Author + information
- Published online October 29, 2018.
- aInstitute of Cardiovascular Sciences, University of Birmingham, Birmingham, United Kingdom
- bCardiovascular and Arrhythmia Center, Chung-Ang University Hospital, Chung-Ang University, Seoul, Republic of Korea
- cLiverpool Centre for Cardiovascular Science, University of Liverpool, Liverpool, United Kingdom
- ↵∗Address for correspondence:
Prof. G.Y.H. Lip, Institute of Cardiovascular Sciences, University of Birmingham, Dudley Road, Birmingham B18 7QH, United Kingdom.
Heart failure (HF) is one of the most common heart disorders; HF has a prevalence ranging from 1% to 2%, rising to ≥10% among people >70 years of age. Benign prostate hypertrophy (BPH) also is an inexorable problem in elderly men, with a lifetime prevalence of 26.2%, increasing to 36.8% in patients 70 to 79 years of age. The 2 clinical situations usually exist in combination among older patients.
Alpha blockers (ABs), when used for the treatment of hypertension, have been associated with increased risk of HF, which has raised some concerns (1). Unlike the well-demonstrated beneficial effects of beta blockers (BBs) in previous HF trials, the effects of ABs remain controversial, especially in the failing heart where the quantity and function of cardiac alpha-adrenergic receptors are augmented and maintained.
In the ALLHAT (Antihypertensive and Lipid Lowering treatment to prevent Heart Attack Trial), participants randomized to the doxazosin arm experienced an 80% higher risk of HF (relative risk: 1.80; 95% confidence interval [CI]: 1.61 to 2.02; p < 0.001) (1). Several possible reasons were suggested for these increased HF events in hypertensive patients receiving doxazosin, including: 1) unmasking of undiagnosed HF after withdrawing baseline diuretic therapy; 2) a relatively small number of patients in the doxazosin group (the number of patients treated with chlorthalidone was 1.7 times that of patients treated with doxazosin); and 3) differential lowering of blood pressure (136.9/79.3 mm Hg; 57.8% <140/90 mm Hg vs. 140.1/79.5 mm Hg; 50.4% <140/90 mm Hg, respectively, at the 1-year visit).
Recent studies have revealed other reasons for the increased HF risk with ABs, as follows: 1) delayed response to antihypertensive medications (e.g., with doxazosin in ALLHAT) (2); 2) a profibrotic effect of doxazosin independent of AB effect (3); and 3) harmful effects of unopposed alpha receptor antagonism, as ABs were not associated with increased HF where there was background BB therapy (4).
Differences between the study by Jackevicius et al. (5), in this issue of the JACC: Heart Failure, and ALLHAT were that only patients who had previously been hospitalized with HF were followed and that the uncertainty, such as unmasking of undiagnosed HF, was excluded. Moreover, we could reduce concerns about the consequences of doxazosin-specific actions independent of its AB effect by including patients with various ABs analyzed in this study (the most common 2 ABs, terazosin and tamsulosin, comprised 88.1%, and doxazosin was used in only 7.3% of cases) (5). As a result, this study showed that the AB treatment slightly reduced readmissions for HF (hazard ratio [HR]: 0.95; 95% CI: 0.92 to 0.97; p < 0.0001) and also reduced mortality regardless of BB usage (in all AB-treated patients, HR was 0.93; 95% CI: 0.91 to 0.94, p <0.0001; whereas in BB-untreated patients, HR was 0.93; 95% CI: 0.90 to 0.96; p < 0.0001; and in BB-treated patients, HR was 0.91; 95% CI: 0.89 to 0.92; p < 0.0001). Specifically, the lower mortality was confined to patients treated with vasoactive ABs (prazosin, doxazosin, and terazosin), and patients treated with higher doses of ABs had lower mortality without an increase in HF readmission.
Through this large-scale, propensity score-matched cohort study, we may allay some uncertainties and concerns regarding potential risks of ABs, especially among patients with HF (Figure 1).
Nevertheless, the results of this study should be interpreted with caution when it comes to our clinical practice, because of incomplete data for left ventricular systolic function and HF readmissions and deaths outside the Veterans Affairs facilities. Future studies that clarify these remaining uncertainties may provide some reassurance that ABs may be a potential treatment option for HF patients with BPH or hypertension. More randomized trials may be needed.
↵∗ Editorials published in JACC: Heart Failure reflect the views of the authors and do not necessarily represent the views of JACC: Heart Failure or the American College of Cardiology.
Both authors have reported that they have no relationships with industry relevant to the contents of this paper to disclose.
- 2018 American College of Cardiology Foundation
- ↵(2003) Antihypertensive, Lipid-Lowering Treatment to Prevent Heart Attack Trial collaborative research group. Diuretic versus alpha-blocker as first-step antihypertensive therapy: final results from the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT). Hypertension 42:239–246.
- Dhruva S.S.,
- Huang C.,
- Spatz E.S.,
- et al.
- Qian X.,
- Li M.,
- Wagner M.B.,
- Chen G.,
- Song X.
- Jackevicius C.A.,
- Ghaznavi Z.,
- Lu L.,
- Warner A.L.