Long-acting thiazide-type diuretic for resistant hypertension

Question

A 61-year-old man with type 2 diabetes is evaluated for resistant hypertension. He was diagnosed with hypertension 15 years ago. His BP has been poorly controlled despite adherence to his medication regimen and a sodium-restricted diet. His family history is significant for hypertension in several relatives, most of whom were diagnosed between the ages of 40 and 50 years. Recent home BP readings are 150/80–160/90 mm Hg. Medications include ramipril, amlodipine, and labetalol. Physical examination reveals BP 154–158/86–92 mm Hg in both arms, with a heart rate of 62/min. The heart and lung examinations are normal, and there is no edema. Laboratory data: Serum: sodium 139 mEq/L (reference 136–145); potassium 4.7 mEq/L (3.5–5.0); chloride 104 mEq/L (98–106); total CO₂ 23 mEq/L (23–28); BUN 17 mg/dL (8–20); creatinine 1.3 mg/dL (0.7–1.3). Urine: albumin-to-creatinine ratio 182 mg/g (<30 mg/g). Which ONE of the following is the MOST APPROPRIATE addition to this patient's antihypertensive regimen?

Accepted Answer

A. Chlorthalidone — Prescribing chlorthalidone is the most appropriate next step in management for this patient with uncontrolled hypertension.

On average, 3–4 medications are required to control BP in patients with hypertension and diabetes. Most patients with resistant hypertension have improved BP when diuretics are added to the regimen, even when edema is absent. Although either thiazide-type or loop diuretics can be used to control volume expansion and achieve BP target, thiazides are preferred when eGFR is >30 mL/min/1.73 m². Recent data suggests that thiazides may improve BP even in stage 4 CKD. Long-acting thiazide diuretics such as chlorthalidone or indapamide may be more effective than shorter-acting agents such as hydrochlorothiazide. Low-dose chlorthalidone is often favored over hydrochlorothiazide for treating hypertension, as chlorthalidone reduced cardiovascular events in the Antihypertensive and Lipid-Lowering treatment to prevent Heart Attack Trial (ALLHAT).

Loop diuretics are generally less effective than thiazide diuretics in treating hypertension in patients with relatively preserved kidney function. The shorter half-life of loop diuretics relative to thiazides may in part account for this observation. Activation of the renin-angiotensin-aldosterone system results in sodium retention once the loop diuretic effect diminishes. Chronic use of thiazide diuretics also results in decreased peripheral vascular resistance. Use of loop diuretics, either alone or in combination with thiazides, may be advantageous in patients with eGFR <30 mL/min/1.73 m². Twice-daily administration of furosemide or use of a longer acting loop diuretic, such as torsemide, may enhance BP control, but long-term outcome studies are lacking.

Non-dihydropyridine calcium channel blockers such as diltiazem and verapamil may decrease proteinuria but are less effective antihypertensive agents than dihydropyridines. Diltiazem and verapamil also cause bradycardia and are not recommended for use in combination with β-blockers.

Losartan, added to a maximal dose of lisinopril, would not be expected to provide additional BP reduction and could worsen hyperkalemia. In addition, although the combination of an ACEI and an ARB may reduce albuminuria, such “dual blockade” regimens have been associated with adverse clinical outcomes, such as increased rates of AKI, in clinical trials such as ONTARGET (The Ongoing Telmisartan Alone and in Combination with Ramipril Global Endpoint Trail) and TRANSCEND (The Telmisartan Randomized Assessment Study in ACE-intolerant Subjects with Cardiovascular Disease). Routine use of this strategy is not recommended because of the increased risk for complications and the lack of evidence demonstrating improved outcomes such as decreased progression to ESRD or improved survival.

Long-acting thiazide-type diuretic for resistant hypertension

Explanation

Why each option

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