Is doxazosin (alpha-1 adrenergic receptor antagonist) associated with an increased risk of myocardial infarction (heart attacks)?

From the Guidelines

Doxazosin is associated with an increased risk of cardiovascular events, including heart failure, but not directly with myocardial infarction, and its use should be cautious and reserved for specific conditions like benign prostatic hyperplasia or as an add-on therapy for resistant hypertension. The ALLHAT study, published in 2000, showed that doxazosin was associated with a 25% higher risk of combined cardiovascular disease events and twice the risk of heart failure compared to chlorthalidone 1. While doxazosin effectively lowers blood pressure by blocking alpha-1 receptors, causing vasodilation, this mechanism may lead to fluid retention and increased cardiac workload in some patients, potentially explaining the increased heart failure risk. The study didn't conclusively show that doxazosin directly causes heart attacks, but rather demonstrated increased cardiovascular events and heart failure.

Some key points to consider when using doxazosin include:

• Doxazosin is not recommended as a first-line treatment for hypertension due to its increased risk of cardiovascular events 1.
• Doxazosin may be useful for specific conditions like benign prostatic hyperplasia in men or as an add-on therapy for resistant hypertension when other medications have failed 1.
• The choice of antihypertensive therapy should follow contemporary guidelines, and other medications like thiazide-type diuretics, calcium channel blockers, ACE inhibitors, or angiotensin receptor blockers may be preferred over doxazosin for the treatment of hypertension 1.
• Patients with hypertension should be advised on healthy lifestyle modification, weight reduction, reduction of sodium intake, increased consumption of fruits, vegetables, and low-fat dairy products, and moderation of alcohol intake 1.

Overall, while doxazosin may have some benefits in specific conditions, its use should be cautious and reserved due to its increased risk of cardiovascular events. The most recent and highest quality study, published in 2017, confirms that doxazosin is associated with a higher risk of heart failure and should be used with caution 1.

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

The use of doxazosin is associated with a reduction in the risk of myocardial infarction (heart attacks) due to its blood pressure lowering effect 2.

• Key points:
  • Doxazosin is used to lower blood pressure
  • Lowering blood pressure reduces the risk of myocardial infarction
  • The benefit of reduced myocardial infarction risk is due to blood pressure reduction, not other pharmacologic properties of the drug

From the Research

Association between Doxazosin and Myocardial Infarction

• There is no direct evidence in the provided studies to suggest that doxazosin is associated with an increased risk of myocardial infarction (heart attacks) 3, 4, 5, 6, 7.
• The studies primarily focus on the efficacy and safety of doxazosin in treating hypertension and benign prostatic hyperplasia (BPH), with no mention of myocardial infarction as a specific outcome or adverse event.
• However, some studies mention the improvement in risk factors for coronary heart disease, such as lipid profile, insulin sensitivity, left ventricular hypertrophy, platelet aggregation, and fibrinolysis, with doxazosin treatment 5.
• Additionally, one study notes that doxazosin reduces blood pressure and improves symptoms in patients with hypertension and BPH, which may indirectly reduce the risk of cardiovascular events, including myocardial infarction 6.

Safety and Tolerability of Doxazosin

• The studies consistently report that doxazosin is well-tolerated, with common adverse events including dizziness, headache, and fatigue 4, 6, 7.
• The incidence of adverse events is generally low, and most events are considered mild or moderate in severity 4, 7.
• There is no evidence to suggest that doxazosin increases the risk of myocardial infarction or other serious cardiovascular events in the studied populations 3, 4, 5, 6, 7.