{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T04:24:24Z","timestamp":1781670264774,"version":"3.54.5"},"reference-count":46,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2012,9,26]]},"abstract":"\n Background<\/jats:title>\n \n Bromocriptine\u2010\n QR<\/jats:styled-content>\n (a quick\u2010release formulation of bromocriptine mesylate), a dopamine D2 receptor agonist, is a\n US F<\/jats:styled-content>\n ood and\n D<\/jats:styled-content>\n rug\n A<\/jats:styled-content>\n dministrration\u2013approved treatment for type 2 diabetes mellitus (\n T2DM<\/jats:styled-content>\n ). A 3070\u2010subject randomized trial demonstrated a significant, 40% reduction in relative risk among bromocriptine\u2010\n QR<\/jats:styled-content>\n \u2010treated subjects in a prespecified composite cardiovascular (\n CV<\/jats:styled-content>\n ) end point that included ischemic\u2010related (myocardial infarction and stroke) and nonischemic\u2010related (hospitalization for unstable angina, congestive heart failure [\n CHF<\/jats:styled-content>\n ], or revascularization surgery) end points, but did not include cardiovascular death as a component of this composite. The present investigation was undertaken to more critically evaluate the impact of bromocriptine\u2010\n QR<\/jats:styled-content>\n on cardiovascular outcomes in this study subject population by (1) including\n CV<\/jats:styled-content>\n death in the above\u2010described original composite analysis and then stratifying this new analysis on the basis of multiple demographic subgroups and (2) analyzing the influence of this intervention on only the \u201chard\u201d\n CV<\/jats:styled-content>\n end points of myocardial infarction, stroke, and\n CV<\/jats:styled-content>\n death (major adverse cardiovascular events [\n MACE<\/jats:styled-content>\n s]).\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results<\/jats:title>\n \n Three thousand seventy\n T2DM<\/jats:styled-content>\n subjects on stable doses of \u22642 antidiabetes medications (including insulin) with\n HbA1c<\/jats:styled-content>\n \u226410.0 (average baseline\n HbA1c<\/jats:styled-content>\n =7.0) were randomized 2:1 to bromocriptine\u2010\n QR<\/jats:styled-content>\n (1.6 to 4.8 mg\/day) or placebo for a 52\u2010week treatment period. Subjects with heart failure (\n N<\/jats:styled-content>\n ew\n Y<\/jats:styled-content>\n ork\n H<\/jats:styled-content>\n eart\n C<\/jats:styled-content>\n lasses I and II) and precedent myocardial infarction or revascularization surgery were allowed to participate in the trial. Study outcomes included time to first event for each of the 2\n CV<\/jats:styled-content>\n composite end points described above. The relative risk comparing bromocriptine\u2010\n QR<\/jats:styled-content>\n with the control for the cardiovascular outcomes was estimated as a hazard ratio with 95% confidence interval on the basis of\n C<\/jats:styled-content>\n ox proportional hazards regression. The statistical significance of any between\u2010group difference in the cumulative percentage of\n CV<\/jats:styled-content>\n events over time (derived from a\n K<\/jats:styled-content>\n aplan\u2013\n M<\/jats:styled-content>\n eier curve) was determined by a log\u2010rank test on the intention\u2010to\u2010treat population. Study subjects were in reasonable metabolic control, with an average baseline\n HbA1c<\/jats:styled-content>\n of 7.0\u00b11.1, blood pressure of 128\/76\u00b114\/9, and total and\n LDL<\/jats:styled-content>\n cholesterol of 179\u00b142 and 98\u00b132, respectively, with 88%, 77%, and 69% of subjects being treated with antidiabetic, antihypertensive, and antihyperlipidemic agents, respectively. Ninety\u2010one percent of the expected person\u2010year outcome ascertainment was obtained in this study. Respecting the\n CV<\/jats:styled-content>\n \u2010inclusive composite cardiovascular end point, there were 39 events (1.9%) among 2054 bromocriptine\u2010\n QR<\/jats:styled-content>\n \u2010treated subjects versus 33 events (3.2%) among 1016 placebo subjects, yielding a significant, 39% reduction in relative risk in this end point with bromocriptine\u2010\n QR<\/jats:styled-content>\n exposure (\n P<\/jats:italic>\n =0.0346; log\u2010rank test) that was not influenced by age, sex, race, body mass index, duration of diabetes, or preexisting cardiovascular disease. In addition, regarding the\n MACE<\/jats:styled-content>\n end point, there were 14 events (0.7%) among 2054 bromocriptine\u2010\n QR<\/jats:styled-content>\n \u2010treated subjects and 15 events (1.5%) among 1016 placebo\u2010treated subjects, yielding a significant, 52% reduction in relative risk in this end point with bromocriptine\u2010\n QR<\/jats:styled-content>\n exposure (\n P<\/jats:italic>\n <0.05; log\u2010rank test).\n <\/jats:p>\n <\/jats:sec>\n \n Conclusions<\/jats:title>\n \n These findings reaffirm and extend the original observation of relative risk reduction in cardiovascular adverse events among type 2 diabetes subjects treated with bromocriptine\u2010\n QR<\/jats:styled-content>\n and suggest that further investigation into this impact of bromocriptine\u2010\n QR<\/jats:styled-content>\n is warranted.\n <\/jats:p>\n <\/jats:sec>\n \n Clinical Trial Registration<\/jats:title>\n \n URL:\n http:\/\/clinicaltrials.gov<\/jats:ext-link>\n . Unique Identifier: NCT00377676\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/jaha.112.002279","type":"journal-article","created":{"date-parts":[[2013,5,24]],"date-time":"2013-05-24T16:46:06Z","timestamp":1369413966000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":80,"title":["Effect of Bromocriptine\u2010QR (a Quick\u2010Release Formulation of Bromocriptine Mesylate) on Major Adverse Cardiovascular Events in Type 2 Diabetes Subjects"],"prefix":"10.1161","volume":"1","author":[{"given":"J. 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