PracticeUpdate: Diabetes

EDITOR’S PICKS 8

Add-On Antihypertensive Medications to Angiotensin– Aldosterone System Blockers in Diabetes Clinical journal of the American Society of Nephrology: CJASN Take-home message • This observational, multicenter, cohort study examined outcomes in 21,897 peoplewith diabetes in the Surveillance, Prevention, and Effectiveness of Management of Diabetes cohort treated with ACE inhibitors or ARBs who added a variety of antihypertensive medications. These add-on medications include dihydropyridine calcium channel blockers, β-blockers, thiazide diuretics, and loop diuretics. Almost half (45%) of the participants began the study taking thiazide diuretics. β-blockers, calcium channel blockers, and loop diuretics were taken by 34%, 12%, and 10% of patients, respectively. Those taking thiazide diuretics had a greater risk of a significant kidney event compared with those taking calcium channel blockers or β-blockers. However, the risk of a sig- nificant kidney event was greater for those taking loop diuretics than for those taking thiazide diuretics. There was a higher risk of death in the loop diuretic group than in the thiazide diuretic group. The β-blocker and loop diuretic groups had a greater risk of cardiovascular events compared with the thiazide diuretic group. • This study suggests that there may be a benefit in using calcium channel blockers in patients with diabetes taking angiotensin-converting enzyme inhibitors or angi- otensin II receptor blockers. Calcium channel blockers may be associated with lower risk of cardiovascular events and of significant kidney events compared with thiazide diuretics in these patients. Abstract

BACKGROUND AND OBJECTIVES In individuals with diabetes, the comparative effectiveness of add-on antihypertensive medications added to an angiotensin-converting enzyme inhibitor or angiotensin II receptor blocker on the risk of sig- nificant kidney events is unknown. COMMENT By Jan N. Basile MD P atients with hypertension and dia- betes often require 2 or more antihypertensive medications to con- trol their BP. In a comparative effectiveness study from 4 large integrated health care systems, almost 22,000 individuals with diabetes were followed for up to 5 years to determine which antihypertensive class of agent was associated with best renal and cardiovascular (CV) outcomes on an initial background of ACE inhibitor or ARB monotherapy. With a BP > 130/80 mm Hg, the observers used propensity matched scoring to compare the addition of dihy- dropyridine calcium channel blockers (DCCBs), β-blockers, and loop diuretics to the largest group, thiazide diuretics.

enzyme inhibitors or angiotensin II receptor blockers. We examined the hazard of signifi- cant kidney events, cardiovascular events, and death using Cox proportional hazard models with propensity score weighting. The composite significant kidney event end point was defined

DESIGN, SETTING PARTICIPANTS, & MEASUREMENTS We used an observational, multicenter cohort of 21,897 individuals with diabetes to compare individuals who added β-blockers, dihydropyri- dine calcium channel blockers, loop diuretics, or thiazide diuretics to angiotensin-converting

DCCBs were associated with a lower risk of renal events, a similar risk of CV events, and a trend toward a lower risk of death than thiazide diuretics. While β-block- ers were associated with a lower risk of renal events, they increased the risk of CV events compared to thiazide diuret- ics. Loop diuretics were associated with a greater risk of renal events than thiazide diuretics. All other events were not com- paratively different. In this observational study with a strong potential for residual confounding and bias, DCCBs and thiazide diuretics are associ- ated with improved outcomes when added to an initial RAS-blocking agent. These find- ings remain in agreement with the recently

published 2017 ACC/AHA Clinical Practice Guideline on Hypertension and with the 2018 ADA Standards of Medical Care in diabetes which promote calcium channel blocking agents, thiazide diuretics, and ACE inhibitors or ARBs (but not both) as the first three classes of antihypertensive agents recommended in individuals with diabetes and hypertension unless a com- pelling situation dictates otherwise. Dr. Basile is with the Seinsheimer Cardiovascular Health Program at Medical University of South Carolina and the Ralph H Johnson VA Medical Center, both in Charleston, South Carolina. He is also President-Elect of the American Society of Hypertension 2018–2020.

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