Combination of Losartan and Amlodipine
Yes, losartan and amlodipine can and should be combined for patients with hypertension and diabetic nephropathy when monotherapy fails to achieve blood pressure targets of <130/80 mmHg. This combination is particularly effective and well-supported by clinical evidence.
Evidence for Combination Therapy
The combination of amlodipine added to losartan monotherapy is highly effective in achieving blood pressure goals in diabetic patients with hypertension. In the ADHT trial, adding amlodipine to losartan (or quinapril) resulted in 27.5% of patients reaching BP goals (<130/80 mmHg) compared to only 12.5% with placebo addition, representing a significant improvement (OR 2.73; p < 0.001) 1. The combination reduced BP by 8.1/5.4 mmHg compared to 1.6/0.7 mmHg with placebo 1.
Rationale for This Combination
Complementary Mechanisms
- Losartan provides renoprotection by blocking angiotensin II at the AT1 receptor, reducing intraglomerular pressure and proteinuria independent of blood pressure lowering 2
- Amlodipine adds effective BP control through calcium channel blockade, which is particularly useful as part of combination therapy in diabetic patients 3
- The combination addresses both the renin-angiotensin system and vascular resistance through different pathways 1
Specific Benefits in Diabetic Nephropathy
- Losartan reduces progression to end-stage renal disease by 28% in type 2 diabetic patients with nephropathy (P=0.002) 4
- Losartan decreases proteinuria by 35% (P<0.001) 4
- Calcium channel blockers like amlodipine were shown to reduce cardiovascular events in diabetics compared to placebo in multiple trials 3
- In the diabetic cohort of ALLHAT, amlodipine was as effective as chlorthalidone in all categories except heart failure 3
Practical Implementation
Starting Approach
- Initiate losartan first at 25-50 mg daily, titrating to goal dose of 50-100 mg daily 5
- Add amlodipine 5 mg daily if BP goal not achieved after 4-8 weeks, titrating to 10 mg if needed 1
- Target BP should be <130/80 mmHg for diabetic patients 3
Monitoring Protocol
- Check serum creatinine and potassium within 2-4 weeks after initiating losartan or increasing dose 6, 5
- Accept a modest creatinine rise of 10-20% as hemodynamic and expected, not indicative of kidney injury unless persistent 6, 5
- Monitor potassium levels, especially in patients with eGFR <45 mL/min/1.73 m² 6
Critical Caveats
What NOT to Do
- Never combine losartan with ACE inhibitors or direct renin inhibitors (Grade 1B recommendation) as this increases adverse effects (hyperkalemia, acute kidney injury) without additional cardiovascular or renal benefit 3, 6, 2
- Avoid combining losartan with potassium-sparing diuretics like spironolactone due to compounded hyperkalemia risk 6
When to Hold Losartan Temporarily
- During interval illness 6
- Prior to IV radiocontrast administration 6
- Before bowel preparation for colonoscopy 6
- Prior to major surgery 6
Specific Thresholds for Action
- Halve losartan dose if creatinine rises to >220 μmol/L (2.5 mg/dL) 6
- Stop losartan immediately if creatinine rises to >310 μmol/L (3.5 mg/dL) 6
- Halve dose if potassium rises to >5.5 mmol/L 6
- Stop immediately if potassium rises to ≥6.0 mmol/L 6
Tolerability Profile
Both agents are generally well tolerated when combined. Amlodipine, quinapril, and losartan were well tolerated in the ADHT trial 1. Losartan has a significantly lower incidence of cough compared to ACE inhibitors (P=0.006) 7, making it preferable for patients who cannot tolerate ACE inhibitors.
Long-term Outcomes
The combination provides both cardiovascular and renal protection. Losartan reduces cardiovascular morbidity and mortality by 24% in high-risk populations 2, reduces first hospitalization for heart failure by 32% (P=0.005) 4, and provides renoprotection that exceeds blood pressure reduction alone 3, 4. The addition of amlodipine ensures adequate BP control to maximize these benefits 1.