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High Blood Pressure

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Issue 6 Contents


When a ß-blocker is indicated which one should we use?

Adverse effects of ß-blockers

A 2002 meta-analysis7 of 15 placebo-controlled trials involving more than 35,000 people, examined the adverse effects associated with ß-blockers. It determined that, annualised:

  • There was no significant increase in depressive symptoms for people on ß-blockers, 6 per 1000 patients (95% CI; -7–19).
  • 18 people in 1000 reported fatigue (95% CI; 5–30). Number needed to harm (NNH) = 57 per year of ß-blocker treatment. Higher association with the older ß-blockers.
  • 5 per 1000 people reported sexual dysfunction (95% CI; 2–8). NNH = 199 per year of ß-blocker treatment.

The ß-blocker lipid solubility did not appear to be a factor in the rate of adverse effects. The selectivity of the ß-blocker may have a greater influence on some adverse effects than lipid solubility.

A later study investigating the adverse effects of ß-blockers in people with heart failure did not find a significant risk of fatigue associated with ß-blocker therapy, 3 per 1000 (95% CI; -2 to 9).8

In practice, however, people do appear to experience fatigue when ß-blockers are initiated and may complain of feeling very lethargic. The ß-blockers in heart failure study suggests that when starting a ß-blocker for hypertension or another cardiovascular condition, starting with a low dosage and increasing slowly (two to four weekly) should improve tolerance.

Atenolol has been one of the preferred ß-blockers in New Zealand for many years. Doubt was cast on the choice of atenolol for treating high blood pressure, when Carlberg et al9 published part of their larger ß-blocker meta-analysis, focusing only on atenolol. There were nine atenolol studies identified – four comparing atenolol with placebo or no treatment and five comparing atenolol with an alternative blood pressure lowering medicine.

In the placebo studies the extent of blood pressure reduction was variable, but there was no significant improvement in all cause mortality, cardiovascular mortality or myocardial infarction, just a significant reduction in stroke. This has been a major debatable point because, paradoxically, it suggests that a reduction in blood pressure is not related to a reduction in cardiovascular events. This is clearly not in line with extensive evidence. Compared to other blood pressure lowering medicines atenolol, despite similar reductions in blood pressure lowering, was significantly less effective in reducing all cause mortality and appeared less effective in reducing cardiovascular mortality.

Coupled with the meta-analysis of all ß-blockers, showing a difference in outcomes between non-atenolol ß-blockers and atenolol,3 this raised the question of whether atenolol was a poor choice of ß-blocker.

ß-blockers are a heterogeneous class of medicines. Soriano et al10 investigated the effect of ß-blocker ancillary properties such as lipophilicity, intrinsic sympathomimetic activity (ISA) and selectivity and questioned the class effect of ß-blockers. ß-blockers that had the most positive effect post-myocardial infarction were lipophilic, ß1 selective and without ISA. Metoprolol was more effective than atenolol.

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