a time guided 'Protocol/Plan of Action' for early fibrinolysis and implementing a PI approach at the level of general practitioners, non-PCI hospitals/nursing homes with intensive care facility and in PCI capable centers. For STEMI patients with symptom duration < 6 hours, we suggest administration of fibrinolytics either tenecteplase (Grade1A), reteplase (Grade1B), alteplase (Grade1C) or streptokinase (Grade 2B) alongside contemporary adjunctive medical therapy for PI approach. The aim of this Consensus Statement is * To provide explicit recommendations for practicing clinicians about the early management of STEMI and concept of pharmaco-invasive approach * To provide recommendations based on the best available evidences, contextualized to the situation in India. It must be recognized that even when randomized clinical trials have been undertaken, treatment options may be limited by resources. The Cardiocare STEMI experts realize that the recommended diagnostic examinations and treatment options may not be available or affordable in all parts of India. Cost-effectiveness is becoming an increasingly important issue when deciding upon therapeutic strategies. As always with guidelines/consensus statement, they are not prescriptive. Clinical scenario and patients vary so much from one another that individual care is paramount, and there is still an important place for clinical judgment, experience, and common sense. The mandate of the Cardiocare STEMI expert consensus is to recommend evidence-based standards of care, related targets and strategies for implementation of standards in the management of STEMI. CONTEXT AND USE: This document should be taken as consensus recommendations by qualified experts, not as rigid rules. It comprises of published evidence and may not cover every eventuality; new evidence is published every day. Furthermore, this should not be used as a legal resource, as the general nature cannot provide individualized guidance for all patients under all clinical circumstances.