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      Impact of Prior Use of Four Preventive Medications on Outcomes in Patients Hospitalized for Acute Coronary Syndrome--Results from CPACS-2 Study


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          It is widely reported that long-term use of four preventive medications (antiplatelet agents, angiotensin converting enzyme inhibitor / angiotensin receptor blocker, statin and beta-blockers) reduce the risk of subsequent acute coronary syndromes (ACS). It is unclear whether these four medications benefit patients who develop ACS despite its use.

          Methods and Results

          Logistic regression and propensity-score was applied among 14790 ACS patients to assess the association between prior use of four preventive medications and in-hospital outcomes including severity of disease at presentation (type of ACS, systolic blood pressure <90 mmHg, and heart rate> = 100 beats/min), complicating arrhythmia and major adverse cardiovascular events (MACEs, including all deaths, non-fatal myocardial infarction or re-infarction, and non-fatal stroke). Prior use of each of the four medications was significantly associated with less severity of disease (ORs ranged from 0.40 to 0.82, all P<0.05), less arrhythmia (ORs ranged from 0.45 to 0.64, all P<0.05), and reduced risk of MACEs (ORs ranged from 0.59 to 0.73, all P<0.05) during hospitalization. Multiple variable-adjusted ORs of MACEs were 0.77, 0.67, 0.48 and 0.59 respectively in patients with 1, 2, 3 and 4 medications in comparison with patients with none, and other clinical outcomes showed the same trend (P for trend < 0.05).


          Among ACS patients in our study, those with prior use of four preventive medications presented with less disease severity, developed less arrhythmia and had a lower risk of in-hospital MACEs. The value of taking these medications may beyond just preventing occurrence of the disease.

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          Most cited references14

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          Association of statin therapy with outcomes of acute coronary syndromes: the GRACE study.

          Statins administered early in patients with acute coronary syndromes may lead to modest reductions in recurrent ischemic events. To examine the association between previous and early in-hospital statin therapy and the presentation and outcomes of an acute coronary syndrome. Cohort study. 94 hospitals in 14 countries participating in the Global Registry of Acute Coronary Events (GRACE). 19,537 patients with an acute coronary syndrome who were enrolled from April 1999 to September 2002. Statin use before and after presentation with an acute coronary syndrome and associated rates of myocardial infarction, hospital complications, and hospital mortality. The composite end point included death, in-hospital myocardial infarction, and stroke. Patients who were already taking statins when they presented to the hospital were less likely to have ST-segment elevation (odds ratio [OR], 0.79 [95% CI, 0.71 to 0.88]) or myocardial infarction (OR, 0.78 [CI, 0.70 to 0.86]). Patients who continued to take statins in the hospital were less likely to experience complications or die than patients who never received statins (OR, 0.66 [CI, 0.56 to 0.77]). Patients not previously taking statins who began statin therapy in the hospital were less likely to die than patients who never received statin therapy (OR, 0.38 [CI, 0.30 to 0.48]). However, adjustment for the hospital of admission attenuated the association between initiation of statin therapy and the composite end point (OR, 0.84 [CI, 0.65 to 1.10]). This observational study cannot exclude confounding by clinical and hospital factors. These data support the hypothesis that statin therapy can modulate early pathophysiologic processes in patients with acute coronary syndromes. A randomized trial of statin therapy in acute myocardial infarction is warranted.
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            Hospital quality improvement initiative for patients with acute coronary syndromes in China: a cluster randomized, controlled trial.

            Background- Substantial evidence-practice gaps exist in the management of acute coronary syndromes (ACS) in China. Clinical pathways are tools for improving ACS quality of care but have not been rigorously evaluated. Methods and Results- Between October 2007 and August 2010, a quality improvement program was conducted in 75 hospitals throughout China with mixed methods evaluation in a cluster randomized, controlled trial. Eligible hospitals were level 2 or level 3 centers routinely admitting >100 patients with ACS per year. Hospitals were assigned immediate implementation of the American Heart Association/American College of Cardiology guideline based clinical pathways or commencement of the intervention 12 months later. Outcomes were several key performance indicators reflecting the management of ACS. The key performance indicators were measured 12 months after commencement in intervention hospitals and compared with baseline data in control hospitals, using data collected from 50 consecutive patients in each hospital. Pathway implementation was associated with an increased proportion of patients discharged on appropriate medical therapy, with nonsignificant improvements or absence of effects on other key performance indicators. Conclusions- Among hospitals in China, the use of a clinical pathway for the treatment of ACS compared with usual care improved secondary prevention treatments, but effectiveness was otherwise limited. An accompanying process evaluation identified several health system barriers to more successful implementation. Clinical Trial Registration- URL: http://www.anzctr.org.au/default.aspx. Unique identifier: ACTRN12609000491268.
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              Impact of prior statin therapy on arrhythmic events in patients with acute coronary syndromes (from the Global Registry of Acute Coronary Events [GRACE]).

              Animal models of myocardial ischemia have demonstrated reduction in arrhythmias using statins. It was hypothesized that previous statin therapy before hospitalization might be associated with reductions of in-hospital arrhythmic events in patients with acute coronary syndromes. In this multinational, prospective, observational study (the Global Registry of Acute Coronary Events [GRACE]), data from 64,679 patients hospitalized for suspected acute coronary syndromes (from 1999 to 2007) were analyzed. The primary outcome of interest was in-hospital arrhythmic events in previous statin users compared with nonusers. The 2 primary end points were atrial fibrillation and the composite end point of ventricular tachycardia, ventricular fibrillation, and/or cardiac arrest. In-hospital death was also examined. Of the 64,679 patients, 17,636 (27%) had received previous statin therapy. Those taking statins had higher crude rates of histories of angina (69% vs 46%), diabetes (34% vs 22%), heart failure (15% vs 8.4%), hypertension (74% vs 58%), atrial fibrillation (9.3% vs 7.0%), and dyslipidemia (85% vs 35%). Patients previously taking statins were less likely to have in-hospital arrhythmias. In propensity-adjusted multivariable models, previous statin use was associated with a lower risk for ventricular tachycardia, ventricular fibrillation, or cardiac arrest (odds ratio 0.81, 95% confidence interval 0.72 to 0.96, p = 0.002); atrial fibrillation (odds ratio 0.81, 95% confidence interval 0.73 to 0.89, p <0.0001); and death (odds ratio 0.82, 95% confidence interval 0.70 to 0.95, p = 0.010). In conclusion, patients previously taking statins had a lower incidence of in-hospital arrhythmic events after acute coronary syndrome than those not previously taking statins. Our study suggests another possible benefit from appropriate primary and secondary prevention therapy with statins.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                14 September 2016
                : 11
                : 9
                : e0163068
                [1 ]Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Center, Beijing, China
                [2 ]Department of Epidemiology and Biostatistics, Tianjin Medical University Cancer Institute and Hospital, Tianjin, China
                [3 ]The George Institute for Global Health at Peking University Health Science Center, Beijing, China
                [4 ]Beijing Anzhen Hospital, Capital Medical University, Beijing, China
                [5 ]The George Institute for Global Health, University of Sydney, Sydney, Australia
                [6 ]The Department of Cardiology, Cardiovascular Institute and Fuwai Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Bejing, China
                Osaka University Graduate School of Medicine, JAPAN
                Author notes

                Competing Interests: Both studies are funded by Sanofi, China. No author is an employee or consultant of Sanofi, or has any interests related to products of Sanofi. This does not alter the authors' adherence to PLOS ONE policies on sharing data and materials.

                • Conceptualization: YFW.

                • Formal analysis: ML YBH JCJ.

                • Writing – original draft: ML YBH.

                • Writing – review & editing: XD SSL AP RLG YFW.

                Author information
                © 2016 Li 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.

                : 8 July 2016
                : 1 September 2016
                Page count
                Figures: 2, Tables: 4, Pages: 12
                The source of funding used to support the CPACS-2 study is from Sanofi, China, through an unrestricted research grant. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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