TABLE 1

Summary of clinical trials involving α₁-blockers in cardiovascular disease

Trial	Treatment Groups and Patient Numbers		Inclusion Criteria	Result	Interpretation
Trial	Control Groups	α₁-Blocker Groups	Inclusion Criteria	Result	Interpretation
ALLHAT (2000) (ALLHAT, 2000, 2003; SoRelle, 2000; Davis et al., 2002; Piller et al., 2002)	Chlorthalidone (diuretic) [12.5–25 mg/day (N = 15,268)]	Doxazosin (α₁-blocker) [2–8 mg/day (N = 9067)]	Men and women age 55 or older with hypertension (systolic 140 mm Hg and/or diastolic 90 mm Hg, or on medication for hypertension) and at least 1 other risk factor for coronary heart disease	Trial stopped early. Doxazosin increased cardiovascular events by 25% and doubled the risk of heart failure.	α₁-Blockade worsens outcomes in hypertension with cardiac risk factors.
V-HeFT I and II (Cohn et al., 1986; Cohn, 1993)	V-HeFT I Placebo (N = 273); Hydralazine/isosorbide dinitrate (direct vasodilators) [300/160 mg/day (N = 186)]V-HeFT II Hydralazine/isosorbide dinitrate Enalapril (ACE inhibitor) (N = 403)	Prazosin (α₁-blocker) [20 mg/day (N = 183)	Male veterans mean age 58 with symptomatic heart failure due to dilated cardiomyopathy (ischemic or nonischemic), on digoxin and diuretics	Prazosin did not change left ventricular ejection fraction or mortality versus placebo; both were improved with hydralazine/isosorbide.	α₁-Blockade shows no benefit in heart failure and might worsen mortality.
V-HeFT I and II (Cohn et al., 1986; Cohn, 1993)		Prazosin (α₁-blocker) [20 mg/day (N = 183)		Trend toward increased mortality at 5 years in prazosin group versus placebo, survival improved by other vasodilators.
α₁-Blockers in BPH effect on HF (Dhaliwal et al., 2009)		Tamsulosin (58%), terazosin (40%), or doxazosin (2%) (N = 98)	Male veterans with dilated cardiomyopathy admitted with heart failure (N = 388 overall)	Among the 25% of patients taking α₁-blockers, most for BPH, subsequent hospitalizations for heart failure were increased in patients receiving α₁-blockers without β-blockers.	α₁-Blockade worsens outcomes in BPH in the absence of β-blockade.
COMET (Carvedilol or Metoprolol European Trial) (Poole-Wilson et al., 2002, 2003)	Metoprolol tartrate (β₁-selective antagonist) (50 mg bid; N = 1518)	Carvedilol (β_1/2-,α₁-AR antagonist) [25 mg bid (N = 1511)]	Men (80%) and women mean age 62 with NYHA class II–IV heart failure due to dilated cardiomyopathy (ischemic or nonischemic) on stable therapy	Mortality reduced in carvedilol group versus metoprolol.	Carvedilol reduces mortality, possibly related in part to potentiation of α₁-AR signaling.
				Subsequent analyses indicates that benefit might not be due to α₁-blockade (Kubo et al., 2001; Hryniewicz et al., 2003; Van Tassell et al., 2008)

MOXSE (Swedberg et al., 2002)	Placebo (N = 38)	Moxonidine (sympatholytic) [0.3-1.5 mg bid (N = 227 total)]	Patients NYHA class II–IV heart failure due to dilated cardiomyopathy (ischemic or nonischemic)	Moxonidine reduced plasma NE and heart rate but increased adverse events	Some degree of AR signaling is cardioprotective.
MOXCON (Coats, 1999; Cohn et al., 2003; Pocock et al., 2004)	Placebo (N = 944)	Moxonidine (1.5 mg bid [N = 990)]	As in MOXSE	Trial stopped early	Some degree of AR signaling is cardioprotective.
				Moxonidine reduced NE and increased morbidity and mortality

BEST (Bristow et al., 2004)	Placebo [3 month (N = 845); 12 month (N = 654)]; Total for BEST (N = 2708)	Bucindolol (β_1/2-AR antagonist, sympatholytic) [3 month (N = 841); 12 month (N = 642)]	Patients NYHA class III–IV heart failure due to dilated cardiomyopathy (ischemic or nonischemic) on stable therapy, subgroup with NE measured at 3 and 12 months	Bucindolol reduced NE and increased mortality.	Some degree of AR signaling is cardioprotective.