Real-World Effectiveness of Beta-Blockers versus Other Antihypertensives in Reducing All-Cause Mortality and Cardiovascular Events

Abstract

Aim: The aim of the study was to compare the effectiveness of beta-blockers with other antihypertensive classes in reducing all-cause mortality, cardiovascular-related mortality and the risk of cerebrocardiovascular events.

Methods: This noninterventional study was conducted within the UK Clinical Practice Research Datalink. Hypertensive patients who initiated antihypertensive monotherapy were allocated to one of five cohorts: beta-blockers; angiotensin-converting enzyme inhibitors (ACEi); angiotensin II receptor blockers (ARB); calcium channel blockers (CCB); and diuretics. Differences in outcomes were assessed using Cox proportional hazard models with competing risks.

Results: A total of 44,404 patients were prescribed beta-blockers (75% atenolol), 132,545 ACEi, 12,018 ARB, 91,731 CCB, and 106,547 diuretics. At baseline, patients in the beta-blocker cohort presented more frequently with angina, arrhythmia, and atrial fibrillation. The risk of all-cause mortality was lower for those treated with ACEi, ARB, and CCB, and no difference was observed compared with diuretics (adjusted hazard ratio versus beta-blockers (98.75% CI), for ACEi 0.71 (0.61, 0.83), ARB 0.67 (0.51, 0.88), CCB 0.76 (0.66, 0.88), diuretics 1.06 (0.93, 1.22)). No differences were seen in the risk of cardiovascular mortality for patients treated with beta-blockers, ARB, CCB, and diuretics, while a lower risk in patients treated with ACEi was observed (ACEi 0.63 (0.43, 0.91), ARB 0.64 (0.32, 1.28), CCB 0.71 (0.49, 1.03), diuretics 0.97 (0.69, 1.37)).

Conclusions: These data add to the limited pool of evidence from real-world studies exploring the effectiveness of beta-blockers versus other antihypertensive classes. Discrepancies to previously published studies might be partly explained by differences in the selected populations and in the follow-up time.

Figure 1

Study design.

Figure 2

All-cause mortality Kaplan–Meier curves. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; CCB, calcium channel blocker.

Figure 3

Risk of all-cause and cardiovascular mortality and Fine and Gray model for the event of cardiovascular mortality. Differences in risk of all-cause and cardiovascular mortality were assessed using adjusted Cox proportional hazard models (HR) and fine and gray proportional SHR, considering discontinuation as a competing event. Models were adjusted for age at index year; sex; time from hypertension diagnosis; smoking status; BMI; diastolic BP; systolic BP; angina; stroke; arrhythmia; chronic heart failure; myocardial infarction; peripheral vascular diseases; diabetes mellitus; dyslipidemia; and renal impairment. 98.7% CIs were generated using a Bonferroni correction (1–(0.05/4)) to account for multiple comparisons. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PY, person years; SHR, sub-distribution hazard ratio.

Figure 4

Risk of myocardial infarction and Fine and Gray model for the event of myocardial infarction. Differences in risk of myocardial infarction were assessed using adjusted Cox proportional hazard models (HR) and fine and gray proportional SHR, considering discontinuation as a competing event. Models were adjusted for age at index year; sex; time from hypertension diagnosis; smoking status; BMI; diastolic BP; systolic BP; angina; stroke; arrhythmia; chronic heart failure; myocardial infarction; peripheral vascular diseases; diabetes mellitus; dyslipidemia; and renal impairment. 98.7% CIs were generated using a Bonferroni correction (1–(0.05/4)) to account for multiple comparisons. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PY, person years; SHR, sub-distribution hazard ratio.

Figure 5

Risk of stroke and Fine and Gray model for the event of stroke. Differences in risk of stroke were assessed using adjusted Cox proportional hazard models (HR) and fine and gray proportional SHR, considering discontinuation as a competing event. Models were adjusted for age at index year; sex; time from hypertension diagnosis; smoking status; BMI; diastolic BP; systolic BP; angina; stroke; arrhythmia; chronic heart failure; myocardial infarction; peripheral vascular diseases; diabetes mellitus; dyslipidemia; and renal impairment. 98.7% CIs were generated using a Bonferroni correction (1–(0.05/4)) to account for multiple comparisons. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PY, person years; SHR, sub-distribution hazard ratio.

Figure 6

Risk of hemorrhagic stroke and Fine and Gray model for the event of hemorrhagic stroke. Differences in risk of hemorrhagic stroke were assessed using adjusted Cox proportional hazard models (HR) and fine and gray proportional SHR, considering discontinuation as a competing event. Models were adjusted for age at index year; sex; time from hypertension diagnosis; smoking status; BMI; diastolic BP; systolic BP; angina; stroke; arrhythmia; chronic heart failure; myocardial infarction; peripheral vascular diseases; diabetes mellitus; dyslipidemia; and renal impairment. 98.7% CIs were generated using a Bonferroni correction (1–(0.05/4)) to account for multiple comparisons. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PY, person years; SHR, sub-distribution hazard ratio.

Figure 7

Risk of ischemic stroke and Fine and Gray model for the event of ischemic stroke. Differences in risk of ischemic stroke were assessed using adjusted Cox proportional hazard models (HR) and fine and gray proportional SHR, considering discontinuation as a competing event. Models were adjusted for age at index year; sex; time from hypertension diagnosis; smoking status; BMI; diastolic BP; systolic BP; angina; stroke; arrhythmia; chronic heart failure; myocardial infarction; peripheral vascular diseases; diabetes mellitus; dyslipidemia; and renal impairment. 98.7% CIs were generated using a Bonferroni correction (1–(0.05/4)) to account for multiple comparisons. ACEi, angiotensin-converting enzyme inhibitor; ARB, angiotensin II receptor blocker; BMI, body mass index; BP, blood pressure; CCB, calcium channel blocker; CI, confidence interval; HR, hazard ratio; PY, person years; SHR, sub-distribution hazard ratio.