INVEST Revisited: Review of Findings from the International Verapamil SR-Trandolapril Study

The International Verapamil SR-Trandolapril Study (INVEST), a randomized trial of 22,576 predominantly elderly patients with an average 2.7-year follow-up, compared a calcium antagonist-led strategy (verapamil SR plus trandolapril) with a beta-blocker-led strategy (atenolol plus hydrochlorothiazide) for hypertension treatment and prevention of cardiovascular outcomes in coronary artery disease patients. Patients received individualized dose and drug titration following a flexible, multi-drug, guideline-based treatment algorithm, with the objective of achieving optimal blood pressure (BP) control individualized for comorbidities (e.g., diabetes). The primary outcome (PO) was first occurrence of death (all-cause), nonfatal myocardial infarction or nonfatal stroke. The strategies resulted in significant and very similar BP reduction, with approximately 70% of patients in both strategies achieving BP control (<140/90 mmHg). Increasing number of office visits with BP in control was associated with reduced risk of the PO. Overall, there was no difference in the PO comparing the strategies; however, new-onset diabetes occurred more frequently in those assigned the atenolol strategy. This report summarizes findings from INVEST and puts them in perspective with our current state of knowledge derived from other large hypertension treatment trials. INVEST findings support that BP reduction is important for prevention of adverse cardiovascular morbidity and mortality, and selection of antihypertensive agents should be based on patient comorbidities and other risk factors (e.g., risk for diabetes) and not necessarily that any one drug be given to all.