Blood Pressure Control and Improved Cardiovascular Outcomes in the International Verapamil SR-Trandolapril Study

Abstract

Abstract-Uncontrolled blood pressure (BP) increases cardiovascular risk, independent of type of treatment. In this posthoc International Verapamil SR-Trandolapril Study analysis, we determined whether adverse outcomes are related to consistency of BP control, defined as the proportion of visits in which BP was in control. A total of 22 576 patients with hypertension and coronary artery disease were divided into 4 groups according to the proportion of visits in which BP was in control (Ͻ140/90 mm Hg): Ͻ25%, 25% to Ͻ50%, 50% to Ͻ75%, and Ն75%. Risk of primary outcome (first occurrence of death, nonfatal myocardial infarction, or nonfatal stroke), myocardial infarction, and stroke decreased progressively from the group with Ͻ25% to the group with Ն75% of visits with BP control. Adjusted risks of primary outcome (heart rate: 0.60; 95% CI: 0.53 to 0.67), myocardial infarction (heart rate: 0.58; 95% CI: 0.48 to 0.70), and stroke (heart rate: 0.50; 95% CI: 0.37 to 0.67) were less in the group with Ն75% of visits with BP control compared with the group with Ͻ25% of visits with BP control. Baseline BP was not predictive of outcomes. Proportion of visits with BP control was associated with mean follow-up systolic BP (r 2 ϭ0.64), both being independently related to primary outcome. As proportion of visits with BP control increases, there is an associated steep reduction in cardiovascular risk, independent of baseline characteristics and mean on-treatment BP. Consistency of BP control during treatment provides additional information on the protective effect of antihypertensive treatment. Physicians need to be concerned at each visit if BP is not controlled. S everal lines of evidence support the view that blood pressure (BP) lowering, per se protects hypertensive patients, no matter how it is obtained. First, regardless of the treatment used, cardiovascular morbid and fatal events are less in patients in whom on-treatment BP is reduced Ͻ140/ 90 mm Hg than in those in whom on-treatment BP remains uncontrolled. 1-4 Second, regardless of the treatment used, in diabetic or other high-risk individuals, cardiovascular protection is greater if on-treatment BP values Ͻ130/80 mm Hg are achieved. 5-9 Third, there is a type of treatment-independent relationship between the magnitude of the mean BP change throughout the treatment period and the incidence of cerebrovascular and coronary events. 10,11 Analysis of BP control using mean follow-up BP does not provide a complete picture of BP control during a study, because BP may be in control at one visit and not in control at the next visit or vice versa. In the ELSA Study, for example, the number of patients with BP control at any given annual visit was much greater than the number of patients with consistent BP control at all 4 of the annual visits. 12 The purpose of this posthoc analysis of the large database provided by the INternational VErapamil SR-Trandolapril (INVEST) prospective trial was to determine whether study outcomes are related to the consistency of BP control, defined as...

Consistency of Blood Pressure Control After Ischemic Stroke

“…These findings are consistent with the post hoc analysis of data from the INVEST trial, which revealed that as the proportion of visits with BP control increased, there was an associated steep reduction in cardiovascular risk, independent of baseline characteristics and mean on-treatment BP. 4 Consistency of BP control offers information above and beyond mean BP. The visits in which BP is >140/90 reflect periods of absence of BP control: conceivably settings in which individuals are at higher cardiovascular risk.…”

“…Indeed, a post hoc analysis of individuals with hypertension and coronary artery disease enrolled in the INternational VErapamil SR-Trandolapril (INVEST) trial revealed that both proportion of visits with BP control and mean follow-up SBP were independently related to the risk of death, nonfatal MI, or nonfatal stroke. 4 Whether consistency of BP control is also important among stroke survivors remains unknown.…”

Hypertension Treatment

“…4 Although each of these findings generated some interest, none could be viewed as being sufficiently newsworthy to "stop the presses." Such, however, is not the case with the study by Mancia et al 5 in this issue of Hypertension. In a posthoc analysis of the large database compiled from the INVEST Study, they have carefully evaluated a 22 576-patient cohort of patients with hypertension and coronary artery disease as to the relationship between the study's composite outcome (first occurrence of nonfatal myocardial infarction, nonfatal stroke, or death) and the proportion of study visits in which BP was controlled to a value Ͻ140/90 mm Hg.…”

“…It is now apparent from the study of Mancia et al 5 that the functional use of office-based readings can be further fortified if BP control is viewed in a longitudinal fashion, and the better it is controlled during the period of surveillance, the more likely it is that a favorable outcome will arise. This might be best conceptualized as an area under the curve for overall BP control with the time axis being months to years rather than "day(s)," as is the case when 24-hour ambulatory BP monitoring is used.…”

“…It would seem that the more often in the course of a clinical trial that the BP is at goal, the better the outcome. It is surprising that the concept brought forward by Mancia et al 5 has not previously been brought to bear in the analysis of outcome trials. Future studies should analyze their data according to on-treatment control and not just by the change in BP from beginning to end of the study.…”