Drug therapy decision course misleading

Issue: BCMJ, vol. 53, No. 6, July August 2011, Page 259 Letters
By: Adi Mudaliar, MD, CCFP

I wish to share with colleagues my experiences at the 22nd Annual Drug Therapy Decision course on 1–2 April 2011. This course was sponsored by the Therapeutics Education Collaboration and the University of British Columbia.

The following are key learning points for the uninformed audience:

• In systolic heart failure use low-dose ACE and beta blocker doses despite what the major trials and important guidelines tell us.

• The A1C target in diabetes care is 7.5% to 8.0% not the 7% that most competent physicians try to achieve.

•  In atrial fibrillation with a CHADS2 score of 1, 2, or 3 treatment with an oral anticoagulant is debatable.

•  Cardiovascular “screening is a marketing machine, don’t worry about stupid numbers.” Also we should “stop worrying about LDL targets.”

Additional memorable learning points were that the Steno-2 Study[1] (which showed that long-term, multiple-risk factor intervention reduced micro- and macrovascular events) and the UKPDS 10-year follow-up study[2] (or “legacy effect,” which showed persistent risk reduction over time for the intensive glucose control group) were not that important.

Other significant trials like HEALL[3] (low-dose vs high-dose losartan in heart failure), ACTIVE I[4] (irbesartan in atrial fibrillation) and ROADMAP[5] (olmesartan in type 2 diabetes) were presented in a lopsided, negative light without important trial details, thus missing an educational opportunity.

Regarding basal insulin, NPH use was suggested over basal analogue insu­lin despite lower risks of hypoglycemia as shown in the 4T Study[6] with dete­mir compared to NPH in UKPDS[7] and in the Treat to Target Trial[8] with glar­gine vs NPH.

The MOCHA trial[9] with carvedi­lol was one of the first beta blocker trials in heart failure to show mortality reduction. This trial was summed up on a single slide to imply that increasing dosage had no additional benefit. However the actual publication des­cribes a dose-related improvement in LV function, mortality, and hospitalization. 

Also a slide showing a meta-analysis of beta blocker doses in heart failure[10] implies that dose is not associated with mortality benefit. However, the authors’ point was missed—heart rate reduction was associated with reduced mortality. They suggest that this “exploratory” finding was hypothesis generating.

Despite the “evidence-based” im­pression that the course presenters wish to give to any who will listen, they still cling to the low-dose hydro­chlorothiazide first line in hypertension mantra that Mr Bob Nakagawa, assistant deputy minister BC Pharmacare, unwittingly mimics. 

This view is set in stone despite a lack of outcome data for low-dose HCTZ and its inferior ambulatory BP effects compared with other agents.[11-13]

 This was my first and last TEC/TI educational endeavor. The course directors will no doubt continue to mislead new and inexperienced physicians and physicians in training. I am surprised that the College of Family Physicians of Canada accredits this tripe and that UBC seems to endorse it.
—Adi Mudaliar, MD 
Vancouver

References

1. Gaede P. Multifactorial intervention and cardiovascular disease in patients with type 2 diabetes. N Engl J Med 2003;348:383-393.
2. Holman RR. 10-year follow-up of intensive glucose control in type 2 diabetes. N Engl J Med 2008;359:1577-1589.
3. Konstam MA. Effects of high-dose versus low-dose losarten on clinical outcomes in patients with heart failure (HEALL study): A randomised, double-blind trial. Lancet 2009;374:1840-1848.
4. Yusuf S. Irbesartan in patients with atrial fibrillation ACTIVE I. N Engl J Med 2011;364:926-938.
5. Haller H. Olmesartan for the delay or prevention of microalbuminuria in type 2 diabetes ROADMAP. N Engl J Med 2011;364:907-917.
6. Holman RR. Three-year efficacy of complex insulin regimens in type 2 diabetes. N Engl J Med 2009;361:1736-1747. 
7. UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulfonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). Lancet 1998;352:837-853.
8. Riddle MC. The Treat to Target Trial. Randomized addition of glargine or human NPH insulin to oral therapy of type 2 diabetic patients. Diabetes Care 2003;26:3080-3086.
9. Bristow MR. Congestive heart failure/myocardial disease: Carvediol produces dose-related improvements in left ventricular function and survival in subjects with chronic heart failure MOCHA. Circulation 1996;94:2807-2816.
10. McAlister FA. Meta-analysis: B-blocker dose, heart rate reduction, and death in patients with heart failure. Ann Intern Med 2009;150:784-794.
11. Jamerson K. Benazepril plus amlodipine or hydrochlorothiazide for hypertension in high risk patients ACCOMPLISH. N Engl J Med 2008;359:2417-2428.
12. Messerli FH. Antihypertensive efficacy of hydrochlorothiazide as evaluated by ambulatory blood pressure monitoring. A meta-analysis of randomised trials. J Am Coll Cardiol 2011;57:590-600.
13. Dorsch MP. Chlorthalidone reduces cardiovascular events compared with hy­dro­chlorothiazide. A retrospective cohort analysis. Hypertension 2011;57:689-694.

Adi Mudaliar, MD, CCFP. Drug therapy decision course misleading. BCMJ, Vol. 53, No. 6, July, August, 2011, Page(s) 259 - Letters.


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