What was the standard management of acute coronary syndrome in a typical middle‑aged or older adult with traditional cardiovascular risk factors (hypertension, smoking, diabetes, family history of premature coronary disease) before statins were available?

Pre-Statin Era Management of Acute Coronary Syndrome

Before statins became standard therapy, the management of acute coronary syndrome centered on aspirin (75-150 mg daily), beta-blockers, nitrates for symptom control, heparin anticoagulation, and aggressive risk factor modification including mandatory smoking cessation and blood pressure optimization. 1

Core Pharmacological Interventions

Antiplatelet Therapy

• Aspirin 75-150 mg daily was mandatory for all ACS patients, with meta-analyses demonstrating 36 fewer vascular events per 1000 patients and 14 fewer deaths per 1000 patients over 27 months of treatment. 1
• Higher aspirin doses provided no additional benefit according to anti-platelet trialists meta-analysis. 1

Beta-Blocker Therapy

• Beta-blockers were essential after myocardial infarction and continued after all acute coronary syndromes to improve prognosis and reduce mortality. 1
• Short-acting beta-selective blockers without intrinsic sympathomimetic activity were preferred, often given intravenously initially. 1
• Beta-blockers were contraindicated or delayed in hemodynamically unstable patients with heart failure or shock. 1

Anticoagulation Strategy

• Heparin (unfractionated or low-molecular-weight) was administered acutely, though trials showed increased clinical events after heparin withdrawal. 1
• Continuation of low-molecular-weight heparin was considered in high-risk patients with recurrent ischemia who could not undergo revascularization. 1
• Sustained thrombin generation was observed for up to 6 months following unstable angina or myocardial infarction, justifying prolonged anticoagulation in selected cases. 1

Anti-Ischemic Medications

• Nitrates were used for symptom control and blood pressure management in the acute setting. 1
• Intravenous nitroglycerin was the first-line agent for acute severe hypertension with pulmonary edema. 1
• Calcium channel blockers (verapamil or diltiazem) could substitute for beta-blockers if contraindications existed, but not in patients with left ventricular dysfunction. 1

ACE Inhibitor Therapy

ACE inhibitors emerged as important secondary prevention agents in the pre-statin era, particularly after landmark trials demonstrated benefits beyond blood pressure control. 1

• The SAVE and SOLVD trials showed reduced cardiac events in patients with left ventricular impairment treated with ACE inhibitors, with MI rate reductions becoming apparent after 6 months. 1
• The HOPE trial demonstrated cardiovascular death reduction from 8.1% to 6.1% (relative risk 0.74) and MI reduction (relative risk 0.80) over 4-6 years. 1
• ACE inhibitors were indicated for patients with anterior MI, persistent hypertension, left ventricular dysfunction, heart failure, or diabetes mellitus. 1

Risk Factor Modification

Smoking Cessation

• Mandatory smoking cessation was emphasized as a major modifiable risk factor, with referral to smoking cessation clinics recommended and nicotine replacement therapy considered. 1

Blood Pressure Control

• Blood pressure optimization was essential, with target diastolic BP <90 mm Hg (<85 mm Hg in diabetic patients). 2
• Thiazide diuretics could be added for BP control and heart failure management. 1

Lipid Management Before Statins

• Lipid-lowering therapy was recommended but options were limited before widespread statin availability. 1
• Dietary modification was the primary intervention for cholesterol management. 1

Revascularization Considerations

• Early invasive strategy with angiography was considered for high-risk patients with recurrent ischemia, hemodynamic instability, or major arrhythmias. 2
• Percutaneous coronary intervention or coronary artery bypass grafting was performed based on angiographic findings. 1
• Approximately one-fifth of ACS patients were treated conservatively without percutaneous intervention even in later eras. 3

Critical Limitations of Pre-Statin Management

The absence of statin therapy represented a major gap in secondary prevention, as subsequent evidence demonstrated that statins substantially decrease mortality and coronary events. 1 The beneficial effects of statins on plaque stabilization, endothelial function, and prothrombotic factors were not available to patients in the pre-statin era. 1