Blood pressure management in patients with only coronary artery disease (CAD) has not been evaluated in large trials. The benefits of combined therapy with beta blockers and diuretics are well known, but the efficacy of other combination regimens is less established. The International Verapamil-Trandolapril Study is a randomized trial that compares a non-dihydropyridine with a beta blocker to determine the extent to which these medications affect outcomes in older adults with CAD. The trial was designed to test these agents in combination with other antihypertensive drugs.
Patients enrolled in the international, multicenter, prospective, randomized open-blinded study were 50 years or older and had documented CAD with essential hypertension. Patients allocated to a calcium antagonist strategy (CAS) were given verapamil sustained-release (SR), while patients allocated to a noncalcium antagonist strategy (NCAS) were given atenolol. If blood pressure was not adequately controlled, patients in the CAS group could receive trandolapril, an angiotensin-converting enzyme inhibitor, in addition to the verapamil; the NCAS group could receive hydrochlorothiazide in addition to the atenolol. If blood pressure was still too high, dosages were increased. Finally, each group could receive the other group’s second medication (i.e., hydrochlorothiazide in the CAS group and trandolapril in the NCAS group).
Patients were followed every six weeks for the first six months and then biannually. The primary outcome was all-cause death, nonfatal myocardial infarction, or nonfatal stroke. Secondary outcomes included time to most serious event, cardiovascular death, angina, cardiovascular hospitalizations, blood pressure control, cancer, Alzheimer’s disease, Parkinson’s disease, and gastrointestinal tract bleeding.
Of the 22,576 eligible participants, 11,267 were assigned to the CAS group and 11,309 to the NCAS group, with a mean follow-up of 2.7 years. Overall, as expected, calcium antagonist use was more frequent in the CAS group, and beta-blocker use was more frequent in the NCAS group. There was no difference in primary outcomes in the CAS group compared with the NCAS group. Other outcomes also were similar and remained so with subgroup analysis. The only difference was that patients with heart failure seemed to do somewhat better with the NCAS strategy.
In both groups, a little more than two thirds of participants achieved blood pressure control by 24 months. Of note, patients in the CAS group appeared to have a reduced risk of developing diabetes. Further investigation suggested a protective effect of trandolapril in the CAS group only: a 2-mg dosage of trandolapril was associated with a hazard ratio of developing diabetes of 0.86, while a 4-mg dosage was associated with a hazard ratio of 0.77.
The authors conclude that a verapamil SR–based antihypertensive strategy is equivalent to a beta blocker–based strategy. In both groups, most participants required a combination of two to three medications to achieve blood pressure control. Patients with heart failure had better outcomes in the NCAS group. Development of diabetes appeared to be delayed in the CAS group, with a nonsignificant trend toward development of diabetes apparent in patients taking hydrochlorothiazide.