Bisoprolol is well suited as the first-line treatment of angina in primary care: A real-world evidence study

Results of a real-evidence study suggest that bisoprolol is associated with long-term significant
reduction in the risk of mortality and various cardiovascular events versus other β-blockers, and
drugs other than β-blockers. These results confirm the guidelines recommendation that bisoprolol is
suitable as the first-line treatment of angina in primary care.

Atherosclerotic obstruction of one or more of the coronary arteries (CAD) is the most common cause
of myocardial ischemia. The development of angina is the first clinical indication of CAD in most of
the patients. It also indicate the need to initiate treatment to reduce symptoms and their risk of an
acute event. European Society of Cardiology and American Heart Association guidelines recommend
β-blockers are the first-line therapy for patients with angina. Other drugs, such as nitrates, should be
considered when β-blockers or calcium channel blockers (CCB) treatment has been clinically
excluded as a treatment option.

Among the β-blockers, bisoprolol is a β1-selective blocker. Studies suggest that bisoprolol is found to
reduce the ischemic burden in patients with angina in comparison to the nifedipine and angina
attacks. It is also found to improve exercise tolerance in comparison to isosorbidedinitrate. However,
these studies have a small sample size and short- to medium-term follow-up. Therefore, a cohort
analysis using UK Clinical Practice Research Data link (CPRD) was conducted to compare the
incidence and risk of mortality and several cardiovascular (CV) events, including myocardial
infarction (MI), angina, embolism, arrhythmia, or stroke in patients with angina receiving
monotherapy with bisoprolol versus other β-blockers or drugs other than β-blockers in patients with
angina in a real-world primary care setting.

Patient population

The study included
• Patients with newly diagnosed with angina pectoris
• Prescribed bisoprolol, another β-blocker, or another drug as monotherapy within 6 months
of the first diagnosis of angina.
Each patient was followed from first recorded angina event until the date of patient death, last data
collected, or treatment cohort switch, whichever came first.

Treatments

Patients were categorized into three cohorts receiving monotherapy.
• Bisoprolol cohort: patients receiving bisoprolol fumarate.
• Other β-blocker cohort: patients treated with any other β-blocker except bisoprolol
• Drugs other than β-blockers cohort: Patients treated with CCBs, angiotensin-convertingenzyme inhibitors, diuretics, α-blockers, aldosterone receptor antagonists, and digitalis.

Outcomes measured

• Primary outcome: total mortality, defined as date of death by any cause recorded in the
CPRD.
• Secondary outcomes: Nonfatal MI, nonfatal stroke, nonfatal arrhythmia, an embolism event
and an angina episode, all defined by READ codes, mean proportional change of diastolic BP
(DBP), systolic BP (SBP), and heart rate.
The study included 7607 patients of which 987 (12.9%) were treated with bisoprolol, 1348 (17.7%)
with other β-blockers and 5272(69.4%) with drugs other than β-blockers.

Effect on mortality and survival

Bisoprolol treatment significantly improved survival over time compared with other β-blockers, and
drugs other than β-blockers. Mortality rate decreased by 55% in patients treated with bisoprolol
compared with those treated with other β-blockers or by 50% compared to those treated with drugs
other than β-blockers. This benefit was maintained over 14 years.

The mortality incidence rate was 15.27 deaths per 1000 person-year in patients treated with
bisoprolol, 26.64 deaths per 1000 person-year with other β-blockers, and 31.80 deaths per 1000
person-year with drugs other than β-blocker cohort. The mortality incidence rate was lowest in
patients treated with bisoprolol than with other β-blocker and drugs other than β-blocker at 1 year,
2 years, 5 years and 10 years.

Effect on cardiovascular outcomes

Bisoprolol treatment reduced secondary angina (HR: 0.77; 95% CI: 0.68–0.88) and MI (HR: 0.34; 95%
CI: 0.23–0.52) compared with other treatments cohorts.
There was a significant reduction in the risk of arrhythmia with bisoprolol treatment compared with
other treatments.

Risk of stroke also decreased, although, it was only significant after 2 years (HR for<5 years: 0.38;
95% CI: 0.17–0.82 and HR for 10 years: 0.45; 95% CI: 0.21–0.97).

Duration and adherence to treatment

Treatment duration was less in the bisoprolol cohort (1.5 years) than in the cohorts receiving other
β-blocker, or a drug other than a β-blocker (2.6 and 2.5 years, respectively).
Fewer patients discontinued treatment with bisoprolol (12.9%) compared with the other agents
(19% in the β-blocker cohort and 17.6% in the drugs other than β-blocker cohort).
A higher percentage of patients in the bisoprolol cohort (90.6%) were adherent, compared with
patients receiving a different β-blocker (85.9%) or a drug other than a β-blocker (63.2%).

In summary,

In patients with new-onset angina, bisoprolol treatment significantly reduced the risk of mortality
and CV outcomes compared with other treatments in a real-world primary care population. These
results support the recommendation of bisoprolol as a first-line treatment in patients with angina.

Reference

Sabidó M, Thilo H, Guido G. Long-term effectiveness of bisoprolol in patients with angina: A realworld evidence study. Pharmacol Res. 2019;139:106-112.