Blood Pressure Targets Recommended by Guidelines and Incidence of Cardiovascular and Renal Events in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)

Study Questions:

What are the cardiovascular and renal benefits associated with blood pressure treatment targets of <140/90 mm Hg or <130/80 mm Hg in patients at high cardiovascular risk?

Methods:

The authors reported on a post-hoc analysis of the ONTARGET (Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial) study, a multicenter, randomized trial of telmisartan versus ramipril versus both in subjects with known atherosclerotic disease or diabetes with end-organ damage. Patients with heart failure or blood pressure >160 mm Hg systolic or >100 mm Hg diastolic were excluded. The median follow-up was 56 months, with visits at 6 weeks, 6 months, and then every 6 months. The primary endpoint was the composite outcome of death from cardiovascular causes, nonfatal myocardial infarction (MI), nonfatal stroke, and hospitalization for heart failure. Secondary endpoints were the composite of the first three above outcomes and the specific cardiovascular events included in the composite outcome, as well as events such as end-stage renal disease, new-onset microalbuminuria, or new-onset macroalbuminuria. The three treatment groups were pooled for this analysis, because outcomes were not different among them. For the current analysis, four groups of subjects were created according to percentage of in-treatment visits at which blood pressure was found to be controlled: <25%, 25-49%, 50-74%, and ≥75%. Cox proportional hazard models were created, generating hazard ratios for risk of endpoints, adjusted for multiple potential confounders, and also adjusted for, in one model, whether blood pressure was controlled in a time-dependent fashion.

Results:

The original study included 12,554 to 11,782 subjects, depending on the time of endpoint occurrence. The authors reported that in a progressive fashion, the increase in the proportion of visits in which blood pressure was controlled (by the above definitions) was associated with a progressive reduction in the risk of stroke, new-onset microalbuminuria, or macroalbuminuria. However, the risk of MI and heart failure were not associated with an increased frequency of blood pressure control. A reduction in the risk of cardiovascular events was associated with increasing frequency of blood pressure control.

Conclusions:

The authors concluded that the more frequent achievement of the blood pressure targets recommended by guidelines led to cerebrovascular and renal protection, but did not increase protection from cardiac events. Overall, cardiovascular protection was favorably affected by the less tight, but not the tighter blood pressure control target.

Perspective:

The data from the ONTARGET study provide a large and rich clinical observational opportunity that the authors have exploited in this post-hoc analysis to gain further insight into the clinical effect of achieving guideline-based blood pressure control targets. Clearly, there is a mountain of evidence showing that the greatest benefit from blood pressure control is stroke risk reduction. The current study strongly corroborates that, and also demonstrates a strong association between increasingly better blood pressure control and decreased frequency of renal failure outcomes. While the data in this study did not show a trend toward lower MI rates with greater blood pressure control, it should be noted that the MI rate in the group with best blood pressure control was significantly lower than in any of the other groups. The potential for type II error is significant, even in a study as large as this. For that reason, the positive findings—strong association between blood pressure control and reduced rate of stroke and renal failure—are probably meaningful, and certainly support current therapy. The negative finding with regard to the lack of a trend toward lower MI rates with better blood pressure control should not lead to withholding of preventive therapy.

Clinical Topics: Heart Failure and Cardiomyopathies, Prevention, Novel Agents, Acute Heart Failure, Hypertension

Keywords: Myocardial Infarction, Follow-Up Studies, Risk Reduction Behavior, Risk Factors, Benzoates, Incidence, Renal Insufficiency, Benzimidazoles, Cardiology, Heart Failure, Cardiovascular Diseases, Blood Pressure Determination, Diastole, Hypertension


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