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      Drivers of the Sex Disparity in Statin Therapy in Patients with Coronary Artery Disease: A Cohort Study

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          Abstract

          Background

          Women are less likely to be prescribed statins than men. Existing reports explain only a fraction of this difference. We conducted a study to identify factors that account for sex differences in statin therapy among patients with coronary artery disease (CAD).

          Methods and Results

          We retrospectively studied 24,338 patients with CAD who were followed for at least a year between 2000 and 2011 at two academic medical centers. Women (9,006 / 37% of study patients) were less likely to either have initiated statin therapy (81.9% women vs. 87.7% men) or to have persistent statin therapy at the end of follow-up (67.0% women vs. 71.4% men). Women were older (72.9 vs. 68.4 years), less likely to have ever smoked (49.8% vs. 65.6%), less likely to have been evaluated by a cardiologist (57.5% vs. 64.5%) and more likely to have reported an adverse reaction to a statin (27.1% vs. 21.7%) (p < 0.0001 for all). In multivariable analysis, patients with history of smoking (OR 1.094; p 0.017), younger age (OR 1.013 / year), cardiologist evaluation (OR 1.337) and no reported adverse reactions to statins (OR 1.410) were more likely (p < 0.0001 for all) to have persistent statin therapy. Together, these four factors accounted for 90.4% of the sex disparity in persistent statin therapy.

          Conclusions

          Several specific factors appear to underlie divergent statin therapy in women vs. men. Identifying such drivers may facilitate programmatic interventions and stimulate further research to overcome sex differences in applying proven interventions for cardiovascular risk reduction.

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          Most cited references37

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          2013 ACC/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults

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            Pravastatin in elderly individuals at risk of vascular disease (PROSPER): a randomised controlled trial.

            Although statins reduce coronary and cerebrovascular morbidity and mortality in middle-aged individuals, their efficacy and safety in elderly people is not fully established. Our aim was to test the benefits of pravastatin treatment in an elderly cohort of men and women with, or at high risk of developing, cardiovascular disease and stroke. We did a randomised controlled trial in which we assigned 5804 men (n=2804) and women (n=3000) aged 70-82 years with a history of, or risk factors for, vascular disease to pravastatin (40 mg per day; n=2891) or placebo (n=2913). Baseline cholesterol concentrations ranged from 4.0 mmol/L to 9.0 mmol/L. Follow-up was 3.2 years on average and our primary endpoint was a composite of coronary death, non-fatal myocardial infarction, and fatal or non-fatal stroke. Analysis was by intention-to-treat. Pravastatin lowered LDL cholesterol concentrations by 34% and reduced the incidence of the primary endpoint to 408 events compared with 473 on placebo (hazard ratio 0.85, 95% CI 0.74-0.97, p=0.014). Coronary heart disease death and non-fatal myocardial infarction risk was also reduced (0.81, 0.69-0.94, p=0.006). Stroke risk was unaffected (1.03, 0.81-1.31, p=0.8), but the hazard ratio for transient ischaemic attack was 0.75 (0.55-1.00, p=0.051). New cancer diagnoses were more frequent on pravastatin than on placebo (1.25, 1.04-1.51, p=0.020). However, incorporation of this finding in a meta-analysis of all pravastatin and all statin trials showed no overall increase in risk. Mortality from coronary disease fell by 24% (p=0.043) in the pravastatin group. Pravastatin had no significant effect on cognitive function or disability. Pravastatin given for 3 years reduced the risk of coronary disease in elderly individuals. PROSPER therefore extends to elderly individuals the treatment strategy currently used in middle aged people.
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              Insights from the NHLBI-Sponsored Women's Ischemia Syndrome Evaluation (WISE) Study: Part II: gender differences in presentation, diagnosis, and outcome with regard to gender-based pathophysiology of atherosclerosis and macrovascular and microvascular coronary disease.

              Coronary heart disease is the leading cause of death and disability in the U.S., but recent advances have not led to declines in case fatality rates for women. The current review highlights gender-specific issues in ischemic heart disease (IHD) presentation, evaluation, and outcomes with a special focus on the results derived from the National Institutes of Health-National Heart, Lung, and Blood Institute-sponsored Women's Ischemia Syndrome Evaluation (WISE) study. In the second part of this review, we will assess new evidence on gender-based differences in vascular wall or metabolic alterations, atherosclerotic plaque deposition, and functional expression on worsening outcomes of women. Additionally, innovative cardiovascular imaging techniques will be discussed. Finally, we identify critical areas of further inquiry needed to advance this new gender-specific IHD understanding into improved outcomes for women.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                5 May 2016
                2016
                : 11
                : 5
                : e0155228
                Affiliations
                [1 ]Department of Endocrinology, Key Laboratory of Endocrinology, Ministry of Health, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences, Beijing, China
                [2 ]Harvard Medical School, Boston, Massachusetts, United States of America
                [3 ]Brigham and Women's Hospital, Boston, Massachusetts, United States of America
                [4 ]Harvard Clinical Research Institute, Boston, Massachusetts, United States of America
                Universite de Montreal, CANADA
                Author notes

                Competing Interests: AT received investigator-initiated research grant funding from Merck, Sharp and Dohme. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

                Conceived and designed the experiments: HZ JP MS AT. Performed the experiments: HZ JP MS AT. Analyzed the data: HZ JP MS AT. Contributed reagents/materials/analysis tools: HZ JP MS AT. Wrote the paper: HZ MS AT.

                Article
                PONE-D-15-45742
                10.1371/journal.pone.0155228
                4858152
                27148965
                53f33f55-dc1a-42fe-929c-a0da23d486fc
                © 2016 Zhang et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 20 October 2015
                : 26 April 2016
                Page count
                Figures: 0, Tables: 4, Pages: 13
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100000092, U.S. National Library of Medicine;
                Award ID: 5RC1LM010460
                Award Recipient :
                Funded by: Chinese National Key Program of Clinical Science
                Award ID: WBYZ2011873
                Award Recipient :
                Funded by: Young Scientific Research Fund of Peking Union Medical College Hospital
                Award ID: PUMCH-2013-060
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/501100001809, National Natural Science Foundation of China;
                Award ID: NSFC71432004
                Award Recipient :
                AT: National Library of Medicine (5RC1LM010460). http://www.nlm.nih.gov. HZ: Chinese National Key Program of Clinical Science (WBYZ2011873), http://www.nhfpc.gov.cn. HZ: Young Scientific Research Fund of Peking Union Medical College Hospital (pumch-2013-060), http://www.pumch.cn/. HZ: National Natural Science Foundation of China (NSFC71432004), http://www.nsfc.gov.cn. JP: Brigham and Women's Hospital Linda Joy Pollin Women's Heart Center. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Medicine and Health Sciences
                Pharmacology
                Drugs
                Statins
                Medicine and Health Sciences
                Vascular Medicine
                Coronary Artery Disease
                Medicine and Health Sciences
                Pharmacology
                Adverse Reactions
                Medicine and Health Sciences
                Pharmaceutics
                Drug Therapy
                Cardiovascular Therapy
                Medicine and Health Sciences
                Cardiovascular Medicine
                Cardiovascular Diseases
                Cardiovascular Diseases in Women
                Medicine and Health Sciences
                Women's Health
                Cardiovascular Diseases in Women
                Medicine and Health Sciences
                Endocrinology
                Endocrine Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Metabolic Disorders
                Diabetes Mellitus
                Medicine and Health Sciences
                Surgical and Invasive Medical Procedures
                Cardiovascular Procedures
                Coronary Artery Bypass Grafting
                Medicine and Health Sciences
                Health Care
                Primary Care
                Custom metadata
                Partners HealthCare policy requires a data use agreement for release of de-identified patient data. Consequently, we will not be able to make the de-identified data used in this study public but will be able to provide it to interested investigators upon request from Dr. Turchin ( aturchin@ 123456partners.org ), conditional on their signing a data use agreement with Partners HealthCare.

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