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 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.

Therapeutic adherence in hypertension: Current evidence and expert opinion from India.

Hypertension (HTN) is a globally prevalent non-communicable disease contributing significantly to cardiovascular (CV) morbidity and mortality. In achieving control of HTN, therapeutic adherence plays a crucial role. Studies from India identify varying rates of adherence to antihypertensive medications. Multiple factors determine treatment adherence in HTN. In India, factors such as lower socioeconomic status, health literacy, asymptomatic nature of disease, forgetfulness, cost of medications, and duration of HTN determine the adherence. An excellent physician-patient relationship incorporating adequate counseling along with the use of other methods can identify poor adherence. Improving adherence necessitates incorporating a multipronged approach with strategies directed at physicians, patients, and health systems. With innovation in therapeutics, the pharmaceutical sector can contribute significantly to improve adherence. Furthermore, increasing adherence to lifestyle interventions can help achieve better HTN control and improve CV outcomes. In the Indian context, more emphasis is necessary on patient education, enhanced physician-patient relationship and communication, increased access to health care, and affordability in improving therapeutic adherence in HTN.

Heart Rate in Hypertension: Review and Expert Opinion.

Heart rate (HR) is strongly associated with both peripheral and central blood pressures. This association has implications in hypertension (HTN) prognosis and management. Elevated HR in HTN further elevates the risk of adverse outcomes. Evidence suggests that HR is an independent risk factor for cardiovascular (CV) and total mortality in patients with HTN. With objective to engage physicians and researchers in India to identify and discuss the implications related to HR management in HTN, experts in the HTN management provided consensus recommendations. The key expert recommendations included the following. (i) Heart rate (HR) has inverse relationship with the central aortic pressure, whereby reduction in HR is associated with an increase in central aortic pressure. This counter-balances the benefit of HR reduction with the harmful effects of rising central aortic pressure. (ii) Increase in the resting HR is associated with increased risk of incident HTN. A linear association between the two is observed especially in individuals with HR >80 bpm. (iii) A reduced HR variability further adds to the propensity for the development of HTN, especially in men. (iv) Each 10 beats per minute increase in the resting HR can substantially increase the risk of adverse CV and mortality outcomes. On treatment HR provides a better prognostic guide. (v) Ambulatory HR with day-time and night-time HR evaluation may also suggest different impact on outcomes. (vi) Target HR in patients with HTN remains unclear. Generally, HR<70 bpm on beta blocker (BB) treatment is advised which may be further lowered in patients with comorbidities like heart failure and coronary artery disease. (vii) Adopting healthy lifestyle approaches to keep check on BP and HR is essential. (viii) Use selective beta-1 blocker in symptomatic cases with elevated HR beyond 80-85 mmHg. BBs are expected to benefit by lowering HR by nearly 10 bpm. Preference should be given to newer beta-blockers which reduce HR and both peripheral and central blood pressure to derive comprehensive advantage of this dual action. (ix) It still remains unclear whether reducing HR in HTN without comorbidities alters the CV and mortality outcomes.

Pharmaco-invasive Therapy with Fibrinolytic Agents: A Potent Lifesaving Reperfusion Strategy in STEMI Patients in Metro/Tier-I Cities in India.

Background: Primary Sjogren's Syndrome (pSS) with Hypokalemic Periodic Paralysis(HPP) whether an association or a different clinical subset needs review. Aim: To generate a consensus on the importance of pharmaco-invasive therapy for STEMI patients when primary PCI cannot be expeditiously performed in metro and tier-I cities in India. Methodology: A total of 8 expert panel groups comprising 48 experts from Cardiology specialty in India were convened. These groups individually reviewed the evidence on various types of fibrinolytic agents, their importance in STEMI management in general and in India and finally shared their experience and views on the importance of pharmaco-invasive therapy during STEMI management in metro and tier-I cities in India. Individual group opinions were compiled into one document and the consensus was finalized after it was approved by all panel members. Results: The board concluded that in metro and tier-I cities, pharmaco-invasive therapy, preferably using third generation fibrinolytic agents such as Reteplase and Tenecteplase, should be instituted to all patients for whom a delay in primary PCI of greater than 120 minutes from the time of ECG confirmation is anticipated. This will enhance the time window to preserve the myocardium from further damage arising due to patient related, transportation related or in- hospital delays. The present article also highlights the importance of third generation fibrinolytics in pharmaco-invasive therapy and looks at strategies to augment their use. Conclusion: Pharmaco-invasive therapy is recommended in STEMI patients even in metro and tier-I cities of India, where delay in access to PCI is anticipated, in place of a strategy of promoting only primary PCI.

S-Amlodipine: An Isomer with Difference-Time to Shift from Racemic Amlodipine.

Calcium channel blockers are among the first-line drugs for treatment of hypertension (HTN). S-amlodipine (S-AM), an S-enantiomer of amlodipine, is available in India and in other countries like China, Korea, Russia, Ukraine, and Nepal. Being clinically researched for nearly two decades, we performed in-depth review of S-AM. This review discusses clinical evidence from total 42 studies (26 randomized controlled trials, 14 observational studies, and 2 meta-analyses) corroborating over 7400 patients treated with S-AM. Efficacy and safety of S-AM in HTN in comparison to racemic amlodipine, used as monotherapy and in combination with other antihypertensives, efficacy in angina, and pleiotropic benefits with S-AM, are discussed in this review.

Apolipoproteins AI/B/E gene polymorphism and their plasma levels in patients with coronary artery disease in a tertiary care-center of Eastern India.

AIM: The present study was designed to investigate whether the three-apolipoprotein (AI, B, E) gene polymorphisms were related to alter their plasma protein levels and hence associated to coronary artery disease (CAD). METHODS: We determined distribution of MspI apo AI, EcoRI apo B, HhaI apo E gene polymorphisms, plasma apolipoproteins and lipids levels among 150 patients having CAD admitted to the Department of Cardiology, N.R.S. Medical College & Hospital, Kolkata, India during June 2010-June 2012 and 150 age sex matched healthy controls. RESULTS: We found that ApoAI concentration of studied population was significantly different in each genotypes of -75 G/A apo AI (p < 0.0001) gene polymorphism. A significant association was found in multivariate analysis for the genotypes with apo E4 allele [odds ratio (OR): 3.639; 95% confidence interval (CI): 1.019-12.995, p = 0.040] with four conventional risk factors (i.e. smoking, low-density lipoprotein, ApoAI and ApoB) with CAD. In contrast E2 allele has reverse effect, but the genotypes with apo E2 allele was no longer significant in the multivariate model (OR: 1.788; 95% CI: 0.400-8.001, p = 0.447) where as being significant in univariate analysis (OR: 0.219; 95% CI: 0.087-0.552, p = 0.001). CONCLUSIONS: Our findings suggest that the polymorphisms apo AI MspI and apo B EcoRI do not seem to affect CAD. But the genotype with E4 allele of apo E gene independent of other risk factors is associated with this disease.

A comparative evaluation of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention.

OBJECTIVE: Primary objective of this study was to compare the efficacy of Prasugrel vs. Clopidogrel in the patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) by measuring inhibition of platelet aggregation after loading and maintenance dose of both the drugs. The patients were also assessed for safety of the drugs. METHODS: This was a randomised, double-blind, double-dummy, comparative, multicentric clinical trial in patients with acute coronary syndrome (unstable angina, non-ST elevation MI and ST elevation MI) undergoing PCI. The patients were randomly assigned to receive prasugrel (loading dose of 60 mg followed by maintenance dose of 10-mg once daily) or clopidogrel (loading dose of 300 mg followed by maintenance dose of 75 mg once daily) for a period of 12 weeks. All the patients were co-prescribed aspirin 325 mg with both the drugs. The primary efficacy end point in this study was percentage inhibition of ADP induced platelet aggregation (IPA) at 4 +/- 1 hours after the loading dose and at 30 +/- 3 days during maintenance treatment. The platelet aggregation of both the drugs was measured by whole blood aggregometer using 10 mmol of ADP as an aggregant. Though this study was not powered to see the difference in clinical efficacy parameters, the patients were observed for the incidence of nonfatal MI, nonfatal stroke, re-hospitalization, death, or need for urgent revascularization due to a cardiac ischemic event at days 30 and 90 during the study. The safety of study drugs were evaluated by incidence of major bleeding, reported adverse drug reaction and alterations of any laboratory parameters. RESULT: A total of 220 patients were enrolled at 11 centres across India. Ten patients were given the loading dose of prasugrel or clopidogrel but did not underwent PCI due to change in investigator's decision to go for PCI. Out of 210 eligible patients, 21 patients were discontinued during the study. 157 patients were evaluated for platelet inhibition after loading dose at 4 hours and 150 patients at day 30 during maintenance phase of antiplalelet therapy. The investigators could not perform this test in remaining patients due to urgency and criticality of the patients. 189 patients were observed for the incidence of nonfatal MI, nonfatal stroke, rehospitalisation, urgent revascularisation or death due to a cardiac ischemic event. All eligible patients who received at least a loading dose were evalauted for safety. In prasugrel group, 85 and 77 patients were evaluated for IPA at 4 hours and day 30 respectively whereas in clopdogrel group 72 and 73 patients were tested for IPA at 4 hours and at 30 days. Patients in prasugrel group have demonstrated significantly higher inhibition of platelets as compared to clopidogrel group (82.5% vs 71.1%) at 4 hours and at 30 days (84.1% vs 67.4%). The difference in inhibition of platelets between prasugrel and clopidogrel after loading dose and maintenenace dose was statistically significant (p < or = 0.01). The patients were also evaluated for drug hyporesponsiveness to antiplatelet therapy if IPA was < 20% at day 30 from the baseline. More patients on prasugrel have shown response to antiplatlet therapy than on clopidogrel (97.4% vs 87.6%). The difference between the two groups was statistically significant (p < 0.05). There was no difference observed during the study in the incidence of nonfatal MI, nonfatal stroke, death, rehospitalisation or need for urgent revascularisation due to a cardiac event between prasugrel and clopidogrel. Both the drugs were found to be to be well tolerated and have comparable safety profile. CONCLUSION: This study suggests that prasugrel is more effective than clopidogrel as an anti platelet drug as evident by inhibition of platelet aggregation. More patients on clopidogrel are likely to have poor response to therapy as compared to prasugrel. Both the drugs were well tolerated and have comparable safety profile.

Cardiological Society of India practice guidelines for angiography in patients with renal dysfunction.

PREAMBLE: The potential risk of contrast-induced acute kidney injury (CI-AKI) has made utilization of coronary angiography in the work-up for the diagnosis of coronary artery disease in CKD quite low.(1) This is in contrast to increasing prevalence and severity of CAD as the serum creatinine rises.(2) In fact most CKD patients will succumb to CAD and not to ESRD.(3) Thus the judicious use of CAG/PCI in this setting is of prime importance but underused. The CSI began to develop guidelines for Indian context as most guidelines are those developed by ACC/AHA or ESC. The aim was to assist the physicians in selecting the best management strategy for an individual patient under his care based on an expert committee who would review the current data and write the guidelines with relevance to the Indian context. The guidelines were developed initially in June 2010 as an initiative of Delhi CSI. Three interventional cardiologist (SB, AS, KKS), one nephrologist (SCT) and two clinical cardiologists (ST, RG) along with Dr. Roxana Mehran (New York) and Dr. Peter McCullough (Missouri), U.S.A.; were involved in a three-way teleconference to discuss/debate the data. This was presented by SB, and over the next two hours each data subset was debated/agreed/deleted and this resulted in the "Guidelines for CAG in Renal Dysfunction Patients". These were then written and re- circulated to all for final comments. Further, these guidelines were updated and additional Task Force Members nominated by Central CSI were involved in the formation of the final CSI Guidelines. Both (Roxana Mehran and Peter McCullough) reviewed these updated Guidelines in October 2012 and after incorporating the views of all the Task Force members-the final format is as it is presented in this final document.

Our experience of coronary angiography with and without heparin.

AIM: Coronary angiography is usually done with heparin. Our aim is to see whether it can be done without heparin through femoral route and its effect on local complications. METHOD: We have studied 3780 patients from 2006 to 2010 using standard dose Heparin (5000 units), low dose heparin (2000 units) and no heparin. We have compared safety and complications in these three groups. RESULTS: Local complications were lowest in no heparin group. Blood transfusion requirements and surgical interventions were lowest in no heparin group. Thrombosis rate did not increase in no heparin group. CONCLUSION: Coronary angiography can be done safely without heparin through femoral route.

S-metoprolol: the 2008 clinical review.

Metoprolol is a widely used cardioselective beta-blocker. However, like all other beta-blockers it is also a racemic mixture of R- and S- isomers. The beta 1 blocking activity (cardioselectivity) of metoprolol resides in S-isomer while R-isomer exhibits beta 2 blocking activity. As both these isomers have different pharmacological properties, racemic metoprolol can be considered a combination of two different drugs in a fixed 1:1 ratio. The needless administration of the non beta-blocking R-enantiomer that makes up 50% of racemate actually puts the patient at an increased risk of side-effects, drug interactions and loss of cardioselectivity with up-titration of dosing. Clinical experience with chirally pure S-metoprolol at half the dose of racemate has shown it to be as effective as racemate in the treatment of patients with hypertension and angina. S-metoprolol has been shown to be effective and well-tolerated in patients with coexisting diabetes, COPD, and hyperlipidaemia. This confirms higher cardioselectivity of S-metoprolol in clinical settings. Less interaction potential of S-metoprolol compared to R-isomer further makes it a sensible choice in patients taking CYP2D6 inhibitors or in patients with heart failure or hepatic insufficiency. This article reviews differing properties of two isomers of metoprolol with focus on clinical experience with S-metoprolol.