Can a Patient Stop Ramipril and Switch to Amlodipine?
No, a patient should not simply stop ramipril and switch to amlodipine monotherapy, as this represents a step backward in hypertension management. The evidence strongly supports adding amlodipine to ramipril rather than substituting one for the other, creating a guideline-recommended combination therapy that provides superior blood pressure control and cardiovascular protection 1, 2, 3.
Why Combination Therapy is Superior to Switching
The optimal approach is to combine ramipril with amlodipine rather than switching between them. This strategy is supported by multiple lines of evidence:
ACE inhibitors like ramipril provide proven cardiovascular mortality and morbidity benefits that extend beyond blood pressure lowering, particularly in patients with coronary artery disease, heart failure, diabetes, or chronic kidney disease 1.
The 2017 ACC/AHA guidelines explicitly recommend combination therapy with an ACE inhibitor plus a calcium channel blocker as a preferred two-drug regimen for most patients requiring more than one antihypertensive agent 1.
Fixed-dose combinations of ramipril/amlodipine demonstrate superior adherence compared to either agent alone, with one-year persistence rates of 54% for the combination versus 30% for ramipril monotherapy 4, 5.
Clinical Decision Algorithm
Step 1: Assess Why the Switch is Being Considered
If ramipril is causing intolerable side effects:
For ACE inhibitor-induced cough that disrupts sleep, substitution with an ARB (not amlodipine) is the recommended alternative 1. The cough does not always require discontinuation unless it significantly impacts quality of life 1.
For hyperkalemia (K+ >5.5 mmol/L) or excessive creatinine rise (>100% increase or >310 μmol/L), the ACE inhibitor should be stopped and specialist advice sought 1. In this scenario, amlodipine monotherapy may be temporarily necessary while addressing the underlying issue.
For angioedema, ramipril must be discontinued immediately and amlodipine can be used, though ARBs should be avoided for at least 6 weeks 1.
If blood pressure is inadequately controlled on ramipril alone:
Add amlodipine to ramipril rather than switching 1, 2, 3. Start amlodipine at 5 mg once daily and titrate to 10 mg if needed after 2-6 weeks 2.
The combination of ACE inhibitor plus calcium channel blocker provides complementary mechanisms: ramipril blocks the renin-angiotensin system while amlodipine provides vasodilation through calcium channel blockade 3, 6.
Step 2: Understand the Evidence for Combination Therapy
Multiple high-quality trials demonstrate the superiority of ACE inhibitor/calcium channel blocker combinations:
The ATAR study showed significantly greater blood pressure reductions with ramipril/amlodipine combination versus amlodipine monotherapy: ambulatory SBP decreased by -20.76 mm Hg versus -15.80 mm Hg (p=0.004) and DBP by -11.71 mm Hg versus -8.61 mm Hg (p=0.004) 7.
The RAMONA trial demonstrated that 69.8% of hypertensive diabetic patients achieved target blood pressure (<140/85 mm Hg) with ramipril/amlodipine fixed-dose combinations 8.
In patients with chronic kidney disease, ACE inhibitors provide cardiovascular mortality benefits that calcium channel blockers alone do not replicate. The SAVE trial showed a 31% reduction in cardiovascular morbidity and mortality (RR 0.69,95% CI 0.55-0.86) with captopril in CKD patients 1.
Step 3: Consider Special Populations
For patients with heart failure with reduced ejection fraction (HFrEF):
ACE inhibitors are first-line, life-saving therapy and should not be discontinued 1. Amlodipine or felodipine are the only calcium channel blockers safe to add if needed for blood pressure control 1.
Diltiazem and verapamil are contraindicated in HFrEF due to negative inotropic effects 1.
For patients with diabetes or metabolic syndrome:
- The combination of ramipril/amlodipine is particularly beneficial, as it improved lipid profiles and glycemic control in the RAMONA trial: fasting glucose decreased from 7.20 to 6.70 mmol/L (p<0.001) and HbA1c from 7.90% to 7.60% (p<0.001) 8.
For patients with chronic kidney disease:
- ACE inhibitors provide renoprotection and cardiovascular benefits that are especially important in this population 1. The PROGRESS trial showed a 30% reduction in cardiovascular events (RR 0.70,95% CI 0.58-0.86) in CKD patients with cerebrovascular disease 1.
Common Pitfalls to Avoid
Do not discontinue ramipril without a compelling reason, as clinical deterioration is likely if ACE inhibitor treatment is withdrawn in patients with cardiovascular disease or heart failure 1.
Do not assume amlodipine alone provides equivalent cardiovascular protection to an ACE inhibitor. While the ALLHAT trial showed similar cardiovascular outcomes between amlodipine and lisinopril in some populations, ACE inhibitors have broader indications and proven benefits in heart failure, post-MI, and diabetic nephropathy 1.
Verify medication adherence before making any changes, as non-adherence is a common cause of apparent treatment failure 2, 3. Chemical adherence testing or pill counts may be helpful 1.
Monitor for peripheral edema with amlodipine, which occurs in a dose-dependent manner and is more common in women 1. The combination of ramipril with amlodipine actually reduces edema prevalence (7.6% versus 18.7% with amlodipine monotherapy, p=0.011) 7.
Practical Implementation
If adding amlodipine to ramipril:
- Start with amlodipine 5 mg once daily, which can be taken at any convenient time to improve adherence 2.
- Titrate to 10 mg once daily after 2-6 weeks if blood pressure remains above target (≥130/80 mm Hg) 2.
- Consider a fixed-dose combination product to improve adherence, as persistence rates are 58.8% higher with fixed versus free combinations 5.
If ramipril must be discontinued due to side effects: