Correlation between Stroke Risk and Systolic Blood Pressure in Patients over 50 Years with Uncontrolled Hypertension: Results from the SYSTUP-India Study.

OBJECTIVES: To assess mean systolic and diastolic blood pressure (SBP and DBP) levels in patients ≥50 years with uncontrolled hypertension (HTN) and evaluate the correlation between BP and stroke risk. It also assessed therapeutic drug classes prescribed in these patients. METHODS: A cross-sectional, observational study was conducted at 176 outpatient centers across India, including patients aged ≥50 years with elevated SBP (≥140 mmHg). The relationship between stroke risk, calculated using Stroke Riskometer™, and mean SBP, mean DBP, and other risk factors was evaluated using Pearson correlation coefficient and logistic regression analysis. RESULTS: The study included 3791 patients (men, 60.0%; mean age: 62.1 ± 8.3 years; mean BMI: 27 kg/m2) with mean SBP 157.3 ± 12.8 mmHg and mean DBP 89.8 ± 9.7 mmHg. Five-year stroke risk in 33.9% and 10-year stroke risk in 70% patients were moderate to severe. A ~4% increase in both 5- and 10-year stroke risk with each 1 mmHg increase in mean SBP (p < 0.0001) was seen. However, mean DBP did not exhibit any significant correlation with 5-year (p = 0.242) or 10-year (p = 0.8038) stroke risk. There was a positive correlation between mean SBP and patient age, comorbid diabetes, and smoking and alcohol habits (p < 0.0001). Comorbid diabetes and smoking increased 5- and 10-year stroke risk by 2- to 5-fold. Irrespective of the risk category, most patients received antihypertensive therapy with an angiotensin receptor blocker. CONCLUSION: Findings corroborate an association between stroke risk and mean SBP. These real-world clinical findings indicate that efforts are required to improve primary prevention of stroke and reduce the prevalence of recurrent stroke in India.

Genome Sequence of Classical Swine Fever Virus NIVEDI-165, Subtype 1.1, a Field Virus Strain Isolated from the Southern Part of India.

The whole-genome sequence of an Indian field isolate of classical swine fever virus, NIVEDI-165, was found to be subtype 1.1, and it showed 89 to 99% amino acid identity and 84 to 99% nucleotide identity with four and five Indian classical swine fever virus (CSFV) isolates, respectively. To the best of our knowledge, this is the first report on a full-genome sequence of CSFV from South India.

Dabigatran - the First Approved DTI for SPAF.

Atrial fibrillation (AF) is commonly occurring arrhythmia in clinical practice. AF is easy to recognize but difficult to treat. Stroke is the most devastating complication of AF and is associated with a huge disease burden on the society. Effective stroke prevention is a priority for patients with AF. Two-thirds of strokes due to AF are preventable with suitable anticoagulant therapy. VKA like warfarin, acenocoumarol remains the gold standard for stroke prevention in AF (SPAF). However, it is associated with numerous limitations such as a high risk of drug-drug, drug-food interactions and need for frequent PT/INR monitoring. Dabigatran etexilate is a selective, specific, reversible direct thrombin inhibitor that has been approved in United States, European countries and in India for SPAF and primary venous thromboembolism prevention and treatment. The efficacy and safety of dabigatran in AF has been established the "Randomized Evaluation of Long-Term Anticoagulant Therapy (RE-LY)", a randomized clinical trial. As per RE-LY trial 150-mg dose of dabigatran was superior to warfarin with respect to stroke or systemic embolism, and the 110-mg dose was superior to warfarin with respect to major bleeding. The adverse event profile of dabigatran etexilate was generally similar to that of warfarin in the RE-LY study, except for the incidence of dyspepsia. Dabigatran has edge over VKAs like warfarin and acenocoumarol including predictable pharmacokinetic and pharmacodynamic profile, minimal drug-drug and no drug-food interactions while no monitoring is needed. Dosing schedule is dabigatran 150mg BID patients with normal renal function. 110 mg BID is specifically for elderly patients above 80 years and over, as well as for patients at an increased risk of bleeding and in renal impairment CrCL 15-30 mL/min dosing is 75mg twice daily. Dabigatran is only NOAC with approved specific reversal agent.

A Randomized, Double-blinded, Controlled, Multicentre Phase III Study to Evaluate the Efficacy and Safety of Telmisartan /Amlodipine/Hydrochlorothiazide Compared to Telmisartan/Hydrochlorothiazide in Patients with Essential Hypertension.

OBJECTIVE: Triple drug combination has shown to be effective in controlling blood pressure (BP) with low rates of drug-related side effects. The present study was conducted to compare the efficacy and safety of a triple pill of telmisartan/amlodipine/hydrochlorothiazide (HCTZ) with a dual combination of telmisartan/HCTZ in treating hypertensive patients who did not respond to monotherapies. METHODS: A total of 512 patients were randomized to receive either low-dose triple pill or the dual combination therapy. The primary endpoint was BP normalization after 8 weeks. The secondary endpoints were BP normalization at 4 weeks, changes in BP from baseline to Week 8, comparison of BP normalization between treatment groups, and difference in BP responder rates. The analysis was conducted on the intent-to-treat (ITT), modified intent-to-treat (mITT) and per protocol (PP) population. RESULTS: Statistically significant difference was noted between triple pill and telmi+HCTZ in the normalization of BP at Week 8 in the mITT (p=0.041) and PP (p=0. 038) populations. Also, a statistically significant improvement was observed in BP normalization in triple pill group compared with telmi+HCTZ group in ITT (p=0.022) and mITT (p=0.015) populations after 4 weeks. At Week 8, a significant reduction in BP was seen compared to the baseline in both the treatment groups. There was no statistically significant difference between the two treatment groups in BP normalization. Diastolic BP responder rates were significantly better for triple pill group in PP population (p=0.046). CONCLUSIONS: The triple pill was found to be effective in achieving early normalization of BP in hypertensive patients who did not respond to monotherapies.

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.

Pharmacologic reperfusion therapy with indigenous tenecteplase in 15,222 patients with ST elevation myocardial infarction - the Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase (TNK-tPA) in the management of patients with ST-elevation myocardial infarction (STEMI) in clinical practice. METHODS: Observational, prescription-event monitoring study. RESULTS: Data of 15,222 patients who had STEMI and received weight adjusted TNK injection was analyzed. Overall 95.43% patients had clinically successful thrombolysis (CST). In the different subgroups, hypertensives, diabetics, smokers and hyperlipidemic patients had CST rates comparable to the general patient data. CST rates were significantly lower in the elderly patients (>70 years; 92.11%; p < 0.0001), in patients with history of Ischemic Heart Disease (IHD, 93.86%; p = 0.0004) and in patients receiving delayed treatment (>6 h after onset of chest pain; 85.38%; p < 0.0001). CST was significantly higher in patients who received an early thrombolysis (<3 h after onset of chest pain; 96.54%; p = 0.006). Overall mortality was 1.69%, while it was significantly higher in the elderly (4.42%), patients with history of IHD (2.67%), females (2.93%) and in those who received delayed treatment (4.98%). The overall incidences of intracranial hemorrhage (ICH), bleeding excluding ICH, stroke and ventricular tachyarrhythmia were 0.39%, 2.01%, 0.16% and 2.35% respectively. Age >70 years, diabetes, hyperlipidemia and history of IHD were associated with a higher incidence of heart failure, myocardial re-infarction or ventricular tachyarrhythmias. However, incidence of ICH and bleeding other than ICH was comparable amongst all patient subgroups. CONCLUSION: This study confirms the safety and efficacy of indigenous tenecteplase in Indian patients with STEMI, including high risk subgroups. It also highlights the fact that delayed treatment denotes denial of benefits of pharmacologic reperfusion therapy.

Efficacy & safety of tenecteplase in 6000 patients with ST-elevation myocardial infarction from the Elaxim Indian Registry.

OBJECTIVE: To study the efficacy and safety of single intravenous bolus administration of indigenously developed tenecteplase in the management of patients presenting with ST-elevation myocardial infarction in clinical practice. METHODS: Post-licensure, observational, prescription-event monitoring study. RESULTS: Data of 6000 patients who had ST-elevation myocardial infarction and received weight-adjusted tenecteplase injection was analyzed. Overall 90.93% patients had clinically successful thrombolysis, with highest success rate (93.2%) in patients treated within 3 hours. Overall mortality was 3.23%. The elderly (< or = 65 yrs; 24.58%) and diabetics (38.2%) had clinically successful thrombolysis of 87.73% and 90.49% respectively. Female patients (16.38%) had success rates comparable to males but with higher (6.41%) mortality. The overall incidences of intracranial hemorrhage (ICH), severe bleeding, stroke and ventricular tachyarrhythmia were 0.62%, 3.18%, 0.12% and 3.07% respectively and were not significantly different in females, diabetics and elderly patients. Delay in treatment beyond 6 hours was associated with increased incidence of heart failure, ventricular tachyarrhythmia and mortality. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in the management of patients with ST-elevation myocardial infarction.

Future of thrombolytic therapy--an Indian context.

Acute myocardial infarction has two main treatment modalities in the form of direct angioplasty (PAMI) and intravenous thrombolysis. PAMI is statistically clearly superior to intravenous thrombolysis. However, as ground reality in Indian conditions PAMI remains a distant ideal option for many ST elevation MI patients. In order to bridge the gap between IV thrombolysis and PAMI, early/pre-hospital IV thrombolysis to all and early angiography within 3 to 24 hours is the treatment modality, which needs to be exercised in India. Because of the encouraging results of pharmaco-invasive treatment in acute and long-term morbidity and mortality, it should be the prime treatment of management of ST elevation myocardial infarction in India. The future of IV thrombolysis will remarkably be based on whether Indian physicians switch to direct Fibrin Inhibitors like Tenectaplase and Reteplase and whether every patient of ST elevation MI undergoes early angiography or not. If these two changes are accepted for treatment of ST elevation MI, remarkably successful and effective treatment could be offered in a place like India, which is too vast and too diversioned and too socio-economically irrelevant for the ideal treatment of PAMI. In conclusion, early/pre-hospital thrombolysis with Tenectaplase/Retelase and angiography within 3 to 24 hours is the way to go in future in India.

Efficacy and safety of tenecteplase in ST elevation myocardial infarction patients from the Elaxim Indian Registry.

OBJECTIVE: to study the efficacy and safety of indigenously developed tenecteplase injection in the management of Indian STEMI patients in clinical practice. METHODS: post-licensure, observational, prescription event monitoring study. RESULTS: 2100 patients received weight-adjusted tenecteplase injection. More than 90% patients received aspirin, clopidogrel, and enoxaparin/heparin. Clinically successful thrombolysis was reported in 86.71%, in-hospital mortality was 3.48%. The adverse events recorded were comparable with previously published data. Any bleeding (excluding intra-cranial hemorrhage) was seen in 4.62% patients which was reported in 0.90% patients of which 47.34% patients had also received GpIIb/IIIa inhibitors. CONCLUSION: This study confirms the efficacy and safety of indigenous tenecteplase in Indian STEMI patients.

Optimal platelet inhibition in patients undergoing PCI: data from the Multicenter Registry of High-Risk Percutaneous Coronary Intervention and Adequate Platelet Inhibition (MR PCI) study.

BACKGROUND: Optimal inhibition of platelet aggregation (IPA) may afford greater protection against ischemic events during percutaneous coronary intervention (PCI). The objective of this study was to test several antiplatelet regimens in elective high-risk PCI patients by comparing different combinations of glycoprotein IIb/IIIa inhibitors and clopidogrel. METHODS: The study was a randomized open-label study at 3 heart centers in India. One hundred twenty patients were enrolled between July 2006 and September 2006. Patients were randomized to 1 of the 4 groups: group A--tirofiban, group B--eptifibatide, group C--tirofiban + clopidogrel 600-mg loading dose, and group D--eptifibatide + clopidogrel 600-mg loading dose. All patients received a clopidogrel maintenance dose after PCI. The primary outcome measure was the IPA assessed at 10 minutes, at 6 to 8 hours, and at 24 hours. RESULTS: The IPA was higher with high-dose tirofiban compared with eptifibatide at 10 minutes (95.88 +/- 5.85% vs 91.22 +/- 7.52%, P = .003) and at 6 to 8 hours (93.11 +/- 7.6% vs 85.45 +/- 11.03, P < .001). Significantly more patients achieved >95% IPA with the high-dose tirofiban regimen. CONCLUSIONS: This head-to-head study comparing high-dose tirofiban with double-bolus eptifibatide demonstrated higher degree of platelet inhibition with high-dose tirofiban at 10 minutes and at 6 to 8 hours in patients undergoing elective high-risk PCI. The addition of clopidogrel did not acutely extend the IPA from intravenous glycoprotein IIb/IIIa inhibitors, but did so at 24 hours.

Indigenous recombinant streptokinase vs natural streptokinase in acute myocardial infarction patients: Phase III multicentric randomized double blind trial.

BACKGROUND: Streptokinase is the most widely used thrombolytic agent and can now be made using recombinant DNA technology. The present trial was initiated to assess an indigenous recombinant streptokinase (Shankinase, r-SK). AIM: To compare the efficacy and safety of indigenous recombinant streptokinase (Shankinase, r-SK) and natural streptokinase (Streptase, n-SK). SETTINGS AND DESIGN: Double blind, randomized, non-inferiority, multicentric, parallel study. MATERIALS AND METHODS: Patients of AMI < 6 hours of chest pain and 2 mm ST elevation in 2 contiguous chest leads V(1)-V(6) or 1 mm in limb leads were randomized to receive 1.5 miu of either r-SK or n-SK. CK Peaking and decrease of > or = 50% ST segment were used to assess reperfusion. STATISTICAL ANALYSIS: Difference in the groups was assessed by chi-square or paired t test as required. Probability value < 0.05 was considered significant with 95% confidence interval. RESULTS: Overall 150 patients were recruited (96 r-SK group and 54 in n-SK group) and demographic and clinical profile of the groups was comparable. Reperfusion was seen in 68.2% (58) and 69.4% (34) patients in r-SK and n-SK groups respectively. Commonly seen adverse events were fever in 7 (8.5%), hypotension in 3 (3.6%), nausea in 2 (2.4%) patients. Minor bleeding were seen in 4 (4.8%) of patients. CONCLUSION: Indigenous recombinant Streptokinase (r-SK) is as efficacious as natural streptokinase (n-SK) in establishing reperfusion as assessed by non-invasive parameters with comparable side effect profile.