Expert Consensus on Ivabradine-based Therapy for Heart Rate Management in Chronic Coronary Syndrome and Heart Failure with Reduced Ejection Fraction in India.

Heart rate is an important indicator of health and disease and the modulation of heart rate can help to improve cardiovascular outcomes. Besides ß-blockers, Ivabradine is a wellestablished heart rate modulating drug that reduces heart rate without any hemodynamic effects. This consensus document was developed with the help of expert opinions from cardiologists across India on effective heart rate management in routine clinical practice and choosing an appropriate Ivabradine-based therapy considering the available scientific data and guideline recommendations. Based on the discussion during the meetings, increased heart rate was recognized as a significant predictor of adverse cardiovascular outcomes among patients with chronic coronary syndromes and heart failure with reduced ejection fraction making heart rate modulation important in these subsets. Ivabradine is indicated in the management of chronic coronary syndromes and heart failure with reduced ejection fraction for patients in whom heart rate targets cannot be achieved despite guideline-directed ß-blocker dosing or having contraindication/intolerance to ß-blockers. A prolonged release once-daily dosage of Ivabradine can be considered in patients already stabilized on Ivabradine twice-daily. Ivabradine/ß-blocker fixed-dose combination can also be considered to reduce pill burden. Two consensus algorithms have been developed for further guidance on the appropriate usage of Ivabradine-based therapies. Ivabradine and ß-blockers can provide more pronounced clinical improvement in most chronic coronary syndromes and heart failure with reduced ejection fraction patients with a fixed-dose combination providing an opportunity to improve adherence.

Evaluation of Effectiveness and Tolerability of Fondaparinux in the Management of Symptomatic Acute Coronary Syndrome: A Real-World Evidence-Based Study on an Indian Population.

INTRODUCTION: Fondaparinux is a low molecular weight heparin anticoagulant used to manage the full spectrum of acute coronary syndrome (ACS) patients and has proved its efficacy and safety in multiple clinical trials. However, there are limited data available showing whether the same results could be reproduced in real-world practice on an Indian population. Our objective was to determine the effectiveness and tolerability of fondaparinux in the management of symptomatic ACS in real-world clinical practice. METHODS: The EMR data of hospitalized ACS patients (n = 611), from January 2015 to January 2020, representing UA or NSTEMI or STEMI and were prescribed fondaparinux (2.5 mg once daily) to manage ACS were analyzed. The effectiveness was analyzed as recurrence of ACS and tolerability as total incidence of major bleeding during hospitalization, at 30 days and 180 days. Appropriate statistical analysis was used with a statistically significance of p value < 0.05. RESULTS: The incidence of recurrent ACS was not seen during hospitalization and in the first 30 days, while in only 0.65% (n = 4) patients, ACS reoccurred within 180 days. In a mean duration of 172.75 ± 3.20 days, UA was reported in 0.49% (n = 3) patients, NSTEMI in 0.16% (n = 1) of patients, and STEMI was not documented. None of the major bleeding events occurred during the entire study period, whereas minor bleeding events were reported during hospitalization 0.98% (n = 6) and at 30 days 0.16% (n = 1). The bleeding events were statistically insignificant (p value > 0.05). No incidences of stent thrombosis were reported during the entire study period. CONCLUSIONS: In the real world, fondaparinux was found to be effective and tolerable when used to manage symptomatic ACS patients regardless of revascularization procedure with no incidence of stent thrombosis, and minimal recurrent ACS and insignificant increase in bleeding events.

Renal denervation therapy for hypertension: truths and half-truths: Renal denervation therapy for hypertension.

Systemic hypertension is a major contributing factor for excessive morbidity and mortality globally. Experimental studies and early clinical trials showed excellent therapeutic responses to renal denervation (RDN) in patients with hypertension. However meta-analyses and objective assessments have failed to show that RDN therapy has any significant effect on blood pressure.  The aim of this review is to introduce the different methods that can be used in RDN, along with the benefits and disadvantages of these methods. Radiofrequency (RF) ablation (of renal nerves) is the most com-mon method of RDN, and we discuss the clinical evaluation of this method in the SYMPLICITY RDN trials. Finally, the development of second-generation RF devices and more comprehensive RDN procedures lead us to consider the current status and future path for RDN.

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.

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.

Blood Pressure Variability in Patients with Diabetes Mellitus with Hypertension: Treatment Recommendations and Role of Amlodipine.

Recently, blood pressure variability (BPV) has gained focus owing to its role in predicting cardiovascular (CV) outcomes. Additionally, alterations in BPV contribute to the progression of end organ damage and trigger vascular events in hypertensive patients. Therefore, amelioration of BPV is considered a potentially important target and different classes of drugs are used to achieve the desired blood pressure (BP) goal. Based on several studies and clinical trials, treatments with CCB such as amlodipine have been found to be most effective in the management of BPV in hypertensive patients with diabetes. Growing evidence substantiates the role of amlodipine in significant reduction of BPV, thus, lowering the risk of diabetes related complications. This review sheds light on the importance of BPV reduction and the effectiveness of amlodipine in preventing cardiovascular morbidity and mortality in hypertensive patients with diabetes.

Impact of Non-Infarct-Related Artery Disease on Infarct Size and Outcomes (from the CRISP-AMI Trial).

BACKGROUND: Non-infarct-related artery (non-IRA) disease is prevalent in patients with ST-segment elevation myocardial infarction (STEMI). We aimed to assess the impact of non-IRA disease on infarct size and clinical outcomes in patients with acute STEMI. METHODS: The Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction (CRISP-AMI) trial randomized patients to intra-aortic balloon counterpulsation (IABC) vs no IABC prior to percutaneous coronary intervention in patients with acute STEMI. Infarct size (% left ventricular mass) at 3-5 days post percutaneous coronary intervention and 6-month clinical outcomes were compared between patients with and without non-IRA disease (defined as ≥50% stenosis in at least one non-IRA). RESULTS: A total of 324 (96.1%) patients had anterior STEMI, of whom 34.9% had non-IRA disease. There was no difference in infarct size (% left ventricular mass) between patients with and without non-IRA disease (median 39% vs 39%; P = .73). At 6 months, there was no difference in rates of recurrent myocardial infarction (0.9% vs 0.9%; P = .78), major Thrombolysis In Myocardial Infarction bleeding (0.9% vs 0.5%; P = .77), or all-cause death (3.5% vs 2.4%; P = .61) in patients with and without non-IRA disease, respectively. Patients with non-IRA disease had a higher rate of new/worsening heart failure with hospitalization (8.8% vs 1.9%; P = .0050). CONCLUSIONS: More than one-third of patients with anterior STEMI in the CRISP-AMI study had non-IRA disease. These patients had similar infarct sizes and rates of recurrent myocardial infarction, major bleeding, and all-cause death. Patients with non-IRA disease did have a higher rate of new/worsening heart failure with hospitalization. Further study is needed to understand the mechanisms of outcomes of patients with non-IRA disease.

Clinical characteristics and outcomes after unplanned intraaortic balloon counterpulsation in the Counterpulsation to Reduce Infarct Size Pre-PCI Acute Myocardial Infarction trial.

BACKGROUND: Despite advances in primary percutaneous coronary intervention (pPCI) and regional systems of care, the development of cardiogenic shock is associated with poor clinical outcomes in patients with ST-segment elevation myocardial infarction (STEMI). We sought to better characterize the baseline characteristics and clinical outcomes of patients who underwent crossover to intraaortic balloon counterpulsation (IABC) in the CRISP AMI trial. METHODS: Patients with anterior STEMI were randomized to IABC before pPCI or pPCI alone. Infarct size and 6-month clinical outcomes were evaluated in patients both in the pPCI-alone group who did undergo crossover to IABC and those who did not undergo crossover to IABC. RESULTS: Among 176 patients randomized to pPCI alone, 161 patients did not later receive IABC during the index hospitalization, and 15 patients (8.5%) underwent crossover and did receive unplanned IABC. Hypotension and/or cardiogenic shock precipitated crossover to IABC in 12 patients (80%). Patients who underwent crossover to IABC demonstrated lower systolic and diastolic blood pressures on admission. At 6 months, rates of death (26.7% vs 3.1%, P = .003), readmission for severe hypotension (53.3% vs 3.7%, P < .001), resuscitated cardiac arrest, and ventricular arrhythmia were higher in the group that did crossover to IABC. Crossover to IABC was not associated with increased infarct size. CONCLUSIONS: The most significant predictor of crossover to IABC in the setting of anterior STEMI was relative hypotension at the time of hospital admission, and crossover to IABC in CRISP AMI was associated with significantly worse clinical outcomes.

The impact of processes of care on myocardial infarct size in patients with ST-segment elevation myocardial infarction: observations from the CRISP-AMI trial.

BACKGROUND: Primary percutaneous coronary intervention (PCI) is the most common method of reperfusion in patients with ST-segment elevation myocardial infarction (STEMI) in the United States. The intersection between processes of care and performance measures such as door-to-balloon (D2B) times and clinical trials evaluating novel therapies for STEMI has not been fully investigated. HYPOTHESIS: Processes of STEMI care, incorporating clinical trial enrollment and randomization, in patients undergoing reperfusion with primary PCI in the Counterpulsation Reduces Infarct Size Pre-Percutaneous Coronary Intervention Acute Myocardial Infarction trial (CRISP-AMI) will conform to current standards of care. METHODS: Patients enrolled in CRISP-AMI were included in the current analysis. Processes of care during reperfusion were recorded prospectively and compared between groups. RESULTS: A total of 337 patients with anterior STEMI without cardiogenic shock were randomized in CRISP-AMI. Complete processes-of-care data were available for 303 patients (89.9%). In this cohort, 68.0% of patients underwent reperfusion within 90 minutes of hospital contact, and the median D2B time was 71 minutes. Time from hospital contact to informed consent was significantly different across different regions (North America, 45 minutes; India, 35 minutes; Europe, 20 minutes). CONCLUSIONS: In CRISP-AMI, reperfusion was accomplished in a timely fashion while incorporating informed consent and randomization among patients with anterior myocardial infarction. Further study of patients' comprehension and preferences during the informed-consent process in STEMI patients is warranted so that innovative drugs and devices can be safely and ethically tested.

Randomized, double-blind, phase I/II study of intravenous allogeneic mesenchymal stromal cells in acute myocardial infarction.

BACKGROUND AIMS: Cell therapy is promising as an exploratory cardiovascular therapy. We have recently developed an investigational new drug named Stempeucel (bone marrow-derived allogeneic mesenchymal stromal cells) for patients with acute myocardial infarction (AMI) with ST-segment elevation. A phase I/II randomized, double-blind, single-dose study was conducted to assess the safety and efficacy of intravenous administration of Stempeucel versus placebo (multiple electrolytes injection). METHODS: Twenty patients who had undergone percutaneous coronary intervention for AMI were randomly assigned (1:1) to receive intravenous Stempeucel or placebo and were followed for 2 years. RESULTS: The number of treatment-emergent adverse events observed were 18 and 21 in the Stempeucel and placebo groups, respectively. None of the adverse events were related to Stempeucel according to the investigators and independent data safety monitoring board. There was no serious adverse event in the Stempeucel group and there were three serious adverse events in the placebo group, of which one had a fatal outcome. Ejection fraction determined by use of echocardiography showed improvement in both Stempeucel (43.06% to 47.80%) and placebo (43.44% to 45.33%) groups at 6 months (P = 0.26). Perfusion scores measured by use of single-photon emission tomography and infarct volume measured by use of magnetic resonance imaging showed no significant differences between the two groups at 6 months. CONCLUSIONS: This study showed that Stempeucel was safe and well tolerated when administered intravenously in AMI patients 2 days after percutaneous coronary intervention. The optimal dose and route of administration needs further evaluation in larger clinical trials (http://clinicaltrials.gov/show/NCT00883727).