Effects of alirocumab on types of myocardial infarction: insights from the ODYSSEY OUTCOMES trial

Aims  The third Universal Definition of Myocardial Infarction (MI) Task Force classified MIs into five types: Type 1, spontaneous; Type 2, related to oxygen supply/demand imbalance; Type 3, fatal without ascertainment of cardiac biomarkers; Type 4, related to percutaneous coronary intervention; and Type 5, related to coronary artery bypass surgery. Low-density lipoprotein cholesterol (LDL-C) reduction with statins and proprotein convertase subtilisin–kexin Type 9 (PCSK9) inhibitors reduces risk of MI, but less is known about effects on types of MI. ODYSSEY OUTCOMES compared the PCSK9 inhibitor alirocumab with placebo in 18 924 patients with recent acute coronary syndrome (ACS) and elevated LDL-C (≥1.8 mmol/L) despite intensive statin therapy. In a pre-specified analysis, we assessed the effects of alirocumab on types of MI. Methods and results  Median follow-up was 2.8 years. Myocardial infarction types were prospectively adjudicated and classified. Of 1860 total MIs, 1223 (65.8%) were adjudicated as Type 1, 386 (20.8%) as Type 2, and 244 (13.1%) as Type 4. Few events were Type 3 (n = 2) or Type 5 (n = 5). Alirocumab reduced first MIs [hazard ratio (HR) 0.85, 95% confidence interval (CI) 0.77–0.95; P = 0.003], with reductions in both Type 1 (HR 0.87, 95% CI 0.77–0.99; P = 0.032) and Type 2 (0.77, 0.61–0.97; P = 0.025), but not Type 4 MI. Conclusion  After ACS, alirocumab added to intensive statin therapy favourably impacted on Type 1 and 2 MIs. The data indicate for the first time that a lipid-lowering therapy can attenuate the risk of Type 2 MI. Low-density lipoprotein cholesterol reduction below levels achievable with statins is an effective preventive strategy for both MI types.For complete list of authors see http://dx.doi.org/10.1093/eurheartj/ehz299</p

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Survey on Various Cryptography Methods

Abstract: To make secure data transmission over networks cryptography is used. The algorithm selected for cryptography should fulfil the conditions of integrity protection, conventional message authentication and digital signatures. Key exchange algorithms, hash functions, PN numbers are used for encryption and decryption of data. This encryption can be applied on data in stream format or in blocks. Moreover the length of key is the biggest constraint in encryption. Here in our paper we have studied present algorithms currently used for encryption

Review of various e-Learning Methodologies

Abstract — E-learning is among the most important explosion propelled by the internet alteration. This allows users to successfully gather knowledge and education both by synchronous and asynchronous methodologies to effectively face the need to rapidly acquire up to date know-how within productive environments. This review paper focuses various on e-learning methodologies The different categories of e-learning that includes informal and combination learning, network and based on worked learning. The most important focus of e-learning methodologies is on both asynchronous and synchronous methodology

Analysis of Secure Electronic Transmission (SET) System for Electronic Transactions

Abstract — In this paper, we introduce about protection of electronic payment for those whoever uses Internet transaction. This system is use to secure Internet transaction for three types of participants, 1) Payment gateway server, 2) Merchant server, and 3) Bank Server. SET has been developed by both Visa and MasterCard, as a way to secure our card transactions over internet, and industrial interest in the protocol is high. The security architecture of the system is designed by using Many Security Protocols and techniques, which eliminates the fraud that occurs today with stolen credit card/debit card payment information and customer information. Electronic commerce involves the exchange of some form of money for goods and services over the Internet but today, Internet is an insecure and unreliable media. Index Terms- SSL/TLS and SET Protocol, symmetric &amp; asymmetric Methodology, Dual signatures, and Communication tunnel techniques, e-payment protocol. 1

Renal sympathetic denervation for treatment of resistant hypertension – Indigenous technique

Background: The endovascular approach of ablation of renal sympathetic nerves is found to be effective in the treatment of uncontrolled hypertension. We report here our experience with the procedure in eight patients with drug resistant hypertension. Methods: We included patients in whom the blood pressure remained above 150/90 mmHg despite being on minimum three antihypertensive drugs. Radiofrequency ablation of the sympathetic nerves of both the renal arteries was done using conventional ablation catheters. The patients were followed at 1-month, 3 months and 6 months post procedure and blood pressure recorded. Results: All patients underwent successful renal sympathetic denervation. The mean blood pressure of the patients was 181/102.5 mmHg before the procedure and the average requirement of antihypertensive drugs per day was 4. A significant reduction in both systolic and diastolic blood pressure was observed post procedure which sustained over the follow up period of six months. The mean blood pressure observed at 1-month, 3 and 6 months were 137.5/80 mmHg, 136/81 mmHg and 137.5/81 mmHg, respectively. The average requirement of the number of antihypertensives also was reduced to 2.5 at the end of 6 months. There were no procedural complications. Conclusion: Catheter based renal denervation causes substantial and sustained blood pressure reduction without serious adverse events in patients with resistant hypertension