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      Statin therapy/lipid lowering therapy among Indian adults with first acute coronary event: The dyslipidemia Residual and Mixed Abnormalities IN spite of Statin therapy (REMAINS) study

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          Abstract

          Objective

          The primary objective was to evaluate the effect of statin therapy/lipid lowering therapy (LLT) on lipid profile, in adults presenting with first acute coronary event.

          Methods and material

          A multicentre, observational, prospective cohort study of lipid profiles pre- and post-statin therapy/LLT, among adult patients with confirmed diagnosis of first acute coronary event. The primary outcome measures were low-density lipoprotein cholesterol (LDL-C) in mg/dl, high-density lipoprotein cholesterol (HDL-C) in mg/dl and triglycerides (TG) in mg/dl at baseline and end of study (EOS, 12 weeks [mean: 13.5 weeks]).

          Results

          Totally 474 patients completed the study. Number of patients with any LDL-C abnormality (LDL-C [all; LDL was abnormal, either alone or along with other lipid parameter(s)]) decreased from 118 (24.9%) to 27 (5.7%), and for LDL-C (only; only the LDL was abnormal), from 46 (9.7%) to 13 (2.7%), both from baseline to EOS. Of 118 patients with high LDL-C (all) at baseline, 91 (77.1%) had reduction in LDL-C to <100 mg/dl, of which 54 (45.8%) had LDL-C <70 mg/dl at EOS. The patients with LDL-C fraction abnormalities decreased, while HDL-C abnormalities increased at EOS from baseline. No major difference was observed at baseline and EOS in levels of TG (all [TG was abnormal, either alone or along with other lipid parameter(s)]) and TG (only [only the TG was abnormal]). Six (1.3%) had seven serious adverse events.

          Conclusions

          Though statin therapy is effective in lowering LDL-C, there still remains residual dyslipidemia, which probably should be tackled with therapeutic and non-therapeutic options.

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          Most cited references26

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          Randomised trial of cholesterol lowering in 4444 patients with coronary heart disease: the Scandinavian Simvastatin Survival Study (4S)

          Drug therapy for hypercholesterolaemia has remained controversial mainly because of insufficient clinical trial evidence for improved survival. The present trial was designed to evaluate the effect of cholesterol lowering with simvastatin on mortality and morbidity in patients with coronary heart disease (CHD). 4444 patients with angina pectoris or previous myocardial infarction and serum cholesterol 5.5-8.0 mmol/L on a lipid-lowering diet were randomised to double-blind treatment with simvastatin or placebo. Over the 5.4 years median follow-up period, simvastatin produced mean changes in total cholesterol, low-density-lipoprotein cholesterol, and high-density-lipoprotein cholesterol of -25%, -35%, and +8%, respectively, with few adverse effects. 256 patients (12%) in the placebo group died, compared with 182 (8%) in the simvastatin group. The relative risk of death in the simvastatin group was 0.70 (95% CI 0.58-0.85, p = 0.0003). The 6-year probabilities of survival in the placebo and simvastatin groups were 87.6% and 91.3%, respectively. There were 189 coronary deaths in the placebo group and 111 in the simvastatin group (relative risk 0.58, 95% CI 0.46-0.73), while noncardiovascular causes accounted for 49 and 46 deaths, respectively. 622 patients (28%) in the placebo group and 431 (19%) in the simvastatin group had one or more major coronary events. The relative risk was 0.66 (95% CI 0.59-0.75, p < 0.00001), and the respective probabilities of escaping such events were 70.5% and 79.6%. This risk was also significantly reduced in subgroups consisting of women and patients of both sexes aged 60 or more. Other benefits of treatment included a 37% reduction (p < 0.00001) in the risk of undergoing myocardial revascularisation procedures. This study shows that long-term treatment with simvastatin is safe and improves survival in CHD patients.
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            Plasma triglyceride level is a risk factor for cardiovascular disease independent of high-density lipoprotein cholesterol level: a meta-analysis of population-based prospective studies.

            Despite nearly 40 years of research, the role of plasma triglyceride as a risk factor for cardiovascular disease remains elusive. The objectives of the present study were to quantify the magnitude of the association between triglyceride and cardiovascular disease in the general population, and to determine whether this relationship is independent of high-density lipoprotein (HDL) cholesterol, using the semi-quantitative techniques of metaanalysis. Seventeen studies were selected for the analysis based on published reports of population-based, prospective studies, including 46413 men and 10864 women. To insure comparability, only studies reporting the association between fasting triglyceride levels and incident cardiovascular endpoints were included. Using standard meta-analysis calculations, relative risks (RR) and 95% confidence intervals (CI) were calculated and standardized with respect to a 1 mmol/l increase in triglyceride. Multivariable-adjusted RRs were determined for the six studies in men and two studies in women that reported adjustments for HDL cholesterol. For men and women, the univariate RRs for triglyceride were 1.32 (95% Cl 1.26-1.39) and 1.76 (95% Cl 1.50-2.07), respectively, indicating an approximately 30% increased risk in men and a 75% increase in women. Adjustment of HDL cholesterol and other risk factors attenuated these RRs to 1.14 (95% Cl 1.05-1.28) and 1.37 (95% Cl 1.13-1.66), respectively, which were still statistically significant values. Based on combined data from prospective studies, triglyceride is a risk factor for cardiovascular disease for both men and women in the general population, independent of HDL cholesterol. These finding demonstrate the necessity for clinical trials to evaluate whether lowering plasma triglyceride decreases the risk of cardiovascular disease.
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              Primary prevention of acute coronary events with lovastatin in men and women with average cholesterol levels: results of AFCAPS/TexCAPS. Air Force/Texas Coronary Atherosclerosis Prevention Study.

              Although cholesterol-reducing treatment has been shown to reduce fatal and nonfatal coronary disease in patients with coronary heart disease (CHD), it is unknown whether benefit from the reduction of low-density lipoprotein cholesterol (LDL-C) in patients without CHD extends to individuals with average serum cholesterol levels, women, and older persons. To compare lovastatin with placebo for prevention of the first acute major coronary event in men and women without clinically evident atherosclerotic cardiovascular disease with average total cholesterol (TC) and LDL-C levels and below-average high-density lipoprotein cholesterol (HDL-C) levels. A randomized, double-blind, placebo-controlled trial. Outpatient clinics in Texas. A total of 5608 men and 997 women with average TC and LDL-C and below-average HDL-C (as characterized by lipid percentiles for an age- and sex-matched cohort without cardiovascular disease from the National Health and Nutrition Examination Survey [NHANES] III). Mean (SD) TC level was 5.71 (0.54) mmol/L (221 [21] mg/dL) (51 st percentile), mean (SD) LDL-C level was 3.89 (0.43) mmol/L (150 [17] mg/dL) (60th percentile), mean (SD) HDL-C level was 0.94 (0.14) mmol/L (36 [5] mg/dL) for men and 1.03 (0.14) mmol/L (40 [5] mg/dL) for women (25th and 16th percentiles, respectively), and median (SD) triglyceride levels were 1.78 (0.86) mmol/L (158 [76] mg/dL) (63rd percentile). Lovastatin (20-40 mg daily) or placebo in addition to a low-saturated fat, low-cholesterol diet. First acute major coronary event defined as fatal or nonfatal myocardial infarction, unstable angina, or sudden cardiac death. After an average follow-up of 5.2 years, lovastatin reduced the incidence of first acute major coronary events (1 83 vs 116 first events; relative risk [RR], 0.63; 95% confidence interval [CI], 0.50-0.79; P<.001), myocardial infarction (95 vs 57 myocardial infarctions; RR, 0.60; 95% CI, 0.43-0.83; P=.002), unstable angina (87 vs 60 first unstable angina events; RR, 0.68; 95% CI, 0.49-0.95; P=.02), coronary revascularization procedures (157 vs 106 procedures; RR, 0.67; 95% CI, 0.52-0.85; P=.001), coronary events (215 vs 163 coronary events; RR, 0.75; 95% CI, 0.61-0.92; P =.006), and cardiovascular events (255 vs 194 cardiovascular events; RR, 0.75; 95% CI, 0.62-0.91; P = .003). Lovastatin (20-40 mg daily) reduced LDL-C by 25% to 2.96 mmol/L (115 mg/dL) and increased HDL-C by 6% to 1.02 mmol/L (39 mg/dL). There were no clinically relevant differences in safety parameters between treatment groups. Lovastatin reduces the risk for the first acute major coronary event in men and women with average TC and LDL-C levels and below-average HDL-C levels. These findings support the inclusion of HDL-C in risk-factor assessment, confirm the benefit of LDL-C reduction to a target goal, and suggest the need for reassessment of the National Cholesterol Education Program guidelines regarding pharmacological intervention.
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                Author and article information

                Contributors
                Journal
                Indian Heart J
                Indian Heart J
                Indian Heart Journal
                Elsevier
                0019-4832
                Sep-Oct 2016
                28 February 2016
                : 68
                : 5
                : 646-654
                Affiliations
                [a ]Associate Director, Medical Affairs, MSD, India
                [b ]Senior Specialist, MSD, India
                [c ]Ex-Senior Specialist, MSD, India
                [d ]Associate Manager, Medical Affairs, MSD, India
                Author notes
                [* ] Corresponding author. viraj.salgaonkar@ 123456merck.com
                Article
                S0019-4832(15)00946-3
                10.1016/j.ihj.2015.12.016
                5079128
                27773403
                f2c27c18-f0de-45a4-99b9-741e7de30c85
                © 2016 Cardiological Society of India. Published by Elsevier B.V.

                This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

                History
                : 19 October 2015
                : 22 December 2015
                Categories
                Original Article

                acute coronary event,dyslipidemia,lipid profile,lipid lowering therapy,statin therapy

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