Dogma disputed: Can aggressively hypertensive patients with coronary artery lowering blood pressure in disease be dangerous?

Background: Because coronary perfusion occurs mainly during diastole, patients with coronary artery disease (CAD) could be at increased risk for coronary events if diastolic pressure falls below critical levels. Objective: To determine whether low blood pressure could be associated with excess mortality and morbidity in this population. Design: A secondary analysis of data from the International Verapamil-Trandolapril Study (INVEST), which was conducted from September 1997 to February 2003. Setting: 862 sites in 14 countries. Patients: 22 576 patients with hypertension and CAD Interventions: Patients from INVEST were randomly assigned to a verapamil sustained-release- or atenolol-based strategy; blood pressure control and outcomes were equivalent. Measurements: An unadjusted quadratic proportional hazards model was used to evaluate the relationship between average on-treatment blood pressure and risk for the primary outcome (all-cause death, nonfatal stroke, and nonfatal myocardial infarction [MI]), all-cause death, total MI, and total stroke. A second model adjusted for differences in baseline covariates. Results: The relationship between blood pressure and the primary outcome, all-cause death, and total MI was J-shaped, particularly for diastolic pressure, with a nadir at 119/84 mm Hg. After adjustment, the J-shaped relationship persisted between diastolic pressure and primary outcome. The MI-stroke ratio remained constant over a wide blood pressure range, but at a lower diastolic blood pressure, there were substantially more MIs than strokes. An interaction between decreased diastolic pressure and history of revascularization was observed; low diastolic pressure was associated with a relatively lower risk for the primary outcome in patients with revascularization than in those without revascularization. Limitations: This is a post hoc analysis of hypertensive patients with CAD. Conclusions: The risk for the primary outcome, all-cause death, and MI, but not stroke, progressively increased with low diastolic blood pressure. Excessive reduction in diastolic pressure should be avoided in patients with CAD who are being treated for hypertension.