ALLHAT study

In patients with BPH and hypertension, it is not recommended to use an a-adrenergic antagonist alone to treat both disorders. In the ALLHAT study, where doxazosin was compared to other agents for treatment of essential hypertension, doxazosin was associated with a higher incidence of congestive heart failure. Therefore, in patients with hypertension and BPH, it is recommended that an appropriate antihypertensive be added to an a-adrenergic antagonist.11... 

Geriatric Considerations - Summary Alpha-adrenergic blockers are modestly effective alone, and in combination with 5-alpha reductase inhibitors (e g, finasteride) in the treatment of urinary obstructive symptoms related to benign prostatic hyperplasia, The main side effect of these agents is orthostatic hypotension, and in hypertensive patients, these agents may increase the risk of congestive heart failure as reported in the ALLHAT study. 

The doxazosin arm of the ALLHAT study was stopped early the doxazosin group had a 25%greater risk of combined cardiovascular disease events which was primarily accounted for by a doubled risk of CHF vs the chlorthalidone group doxazosin was also found to be less effective at controlling systolic BP an average of 3 mm Hg may want to consider primary antihypertensives in addition to a-blockers for BPH symptoms... 

Elevated SBP has been shown to be associated with an increased risk of stroke, CHF, myocardial infarction and death [140,141]. The authors of the ALLHAT study suggested that a 3 mm Hg increase in SBP could explain a 10 % to 20% increase in the incidence of CHF [142]. In a meta-analysis of 15, 693 older patients with isolated systolic hypertension from 8 trials, a 10 mmHg higher initial SBP was associated with relative hazard rates of 1.26 (p=0.001) for total mortality, 1.22 (p=0.007) for cardiovascular mortality, and 1.22 (p=0.02) for stroke [143]. The recent meta-analysis by Aw et al [66A] involving 45451 patients found that rofecoxib was associated with a higher risk of developing hypertension compared to celecoxib. 

A recent very large study (over 30,000 participants) has shown that inexpensive diuretics are similar or superior in outcomes to ACE inhibitor or calcium channel blocker therapy (ALLHAT, 2002). 

In high-risk individuals and groups people with clinical evidence of macrovascular disease other than CHD, the Heart Protection Study (HPS) (II) with diabetes, the HPS and Collaborative Atorvastatin Diabetes Study (CARDS) (12) the elderly, Prospective Study of Pravastatin in the Elderly at Risk (PROSPER) (13) or with hypertension, Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) (14) and Anglo-Scandinavian Cardiac Outcomes Trial (ASCOT) (15). 

ACE inhibitors are considered second-line therapy to diuretics in most patients with hypertension. The ALLHAT demonstrated less heart failure and stroke with chlorthalidone versus lisinopril. This difference in stroke is consistent with another outcomes trial, the Captopril Prevention Project (CAPPP). However, other outcome studies have demonstrated similar, if not better, outcomes with ACE inhibitors versus thiazide diuretics." " In the elderly, one study found that they were at least as effective when compared with diuretics and P-blockers, and another study found that they were more effective." In addition, ACE inhibitors have many roles for patients with hypertension and coexisting conditions. Nonetheless, most clinicians will agree that if ACE inhibitors are not first-line therapy in most patients with hypertension, they are a very close second to diuretics. 

AECAPS/TexCAPS = Air ForceAexas Coronary Atherosclerosis Prevention Study (Downs et ah, 1998) Helsinki = The Helsinki Heart Study (Frick et al., 1 987) LRC-CPPT = The Lipid Research Clinics Coronary Primary Prevention Trial (insull et al., 1984) Oslo = The Oslo Study (Hjermann et ah, 1988) WOSCOPS = The West of Scotland Coronary Prevention Study (Shepherd et al., 1995) ALLHAT = Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial approximately 13-15% of patients had a history of coronary heart disease (CHD) events are CHD events only WHI = Women s Health initiative RRR = relative risk reduction ARR = absolute risk reduction NNT = number needed to treat NA = not available CEE = conjugated equine estrogen MPA = medroxyprogesterone acetate CARDS = Collaborative Atorvastatin Diabetes Study (presented at the 2004 American Diabetes Association meeting). 

Epidemiological studies have suggested that an increase of 3 mmHg in blood pressure is associated with a 10-20% increase in congestive heart failure (ALLHAT Collaborative Research Group 2000). Conversely, a 3 mmHg reduction in blood pressure in hypertensive individuals decreases risk of myocardial infarction by 22 % and of stroke by 33 % (Heart Outcomes Prevention Evaluation Study Investigators... 

The study cohort was derived from 33,357 ALLHAT participants, who were aged 55 years or older, had hypertension and at least one additional cardiovascular disease risk factor. The participants who were normokalemic at baseline were randomised to chlorthalidone versus amlodipine or lisinopril and were stratified by level of potassium at year 1 into hypokalemia (<3.5 mmol/L) normokalemia (3.5-5.4 mmol/L) and hyperkalemia (>5.4 mmol/L). Incidence of hypokalemia in chlorthalidone was 12.9% and this differed significantly from amlodipine (2.1%, p < 0.001) and lisinopril (1.0%, p < 0.01). Incidence of hyperkalemia was greatest in lisinopril arm (3.6%) than in chlorthalidone arm (1.2%, p < 0.01) or amlodipine (1.9%, p < 0.01). Coronary heart disease occurred in 8.1%, 8.0% and 11% in patients with hypokalemia, normokalemia and hyperkalemia, respectively. 

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