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From the Authors:
Clinicians are strongly encouraged to redouble efforts to control blood pressure to lower than 130/80 mmHg in people with diabetes. Vos et al question the validity of the evidence for our ‘Call to Action’. On the contrary, the ‘Call to Action’ is supported by strong clinical trial evidence, backed by major national health care organizations and based on an ongoing clinical care gap demonstrated in Canada (1,2). The original ‘Call to Action’ appropriately referenced evidence from a meta-analysis of randomized controlled clinical trials that documented the large reduction in death and disability that occurs over a short time period, and also referenced individual randomized controlled trials (1). Canadians with diabetes are at twice the risk of death compared with those without diabetes, are at three, seven and 23 times the risk of hospitalization for cardiovascular disease, chronic kidney disease and lower-leg amputation, respectively, and represent a large disease burden in Canada (3).
Vos et al focus on total mortality, while many of the trials cited, due to size and duration, were not designed to examine changes in total mortality rates. Although the meta-analysis and larger trials showed clear and substantive mortality advantages, Vos et al indicate that the cited meta-analysis did not provide the average duration of the individual studies, making it difficult for them to calculate a number needed to treat (NNT) per year. However, NNT is simple and quick to calculate, and the data required for the calculations are generally provided in the original publications. It is concerning that Vos et al selected a few trials to insinuate that blood pressure-lowering treatment is relatively ineffective based on published NNTs. In the Action in Diabetes and Vascular Disease: Preterax and Diamicron MR Controlled Evaluation (ADVANCE) trial (4), 78 people were required to be treated for five years to prevent a death, but people with normal blood pressure who were not recommended for blood pressure-lowering treatment in the ‘Call to Action’ were included. In this worst-case scenario (78 people treated for five years to prevent a death), the worldwide application of the treatment has been estimated to prevent 400,000 deaths per year (4). In the other trial cited by Vos et al (Micro Heart Outcomes Prevention Evaluation [MICRO-HOPE] trial ), 31 people with diabetes would need to be treated with a relatively inexpensive therapy for 4.5 years to prevent one death (or extrapolated to 10 years, 14 treated to prevent a death). The NNTs are lower in several of the other trials not selected by Vos et al.
Furthermore, people are concerned about being disabled as well as dying. For every cardiovascular death in Canada, there are four nonfatal cardiovascular events that result in hospitalization (6). The NNTs to prevent cardiovascular disability are therefore very much lower than to prevent death. For example, the NNT with ramipril for 4.5 years in MICRO-HOPE was 15 to prevent one individual from having a cardiovascular death, myocardial infarction, stroke, admission to hospital for heart failure, a revascularization procedure, development of overt nephropathy, laser therapy for retinopathy or renal dialysis. Treatment of hypertension in people with diabetes very substantially reduces disability as well as death.
Vos et al also suggest that the use of calcium channel blockers in the Systolic Hypertension in Europe (Syst-Eur) trial (7) had no mortality benefit and indicate that the study mentioned harm. In direct contrast, in the Syst-Eur trial, being randomly selected for treatment with a long-acting dihydropyridine calcium channel blocker-based therapy reduced cardiovascular mortality (76% reduction, P=0.01), all cardiovascular events (69% reduction, P=0.002) and all strokes (73% reduction, P=0.02). The reductions in total mortality rate (55% reduction, P=0.09, multifactorial adjusted P=0.04) and in cardiac event rate (63% reduction, P=0.06) were not statistically significant. The only harm to the trial participants that was cited in the publication was the higher cardiovascular death and event rates associated with placebo-based treatment. In the Syst-Eur trial, 21 people with diabetes would need to be treated for two years to prevent a cardiovascular death (extrapolated to 10 years, four treated to prevent a cardiovascular death), and 13 people treated to prevent a cardiovascular event (extrapolated to 10 years, two to three people treated to prevent a cardiovascular event). Notably, the calcium channel blocker-based therapy prevented the majority of the fatal and disabling cardiovascular events that occurred in the two-year trial.
Vos et al critique one of the most effective preventive therapies that are available to health care professionals, where much greater implementation is required. Preventing death and disability is a fundamental aspect of health care delivery and a major responsibility for government, health care professional organizations and all health care professionals. While we agree with Vos et al that greater attention to the prevention of hypertension and diabetes is required, the ‘Call to Action’ addresses the prevention of death and disability in the expanding ranks of those afflicted with diabetes.