Omics and EBM: Towards the Art of Individualization or the Standardization of Science - Which Way is this Train Headed? (original) (raw)
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Primary prevention with over-the-counter statins: a cautionary tale
Clinical pharmacology and therapeutics, 2005
On January 14, 2005, I voted, reluctantly, against making a statin (lovastatin) available over the counter (OTC) for primary prevention of cardiovascular disease. I was one of the 20 members of a Food and Drug Administration (FDA) advisory committee who did so (4 committee members voted in favor). Why my reluctance?
Cholesterol treatment with statins: Who is left out and who makes it to goal?
BMC Health Services Research, 2010
Background: Whether patient socio-demographic characteristics (age, sex, race/ethnicity, income, and education) are independently associated with failure to receive indicated statin therapy and/or to achieve low density lipoprotein cholesterol (LDL-C) therapy goals are not known. We examined socio-demographic factors associated with a) eligibility for statin therapy among those not on statins, and b) achievement of statin therapy goals. Surveys, 1999Surveys, -2006 were studied. Statin eligibility and achievement of target LDL-C was assessed using the US Third Adult Treatment Panel (ATP III) on Treatment of High Cholesterol guidelines.
Circulation: Cardiovascular Quality and Outcomes, 2009
Rosuvastatin (JUPITER), however, indicate that statin therapy to reduce cardiovascular risk is also effective among older persons with at-goal low-density lipoprotein but elevated high-sensitivity C-reactive protein levels. We estimate the size of and describe this new population for whom statin therapy may now be indicated based on JUPITER's findings. Methods and Results-Using data from the 1999 to 2004 National Health and Nutrition Examination Survey, we estimate that 57.9% of older adults (men Ն50 years and women Ն60 years), or 33 547 000 (95% CI, 32 217 000 to 34 877 000) Americans, are currently taking a statin (24.4%) or indicated for statin therapy (33.5%). In addition, we estimate that 19.2%, or 11 144 000 (95% CI, 10 053 000 to 12 235 000), may become newly eligible for statin therapy. This includes 8 071 000 (13.9%; 95% CI, 7 173 000 to 8 969 000) with high-sensitivity C-reactive protein Ն2 mg/L and low-density lipoprotein Ͻ130 mg/dL (ie, those meeting "strict" JUPITER criteria) and an additional 3 073 000 (5.3%; 95% CI, 2 404 000 to 3 743 000) with high-sensitivity C-reactive protein Ն2 mg/L and low-density lipoprotein of 130 to 160 mg/dL for whom JUPITER's findings might reasonably be extended. Thus, Ϸ80% of older persons may now have an indication for statin therapy. Compared with those who would continue to have no indication for statin therapy, the JUPITER group was more likely to be female, to be older, and to have obesity, hypertension, and the metabolic syndrome. Conclusions-JUPITER's findings have the potential to impact treatment recommendations for Ϸ20% of middle-aged to elderly adults, thus increasing the proportion of this segment of the population with an indication for statin therapy to nearly 80%. (Circ Cardiovasc Qual Outcomes. 2009;2:41-48.)
2012
Hypercholesterolemia and dyslipidemia are independent risk factors for cardiovascular disease and death. Statins are the drugs of choice to decrease plasma cholesterol and have other beneficial actions beyond lipid-lowering leading to substantial improvements in cardiovascular morbidity and mortality. However, evaluation of the effects of statins to reduce overall morbidity and mortality must integrate metabolic consequences of statin therapy with its lipid-lowering effect. Indeed, reduction in LDL-cholesterol to target level achieved by statins does not completely eliminate risk of cardiovascular disease and may elevate metabolic risk factors that contribute to dysregulation of metabolic homeostasis. This may lead to increased incidence of diabetes and its cardiovascular complications that are explained, in part, by reciprocal relationships between insulin resistance and endothelial dysfunction. Genetic factors may determine 40-60% of total cholesterol levels and 70% of the efficacy of statin treatments. Metabolic and cardiovascular phenotypes that are either genetically determined or environmentally acquired are also important determinants of responses to specific statins. Moreover, differences between biological outcomes of specific statins or increasing dosages of statins result in differential metabolic actions due to off-target or unknown mechanism that have important implications for the use of statins to reduce overall morbidity and mortality. In this review, we discuss differential cardiovascular and metabolic pleiotropic actions of specific statins that interact in a context-dependent manner with patient phenotypes and genotypes. These important considerations may influence progression of atherosclerosis, risk of diabetes, and modulation of insulin resistance that help determine overall morbidity and mortality in patients undergoing statin therapy.
American Journal of Epidemiology, 2012
. Hazard ratio (HR) for mortality (squares) according to statin use in secondary-prevention observational studies comparing prevalent users with nonusers and pooled HR for users versus nonusers (diamond). A) unadjusted results; B) adjusted results. Bars, 95% confidence interval (CI). 254 Danaei et al. Am J Epidemiol. 2012;175(4):250-262 by guest on October 16, 2016 http://aje.oxfordjournals.org/ Downloaded from Overall (I 2 = 84.2%, Leeper, 2007 (79) Muhlestein, 2004 (80) Age 80 years De Luca, 2006 (75) Allen-Maycock, 2002 (72) Age <65 years Ages 65−79 years 0.47 (0.32, 0.69) 0.81 (0.68, 0.96) 0.44 (0.29, 0.65) 0.49 (0.26, 0.93) 0.16 (0.09, 0.32) 0.52 (0.35, 0.79) 0.53 (0.38, 0.73) 0.01 0.10 1 10 100 Overall (I 2 = 57.5%, Allen.70 (0.64, 0.78) Meta-Analysis of Observational Studies of Statins 255 Am J Epidemiol. 2012;175(4):250-262 by guest on October 16, 2016 http://aje.oxfordjournals.org/ Downloaded from P = 0.000) Figure 5. Multivariate-adjusted hazard ratio (HR) for mortality (squares) according to statin use in secondary-prevention observational studies comparing incident users with nonusers and pooled HR for users versus nonusers (diamond). Bars, 95% confidence interval (CI).
Circulation: Cardiovascular Quality and Outcomes, 2014
T he clinical benefits from early detection and treatment of cardiovascular disease (CVD) risk factors are significant and well established. 1,2 There is less agreement on what form an optimal CVD screening strategy should take in light of the various screening mechanisms available to stratify high-and low-risk persons for intervention. 3-6 A recent review of CVD screening guidelines from major professional organizations in Western countries found that most guidelines called for assessments based on total CVD risk scores, and all of these risk scores included ≥1 laboratorybased component (ie, total and high-density lipoprotein cholesterol). 7 Non-laboratory-based risk assessment approaches use risk factors that can be assessed in a 5-or 10-minute clinical evaluation (such as age, smoking, blood pressure, and body mass index) to predict CVD risk using less time and fewer resources compared with laboratory-based risk scores. 8 We previously found that a non-laboratory-based CVD risk score discriminated CVD mortality risk similar to the Framingham risk scores in a representative US population in men, but there were significant differences in women. 9 A potential 2-staged CVD screening strategy could incorporate non-laboratorybased risk assessment as an initial step to identify patients who would benefit the most from further laboratory-based testing (eg, using Framingham risk) and recommend treatment decisions accordingly (ie, those determined to be high risk at either stage would receive treatment, others would not), thus optimizing the trade-offs in predictive accuracy and Background-Early detection and treatment of cardiovascular disease (CVD) risk factors produces significant clinical benefits, but no consensus exists on optimal screening algorithms. This study aimed to evaluate the comparative and costeffectiveness of staged laboratory-based and non-laboratory-based total CVD risk assessment. Methods and Results-We used receiver operating characteristic curve and cost-effectiveness modeling methods to compare strategies with and without laboratory components and used single-stage and multistage algorithms, including approaches based on Framingham risk scores (laboratory-based assessments for all individuals). Analyses were conducted using data from 5998 adults in the Third National Health and Nutrition Examination Survey without history of CVD using 10-year CVD death as the main outcome. A microsimulation model projected lifetime costs, quality-adjusted life years (QALYs), and incremental cost-effectiveness ratios for 60 Framingham-based, non-laboratory-based, and staged screening approaches. Across strategies, the area under the receiver operating characteristic curve was 0.774 to 0.780 in men and 0.812 to 0.834 in women. There were no statistically significant differences in area under the receiver operating characteristic curve between multistage and Framingham-based approaches. In cost-effectiveness analyses, multistage strategies had incremental cost-effectiveness ratios of 52000/QALYand52 000/QALY and 52000/QALYand83 000/QALY for men and women, respectively. Single-stage/Framingham-based strategies were dominated (higher cost and lower QALYs) or had unattractive incremental cost-effectiveness ratios (>$300 000/QALY) compared with single-stage/non-laboratorybased and multistage approaches. Conclusions-Non-laboratory-based CVD risk assessment can be useful in primary CVD prevention as a substitute for laboratory-based assessments or as the initial component of a multistage approach. Cost-effective multistage screening strategies could avoid 25% to 75% of laboratory testing used in CVD risk screening with predictive power comparable with Framingham risks. (Circ Cardiovasc Qual Outcomes. 2014;7:25-32.)
Impact of the JUPITER Trial on Statin Prescribing for Primary Prevention
Pharmacotherapy: The Journal of Human Pharmacology and Drug Therapy, 2013
Rosuvastatin (JUPITER) trial identified a new population of individuals with cholesterol levels below traditional treatment thresholds but with elevated high-sensitivity C-reactive protein (hs-CRP) levels who may benefit from primary prevention with statin therapy, we sought to evaluate the impact of this trial on the incident prescription rates of rosuvastatin alone as well as all statins in a primary prevention population. DESIGN Population-based, cross-sectional time-series analysis. DATA SOURCE Administrative health care databases in Ontario, Canada. PATIENTS A total of 299,809 incident statin users 66 years or older were identified during the study period, from January 1, 2003, to March 31, 2011, who were prescribed statin therapy for primary prevention. MEASUREMENTS AND MAIN RESULTS We evaluated the incident rate of rosuvastatin and all statin use during each quarter of the study period. Overall, no significant trends in all incident statin use were observed (p=0.99). Furthermore, no significant differences were observed in incident rates of rosuvastatin (p=0.21) or all statin (p=0.41) use after the publication of the JUPITER trial. Despite the lack of impact of the JUPITER trial on rosuvastatin or all statin utilization, the relative market share of rosuvastatin increased from 9% to 65% over the study period. CONCLUSION The publication of the JUPITER trial did not significantly affect trends in overall statin and rosuvastatin prescribing patterns for primary prevention in this study. Increases in the relative market share of rosuvastatin may be attributed to the impact of the pharmaceutical industry on prescribing patterns. Our results highlight the need to further improve the integration of evidencebased prescribing into cost-effective clinical practice.