What are the differences in side effect profiles between perindopril (Angiotensin-Converting Enzyme (ACE) inhibitor) and ramipril (ACE inhibitor)?

Side Effect Profiles: Perindopril vs Ramipril

Both perindopril and ramipril share the same core ACE inhibitor adverse effect profile, with cough, hypotension, hyperkalemia, and angioedema being the primary concerns for both agents, though perindopril may have a slightly lower incidence of cough and first-dose hypotension compared to ramipril. 1, 2

Common Adverse Effects Shared by Both Agents

Both ACE inhibitors produce similar adverse effects due to their shared mechanism of ACE inhibition and kininase inhibition:

Cough

• Ramipril: Cough occurs in approximately 12% of patients, with about 4% requiring discontinuation 1
• Perindopril: Cough is the most common side effect but affects less than 2% of patients severely enough to require discontinuation 2
• This represents a potentially clinically meaningful difference, with perindopril appearing to cause less problematic cough 2

Hypotension

• Ramipril: Symptomatic hypotension reported in 0.5% of patients in U.S. trials, with syncope and palpitations occurring rarely 1
• Perindopril: First-dose hypotension appears to occur less frequently than with other ACE inhibitors in this class 2
• Both agents require caution in patients with systolic blood pressure <80 mmHg 3

Angioedema

• Ramipril: Angioedema reported in 0.3% of patients in U.S. clinical trials 1
• Perindopril: Angioedema occurs at rates similar to other ACE inhibitors, though perindopril-treated patients who previously experienced ACE inhibitor-induced angioedema should still exercise caution 2
• Both agents are absolutely contraindicated in patients with prior ACE inhibitor-associated angioedema 3

Renal and Electrolyte Effects

Hyperkalemia and Renal Function

• Ramipril: Can cause increases in blood urea nitrogen and serum creatinine, particularly when combined with diuretics; requires monitoring within 1-2 weeks of initiation 1, 3
• Perindopril: Hyperkalemia appears to occur less frequently than with other ACE inhibitors, and the drug reduces proteinuria in patients with renal disease 2
• Both agents should be used with extreme caution when serum potassium >5.0 mEq/L or serum creatinine >3 mg/dL 3

Gastrointestinal Effects

• Ramipril: Rare cases of hepatic failure, hepatitis, jaundice, pancreatitis, abdominal pain, anorexia, constipation, diarrhea, dry mouth, dyspepsia, dysphagia, and taste disturbance 1
• Perindopril: Generally well tolerated with an adverse effect profile similar to other ACE inhibitors 4

Hematologic Effects

• Ramipril: Rare occurrences of pancytopenia, hemolytic anemia, and thrombocytopenia; decreases in hemoglobin or hematocrit occur in 0.4% receiving ramipril alone and 1.5% when combined with a diuretic 1
• Perindopril: No specific hematologic adverse effects highlighted in available data, suggesting similar low incidence to the class 4, 2

Metabolic Effects

• Perindopril: Has no negative effects on lipids in patients with hyperlipidemia or on glycemic control in patients with type 2 diabetes mellitus 2
• Ramipril: No specific metabolic advantages documented in the evidence provided

Drug Interactions

• Perindopril: Has no known clinically significant drug-drug interactions 2
• Ramipril: Standard ACE inhibitor interactions apply, particularly with potassium supplements, potassium-sparing diuretics, and NSAIDs 1

Discontinuation Rates

• Ramipril: Approximately 3% of U.S. patients discontinued therapy due to side effects, most commonly cough (1.0%), dizziness (0.5%), and impotence (0.4%) 1
• Perindopril: Less than 2% discontinue due to cough, suggesting potentially better overall tolerability 2

Special Populations

Elderly Patients

• Perindopril: Documented safety and tolerability in elderly patients 2
• Ramipril: Standard monitoring applies; no specific elderly safety data highlighted 1

Heart Failure Patients

• Ramipril: In the AIRE study, adverse reactions in heart failure post-MI patients showed headache (2.2%), dizziness (3.5%), and fatigue (2.0%) as most common 1
• Perindopril: Favorable safety profile extends to patients with heart failure 2

Critical Monitoring Requirements for Both Agents

Both drugs require identical monitoring protocols:

• Check renal function and serum potassium within 1-2 weeks of initiation and after each dose adjustment 3
• Accept up to 30% increase in serum creatinine within 4 weeks of initiation 3
• Discontinue if creatinine rises >30% from baseline or refractory hyperkalemia develops 3