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.