Impact of resting heart rate on outcomes in hypertensive patients with coronary artery disease: findings from the INternational VErapamil-SR/trandolapril STudy (INVEST)

Abstract

Aim: To determine the relationship between resting heart rate (RHR) and adverse outcomes in coronary artery disease (CAD) patients treated for hypertension with different RHR-lowering strategies.

Methods and results: Time to adverse outcomes (death, non-fatal myocardial infarction, or non-fatal-stroke) and predictive values of baseline and follow-up RHR were assessed in INternational VErapamil-SR/trandolapril STudy (INVEST) patients randomized to either a verapamil-SR (Ve) or atenolol (At)-based strategy. Higher baseline and follow-up RHR were associated with increased adverse outcome risks, with a linear relationship for baseline RHR and J-shaped relationship for follow-up RHR. Although follow-up RHR was independently associated with adverse outcomes, it added less excess risk than baseline conditions such as heart failure and diabetes. The At strategy reduced RHR more than Ve (at 24 months, 69.2 vs. 72.8 beats/min; P < 0.001), yet adverse outcomes were similar [Ve 9.67% (rate 35/1000 patient-years) vs. At 9.88% (rate 36/1000 patient-years, confidence interval 0.90-1.06, P = 0.62)]. For the same RHR, men had a higher risk than women.

Conclusion: Among CAD patients with hypertension, RHR predicts adverse outcomes, and on-treatment RHR is more predictive than baseline RHR. A Ve strategy is less effective than an At strategy for lowering RHR but has a similar effect on adverse outcomes.

Figure 1

Top panel: incidence of adverse outcomes (time to first event of all-cause death, non-fatal myocardial infarction, or non-fatal stroke) among randomized patients without an electronic pacemaker for each treatment strategy by resting heart rate at baseline. Bottom panel: distribution of patients by baseline resting heart rate

Figure 2

Conditions present at baseline that were associated with risk for adverse outcomes from a stepwise Cox proportional hazards model; n, number of patients with adverse outcome; N, number patients with baseline condition; event rate, adverse outcome incidence; HR, hazard ratio; CI, confidence interval; TIA, transient ischaemic attack; b.p.m., beats per minute; strategy, randomized treatment strategy

Figure 3

Relationship between follow-up resting heart rate for all patients and incidence of adverse outcomes (left axis, bars) and risk (right axis –•–, hazard ratio) derived from a stepwise Cox proportional hazards model. Among all patients, the nadir for follow-up resting heart rate was 59 b.p.m

Figure 4

Relationship between follow-up resting heart rate among patients with diabetes and incidence of adverse outcomes (left axis, bars) and risk (right axis –•–, hazard ratio) derived from a stepwise Cox proportional hazards model

Figure 5

Relationship between follow-up resting heart rate among patients with prior myocardial infarction and incidence of adverse outcomes (left axis, bars) and risk (right axis -•-, hazard ratio) derived from a stepwise Cox proportional hazards model. MI, myocardial infarction