Multidrug antihypertensive therapy

A 59-year-old black man is evaluated during a routine follow-up office visit. He has occasional headaches but has otherwise been well. He had an anterior myocardial infarction 18 months ago and has hypertension, compensated congestive heart failure, type 2 diabetes mellitus, dyslipidemia, and mild chronic renal insufficiency. He is compliant with therapy, which includes metoprolol, lisinopril, amlodipine, metformin, atorvastatin, and aspirin.

On physical examination, heart rate is 62/min and blood pressure is 142/88 mm Hg. BMI is 24. Jugular venous pressure is 6 cm H2O. Cardiac examination reveals a regular rhythm; normal S1 and S2; and no S3, S4, or murmurs. The lungs are clear. There is no edema.

Laboratory studies: serum creatinine, 1.3 mg/dL; LDL cholesterol, 68 mg/dL; and spot urine albumin–creatinine ratio, 45 mg/g.

Which of the following is the most appropriate next step in this patient's management?
A Add clonidine
B Add hydrochlorothiazide
C Discontinue metoprolol; add hydralazine and isosorbide mononitrate
D Measure 24-hour urine catecholamines
E Reevaluate blood pressure in 2 to 3 months

Answer and Critique (Correct Answer = B)

Key Points

* Multidrug antihypertensive therapy is often needed to achieve optimal blood pressure control in patients with diabetes mellitus.
* An ineffective multidrug antihypertensive regimen should be considered a failure only if it includes a diuretic.

The addition of hydrochlorothiazide to this patient's medication regimen is the most appropriate next step. Patients with concomitant diabetes mellitus and hypertension typically require multidrug therapy to achieve target blood pressure goal (<130/80 mm Hg in this patient). Because this patient also has mild chronic kidney disease (calculated creatinine clearance, 69 mL/min) with microalbuminuria, ischemic heart disease, and congestive heart failure, blood pressure control is imperative. Adding a diuretic to a multidrug antihypertensive regimen may help to achieve a patient's blood pressure goal, and a regimen is not considered ineffective until a diuretic has been included.

Hydrochlorothiazide is administered once daily and is inexpensive and effective. Black patients usually respond less predictably well to angiotensin-converting enzyme (ACE) inhibitors, but the addition of a diuretic can help to equalize the effectiveness of these agents to that of white patients. Multiple trials have shown that β-blockers and ACE inhibitors are indicated in this setting. These agents prevent the progression of diabetic nephropathy, improve survival in heart failure, and provide secondary prevention of the acute coronary syndrome. Routine questioning of the patient about compliance is indicated, because compliance with therapy is a significant problem in hypertension management.

Clonidine has more side effects than similar agents and is not vasculo- or renoprotective; therefore, it is not indicated until all first-line agents have been tried. Hydralazine combined with nitrates is used as an alternative to ACE inhibitors or angiotensin-receptor blockers in patients intolerant to both, and can be added to standard heart failure therapy in black patients with heart failure. Hydralazine and nitrates have not been shown to have the same cardioprotective properties as ACE inhibitors. Patients with diabetes typically require three to four antihypertensive drugs, and this patient's medication regimen should not raise suspicion for a secondary cause of hypertension, such as pheochromocytoma. Moreover, this patient has no additional signs or symptoms suggestive of pheochromocytoma. Measurement of 24-hour urine catecholamines is therefore not indicated. Reevaluation in 2 to 3 months is not appropriate because blood pressure control in this setting is imperative to prevent morbidity and mortality.