1.8.5.0 Cardiovascular Disease and Blood Pressure
Hypertension is a strong risk factor for the development and progression of CKD (56). Antihypertensive therapy reduces the risk of albuminuria (57-60), and among patients with type 1 or 2 diabetes with established CKD (eGFR <60 mL/min/1.73 m2 and UACR ≥300 mg/g Cr), ACE inhibitor or ARB therapy reduces the risk of progression to ESRD (61-63). Moreover, antihypertensive therapy reduces risks of cardiovascular events (57).
Blood pressure levels <140/90 mmHg are generally recommended to reduce CVD mortality and slow CKD progression among people with diabetes (60). Lower blood pressure targets (e.g., <130/80 mmHg) may be considered for patients based on individual anticipated benefits and risks. Patients with CKD are at increased risk of CKD progression (particularly those with albuminuria) and CVD and therefore may be suitable in some cases for lower blood pressure targets.
ACE inhibitors or ARBs are the preferred first-line agent for blood pressure treatment among patients with diabetes, hypertension, eGFR <60 mL/min/1.73 m2, and UACR ≥300 mg/g Cr because of their proven benefits for prevention of CKD progression (61-64). In general, ACE inhibitors and ARBs are considered to have similar benefits (65,66) and risks. In the setting of lower levels of albumin-uria (30–299 mg/g Cr), ACE inhibitor or ARB therapy has been demonstrated to reduce progression to more advanced albuminuria (≥300 mg/g Cr) and cardiovascular events but not progression to ESRD (64,67). While ACE inhibitors or ARBs are often prescribed for albumin-uria without hypertension, clinical trials have not been performed in this setting to determine whether this improves renal outcomes.
Absent kidney disease, ACE inhibitors or ARBs are useful to control blood pressure but may not be superior to alternative proven classes of antihypertensive therapy, including thiazide-like diuretics and dihydropyridine calcium channel blockers (68). In a trial of people with type 2 diabetes and normal urine albumin excretion, an ARB reduced or suppressed the development of albuminuria but increased the rate of cardiovascular events (69). In a trial of people with type 1 diabetes exhibiting neither albuminuria nor hypertension, ACE inhibitors or ARBs did not prevent the development of diabetic glomerulopathy assessed by kidney biopsy (70). Therefore, ACE inhibitors or ARBs are not recommended for patients without hypertension to prevent the development of CKD.
Two clinical trials studied the combinations of ACE inhibitors and ARBs and found no benefits on CVD or CKD, and the drug combination had higher adverse event rates (hyperkalemia and/or AKI) (71,72). Therefore, the combined use of ACE inhibitors and ARBs should be avoided.
Mineralocorticoid receptor antagonists (spironolactone, eplerenone, and finerenone) in combination with ACE inhibitors or ARBs remain an area of great interest. Mineralocorticoid receptor antagonists are effective for management of resistant hypertension, have been shown to reduce albuminuria in short-term studies of CKD, and may have additional cardiovascular benefits (73-75). There has been, however, an increase in hyperkalemic episodes in those on dual therapy, and larger, longer trials with clinical outcomes are needed before recommending such therapy.