Add a Thiazide or Thiazide-Like Diuretic
The next medication to add is a thiazide or thiazide-like diuretic, as this patient is on maximal doses of three antihypertensive agents from different classes (beta-blocker, ACE inhibitor, and calcium channel blocker) and requires a fourth agent to achieve blood pressure control.
Rationale for Adding a Diuretic
- This patient is already taking three antihypertensive medications at maximal doses: atenolol 100mg (beta-blocker), lisinopril 40mg (ACE inhibitor), and felodipine 10mg (dihydropyridine calcium channel blocker) 1
- Multiple guidelines confirm that most patients with diabetes and hypertension require two or more drugs at maximal doses to achieve blood pressure targets 2, 1
- The American Heart Association recommends that after ACE inhibitor or ARB initiation, a thiazide or thiazide-like diuretic should be added as one of the first two drugs in diabetic hypertensive patients 1
- The blood pressure target for this patient should be <140/90 mmHg (or <130/80 mmHg if tolerable), and failure to achieve this with three agents necessitates adding a fourth medication 2, 1
Why Thiazide Diuretics Are the Appropriate Choice
- Thiazide diuretics have strong outcome trial evidence showing reduction in cardiovascular events and mortality in diabetic patients with hypertension 2
- The combination of ACE inhibitor plus calcium channel blocker plus diuretic is a well-established triple therapy regimen supported by guidelines 2, 1
- Diuretics are particularly effective in elderly patients (this patient is in their early 60s) and address the volume component of hypertension that is almost always present in diabetic patients 2
Specific Diuretic Recommendations
- Chlorthalidone 12.5-25mg daily or hydrochlorothiazide 12.5-25mg daily are appropriate choices, with chlorthalidone having slightly more robust outcome data 1
- Low-dose thiazide therapy minimizes metabolic side effects (hyperglycemia, hypokalemia, dyslipidemia) while maintaining antihypertensive efficacy 2, 3
- Indapamide is an alternative thiazide-like diuretic that is considered metabolically neutral and may be preferable in diabetic patients 3
Important Monitoring Requirements
- Check serum electrolytes (particularly potassium) and renal function approximately 1-2 weeks after initiating diuretic therapy, with each dose increase, and at least yearly thereafter 2
- Monitor for hyperglycemia, as thiazides can impair glucose tolerance, though this effect is dose-dependent and less pronounced at lower doses 3
- Continue monitoring renal function and potassium given the concurrent use of lisinopril (ACE inhibitor), as the combination of ACE inhibitor plus diuretic increases risk of electrolyte abnormalities 2, 1
Common Pitfalls to Avoid
- Do not use high-dose thiazides (e.g., hydrochlorothiazide >25mg daily), as metabolic side effects increase substantially without proportional blood pressure benefit 2, 3
- Avoid combining the ACE inhibitor (lisinopril) with an ARB, as this combination increases adverse events without additional cardiovascular benefit 2, 4
- Do not discontinue the beta-blocker (atenolol) despite concerns about metabolic effects, as beta-blockers have proven cardiovascular benefit in diabetic patients, particularly in younger/middle-aged individuals and those with prior myocardial infarction 5
Alternative Consideration: Mineralocorticoid Receptor Antagonist
- If blood pressure remains uncontrolled after adding a thiazide diuretic (resistant hypertension), the next step would be adding a mineralocorticoid receptor antagonist such as spironolactone 25mg daily 4
- This represents fourth-line therapy and requires careful monitoring of potassium and renal function given concurrent ACE inhibitor use 4