Mortality implications of angina and blood pressure in hypertensive patients with coronary artery disease: New data from extended follow-up of the International Verapamil/Trandolapril Study (INVEST)

Abstract

Background: Angina and hypertension are common in patients with coronary artery disease (CAD); however, the effect on mortality is unclear. We conducted this prespecified analysis of the International Verapamil/Trandolapril Study (INVEST) to assess relationships between angina, blood pressure (BP), and mortality among elderly, hypertensive CAD patients.

Hypothesis: Angina and elevated BP will be associated with higher mortality.

Methods: Extended follow-up was performed using the National Death Index for INVEST patients in the United States (n = 16 951). Based on angina history at enrollment and during follow-up visits, patients were divided into groups: persistent angina (n = 7184), new-onset angina (n = 899), resolved angina (n = 4070), and never angina (n = 4798). Blood pressure was evaluated at baseline, during drug titration, and during follow-up on-treatment. On-treatment systolic BP was classified as tightly controlled (<130 mm Hg), controlled (130-139 mm Hg), or uncontrolled (≥140 mm Hg). A Cox proportional hazards model was created adjusting for age, heart failure, diabetes, renal impairment, myocardial infarction, stroke, and smoking. The angina groups and BP control groups were compared using the never-angina group as the reference.

Results: Only in the persistent-angina group was a significant association with mortality observed, with an apparent protective effect (hazard ratio: 0.82, 95% confidence interval: 0.75-0.89, P < 0.0001). Uncontrolled BP was associated with increased mortality risk (hazard ratio: 1.29, 95% confidence interval: 1.20-1.40, P < 0.0001), as were several other known cardiovascular risk factors.

Conclusions: In hypertensive CAD patients, persistent angina was associated with lower mortality. The observed effect was small compared with other cardiovascular risk factors, such as BP, which were associated with increased mortality.

Trial registration: ClinicalTrials.gov NCT00133692.

Figure 1

Strategy for assigning INVEST patients to one of 4 groups based on the presence or absence of angina at baseline and during the study. Abbreviations: INVEST, International Verapamil/Trandolapril Study.

Figure 2

Kaplan‐Meier mortality curves. Each curve demonstrates the survival for patients in each of the 4 angina groups.

Figure 3

Hazard ratio plots demonstrating the hazard ratios and confidence intervals for the variables included in our multivariate Cox regression analysis model. Variables which did not contribute to the model were omitted from the figure. Abbreviations: LVH, left ventricular hypertrophy; MI, myocardial infarction; PCI, percutaneous coronary intervention; PVD, peripheral vascular disease; SBP, systolic blood pressure; TIA, transient ischemic attack.