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type=\u0022text\/css\u0022 rel=\u0022stylesheet\u0022 href=\u0022\/\/d282kpwvnogo5m.cloudfront.net\/sites\/default\/files\/cdn\/css\/http\/css_Xg7z6oCTVgud_Q0huYz9x9iiD5H_2YPSJ5z2ZViSWdY.css\u0022 media=\u0022all\u0022 \/\u003E\n\u003Clink rel=\u0027stylesheet\u0027 type=\u0027text\/css\u0027 href=\u0027\/sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css\u0027 \/\u003E\u003C\/head\u003E\u003Cbody\u003E\u003Cdiv class=\u0022panels-ajax-tab-panel panels-ajax-tab-panel-sageoa-tab-art\u0022\u003E\u003Cdiv class=\u0022panel-display panel-1col clearfix\u0022 \u003E\n  \u003Cdiv class=\u0022panel-panel panel-col\u0022\u003E\n    \u003Cdiv\u003E\u003Cdiv class=\u0022panel-pane pane-highwire-markup\u0022 \u003E\n  \n      \n  \n  \u003Cdiv class=\u0022pane-content\u0022\u003E\n    \u003Cdiv class=\u0022highwire-markup\u0022\u003E\u003Cdiv xmlns=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022 id=\u0022content-block-markup\u0022 xmlns:xhtml=\u0022http:\/\/www.w3.org\/1999\/xhtml\u0022\u003E\u003Cdiv class=\u0022article fulltext-view \u0022\u003E\u003Cspan class=\u0022highwire-journal-article-marker-start\u0022\u003E\u003C\/span\u003E\u003Cdiv class=\u0022section abstract\u0022 id=\u0022abstract-1\u0022\u003E\u003Ch2\u003ESummary\u003C\/h2\u003E\n            \u003Cp id=\u0022p-1\u0022\u003EPatients who are at high risk for cardiovascular events face a vicious cycle in which treatment nonadherence increases event rates while events themselves reinforce nonadherence, according to new findings from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial [ONTARGET].\u003C\/p\u003E\n         \u003C\/div\u003E\u003Cul class=\u0022kwd-group\u0022\u003E\u003Cli class=\u0022kwd\u0022\u003EDiabetes Mellitus Clinical Trials\u003C\/li\u003E\u003Cli class=\u0022kwd\u0022\u003ELipid Disorders\u003C\/li\u003E\u003C\/ul\u003E\u003Cp id=\u0022p-2\u0022\u003EPatients who are at high risk for cardiovascular (CV) events face a vicious cycle in which treatment nonadherence increases event rates while events themselves reinforce nonadherence, according to new findings from the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET).\u003C\/p\u003E\u003Cp id=\u0022p-3\u0022\u003EONTARGET included 25,620 patients with coronary heart disease or diabetes plus two additional risk factors for vascular events. In the main study analysis, telmisartan was noninferior to ramipril for the primary composite endpoint of CV death, myocardial infarction (MI), stroke, or heart failure (HF) hospitalization (p=0.0045) and for the secondary endpoint of CV death, MI, or stroke (p=0.001) [Yusuf S et al. \u003Cem\u003EN Engl J Med\u003C\/em\u003E 2008].\u003C\/p\u003E\u003Cp id=\u0022p-4\u0022\u003EThe current ONTARGET analysis focused on risk factors and outcomes that are associated with nonadherence, the latter defined as premature permanent discontinuation of all study medications. Michael B\u00f6hm, MD, University of the Saarland, Saarbr\u00fccken, Germany, presented findings from the study.\u003C\/p\u003E\u003Cp id=\u0022p-5\u0022\u003EThroughout ONTARGET, there was a continuous increase in the proportion of patients who permanently discontinued treatment. After 72 months of follow-up, 4629 patients (18.6%) had discontinued treatment. Increasing age, female gender, black race, physical inactivity, smoking status, diabetes, and depression were significantly associated with non-adherence.\u003C\/p\u003E\u003Cp id=\u0022p-6\u0022\u003EThe strongest factor that was associated with premature permanent drug cessation was the occurrence of a non-fatal event during trial follow-up. Premature discontinuation significantly increased after nonfatal MI (HR, 2.24; 95% CI, 1.95 to 2.57; p\u0026lt;0.0001), stroke (HR, 2.28; 95% CI, 1.98 to 2.63; p\u0026lt;0.0001), and HF hospitalization (HR, 2.85; 95% CI, 2.49 to 3.27; p\u0026lt;0.0001). Other nonfatal events, such as revascularization, angina, end-stage renal disease, malignancy, and new-onset HF, diabetes, and atrial fibrillation also increased the risk of treatment discontinuation (p\u0026lt;0.0001 for each event). The risk of premature permanent cessation also increased with early events and with an increasing number of total events.\u003C\/p\u003E\u003Cp id=\u0022p-7\u0022\u003EOver time, the risk of CV events increased sharply and soon after premature cessation of study medication. Compared with patients who remained on treatment, patients who stopped were 29% more likely to reach the primary endpoint of CV death, MI, stroke, or HF hospitalization (HR, 1.298; 95% CI, 1.181 to 1.427; p\u0026lt;0.0001) and 38% more likely to reach the secondary endpoint of CV death, MI, or stroke (HR, 1.385; 95% CI, 1.255 to 1.528; p\u0026lt;0.0001). Premature permanent cessation was also strongly associated with the individual endpoints of CV death (HR, 2.050; 95% CI, 1.824 to 2.303; p\u0026lt;0.0001) and HF hospitalization (HR, 1.464; 95% 1.228 to 1.745; p\u0026lt;0.0001).\u003C\/p\u003E\u003Cp id=\u0022p-8\u0022\u003EThe authors conclude that the ONTARGET trial revealed a deleterious \u201cnonadherence-event\u201d cycle, in which stopping study medications increased CV events, leading to increased morbidity, less trust in therapy, and further nonadherence. To break this cycle, interventions that promote treatment adherence are needed for patients who are at high risk of nonadherence, and for all patients immediately after a CV event, Prof. B\u00f6hm concluded.\u003C\/p\u003E\u003Cp id=\u0022p-9\u0022\u003E\n         \u003Cem\u003EEditors Note\u003C\/em\u003E: While these observations raise an important hypothesis, it is important to note that the strongest predictors of premature cessation were the occurrences of clinical events during the trial. Patients who experience events (eg non-fatal MI) are at a heightened risk of a recurrent event and therefore it is unclear that treatment cessation led to recurrent events or was just associated with sicker patients. In addition, it is important to recognize that patients may stop therapy prematurely for many reasons in a trial, including related adverse events and acute illnesses for which treatment cessation may be medically indicated (eg, cessation of antihypertensive patients who are in shock). Thus while drug discontinuation may be followed shortly by a clinical event (eg, MI), therefore suggesting a temporal association, establishing a true causal relationship may be difficult. Additional analyses that show consistency in patients with no preceding hospitalization or CV event as well a description of reasons for treatment cessation would strengthen the overall findings.\u003C\/p\u003E\u003Cul class=\u0022copyright-statement\u0022\u003E\u003Cli class=\u0022fn\u0022 id=\u0022copyright-statement-1\u0022\u003E\u00a9 2011 MD Conference Express\u003C\/li\u003E\u003C\/ul\u003E\u003Cspan class=\u0022highwire-journal-article-marker-end\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Cspan id=\u0022related-urls\u0022\u003E\u003C\/span\u003E\u003C\/div\u003E\u003Ca href=\u0022http:\/\/mdc.sagepub.com\/content\/11\/10\/26.abstract\u0022 class=\u0022hw-link hw-link-article-abstract\u0022 data-icon-position=\u0022\u0022 data-hide-link-title=\u00220\u0022\u003EView Summary\u003C\/a\u003E\u003C\/div\u003E  \u003C\/div\u003E\n\n  \n  \u003C\/div\u003E\n\u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n\u003C\/div\u003E\u003Cscript type=\u0022text\/javascript\u0022 src=\u0022http:\/\/mdc.sagepub.com\/sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js?nzmz01\u0022\u003E\u003C\/script\u003E\n\u003C\/body\u003E\u003C\/html\u003E"}