Which classes of antihypertensive (blood pressure-lowering) medications have shown the largest benefit in reducing the risk of myocardial infarction (heart attack) and cerebrovascular accident (stroke) in patients with established cardiovascular disease (CVD)?

From the Guidelines

Diuretics, ACE inhibitors, and ARBs have shown the largest benefit in reducing the risk of myocardial infarction and cerebrovascular accident in patients with established cardiovascular disease.

Key Findings

• The 2017 ACC/AHA/AAPA/ABC/ACPM/AGS/APhA/ASH/ASPC/NMA/PCNA guideline for the prevention, detection, evaluation, and management of high blood pressure in adults recommends the use of diuretics, ACE inhibitors, and ARBs for the management of hypertension in patients with established cardiovascular disease 1.
• A meta-analysis of 13 trials involving 80,594 individuals found that ACE inhibitors or ARB therapy reduced the risk of a composite primary outcome including stroke by 11%, without variability by baseline BP 1.
• The reduction in blood pressure appears to be more important than the choice of specific agents used to achieve this goal, and if diuretic and ACE inhibitor or ARB treatment do not achieve blood pressure target, other agents such as calcium channel blockers and/or mineralocorticoid receptor antagonist may be added 1.

Medication Options

• Diuretics, such as thiazide diuretics, can be used as first-line therapy for the management of hypertension in patients with established cardiovascular disease.
• ACE inhibitors, such as ramipril, lisinopril, or perindopril, have demonstrated significant cardiovascular protection, especially in patients with left ventricular dysfunction, diabetes, or chronic kidney disease.
• ARBs, such as valsartan or candesartan, provide similar benefits for patients who cannot tolerate ACE inhibitors due to cough.

Treatment Approach

• Treatment should be initiated at lower doses and titrated upward as tolerated, with regular monitoring of blood pressure, heart rate, renal function, and electrolytes.
• The goal of treatment is to achieve a blood pressure target that reduces the risk of cardiovascular events, while minimizing the risk of adverse effects.
• Lifestyle modifications, such as dietary changes and increased physical activity, should also be encouraged to help achieve blood pressure targets and reduce cardiovascular risk.

From the FDA Drug Label

Numerous antihypertensive drugs, from a variety of pharmacologic classes and with different mechanisms of action, have been shown in randomized controlled trials to reduce cardiovascular morbidity and mortality, and it can be concluded that it is blood pressure reduction, and not some other pharmacologic property of the drugs, that is largely responsible for those benefits The largest and most consistent cardiovascular outcome benefit has been a reduction in the risk of stroke, but reductions in myocardial infarction and cardiovascular mortality also have been seen regularly

The classes of antihypertensive medications that have shown the largest benefit in reducing the risk of myocardial infarction and cerebrovascular accident in patients with established cardiovascular disease are not explicitly specified in the provided drug labels. Key points to consider are:

• Blood pressure reduction is largely responsible for the benefits in reducing cardiovascular morbidity and mortality.
• The largest and most consistent benefit has been a reduction in the risk of stroke.
• Reductions in myocardial infarction and cardiovascular mortality have also been seen regularly 2, 3.

From the Research

Antihypertensive Medications and Cardiovascular Risk

The classes of antihypertensive medications that have shown the largest benefit in reducing the risk of myocardial infarction (heart attack) and cerebrovascular accident (stroke) in patients with established cardiovascular disease (CVD) are:

• Angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin II receptor blockers (ARBs) 4, 5, 6, 7
• Calcium antagonists, which are effective in managing hypertension induced by cyclosporine and in patients with angina pectoris, paroxysmal supraventricular tachycardia, and atrial fibrillation with rapid ventricular rate 8

Comparison of ACEIs and ARBs

Studies have compared the effectiveness of ACEIs and ARBs in preventing cardiovascular events:

• A study found that ARB use was associated with lower rates of cardiovascular events compared with ACEIs, especially in patients with established CVD 7
• Another study found that ACEIs and ARBs have equivalent effectiveness in preventing CV events, but ARBs have fewer adverse events 6
• A review of clinical trials found that ACEIs and ARBs do not have special cardiovascular protective effects, and that the key to reducing cardiovascular outcome is to appropriately control blood pressure and treat all other coronary risk factors 5

Specific Indications for Antihypertensive Medications

Certain antihypertensive medications have specific indications:

• ACEIs are particularly indicated for managing patients with congestive heart failure due to systolic dysfunction and patients with diabetic nephropathy 8
• ARBs are considered an alternative for ACE inhibitor-intolerant patients, but may provide superior protection against CV events than ACEIs in high-risk patients 7
• Calcium antagonists have specific indications, including angina pectoris, paroxysmal supraventricular tachycardia, and atrial fibrillation with rapid ventricular rate 8