Does doxazosin (alpha-1 adrenergic receptor antagonist) cause or prevent myocardial infarction (heart attacks)?

From the Guidelines

Doxazosin does not prevent heart attacks and may actually increase the risk of heart failure. Doxazosin is an alpha-blocker primarily used to treat high blood pressure and symptoms of benign prostatic hyperplasia (enlarged prostate). The ALLHAT trial, a large clinical study, found that patients taking doxazosin had a higher risk of developing heart failure compared to those taking other blood pressure medications like diuretics 1. For this reason, doxazosin is not typically recommended as a first-line treatment for high blood pressure. Instead, medications like ACE inhibitors, ARBs, calcium channel blockers, or thiazide diuretics are preferred for cardiovascular protection.

Some key points to consider:

• 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 using ACE inhibitors, ARBs, calcium channel blockers, or thiazide diuretics as first-line treatments for hypertension 1.
• Alpha-1 blockers like doxazosin are associated with orthostatic hypotension, especially in older adults, and may be considered as second-line agents in patients with concomitant benign prostatic hyperplasia (BPH) 1.
• The ALLHAT trial demonstrated that doxazosin was inferior to chlorthalidone for the prevention of heart failure and was associated with a doubling of heart failure risk compared to chlorthalidone 1.

Overall, doxazosin is not recommended as a first-line treatment for high blood pressure due to its potential to increase the risk of heart failure. If you're taking doxazosin and have concerns about heart attack risk, consult with your healthcare provider about potentially more cardioprotective alternatives for your specific situation.

From the FDA Drug Label

Lowering blood pressure reduces the risk of fatal and nonfatal cardiovascular events, primarily strokes and myocardial infarctions. 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

Doxazosin may help prevent myocardial infarction (heart attacks) by lowering blood pressure, which reduces the risk of fatal and nonfatal cardiovascular events, including myocardial infarctions 2.

• The benefit of reducing myocardial infarction is largely due to blood pressure reduction, not the specific pharmacologic property of doxazosin.
• Reductions in myocardial infarction have been seen regularly in randomized controlled trials of antihypertensive drugs, including doxazosin.

From the Research

Effect of Doxazosin on Myocardial Infarction

• Doxazosin, an alpha-1 adrenergic receptor antagonist, has been found to have a beneficial effect on blood pressure and lipid profiles, which can help prevent myocardial infarction (heart attacks) 3, 4, 5, 6, 7.
• The drug reduces total peripheral resistance by selective postsynaptic alpha 1-blockade, without reducing cardiac output, and has a negligible effect on heart rate 5.
• Doxazosin also has favorable effects on the plasma lipid profile, decreasing total cholesterol and triglycerides, and increasing high-density lipoprotein (HDL) cholesterol as well as the HDL/total cholesterol ratio 3, 5, 7.
• Studies have shown that doxazosin can reduce the risk of developing coronary heart disease in patients with mild to moderate hypertension, although this remains to be confirmed in long-term prospective studies 7.

Mechanism of Action

• Doxazosin's antihypertensive effect is produced by a reduction in the smooth muscle tone of peripheral vascular beds, resulting in a decrease in total peripheral resistance without significant effect on cardiac output or heart rate 7.
• The drug's effect on benign prostatic hyperplasia is produced through a reduction in prostatic tone mediated via alpha 1-adrenoceptor blockade 7.

Clinical Applications

• Doxazosin has been used in a variety of patient populations, including the elderly, Blacks, smokers, and patients with concomitant disease states such as renal dysfunction, hypercholesterolaemia, non-insulin dependent diabetes mellitus (NIDDM), and respiratory disease 4, 7.
• The drug has been used successfully in combination with beta-adrenoceptor antagonists, diuretics, calcium channel antagonists, and angiotensin-converting enzyme inhibitors in patients with hypertension that is uncontrolled with monotherapy 4, 7.