What single pill combination of medications would you prescribe for a 60-year-old male with stage 2 hypertension and a sedentary lifestyle?

Single-Pill Combination for Stage 2 Hypertension in a 60-Year-Old Male

For a 60-year-old male with stage 2 hypertension and a sedentary lifestyle, prescribe a single-pill combination containing an ACE inhibitor or ARB, a calcium channel blocker (amlodipine), and a thiazide-type diuretic (preferably chlorthalidone). 1

Rationale for Triple Combination Therapy

Stage 2 hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg with BP >20/10 mm Hg above target) requires combination therapy from the outset rather than sequential monotherapy escalation. 1 The ACC/AHA guidelines specifically recommend combination therapy for adults with more severe hypertension (SBP ≥140 mm Hg or DBP ≥90 mm Hg and an average SBP/DBP >20/10 mm Hg above their target BP). 1

Both the ACC/AHA and ESC/ESH guidelines recommend a core drug combination treatment strategy comprising an ACE inhibitor or ARB, a calcium channel blocker, and a thiazide diuretic, preferably in a single-pill combination. 1 This triple combination targets three complementary mechanisms: renin-angiotensin system blockade, vasodilation through calcium channel blockade, and volume reduction through diuresis. 2

Specific Drug Recommendations

First Choice: ARB + Amlodipine + Chlorthalidone

• Valsartan 160 mg + Amlodipine 5-10 mg + Chlorthalidone 12.5-25 mg as a single-pill combination 1, 2
• Chlorthalidone is preferred over hydrochlorothiazide because it was the diuretic used in many landmark event-based randomized clinical trials and has superior 24-hour ambulatory BP reduction. 1, 2

Alternative: ACE Inhibitor + Amlodipine + Chlorthalidone

• Lisinopril 10-20 mg + Amlodipine 5-10 mg + Chlorthalidone 12.5-25 mg 2, 3
• This combination provides equivalent efficacy with complementary mechanisms of action. 2

If Chlorthalidone Unavailable

• Substitute hydrochlorothiazide 25 mg in place of chlorthalidone, though this is less optimal. 2, 3

Race-Specific Considerations

If the patient is Black, the initial combination should prioritize a thiazide-type diuretic and calcium channel blocker, either in combination with each other or with an ACE inhibitor or ARB. 1 The ACC/AHA guideline specifically recommends that initial antihypertensive drug therapy in Black patients should include a thiazide-type diuretic or CCB. 1

Blood Pressure Targets

• Primary target: <130/80 mm Hg if tolerated 1, 2
• Minimum acceptable target: <140/90 mm Hg 1
• For this 60-year-old patient (under 65 years), the ACC/AHA recommends SBP/DBP <130/80 mm Hg as the general treatment target if tolerated. 1

Monitoring Requirements

• Reassess blood pressure within 2-4 weeks after initiating triple therapy 2
• Check serum potassium and creatinine 2-4 weeks after starting therapy to detect potential hypokalemia (from diuretic) or hyperkalemia (from ACE inhibitor/ARB) 2
• Monitor for peripheral edema, which is more common with amlodipine but may be attenuated by the ACE inhibitor or ARB component 2
• Goal: achieve target BP within 3 months of initiating therapy 2

Critical Pitfalls to Avoid

• Never combine an ACE inhibitor with an ARB in the same regimen—this increases adverse events (hyperkalemia, acute kidney injury) without additional cardiovascular benefit. 1, 2
• Do not use beta-blockers as part of initial triple therapy unless there are compelling cardiac indications (prior MI, heart failure with reduced ejection fraction, angina, or atrial fibrillation requiring rate control). 1, 2
• Do not delay treatment intensification—stage 2 hypertension requires prompt triple therapy to reduce cardiovascular risk. 2
• Verify medication adherence before assuming treatment failure, as non-adherence is the most common cause of apparent treatment resistance. 2

Advantages of Single-Pill Combinations

Single-pill combinations significantly improve treatment adherence and persistence compared with separate pills, though they may contain lower-than-optimal doses of the thiazide diuretic component. 1 The ESC/ESH strongly prefers single-pill combinations over separate pills as they improve adherence and efficacy. 1, 2

If Blood Pressure Remains Uncontrolled

If BP remains ≥140/90 mm Hg despite optimized triple therapy, add spironolactone 25-50 mg daily as the preferred fourth-line agent for resistant hypertension. 2 This addresses occult volume expansion that commonly underlies treatment resistance and provides additional BP reductions of 20-25/10-12 mm Hg. 2

Lifestyle Modifications (Additive to Pharmacotherapy)

• Sodium restriction to <2 g/day (provides 5-10 mm Hg systolic reduction) 2, 3
• Weight loss if overweight (10 kg loss associated with 6.0/4.6 mm Hg reduction) 2
• Regular aerobic exercise (minimum 30 minutes most days, provides 4/3 mm Hg reduction) 2
• DASH diet (reduces BP by 11.4/5.5 mm Hg) 2
• Alcohol limitation to <100 g/week 2