Outcomes in patients with cardiometabolic disease who develop hyperkalemia while treated with a renin-angiotensin-aldosterone system inhibitor.

BACKGROUND: Many patients with indications for renin-angiotensin-aldosterone system inhibitor (RAASi) therapy are not receiving these medications. Concern about hyperkalemia is thought to contribute to this lack of evidence-based therapy. METHODS: A retrospective cohort study included adult patients in primary care practices affiliated with an integrated health care delivery system treated with RAASi between 2000 and 2019 for any of the following indications: (a) coronary artery disease (CAD); (b) heart failure (HF) with a left ventricle ejection fraction ≤ 40%; (c) diabetes mellitus (DM) with proteinuria; or (d) chronic kidney disease (CKD) with proteinuria. Relationship between hyperkalemia (K > 5.0 mEg/L) over the first 12 months of follow-up and a composite end point of cardiovascular events, renal dysfunction, and all-cause mortality was evaluated. RESULTS: Among 82,732 study patients, 7,727 (9.34%) developed hyperkalemia. Patients with hyperkalemia were older (69.0 vs 64.6) and more likely to have CAD (57.8 vs 53.7%), CKD (57.3 vs 51.1%), HF (19.3 vs 9.7%), and DM (45.3 vs 33.3%) (P < .001 for all). Five-year cumulative risk of the primary outcome was higher in patients who did (63.9%; 95% CI: 62.8%-65.1%) versus did not (37.2%; 95% CI: 36.8%-37.6%) develop hyperkalemia. Five-year cumulative risk of ED visit or hospitalization for hyperkalemia was 15.6% (14.7%-16.6%) for patients with versus 2.7% (95% CI: 2.6-2.9) for patients without hyperkalemia, rising to 25.9% (95% CI: 22.4-29.9) for patients with severe (K > 6.0 mEq/dL) hyperkalemia. Patients who experienced hyperkalemia were more likely (34.4%) than patients who did not (29.2%) to deintensify RAASi therapy (P < .001). Five-year cumulative risk of the primary outcome was higher in patients who lowered RAASi dose (50.4%; 95% CI: 48.5%-52.4%) or stopped RAASi therapy completely (49.3%; 95% CI: 48.5%-50.1%), compared to patients who continued RAASi therapy (36.1%; 95% CI: 25.7-36.5). Similar findings were observed in multivariable analyses and for individual components of the primary outcome. CONCLUSIONS: Hyperkalemia is a common complication of RAASi therapy and is associated with an increased risk of multiple adverse outcomes. Patients who have their RAASi medications deintensified after a hyperkalemic event have higher incidence of cardiovascular events, renal dysfunction and death.

COVID-19 outcomes in patients taking cardioprotective medications.

INTRODUCTION: The coronavirus disease 2019 (COVID-19) caused a worldwide pandemic and has led to over five million deaths. Many cardiovascular risk factors (e.g. obesity or diabetes) are associated with an increased risk of adverse outcomes in COVID-19. On the other hand, it has been suggested that medications used to treat cardiometabolic conditions may have protective effects for patients with COVID-19. OBJECTIVES: To determine whether patients taking four classes of cardioprotective medications-aspirin, metformin, renin angiotensin aldosterone system inhibitors (RAASi) and statins-have a lower risk of adverse outcomes of COVID-19. METHODS: We conducted a retrospective cohort study of primary care patients at a large integrated healthcare delivery system who had a positive COVID-19 test between March 2020 and March 2021. We compared outcomes of patients who were taking one of the study medications at the time of the COVID-19 test to patients who took a medication from the same class in the past (to minimize bias by indication). The following outcomes were compared: a) hospitalization; b) ICU admission; c) intubation; and d) death. Multivariable analysis was used to adjust for patient demographics and comorbidities. RESULTS: Among 13,585 study patients, 1,970 (14.5%) were hospitalized; 763 (5.6%) were admitted to an ICU; 373 (2.8%) were intubated and 720 (5.3%) died. In bivariate analyses, patients taking metformin, RAASi and statins had lower risk of hospitalization, ICU admission and death. However, in multivariable analysis, only the lower risk of death remained statistically significant. Patients taking aspirin had a significantly higher risk of hospitalization in both bivariate and multivariable analyses. CONCLUSIONS: Cardioprotective medications were not associated with a consistent benefit in COVID-19. As vaccination and effective treatments are not yet universally accessible worldwide, research should continue to determine whether affordable and widely available medications could be utilized to decrease the risks of this disease.

Heart rate, beta-blocker use, and outcomes of heart failure with reduced ejection fraction.

Aims: High resting heart rate (HR ≥70 b.p.m.) is associated with worse clinical outcomes in heart failure with reduced ejection fraction (HFrEF). Heart rate, guideline-directed medical therapy (GDMT) with beta-blocker (BB), and cardiovascular outcomes were evaluated in a large integrated health network. Methods and results: Using electronic health records we examined patients with chronic HFrEF (ejection fraction ≤35%) in sinus rhythm with at least 1 year of follow-up and available serial HR and medication data between 1 January 2000 and 31 December 2014. Among 6071 patients followed for median of 1330 days across 73 586 total visits, median HR remained stable over time with 61.2% of the follow-up period with HR ≥70 b.p.m. At baseline, 27.9% of patients were on ≥ 50% GDMT target BB dose, 16.2% subjects at baseline, and 19.4% at the end of follow-up had HR ≥70 b.p.m. despite receiving ≥50% of target BB dose. In adjusted analyses, baseline HR was associated with all-cause mortality/heart failure (HF) hospitalization (hazard ratio 1.28 per 15 b.p.m. Heart rate increase; P < 0.001). In comparison, hazard ratio for BB dose was 0.97 (per 77.2 mg increase; P = 0.36). When evaluating patients based on HR and BB dose there was a significant difference in the cumulative hazard for all-cause mortality or HF hospitalization (P < 0.001). For HF hospitalization, hazard appeared to be more closely associated with HR rather than BB dose (P = 0.01). Conclusion: In a real-world analysis, high resting HR was common in HFrEF patients and associated with adverse outcomes. Opportunities exist to improve GDMT and achieve HR control.

Design and implementation of an application and associated services to support interdisciplinary medication reconciliation efforts at an integrated healthcare delivery network.

Confusion about patients' medication regimens during the hospital admission and discharge process accounts for many preventable and serious medication errors. Many organizations have begun to redesign their clinical processes to address this patient safety concern. Partners HealthCare, an integrated delivery network in Boston, Massachusetts, has answered this interdisciplinary challenge by leveraging its multiple outpatient electronic medical records (EMR) and inpatient computerized provider order entry (CPOE) systems to facilitate the process of medication reconciliation. This manuscript describes the design of a novel application and the associated services that aggregate medication data from EMR and CPOE systems so that clinicians can efficiently generate an accurate pre-admission medication list. Information collected with the use of this application subsequently supports the writing of admission and discharge orders by physicians, performance of admission assessment by nurses, and reconciliation of inpatient orders by pharmacists. Results from early pilot testing suggest that this new medication reconciliation process is well accepted by clinicians and has significant potential to prevent medication errors during transitions of care.