Recommended Antihypertensive Classes for High-Risk CAD with Asymptomatic Atherosclerosis
For patients with high-risk coronary artery disease and asymptomatic atherosclerosis, ACE inhibitors (or ARBs) and beta-blockers are the two first-line antihypertensive drug classes recommended. 1
Primary Recommendation Framework
The 2025 ACC/AHA guidelines explicitly designate ACE inhibitors, ARBs, or beta-blockers as first-line therapy for compelling indications in chronic coronary disease (CCD) patients with hypertension, particularly those with recent MI or angina. 1 This recommendation carries Class 1, Level of Evidence B-R designation. 1
ACE Inhibitors or ARBs as First Choice
ACE inhibitors have demonstrated a 20% reduction in risk of cardiovascular death, MI, or cardiac arrest in patients with CCD compared with placebo. 1
Ramipril therapy specifically reduced the risk of MI or stroke by 22% in patients with CCD or at high cardiovascular risk. 1
The 2024 ESC peripheral arterial disease guidelines recommend ACE inhibitors or ARBs as first-line antihypertensive therapy in patients with peripheral and aortic disease, which shares the same atherosclerotic continuum. 1
For patients with stable coronary artery disease, ACE inhibitors are recommended even without left ventricular systolic dysfunction. 1
Beta-Blockers as Co-First-Line Therapy
Beta-blockers are particularly effective in CCD patients, especially those with ongoing angina, given their ability to reduce angina, improve angina-free exercise tolerance, reduce exertion-related MI, and reduce risk of cardiovascular events. 1
Multiple well-conducted randomized controlled trials from both precontemporary and modern eras have shown the efficacy of beta-blocker therapy in reducing cardiovascular death and major adverse cardiovascular events among patients with left ventricular systolic dysfunction. 1
The 2024 ESC hypertension guidelines recommend beta-blockers be combined with any of the other major BP-lowering drug classes when there are compelling indications such as angina, post-myocardial infarction, or for heart rate control. 1
Blood Pressure Target
The target blood pressure is 120-129/70-79 mmHg if tolerated in most adults with cardiovascular disease. 1
For patients with CCD and hypertension (systolic BP ≥130 and/or diastolic BP ≥80 mm Hg), treatment should include both nonpharmacological strategies and guideline-directed medical therapy. 1
Additional Antihypertensive Agents When Needed
When beta-blockers, ACE inhibitors, and ARB therapies do not sufficiently control blood pressure, additional guideline-directed medical therapy can be added, including:
- Thiazide diuretics (particularly chlorthalidone or indapamide) 1
- Dihydropyridine calcium channel blockers 1
- Mineralocorticoid receptor antagonists 1
The 2024 ESC guidelines recommend that among all BP-lowering drugs, ACE inhibitors, ARBs, dihydropyridine CCBs, and diuretics have demonstrated the most effective reduction of BP and cardiovascular events as first-line treatments. 1
Combination Therapy Strategy
Combination BP-lowering treatment is recommended for most patients with confirmed hypertension (BP ≥140/90 mmHg) as initial therapy. 1
Preferred combinations are a RAS blocker (either an ACE inhibitor or an ARB) with a dihydropyridine CCB or diuretic. 1
Fixed-dose single-pill combination treatment is recommended in patients receiving combination BP-lowering treatment to improve adherence. 1
Critical Caveat
Combining two RAS blockers (ACE inhibitor and an ARB) is not recommended as this combination has not shown additional benefit and may increase adverse events. 1
The ONTARGET study demonstrated that combined RAS blockade achieved no further benefits in vascular high-risk patients and was associated with more adverse events. 2