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Beta Blockers And the Risk of CV Events in Type 2 Diabetes

Beta-blocker use in patients with T2DM and established CV risk factors associated with increased risk of CV events and severe hypoglycemia, according to recent study.

Diabetes mellitus management mainly aims at preventing diabetes mellitus–related complications. Although appropriate glycemic control prevents complications, the ACCORD trial (Action to Control Cardiovascular Risk in Diabetes) revealed that intensive therapy can increase all-cause and cardiovascular mortalities. A possible explanation for the results is that glucose-lowering therapy increases the frequency of hypoglycemic episodes, which in turn is associated with increased risks for vascular events and death. Patients with diabetes mellitus with severe hypoglycemia face many critical problems, such as severe hypertension, hypokalemia, and QT prolongation, resulting in cardiovascular diseases, fatal arrhythmia, and death.

Recent studies have suggested that β-blockers may prevent or decrease the adverse effects after the occurrence of severe hypoglycemia, such as severe hypertension and hypokalemia, and may reduce severe hypoglycemia-associated cardiac arrhythmias and death. A recent study revealed that the cardiovascular event rate in patients with diabetes mellitus on β-blockers was significantly lower in the intensive therapy group compared with the standard therapy group. Conversely, all-cause and cardiovascular mortalities in patients not on β-blockers were significantly higher in the intensive therapy group. The difference of these results between patients on and those not on β-blockers may be mainly because of the protective effects of β-blockers after the occurrence of severe hypoglycemia. However, this does not necessarily mean that the use of β-blockers is effective in patients with diabetes mellitus because the use of β-blockers poses a potential risk for the occurrence of severe hypoglycemia. It was evaluated whether the use of β-blockers was effective in patients with diabetes mellitus and whether its use was associated with the occurrence of severe hypoglycemia in recent diabetes mellitus management.

Lead author Hiroshi Kajio, MD, PhD, of the National Center for Global Health and Medicine, Tokyo, Japan, and colleagues wrote, “But, according to the results of the ACCORD trial data, this study demonstrated that the use of β-blockers was associated with an increased risk for cardiovascular events and severe hypoglycemia in the modern era. Furthermore, a similar relationship between the use of β-blockers and cardiovascular events was found in patients with heart disease. The indication of β-blockers may need to be reconsidered when this connection is elucidated through future higher-level evidence.”

While going too far for glycemic control to reduce the risk of diabetic complications, it may be counterproductive. Results from the ACCORD trial suggest that intensive glucose-lowering therapy is associated with increased hypoglycemia and mortality, which led to discontinuation of the trial after 3.5 years. One of the explanations for these results is that intensive glucose lowering can increase hypoglycemic episodes, which in turn are associated with a heightened risk of vascular events and death.

During episodes of severe hypoglycemia, β-blockers may serve a protective function by decreasing hypoglycemia-related cardiac arrhythmias, severe hypertension, and CV events. However, β-blockers themselves can increase the risk of severe hypoglycemia. They may also dampen early warning signs and contribute to hypoglycemia unawareness. β-blockers also may lead to weight gain, which may increase the risk of CV events over time.

The question arises as to how effective are β-blockers in patients with T2DM? To find an answer, researchers performed a post-hoc analysis of data from the ACCORD trial. The study took place in 77 clinical centers in the US and Canada and included 10,251 people with T2DM, inadequately controlled hemoglobin A1c, and pre-existing CV disease (or at increased risk for it). Participants were randomized to intensive glucose-lowering therapy or standard therapy. The mean follow-up time was slightly over 4.5 years.

The authors explained that the elevated risk of CV events associated with β-blockers was at least partly related to increased severe hypoglycemia, and that this risk may outweigh the protective effect β-blockers may have during severe hypoglycemia. However, they also noted that some subgroups may not have been large enough to reach statistical significance for variables such as CV death and all-cause death. “Newly randomized controlled trials are required to evaluate whether the use of β-blockers in patients with diabetes mellitus shows beneficial or adverse effects,” they concluded.

From the results, it was concluded that, using the ACCORD trial data, this study demonstrated that the use of β-blockers was associated with an increased risk for cardiovascular events and severe hypoglycemia. And also, a similar relationship between the use of β-blockers and cardiovascular events was found in patients with heart disease. The indication of β-blockers may need to be reconsidered when this connection is elucidated through future higher-level evidence.

Practice Pearls:

  • Post-hoc analysis of the ACCORD trial data suggests that the risk of CV events and severe hypoglycemia is higher in patients with T2DM and established CV risk factors who take β-blockers.
  • β-blockers are associated with a significantly increased risk of CV events in patients with or without CHD/HF and those receiving standard therapy.
  • Increased risk of CV events associated with β-blockers may outweigh their protective effect on the heart and vasculature during hypoglycemia, so the indication for β-blockers in T2DM may need reconsideration.

Tsujimoto T, Sugiyama T, Shapiro MF, et al. Risk of cardiovascular events in patients with diabetes mellitus on β-blockers. Hypertension. 2017;70:103-110. doi: 10.1161/HYPERTENSIONAHA.117.09259.

Action to Control Cardiovascular Risk in Diabetes Study Group, Gerstein HC, Miller ME, Byington RP, et al. Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:2545-2559.

Effects of intensive glucose lowering in type 2 diabetes. N Engl J Med. 2008;358:25452559. https://doi.org/10.1161/HYPERTENSIONAHA.117.09259; Hypertension. 2017;70:103-110