Selection of Antihypertensive Therapy
Selection of Antihypertensive Therapy
Abstract & Commentary
By Michael H. Crawford, MD
Source: Poulter NR, et al. Baseline heart rate, antihypertensive treatment, and prevention of cardiovascular outcomes in ASCOT (Anglo-Scandinavian cardiac outcomes trial). JACC. 2009;54: 1154-1161.
Although heart rate is known to be a marker for the utility of beta blockers in ischemic heart disease and heart failure, there is no comparable trial data in hypertension. Thus, the Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm (ASCOT-BPLA) data in more than 19,000 hypertensive patients without coronary artery disease is of interest, since patients were randomized to an atenolol- vs. an amlodipine-based arm without regard to baseline resting heart rate. The hypothesis tested was that the previously demonstrated superiority of the amlodipine arm would be attenuated in those with higher resting heart rates. Patients were excluded from this analysis if they were on any drugs at baseline that would decrease heart rate (e.g., diltiazem); patients failing other drug therapy were candidates for the trial.
Results: 12,759 patients met the criteria for this analysis, and there were no significant differences in baseline characteristics between those randomized to the two-drug therapy groups. At the last follow-up visit, mean heart rate was 12 ± 14 beats/min. lower in the atenolol group vs. 1 ± 12 in the amlodipine group. The primary combined end-point of death, myocardial infarction, or stroke was not predicted by resting heart rate. The primary endpoint was reduced by amlodipine-based therapy (HR 0.81, CI 0.74-0.88, p < .001), and this effect was not altered by baseline heart rate as a continuous or categorical variable. Poulter et al concluded that the favorable results of amlodipine- vs. atenolol-based therapy for hypertension in patients without coronary disease was not attenuated in patients with higher resting heart rates. This implies that resting heart rate should not be used as criteria for antihypertensive agent selection in such patients.
Commentary
Several recent studies have shown the superiority of amlodipine-based antihypertensive therapy over beta-blocker- or diuretic-based regimes. This study peels away another rationale for beta-blocker therapy: resting heart rate. Although important in ischemic heart disease and heart failure, it apparently is of no predictive value in uncomplicated hypertension and should not dictate pharmacologic therapy choice according to the results of this study.
There are some caveats to this conclusion. There were very few patients with heart rates over 100 beats/min - only 300. However, about 10% had heart rates > 90 bpm, and no trend toward improvement with beta blocker was seen. So, the conclusions probably should be confined to those with normal sinus rhythm (heart rates 60-100 bpm). Also, the conclusions may only apply to those without ischemic heart disease, since there was a trend at six weeks for increased heart rate to be associated with cardiac death and myocardial infarction. It may not always be possible to determine who with hypertension does not have coronary heart disease. In this trial, those with a history or ECG evidence of CAD were excluded, but obviously some had subclinical diseases at baseline since they went on to have ischemic cardiac events. Clearly, in anyone with symptoms or signs of ischemic heart disease, beta-blocker therapy makes sense.
There are limitations to this study. The endpoint was a combined one. Despite the large number of patients, they lacked the power to determine the results with individual endpoints, although trends with individual endpoints were the same as the combined endpoint. This was a substudy of a trial that was already completed and not designed to test this hypothesis. Finally, baseline heart rates in this study may not have been representative of the patient's true resting heart rate, as they were derived from one measure at one visit. On the other hand, the results are consistent with those of the recently reported INVEST study (Am Heart J. 2008;156:241-247), where an atenolol-based regime was compared to a verapamil yet the outcome data was the same.
At this point, if a new hypertensive patient without evidence of CAD or heart failure has a resting heart rate of 80-100, there is no evidence that a beta blocker should be the first-line therapy. An amlodipine-based regimen with a second added agent, one that blocks the rennin angiotensin system, would still be first-line therapy, based upon the ACCOMPLISH trial (N Engl J Med. 2008;359:2417-2428). If the systolic blood pressure is > 160 or > 20 mmHg above the patients target blood pressure, then initial combination therapy is appropriate.
Although heart rate is known to be a marker for the utility of beta blockers in ischemic heart disease and heart failure, there is no comparable trial data in hypertension.Subscribe Now for Access
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