{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T04:03:33Z","timestamp":1792728213798,"version":"4.5.0"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"22","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2019,11,19]]},"abstract":"<jats:sec xml:lang=\"en\">\n                    <jats:title>Background<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      Dosing of renin\u2013angiotensin\u2013aldosterone system inhibitors (\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i) may be modified to manage associated hyperkalemia risk; however, this approach could adversely affect cardiorenal outcomes. This study investigated real\u2010world associations of\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i dose, hyperkalemia, and adverse clinical outcomes in a large cohort of\n                      <jats:styled-content style=\"fixed-case\">UK<\/jats:styled-content>\n                      cardiorenal patients.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Methods and Results<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      This observational study included\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i\u2010prescribed patients with new\u2010onset chronic kidney disease (n=100\u00a0572) or heart failure (n=13\u00a0113) first recorded between January 2006 and December 2015 in Clinical Practice Research Datalink and linked Hospital Episode Statistics databases. Odds ratios associating hyperkalemia and\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i dose modification were estimated using logistic generalized estimating equations with normal (&lt;5.0\u00a0mmol\/L) serum potassium level as the reference category. Patients with serum potassium \u22655.0\u00a0mmol\/L had higher risk of\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i down\u2010titration (adjusted odds ratios, chronic kidney disease: 1.79 [95%\n                      <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                      , 1.64\u20131.96]; heart failure: 1.33 [95% CI, 1.08\u20131.62]). Poisson models were used to estimate adjusted incident rate ratios of adverse outcomes based on total\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i exposure (&lt;50% and \u226550% of the guideline\u2010recommended\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i dose). Incidence of major adverse cardiac events and mortality was consistently higher in the lower dose group (adjusted incident rate ratios: chronic kidney disease: 5.60 [95% CI, 5.29\u20135.93] for mortality and 1.60 [95% CI, 1.55\u20131.66] for nonfatal major adverse cardiac events; heart failure: 7.34 [95% CI, 6.35\u20138.48] for mortality and 1.85 [95% CI, 1.71\u20131.99] for major adverse cardiac events).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec xml:lang=\"en\">\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p xml:lang=\"en\">\n                      The results of this real\u2010world analysis highlight the potential negative impact of suboptimal\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i dosing and the need for strategies that allow patients to be maintained on appropriate therapy, avoiding\n                      <jats:styled-content style=\"fixed-case\">RAAS<\/jats:styled-content>\n                      i dose modification or discontinuation.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/jaha.119.012655","type":"journal-article","created":{"date-parts":[[2019,11,12]],"date-time":"2019-11-12T05:00:23Z","timestamp":1573534823000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":86,"title":["Real\u2010World Associations of Renin\u2013Angiotensin\u2013Aldosterone System Inhibitor Dose, Hyperkalemia, and Adverse Clinical Outcomes in a Cohort of Patients With New\u2010Onset Chronic Kidney Disease or Heart Failure in the United Kingdom"],"prefix":"10.1161","volume":"8","author":[{"given":"Cecilia","family":"Linde","sequence":"first","affiliation":[{"name":"Heart and Vascular Theme Karolinska University Hospital and Karolinska Institutet Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ameet","family":"Bakhai","sequence":"additional","affiliation":[{"name":"Department of Cardiology Royal Free Hospital London United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Furuland","sequence":"additional","affiliation":[{"name":"Department of Nephrology Uppsala University Hospital Uppsala Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Evans","sequence":"additional","affiliation":[{"name":"Diabetes Resource Centre Llandough Hospital Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Phil","family":"McEwan","sequence":"additional","affiliation":[{"name":"Health Economics and Outcomes Research Ltd. Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Ayoubkhani","sequence":"additional","affiliation":[{"name":"Health Economics and Outcomes Research Ltd. Cardiff United Kingdom"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Qin","sequence":"additional","affiliation":[{"name":"Global Health Economics AstraZeneca Gaithersburg MD"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.18553\/jmcp.2007.13.s8-b.9"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2017.05.020"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehw128"},{"key":"e_1_3_2_5_2","unstructured":"National Institute for Health and Care Excellence . Chronic heart failure in adults: management [CG108]. August 2010. Available at: https:\/\/www.nice.org.uk\/guidance\/cg108\/. 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