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.

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.

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.

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).

Evolocumab in patients with homozygous familial hypercholesterolemia in India.

BACKGROUND: Evolocumab is a fully human monoclonal antibody inhibitor of proprotein convertase subtilisin/kexin type 9 approved in India for treatment of homozygous familial hypercholesterolemia (HoFH) in patients aged ≥12 years. OBJECTIVE: RAMAN (NCT03403374) was a single-country, open-label, phase 4 study evaluating the safety and tolerability of evolocumab in patients with HoFH in India. METHODS: Patients ≥12 to ≤80 years of age on stable lipid-lowering therapy with fasting low-density lipoprotein cholesterol (LDL-C) >3.4 mmol/L (>130 mg/dL) received evolocumab 420 mg subcutaneously monthly (every 2 weeks if on apheresis). The primary endpoint was patient incidence of treatment-emergent adverse events. Secondary endpoints included percent changes at week 12 in LDL-C and other lipids. RESULTS: Of 30 enrolled patients, 13 were <18 years of age. Mean±SD baseline levels of LDL-C, apolipoprotein B, and lipoprotein(a) were 12.3 ± 3.5 mmol/L (473.5 ± 135.2 mg/dL), 2.8 ± 0.7 g/L (275.3 ± 69.1 mg/dL), and 201.3 ± 177.6 nmol/L, respectively. Ten patients (33%) reported treatment-emergent adverse events, with 2 (7%) serious adverse events and none leading to discontinuation; no deaths occurred during evolocumab treatment. At week 12, mean (SE) percent changes from baseline in LDL-C, apolipoprotein B, and lipoprotein(a) were -6.4% (4.2), -6.0% (3.7), and -0.2% (4.9), respectively. Reductions in LDL-C among individual patients were variable and greatest in patients ≥18 years of age and with baseline LDL-C <13 mmol/L (<500 mg/dL). CONCLUSIONS: Evolocumab was safe and well tolerated in patients with HoFH in India with smaller reductions in LDL-C and other lipids than those observed in previous studies with HoFH and different populations.

Hypertension in Young Adults in India: Perspectives and Therapeutic Options amongst Clinician's in a Cross Sectional Observational Study.

BACKGROUND: The prevalence of hypertension in the young adult population is rising in India. Increased arterial stiffness due to RAAS activation and increased sympathetic overactivity due to stress have been implicated as primary factors for the same. This study was aimed to understand the Indian clinician's perspective on approach to management of hypertension in young adults. METHODS: A cross sectional observational survey using a structured questionnaire was conducted online with 2287clinicians (cardiologists, diabetologists, consultant physicians and family physicians). RESULTS: The prevalence of hypertension was 10-30% as per opinion of 64.8% clinicians. The top three risk factors for hypertension in young were perceived to be smoking, mental stress and obesity. Around 57.4% respondents opined that both increased heart rate and systolic blood pressure were markers of sympathetic overactivity. More than 60% respondents across specialities preferred ARBs to treat hypertension in young adults. Amongst the ARBs, telmisartan was the preferred ARB by >80% respondents. Metoprolol was the preferred beta blocker by almost 64% respondents. The objective of selection of beta-blocker by majority of clinicians due to sympathetic overactivity. Telmisartan and Metoprolol single pill combination achieved the BP goal in 40-60% of patients as reported by 41.3% of the physicians. The combination therapy was well tolerated in young hypertensive patients. CONCLUSIONS: Initiation of an early and appropriate antihypertensive treatment in young population may lower the burden of cardiovascular disease in this population. ARBs and beta -blockers were the preferred class of anti-hypertensive drugs in the cohort of young hypertensive patients .

Screening for Hypertension in Asymptomatic Individuals in India: An Expert Consensus Statement.

INTRODUCTION: Hypertension (HTN) is a rapidly growing epidemic in India. It is no larger restricted to older adults as more young Indians are being diagnosed with HTN. Despite its significant prevalence, the awareness, treatment, and control of HTN remain low in India. Thus, early diagnosis is essential to control HTN and prevent future complications. Screening for HTN can help identify undiagnosed and asymptomatic HTN, and thereby the early use of interventions to control the blood pressure (BP). However, no comprehensive guidelines have been established for effective HTN screening in asymptomatic individuals in an Indian setting. OBJECTIVE: To provide consensus recommendations for hypertension screening in India. CONSENSUS RECOMMENDATIONS: Screening for HTN can provide more effective control of HTN and reduce the complications. Experts recommended that the initial age at screening should be 18 years. In individuals at a high risk of HTN, targeted screening can be undertaken. BP measurement using an electronic BP recorder (with at least two readings) are required for identifying HTN during screening. In asymptomatic adults with BP <130/85 mmHg and BP of 130-139/85- 89 mmHg, rescreening should be conducted every 3-5 years and at least every year, respectively. Screening for HTN can be cost effective even when universal screening of the entire population is undertaken. CONCLUSION: The consensus recommendations would increase the awareness of HTN screening. Screening for HTN can provide more effective control of HTN and reduce the complications.

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.

The Lipo- Phenotypic Screening Tool for Familial Hypercholesterolaemia.

Familial hypercholesterolaemia (FH) is a common disorder of lipid metabolism. However, it is rarely diagnosed in time, leading to a high burden of preventable cardiovascular (CV) morbidity. The authors describe a lipophenotypic screening tool, which can be used by clinicians to screen for FH. This simple construct is based on history, physical examination, lipid profile and non-invasive cardioimaging. Structured as a bidirectional three column rubric, this tool should be able to improve clinical skills and teaching related to FH.

Low-density lipoprotein cholesterol target attainment in patients with stable or acute coronary heart disease in the Asia-Pacific region: results from the Dyslipidemia International Study II.

BACKGROUND: As mortality due to cardiovascular disease increases throughout the world, accurate data on risk factors such as hyperlipidemia are required. This is lacking in the Asia-Pacific region. DESIGN: The observational Dyslipidemia International Study (DYSIS) II was established to quantify the extent of hyperlipidemia in adults with acute and stable coronary heart disease globally. METHODS: Patients with stable coronary heart disease or hospitalised with an acute coronary syndrome were enrolled across nine Asia-Pacific countries from July 2013 to October 2014. Lipid-lowering therapy and low-density lipoprotein cholesterol target attainment (<70 mg/dL) were assessed. The acute coronary syndrome cohort was followed up 4 months post-discharge. RESULTS: Of the 4592 patients enrolled, 2794 had stable coronary heart disease and 1798 were admitted with an acute coronary syndrome. In the coronary heart disease cohort, the mean low-density lipoprotein cholesterol level was 86.9 mg/dL, with 91.7% using lipid-lowering therapy and 31% achieving low-density lipoprotein cholesterol of less than 70 mg/dL. In the acute coronary syndrome cohort at admission, the corresponding values were 103.2 mg/dL, 63.4% and 23.0%, respectively. Target attainment was significantly higher in lipid-lowering therapy-treated than non-treated patients in each cohort (32.6% vs. 12.9% and 31.1% vs. 9.0%, respectively). Mean atorvastatin-equivalent dosages were low (20 ± 15 and 22 ± 18 mg/day, respectively), with little use of non-statin adjuvants (13.0% and 6.8%, respectively). Low-density lipoprotein cholesterol target attainment had improved by follow-up for the acute coronary syndrome patients, but remained low (41.7%). CONCLUSIONS: Many patients in Asia at very high risk of recurrent cardiovascular events had a low-density lipoprotein cholesterol level above the recommended target. Although lipid-lowering therapy was common, it was not used to its full potential.

Acenocoumarol: A Review of Anticoagulant Efficacy and Safety.

Anticoagulant treatment is required for the treatment and prevention of thromboembolic disorders. Vitamin K antagonists are commonly used oral anticoagulants worldwide. Acenocoumarol is mono-coumarin derivative with racemic mixture of R (+) and S (-) enantiomers. Efficacy and safety of acenocoumarol has been evaluated in atrial fibrillation, cardiac valve replacement, after myocardial infarction, treatment of deep vein thrombosis, after major surgeries and after critical illness requiring prolonged hospitalization. Acenocoumarol is effective and safe in all age groups. It offers an advantage over warfarin in terms of better stability of anti-coagulant effect. Due to its economic advantage acenocoumarol may be suitable oral anticoagulant for long term use in countries like India.

Medical Management and Diagnostic Testing among Stable Angina Patients in India: The STable Angina obseRvational (STAR) Registry.

OBJECTIVE: To study the practice pattern in the management of patients with stable angina (SA) in India. METHODS: The Stable Angina obseRvational Registry (STAR) prospectively enrolled patients provisionally diagnosed with SA by non-interventional practicing internists in India. Patients were followed for 3 months after enrollment to assess medical treatment, diagnostic management, and interventional treatment of coronary artery disease (CAD). At the study conclusion, a statistical analysis retrospectively categorized patients not at risk of CAD by the Morise-Jalisi scale though this was not part of the study protocol. RESULTS: Between January and May 2012, 2079 patients were enrolled at 131 centres. Mean age was 57 ± 11 years, 62% were men, and 40% had a history of diabetes. Over 90% of patients completed follow-up visit, >85% received statins and antiplatelet medications, >70% received beta blockers, and >60% received angiotensin-converting-enzyme inhibitors or angiotensin receptor blockers. Diagnostic testing rates were low: 93% for electrocardiogram, 44% echocardiogram, 42% chest radiography, 12% stress test, and 8% underwent noninvasive CT or invasive coronary angiography, of which, 86% had abnormal results. After the study, the Morise-Jalisi probability of CAD was intermediate in 42% and high in 51% of patients. Only 3.4% of all patients had coronary revascularization. CONCLUSIONS: In a large cohort of Indian patients with SA, disease severity and probability of CAD were high. Clinicians used evidence-based care for medical management, but underutilized diagnostic testing. Patients with SA in India need to be risk-stratified for probability and severity of CAD and, if indicated, receive additional diagnostic testing.