{"id":753,"date":"2015-06-25T08:00:18","date_gmt":"2015-06-25T08:00:18","guid":{"rendered":"http:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/?p=753"},"modified":"2017-08-21T11:46:53","modified_gmt":"2017-08-21T11:46:53","slug":"primary-care-corner-with-geoffrey-modest-md-tight-diabetes-control-and-cardiovasc-disease-followup-of-the-va-study","status":"publish","type":"post","link":"https:\/\/stg-blogs.bmj.com\/bmjebmspotlight\/2015\/06\/25\/primary-care-corner-with-geoffrey-modest-md-tight-diabetes-control-and-cardiovasc-disease-followup-of-the-va-study\/","title":{"rendered":"Primary Care Corner with Geoffrey Modest MD: Tight diabetes control and cardiovasc disease– followup of the VA study"},"content":{"rendered":"

By: Dr. Geoffrey Modest <\/strong><\/p>\n

The Veterans Affairs Diabetes Trial (VADT) was one of the triumvirate published around 2009, along with the ACCORD and ADVANCE trials, which looked at intensive glycemic control and cardiovascular outcomes. These trials basically found that intensive control did not help and perhaps hurt: the ACCORD trial achieved an\u00a0A1c\u00a0of 6.4% in the intensive group vs 7.5% in the standard group, but had no benefit overall for nonfatal MI, nonfatal stroke and cardiovascular disease (CVD)\u00a0deaths and actually had\u00a0a 22%\u00a0increased mortality after 3.5 years; the ADVANCE trial achieved an A1c\u00a0separation of 6.3% vs 7.0% and found no macrovascular or mortality benefit after 5 years; and the VADT achieved an A1c\u00a0separation of\u00a06.9% vs 8.5% and found no CVD or mortality benefit after 5.6 years. \u00a0The current study looked at VADT outcomes in the 1791 military veterans after 11.8 years of followup, up to 5\u00a0years after the study ended\u00a0(see\u00a0N Engl J Med 2015;372:2197-206<\/strong>).<\/p>\n

Findings:<\/p>\n

–followup data available for 92.4% of the participants, with 77.7% agreeing to additional data collection: annual surveys and periodic chart reviews<\/p>\n

–participants in the followup study: mean age 61, 97% male, 63% white\/15% hispanic\/16% black,\u00a0diabetes\u00a0for 12 years, 43% with prior cardiac event, 73% hypertensive, BMI 31, BP 132\/76, LDL 106 mg\/dl, HDL 36 mg\/dl, 15% current smokers<\/p>\n

–the A1c\u00a0separation between the groups decreased from 1.5 percentage points\u00a0(6.9% vs 8.5%)\u00a0during the trial, to 0.2-0.3 percentage points\u00a0(8.0% vs 8.3%)\u00a0by 3 years after the trial ended\u00a0.<\/p>\n

–results:<\/p>\n

–intensive group had lower risk of primary outcome (time to first CVD\u00a0event: heart attack, stroke, new or worsening heart failure, amputation for ischemic\u00a0gangrene, CVD\u00a0death) with HR 0.83 (0.70-0.99), p=0.04,\u00a0after median followup of 9.8 years. \u00a0 Absolute risk reduction of 8.6 major CVD\u00a0events per 1000 person-years, though no reduction in CVD\u00a0mortality<\/p>\n

\u200b–no reduction in total mortality, with HR 1.05 (0.89-1.25) after median followup of 11.8 years<\/p>\n

Conclusion:\u00a0no evidence of any mortality benefit (similar results in\u00a0long-term\u00a0followup of the ADVANCE trial). And, the benefit (significant\u00a017% decrease in major CVD\u00a0events with intensive therapy)\u00a0did come at some expense (increased severe hypoglycemic events in 21.2% vs\u00a09.9% in the standard therapy arm, and likely\u00a0increased medicalization in the intensive arm). Of note, posthoc analysis of the ACCORD trial (see\u00a0Diabetes Care 33:983\u2013990, 2010)\u00a0did find that the achieved A1c still had the strongest relationship with mortality, with a 1% increase in A1c being associated with a 20% increase in mortality. \u00a0But\u00a0they found that higher\u00a0mortality \u00a0was largely explained by which group the patients\u00a0were assigned to, and not by\u00a0the achieved A1c — specifically, those\u00a0patients in the\u00a0intensive control arm\u00a0who could not achieve an A1c<7% had the highest mortality. This analysis suggested that the issue was flogging those in the intensive group who had hard-to-control diabetes with more meds (and, they happened to use a lot of rosiglitazone…).<\/p>\n

So, how does one piece this all together? \u00a0My sense is that the data do support aggressive (even very aggressive) control for younger people who have easy-to-control diabetes. Those with harder-to-control diabetes don’t seem to do so well. This may be because of the long-term sequelae of diabetes and the attendant\u00a0vascular changes, etc. Or the agents we use to improve the A1c\u00a0(metformin is really great, but as we keep adding other agents, there seems to be less cardioprotection). Or because of an interplay of other comorbidities (eg a 5-year Italian study found that those with increasing numbers of comorbidities such as CAD, lung disease, GI problems, heart failure…. had no improvement in cardiovascular events with an A1C < 7 vs <6.5; those without comorbidities did better with the lower A1C threshold. — see\u00a0Ann Intern Med.<\/em>\u00a02009; 151(12):854-860\u200b). Therefore, my bottom line: treat those with long life-expectancy and easy-to-control diabetes as aggressively as I can do safely (as always, as a joint decision with the patient, and largely relying on life-style changes\/nonphamacological management), but avoid just adding on more and more meds in those with difficult-to-treat diabetes to lower the A1c below 7.5-8% or so. My caveat on the last point: there are no good intervention trials looking at higher A1c levels than 8% (ie, is a target of 9% or 10% really\u00a0worse than 8% in difficult-to-treat\u00a0patients with longstanding diabetes and lots of comorbidities??), and I\u00a0certainly have many patients who cannot achieve close to a level of 8%\u00a0(the goal of diabetes management, to me, is not to treat the A1c level, but the patient with diabetes. Although it is important to lower the A1c as much as we can, I have\u00a0several\u00a0patients with blood sugars that range from 45-450 with a very\u00a0high A1c despite many\u00a0mutual attempts to improve diet and exercise, and\u00a0where adding more insulin or other agents is in fact dangerous for them).\u200b<\/p>\n","protected":false},"excerpt":{"rendered":"

By: Dr. Geoffrey Modest The Veterans Affairs Diabetes Trial (VADT) was one of the triumvirate published around 2009, along with the ACCORD and ADVANCE trials, which looked at intensive glycemic control and cardiovascular outcomes. These trials basically found that intensive control did not help and perhaps hurt: the ACCORD trial achieved an\u00a0A1c\u00a0of 6.4% in the […]<\/p>\n

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