Resting heart rate is a known risk factor for cardiovascular and all-cause mortality in patients with and without cardiovascular disease.1 Many physicians feel patients with uncomplicated hypertension (HTN) and elevated heart rates should be given beta blockers as first line agents to manage their blood pressure even though clinical data is lacking to support the benefits of beta blockers in this patient population. Beta blockers’ heart rate lowering effects decrease cardiovascular morbidity and mortality in patients with heart failure or prior myocardial infarction, but it is unknown if these protective benefits extend to patients with uncomplicated hypertension and elevated resting heart rates.
The original ASCOT-BPLA (Anglo-Scandinavian Cardiac Outcomes Trial-Blood Pressure Lowering Arm) was a multicenter, PROBE (prospective randomized open, blinded endpoint) study that followed 19,257 patients for up to 5 years.2 Patients were enrolled in the study if they had untreated hypertension (SBP ≥160 mmHg and/or DBP ≥100 mmHg) or treated hypertension with SBP ≥140 mmHg and/or DBP ≥90 mmHg and aged 40-79 years with at least 3 cardiovascular risk factors. Patients were excluded from the trial if they had a previous history of MI, currently treated angina, cerebrovascular event in last 3 months, fasting triglyceride level >4.5 mmol/L, heart failure, uncontrolled arrhythmias, and any clinically important hematological or biochemical abnormality in routine screening. 6,498 patients were excluded in the analysis because they were taking a beta-blocker or another rate-limiting antihypertensive medication at screening. Patients were randomized to atenolol ± bendroflumethiazide (N=6,361) or amlodipine ± perindopril (N=6,398). There were no significant baseline differences between the two groups. The average age was 63 years; 95% of the patients were Caucasian and 77% were male. The study was stopped prematurely after 5.5 years (106,153 patient-years of observation). The occurrence of the primary outcome (fatal and nonfatal myocardial infarction) was not statistically different between regimens. However, there was a reduction in total cardiovascular events and procedures in the amlodipine-based treatment group (0.84, 0.78-0.90, p<0.0001).
Poulter et al. recently conducted a post hoc analysis on the ASCOT-BPLA to evaluate the efficacy of an atenolol-based and amlodipine-based therapy in patients with uncomplicated hypertension and elevated baseline heart rates.3 The primary outcome of this study was total cardiovascular events or procedures. The secondary outcomes were nonfatal myocardial infarction or fatal coronary heart disease (primary outcome of original ASCOT-BPLA) and total stroke. Their analysis revealed that baseline heart rate did not predict the occurrence of either the primary or the secondary outcomes. Although patients’ heart rate decreased more in the atenolol group than the amlodipine group (12 beats per minute versus 1.3 beats per minute), the amlodipine-based therapy was associated with greater reductions in all three endpoints than the atenolol-based therapy [Total cardiovascular events and procedures HR 0.81 (95% CI 0.74-0.88) p<0.001, Nonfatal MI and fatal coronary heart disease HR 0.88 (95% CI 0.75-1.03) p=0.11, Total stroke HR 0.74 (95% CI 0.62-0.88) p=0.001]. Amlodipine-based therapy was beneficial regardless of baseline heart rate.
The author’s of the original ASCOT-BPLA trial concluded that the amlodipine-based therapy prevented more cardiovascular events than the atenolol-based therapy in patients with uncomplicated hypertension. In the post hoc analysis the authors reinforced these conclusions, even in patients with elevated baseline heart rates. In ...