Despite evidence of efficacy of antihypertensive agents in treating
hypertensive patients, safety and efficacy of antihypertensive agents for
coronary artery disease (CAD) have been discerned only from subgroup analyses
in large trials.
To compare mortality and morbidity outcomes in patients with hypertension
and CAD treated with a calcium antagonist strategy (CAS) or a non–calcium
antagonist strategy (NCAS).
Design, Setting, and Participants
Randomized, open label, blinded end point study of 22 576 hypertensive
CAD patients aged 50 years or older, which was conducted September 1997 to
February 2003 at 862 sites in 14 countries.
Patients were randomly assigned to either CAS (verapamil sustained release)
or NCAS (atenolol). Strategies specified dose and additional drug regimens.
Trandolapril and/or hydrochlorothiazide was administered to achieve blood
pressure goals according to guidelines from the sixth report of the Joint
National Committee on Prevention, Detection, Evaluation, and Treatment of
High Blood Pressure (JNC VI) of less than 140 mm Hg (systolic) and less than
90 mm Hg (diastolic); and less than 130 mm Hg (systolic) and less than 85
mm Hg (diastolic) if diabetes or renal impairment was present. Trandolapril
was also recommended for patients with heart failure, diabetes, or renal impairment.
Main Outcome Measures
Primary: first occurrence of death (all cause), nonfatal myocardial
infarction, or nonfatal stroke; other: cardiovascular death, angina, adverse
experiences, hospitalizations, and blood pressure control at 24 months.
At 24 months, in the CAS group, 6391 patients (81.5%) were taking verapamil
sustained release; 4934 (62.9%) were taking trandolapril; and 3430 (43.7%)
were taking hydrochlorothiazide. In the NCAS group, 6083 patients (77.5%)
were taking atenolol; 4733 (60.3%) were taking hydrochlorothiazide; and 4113
(52.4%) were taking trandolapril. After a follow-up of 61 835 patient-years
(mean, 2.7 years per patient), 2269 patients had a primary outcome event with
no statistically significant difference between treatment strategies (9.93%
in CAS and 10.17% in NCAS; relative risk [RR], 0.98; 95% confidence interval
[CI], 0.90-1.06). Two-year blood pressure control was similar between groups.
The JNC VI blood pressure goals were achieved by 65.0% (systolic) and 88.5%
(diastolic) of CAS and 64.0% (systolic) and 88.1% (diastolic) of NCAS patients.
A total of 71.7% of CAS and 70.7% of NCAS patients achieved a systolic blood
pressure of less than 140 mm Hg and diastolic blood pressure of less than
90 mm Hg.
The verapamil-trandolapril–based strategy was as clinically effective
as the atenolol-hydrochlorothiazide–based strategy in hypertensive CAD