Among patients with chronic kidney disease, SGLT2 inhibitors also decrease the risk of renal disease progres- sion in a manner additive to renin-angiotensin- aldosterone system inhibitors (145). As already indicated, the recent DAPA-HF and EMPEROR-Reduced trials demonstrated that SGLT2 in- hibitor therapy reduced the risk of the composite of CV death or worsening HF in patients with HFrEF, regardless of whether they had T2D (12,44). Dapagli ozin is now approved for this indication, and the role of empagli ozin is under review by the Food and Drug Administration. SGLT2 inhibitors must now be included among the established, evidence-based therapies available to clini- cians managing patients with HFrEF. Dapagli ozin has also demonstrated ef cacy among patients with chronic kidney disease in reducing the composite of disease pro- gression, end-stage kidney disease, or death from renal or CV causes. This effect was independent of the presence of diabetes (157). In a similar manner, empagli ozin slowed the decline of kidney function among patients treated in the EMPEROR-Reduced study (13). Table 15 classi es comorbidities into CV and non-CV processes and provides guidance on appropriate management options. Finally, the recent COVID-19 pandemic has illustrated an association between underlying CV disease, including HF, and worse clinical outcomes (171). It is now known that in patients with HFrEF, renin-angiotensin- aldosterone system inhibition is not associated with risk of infection or severity of disease and should be continued, even in the setting of COVID-19 infection, as long as hemodynamically tolerated (172 176). As ap- proaches to management continue to evolve, readers are encouraged to follow the scienti c literature for updated evidence and recommendations for optimal management of these patients. 5.10. 