ACUTE CORONARY SYNDROME: A SEA CHANGE IN OUR UNDERSTANDING OF PATHOGENESIS AND WAY OF TREATMENT? (PART II)

The second part of review highlights the role of residual lipid and thrombotic risks in coronary heart disease patients and possible ways of its correction. The results of randomized clinical trials dedicated to the efficacy of new class of hypolipidemic drug (PCSK‑9 inhibitors) in acute coronary syndrome setting are discussed. Recently published new guidelines of European Society of Cardiology on acute coronary syndrome management are also highlighted.

Fenofibrate ameliorates neural, mechanical, chemical, and electrical alterations in the murine model of heart failure

Heart failure (HF) is a leading cause of hospitalization across the world and is known to cause ill-health and heavy economic losses. In the present study, a rat model of isoproterenol (ISO, 85 mg/kg subcutaneously for two subsequent days) induced HF was developed. ISO induces HF by its direct effect, that is, rise in left ventricular end-diastolic pressure (mechanical) and indirectly by altering the baroreflex (neural), electrocardiography (electrical), and development of oxidative stress and hyperlipidemia (chemical). Fenofibrate, a hypolipidemic drug, which ameliorates myocardial energy metabolism was seen to improve the both ISO-induced oxidative stress and lipid profile and consequently improved Baroreflex Sensitivity (BRS), partial ventricular functions, and cardiac hypertrophy. Therefore, our result suggests that fenofibrate treatment protected the heart by alleviating the ISO-induced effects, that is, neural, mechanical, electrical, and chemical alterations.

Cost comparisons of seven leading brands of the Hypolipidemic drug, Rosuvastatin available in an India city

Background: Hypolipidemic drugs need to be prescribed lifelong for most of the selected patients, once started. Price variation can lead to huge financial strain on the patients, especially when cost associated issues are not considered by the prescribing medical practitioner. This study was conducted to compare the cost, to the patient, of seven most commonly prescribed preparations of different brands of Rosuvastatin ten milligram, in Kolhapur city.Methods: Authors purchased a strip of 10 capsules each of the seven leading brands of Rosuvastatin ten milligrams. The prices of the strip of 10 capsules of each of the seven chosen brands were compared. Finally, the cost of each of these seven brands for one year, was compared directly as well as using percentages. The data was collected, analysed and presented in tabular forms and figures.Results: The data of the cost of seven different brands of a single hypolipidemic drug, Rosuvastatin ten milligram shows that the cost of the costliest among the seven brands of this drug for one year is almost two times that of the cheapest brand, or in other words almost 200 percent that of the cheapest brand.Conclusions: The cost differences between the cheapest and the costliest brands were substantial. The cost of remaining five brands was dispersed in between these two extremes. India, with a major part of the population being highly concerned about the cost of medications, the prescribing medical practitioner must select the preparation wisely . The most costly preparation of Rosuvastatin ten milligram can substantially add to the financial strain on the patient’s yearly expenses. Thus, Pharmaco economic considerations must be a prime concern while making a decision to prescribe medicines, especially in a country like India.

Gemfibrozil and Nigella Sativa: Comparison

Hyperlipidemia especially LDL-cholesterol may lead to development of coronary artery disease causing morbidity or mortality due to cardiac arrhythmias. Conventional hypolipidemic drugs have unwanted effects. Herbal therapy for Hyperlipidemia is getting attention due to their less frequent side effects. In this study we have compared hypolipidemic effects of Gemfibrozil with Nigella sativa. Seventy five hyperlipidemic patients from Jinnah Hospital Lahore were enrolled for study. After getting consent all patients were divided in three groups comprising 25 patients in each group. Group 1 was on Nigella sativa, group 2 was on Gemfibrozil and third group was on placebo therapy. They were advised to take drugs for two months. After completion of study pretreatment and post treatment values of LDL cholesterol were analyzed statistically. In Nigella sativa group LDL cholesterol decreased from 191.14±3.45 to 159.40±2.98 mg/dl, means 31.7 mg/dl LDL reduction was observed when compared with placebo group. In Gemfibrozil group of patients LDL cholesterol decreased from 197.77±3.91 mg/dl to 159.62±2.20 mg/dl, means LDL reduction in mean values was 38.2 mg/dl, when compared with placebo group. These changes are highly significant with p-values of ‹0.001. We concluded from this study that herbal medicine Nigella sativa is as effective as traditionally used hypolipidemic drug Gemfibrozil.

Drugs that Mimic the Effect of Gene Mutations for the Prevention or the Treatment of Atherosclerotic Disease: From PCSK9 Inhibition to ANGPTL3 Inactivation

Background: Drugs mimicking natural beneficial mutations, including that for familial hypercholesterolemia (FH), might represent the future of hypolipidemic drug treatment. Objective: The aim of this review is to review the properties and the effects of these drugs, which are either already commercially available or are in the process to be approved for the treatment of dyslipidemia. Results: More than a decade ago, it was accidentally discovered that proprotein convertase subtilisin/kexin type 9 (PCSK9) loss-of-function mutations resulted in marked lifelong reduction of LDL-C and the incidence of cardiovascular disease (CVD). This provided the idea for a human anti-PCSK9 antibody. Along with dozens of phase II and III studies demonstrating unprecedented reductions in LDL-C levels, two large clinical trials established the substantial benefits of evolocumab and alirocumab on cardiovascular morbidity and mortality, on top of standard treatment. Evolocumab and alirocumab are now approved and used in clinical practice for the treatment of FH, statin intolerance, and high risk patients not achieving LDL-C targets. Anti RNA, small molecules, peptides and also protein fragments against PCSK9 are in phase 1 trials. Angiopoietin-like protein 3 (ANGPTL3) regulates lipid metabolism increasing triglycerides (TGs), remnants, and LDL-C. In a huge study, ANGPTL3 deficiency due to gene(s) loss-of-function was associated with substantial reductions in circulating TGs, LDL-C, and CVD. Evinacumab, an ANGPTL3 antibody, caused a dose-dependent reduction in fasting TG levels of up to 76% and LDL-C of up to 23% and CVD risk by 41%. There is also antisense oligonucleotide and micro-RNA- 27b (miR-27b) against ANGPTL3. Two naturally occurring mutations in apo3 gene, A23T and K58E, reduce TGs and CVD risk. A monoclonal antibody targeting apoC-III has the same effect. Conclusion: Mimicking the beneficial naturally happening mutations in lipid metabolism pathways with biological drugs is probably the future of hypolipidemic drug treatment.

Pleiotropic effects of niacin: Current possibilities for its clinical use

Niacin was the first hypolipidemic drug to significantly reduce both major cardiovascular events and mortality in patients with cardiovascular disease. Niacin favorably influences all lipoprotein classes, including lipoprotein[a],and belongs to the most potent hypolipidemic drugs for increasing HDL-C. Moreover, niacin causes favorable changes to the qualitative composition of lipoprotein HDL. In addition to its pronounced hypolipidemic action, niacin exerts many other, non-hypolipidemic effects (e.g., antioxidative, anti-inflammatory, antithrombotic), which favorably influence the development and progression of atherosclerosis. These effects are dependent on activation of the specific receptor HCA2. Recent results published by the two large clinical studies, AIM-HIGH and HPS2-THRIVE, have led to the impugnation of niacin’s role in future clinical practice. However, due to several methodological flaws in the AIM-HIGH and HPS2-THRIVE studies, the pleiotropic effects of niacin now deserve thorough evaluation. This review summarizes the present and possible future use of niacin in clinical practice in light of its newly recognized pleiotropic effects.