Macrovascular Residual Risk Studies

COMMENT

Whether intensive blood pressure lowering is associated with significantly greater benefit on clinical outcomes has been much debated. The previous Action to Control Cardiovascular Risk in Diabetes (ACCORD) study (1) investigated this issue in high cardiovascular risk patients with type 2 diabetes, but showed no significant benefit on cardiovascular outcomes (reduction by 12%) with intensification of blood pressure control. There was, however, a significant decrease in stroke, although the number of events was small and hence confidence interval was wide (Hazard ratio 0.59, 95% CI 0.39-0.89, p=0.01), with a 5-year NNT elevated.

The findings from SPRINT, a much larger, adequately powered trial, change the perspective on blood pressure targets, albeit in high-risk patients without diabetes. The obvious question is what to do in patients with type 2 diabetes? Returning to the ACCORD study (1), it should be noted that the 95% confidence interval for the 12% decrease in major cardiovascular events includes the possibility of a 27% lower risk of major cardiovascular outcomes, consistent with the benefit observed in SPRINT. Furthermore, follow-up data from the ACCORD trial, presented at the American Heart Association Scientific Sessions this year (2) provide more insights. Over a median follow-up of 8.8 years, the group allocated to intensive blood pressure lowering did not have a lower rate of the composite endpoint of nonfatal myocardial infarction or stroke or cardiovascular death (annual event rate 2.03% in the intensive group and 2.22% in the standard group, hazard ratio 0.91, 95% CI 0.79 to 1.05, p=0.19). However, the possibility of an interaction between glycaemic and blood pressure control suggested in the ACCORD trial was confirmed in the follow-up data (p for interaction =0.037) (2). Taking this into account, there was a 21% reduction in major cardiovascular events in type 2 diabetes patients allocated to intensive blood pressure control in the standard glycaemic arm (hazard ratio 0.79, 95% CI 0.65–0.96). Although these findings should be regarded as hypothesis-generating and not definitive, the magnitude of benefit is consistent with that observed in SPRINT.

Any change in therapeutic management needs to consider the benefit versus risk profile of the treatment. In SPRINT, intensive blood pressure control was also associated with significant increases in serious adverse events including hypotension, syncope, electrolyte abnormality, and acute kidney injury or acute renal failure. Thus these adverse events need to be weighed against the potential for clinical outcomes benefit with this approach. Additionally, there are practical considerations, as attainment of this lower SBP goal (<120 mmHg) is likely to be particularly challenging in routine practice. Already EUROASPIRE IV has shown that less than 50% of secondary prevention patients attain a blood pressure target of <140/90 mmHg (3); similar findings were reported in ASPIRE-2-PREVENT in patients with coronary heart disease and those at high risk of developing cardiovascular disease (4).

Probably the take home message from SPRINT is that attaining a lower SBP than recommended by current guidelines has clinical benefit in older adults at high cardiovascular risk without diabetes, although the benefit versus risk profile needs to be taken into account. For high risk patients with type 2 diabetes, follow-up data from ACCORD suggest possible benefit in further lowering SBP, in association with recommended standard glycaemic management, to reduce residual cardiovascular risk beyond standard care alone.