References
Brunström M, Carlberg B. Effect of antihypertensive treatment at different blood pressure levels in patients with diabetes mellitus: systematic review and meta-analyses. BMJ. 2016 Feb 24;352:i717. doi: 10.1136/bmj.i717. PubMed PMID: 26920333; PubMed Central PMCID: PMC4770818.ACCORD Study Group, Cushman WC, Evans GW, Byington RP, et al. Effects of intensive blood-pressure control in type 2 diabetes mellitus. N Engl J Med. 2010 Apr 29;362(17):1575-85. doi: 10.1056/NEJMoa1001286. Epub 2010 Mar 14. PubMed PMID: 20228401; PubMed Central PMCID: PMC4123215.
SPRINT Research Group, Wright JT Jr, Williamson JD, Whelton PK, et al. A Randomized Trial of Intensive versus Standard Blood-Pressure Control. N Engl J Med. 2015 Nov 26;373(22):2103-16. doi: 10.1056/NEJMoa1511939. Epub 2015 Nov 9. PubMed PMID: 26551272; PubMed Central PMCID: PMC4689591.
Roman Jaeschke: Let’s switch gears for a moment. You mentioned blood pressure control. You are the first author of the ACCORD trial, which influenced how blood pressure and diabetes was managed. Now we have the SPRINT trial. I wonder, without going into a major academic discourse, whether you could give us your take on blood pressure and diabetes.
Hertzel Gerstein: The ACCORD trial, as you know, tested 3 interventions. One of the interventions it tested was more versus less intense blood pressure lowering in about 4,500 people who had an average duration of diabetes of 10 years plus additional cardiovascular risk factors. As you know, the ACCORD study randomized people to more versus less intense blood pressure lowering and achieved a blood pressure of about 135 versus 119 mm Hg. At the end of the day, there was no significant difference in the primary outcome of nonfatal myocardial infarction, nonfatal stroke, or death from cardiovascular causes. That was done in people, as I said, with diabetes and additional cardiovascular risk factors, with an average duration of diabetes of 10 years. That is a study dedicated to people with diabetes and it had the lowest targets – you know that a target of less than 120 mm Hg for the intervention group was the lowest target. What I think the ACCORD trial showed is targeting less than 120 mm Hg does not have additional bang for the buck compared to getting a blood pressure level that is around 135 mm Hg, in that sort of ballpark.
The SPRINT trial was a trial that explicitly excluded people with diabetes; they also had high risk for cardiovascular disease, and [the study] did show that targeting less than 120 mm Hg did have an additional benefit. The debate will always be whether or not the SPRINT trial results apply to people with diabetes, and I think one can take a liberal and a conservative approach to this. My approach is: Look, there are no people with diabetes in the SPRINT trial. People with diabetes do not just have [elevated] blood pressure and additional cardiovascular risk factors; they also have all of the consequences of dysglycemia. Diabetes is not just a disease that makes your blood pressure higher; it has a whole host of serious problems associated with it, and we do not understand all the mechanisms at which dysglycemia or the elevated glucose level damages your body. So if we have a trial explicitly and exclusively done on people with diabetes and it does not show a clear cardiovascular benefit, I do not think that we are obligated to try and target less than 120 mm Hg in our people with diabetes, because there were more side effects in the ACCORD trial in those people and we may not be benefitting them. Remember that people with diabetes have a higher rate of fractures; if there are proprioceptive or neurological problems they fall more often, and so lowering their blood pressure too much can cause morbidity as well.
On the other hand, the ACCORD trial did also show that one of the components of the composite outcome, which is stroke, was reduced even targeting less than 120 mm Hg. The absolute risk reduction was low because there are very few people that got stroke, but I think that one can at least extrapolate from that data and say: Well, maybe it is fair in people with type 2 diabetes to say if they are at particularly high risk for stroke, because of either previous stroke or other things, then it may very well be worth targeting less than 120 mm Hg for that subgroup of people.
My general approach for people with type 2 diabetes, and I think the Canadian guidelines certainly support that, is that targeting less than 135 mm Hg is a very reasonable target for systolic blood pressure in type 2 diabetes, and until there is evidence to the contrary I think that is the way to go.
RJ: Thank you. Very useful.