High Heart Rate Linked With Increased Mortality in Stable Coronary Heart Disease

October 28, 2010

October 28, 2010 (Montreal, Quebec City) — A large analysis from two contemporary clinical trials provides evidence in stable heart disease patients that a lower heart rate is associated with a significantly lower risk of death. Analyzing data from the TRANSCEND and ONTARGET trials, both reported previously by heartwire , investigators report that compared with stable heart disease patients with lower heart rates, those with baseline heart rates >70 beats per minute (bpm) had a significantly greater risk of all-cause and cardiovascular mortality, as well as a higher risk of heart-failure hospitalizations.

Dr Sherryn Rambihar

"The patients we looked at in TRANSCEND and ONTARGET were people with peripheral arterial disease, cerebrovascular disease and stroke, coronary artery disease, and diabetes mellitus with end-organ complications," Dr Sherryn Rambihar (McMaster University, Hamilton, ON), one of the authors of the analysis, told heartwire . "In these people with stable disease, we can definitely say that the lower your heart rate, the lower your mortality, and the higher your heart rate, the higher your mortality. It's a pretty robust finding. You can't argue with 30 000 patients."

Presented this week at the Canadian Cardiovascular Congress 2010, the analysis is an attempt to identify the role of heart rate in predicting cardiovascular disease risk and mortality, a question that researchers have been addressing in different patient populations for a number of years.

Most of the data on the role of heart rate as a predictor of risk in stable heart disease patients are derived from the Coronary Artery Surgery Study (CASS) registry, explained Rambihar, but this is an older registry and patients weren't receiving contemporary medical care, including statins. The Treating to New Targets (TNT) trial recently showed that heart rate predicts cardiac risk in patients with stable coronary heart disease, but that trial is only one-third as large as the current analysis.

More Than 30,000 Patients

In this analysis of stable patients in ONTARGET and TRANSCEND, which together included a total of 31 531 patients, the investigators looked at the association between baseline heart rate, averaged over the course of 56 months, and a combined end point of cardiovascular mortality, MI, stroke, and heart-failure hospitalizations, as well as the prespecified secondary end point of all-cause mortality and individual end points within the primary composite end point.

In an analysis using a heart-rate cutoff of 70 bpm, the risk of cardiovascular death increased by 41% to 58% (depending on the risk-adjusted model used) among those with a resting heart rate >70 bpm, even after adjustment for all comorbid risk factors using the validated HOPE score, as well as for beta-blocker and calcium-channel–blocker use. The risk of all-cause mortality increased by 34% to 47% and heart-failure hospitalizations increased by 53% to 63% among those with heart rates >70 bpm. All increases were statistically significant.

The investigators also examined the data by quintiles, separating the patients into groups based on baseline heart rate. Compared with stable heart disease patients with the lowest heart rate (<58 bpm), those with the highest heart rate (>78 bpm) had a 77% increased risk of cardiovascular disease death and a 65% increased risk of all-cause death.

"Similarly, from 50 beats per minute, for every 10-beats-per-minute increase in heart rate, the risk increased continuously," said Rambihar. "It wasn't linear, but it was a steady, continuous increase, and the relative risk compared with 50 beats per minute increased every step of the way. The further away you got from 50 beats per minute, the higher the risk for the patient."

Investigators observed a strong positive interaction for age, beta-blocker use, and coronary artery disease, suggesting that the association between elevated heart rate and risk is stronger in patients younger than 65 years of age, in those already taking a beta blocker and who might not be at therapeutic targets, and those already with coronary disease.

Asked about the potential implications of the data, Rambihar urged caution against extrapolating the results outside of stable coronary heart disease. Also, whether clinicians should attempt to lower heart rate in stable heart disease patients is up in the air. Patients in ONTARGET and TRANSCEND were treated with beta blockers, so it remains unknown whether the addition of a heart-rate–lowering drug, such as ivabradine (Procoralan, Servier), would provide any benefit.

"Prevention starts with risk factor-reduction, such as exercising and stopping smoking," Rambihar told heartwire . "We know that people who smoke have higher heart rates and that people who don't exercise have higher heart rates. I would focus on those aspects first. These are good things for your heart rate and for your heart in general. Beyond that, if you already have heart disease, then perhaps doctors should be looking at other medications to lower heart rate."

Recently, in heart failure, the Systolic Heart Failure Treatment with the I f Inhibitor Ivabradine Trial (SHIFT) trial showed that adding ivabradine to treatment resulted in a significant reduction in the composite rate of cardiovascular death or heart-failure hospitalization, while the Morbidity-Mortality Evaluation of the If Inhibitor Ivabradine in Patients With Coronary Artery Disease and Left Ventricular Dysfunction (BEAUTIFUL) trial was negative overall but showed a benefit of ivabradine in patients with high baseline heart rates (>70 bpm).

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