Why does losartan (angiotensin II receptor antagonist) cause chest pain in patients with a history of cardiovascular disease, such as coronary artery disease, heart failure, or impaired renal function?

Losartan Does Not Directly Cause Chest Pain—Evaluate for Underlying Cardiovascular Disease

Losartan itself does not cause chest pain as a direct pharmacological effect; rather, chest pain in patients taking losartan typically reflects underlying cardiovascular pathology that requires immediate evaluation. 1

Why Chest Pain Occurs in Patients on Losartan

Hemodynamic Effects in Susceptible Patients

Losartan can precipitate symptomatic hypotension in volume- or salt-depleted patients, which may manifest as chest discomfort, particularly in those with coronary artery disease. 1 This occurs because:

• Patients with activated renin-angiotensin systems (those on high-dose diuretics, volume-depleted states) are at highest risk for symptomatic hypotension after losartan initiation 1
• Hypotension reduces coronary perfusion pressure, potentially triggering angina in patients with obstructive coronary disease 2
• Volume or salt depletion should be corrected prior to losartan administration to prevent this complication 1

Renal Function Deterioration and Cardiac Stress

Losartan can cause acute renal dysfunction in patients whose renal function depends on angiotensin II, leading to volume overload and cardiac decompensation that manifests as chest pain. 1, 3 This mechanism involves:

• Patients with renal artery stenosis, chronic kidney disease, severe heart failure, or volume depletion are at particular risk 1
• Acute renal failure occurs in approximately 10.5% of elderly heart failure patients, identical to ACE inhibitor rates 3
• Renal dysfunction leads to fluid retention, increased cardiac workload, and potential anginal symptoms 3
• Monitor renal function periodically and consider withholding losartan if clinically significant deterioration occurs 1

Unmasking of Underlying Coronary Disease

Chest pain in losartan-treated patients often represents previously undiagnosed coronary artery disease or coronary microvascular dysfunction, not a drug effect. 2 Key considerations include:

• Up to two-thirds of heart failure patients have underlying coronary disease as the etiology 2
• Coronary microvascular dysfunction causes angina even without epicardial stenosis, particularly in patients with left ventricular hypertrophy 2, 4
• One-third of patients with nonischemic cardiomyopathy experience chest pain that may resemble angina 2
• Coronary angiography is recommended in patients over 40 years with persistent chest pain and risk factors for coronary disease 2

Clinical Evaluation Algorithm

Immediate Assessment Steps

1. Assess hemodynamic status: Check blood pressure and volume status to identify symptomatic hypotension 1
2. Obtain 12-lead ECG within 10 minutes: Look for ST-segment changes, T-wave inversions, or evidence of prior myocardial infarction 2
3. Evaluate for acute coronary syndrome: Typical angina presents as substernal pressure lasting ≥10 minutes, radiating to arms/neck/jaw, with diaphoresis 2
4. Check renal function and electrolytes: Assess for acute kidney injury or hyperkalemia that could indicate losartan-related complications 1

Differential Diagnosis Considerations

Evaluate for life-threatening non-losartan causes that require immediate intervention: 2

• Aortic dissection (back pain, pulse differential, blood pressure asymmetry >15 mmHg between arms) 2
• Acute pericarditis (sharp, pleuritic pain improved by sitting forward, friction rub, widespread ST elevation) 2
• Pulmonary embolism (acute dyspnea, pleuritic pain) 2
• Valvular heart disease, particularly aortic stenosis with coronary microvascular dysfunction 2, 4

Risk Stratification for Coronary Disease

Factors increasing probability of coronary disease in losartan-treated patients: 2

• Age ≥75 years, male sex, positive family history of coronary disease 2
• Diabetes mellitus, renal insufficiency, prior myocardial infarction, peripheral arterial disease 2
• Pressure-type chest pain occurring at rest or with minimal exertion 2
• Known heart failure with reduced ejection fraction (two-thirds have underlying coronary disease) 2

Management Approach

When to Continue Losartan

Continue losartan if chest pain is determined to be from stable coronary disease or non-cardiac causes, as the drug provides mortality benefit in heart failure and post-myocardial infarction patients. 2, 5 Specifically:

• Losartan reduces cardiovascular death and heart failure hospitalization by 16-24% when added to standard therapy 2
• Higher doses (150 mg daily) provide superior outcomes compared to 50 mg daily 2
• The drug improves exercise capacity in both asymptomatic and symptomatic heart failure 5

When to Discontinue or Adjust Losartan

Discontinue losartan immediately if: 1

• Clinically significant renal function deterioration occurs (>20% decrease in eGFR) 1, 6
• Symptomatic hypotension persists despite volume repletion 1
• Hyperkalemia develops (potassium >5.5 mmol/L) that cannot be managed with dietary modification or potassium binders 1, 6

Specific Testing Recommendations

Proceed directly to coronary angiography without noninvasive testing in: 2

• Patients with angina and impaired ventricular function (revascularization indicated regardless of ischemia extent) 2
• Patients over 40 years with persistent chest pain and coronary risk factors 2
• Heart failure patients with chest pain, as nuclear imaging and wall motion abnormalities are commonly nonspecific in cardiomyopathy 2

Critical Caveats

Avoid attributing chest pain to losartan without thorough cardiovascular evaluation, as this delays diagnosis of life-threatening conditions. 2 Common pitfalls include:

• Assuming chest pain is a "side effect" rather than investigating underlying coronary disease 2
• Failing to recognize that elderly patients and women present with atypical symptoms more frequently 2
• Missing bilateral renal artery stenosis, where losartan can precipitate acute renal failure and volume overload 3
• Overlooking that psychiatric disorders can mimic acute coronary syndrome but should be a diagnosis of exclusion 2

Monitor for hyperkalemia and worsening renal function, which occur in approximately 50% of heart failure patients on losartan but do not negate the survival benefit of therapy. 6 Both complications are independently associated with adverse outcomes but are potentially preventable with baseline risk factor assessment 6.