Steve Wong, MD, FRCPC (biography and disclosures)
What I did before
Choosing hypertensive agents took into account underlying diagnoses (eg. CHF, hypertension, renal disease, etc) but beyond that, I generally started with thiazide diuretics (due to cost and proven effectiveness) then added either an ACE inhibitor (ACEi) or a calcium channel blocker (CCB), consistent with the Canadian Hypertension Society Guidelines. Most patients will require more than 1 antihypertensive for control. I generally thought as long as BP targets were met, the specific combination was less important.
What changed my practice
There were trials that suggested ACEi + CCB or ARB + diuretic combinations were better than beta-blockers and diuretics (ASCOT BPLA trial, LIFE trial) however controversy remains whether the benefit seen was as a result of less protection from a beta-blocker based regimen. The ACCOMPLISH trial compared a regimen of a CCB+ACEi (amlodipine/benazepril) vs HCTZ/ACEi (benazepril). This 11,500 patient trial was stopped early: although both arms achieved identical BP lowering, the CCB+ACEi arm had 19.6% fewer primary endpoint events (combined cardiovascular mortality, nonfatal MI and nonfatal stroke, hospitalization for angina, revascularization and resuscitated arrest) for an NNT of 45 over 42 months.
What I do now
I would still advocate choosing first and second line agents based on underlying diseases. In absence of this, I still start with a thiazide diuretic in most patients with BP <160/100.
If they are still not controlled, or their drug-naive BP is >160/100 (or >20/10 above target) I would strongly consider changing to or starting off with an CCB/ACEi combination. Obviously there is a higher cost with this, but the results of the ACCOMPLISH trial would support this strategy.
References: (Note: Direct article downloads and article requests require a login ID with the BC College of Physicians website)- ASCOT BPLA: Dahlöf B, Sever PS, Poulter NR, et al. Lancet. 2005;366:895-906.
- LIFE Trial: Dahlöf B et al, Lancet 2002; 359: 995–1003
- ACCOMPLISH: Jamerson et al., N Engl J Med 2008;359:2417-28 (Article Request Form)
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Excellent rationale for using a higher cost alternatives for treatment of hypertension to result in lower long term costs due to fewer primary endpoint events and better patient outcomes.
Great summary and rationale for HTN approach – one detail, do you have to use amlodipine/benazepril or is this considered a class effect and any such combination will work (For example I generally start patients on ramipril and so I wouldn’t want to have to switch all of them to benzapril)?
Not willing to switch based on a single study, especially as CCB’s have significantly more side effects as a class (headache, nausea, peripheral edema). To be fair, Norvasc (amlodipine) is the best tolerated of them, but still I have reservations. Wait till your female patients come back from holiday and find out its your fault they couldn’t get their shoes on. It would be interesting to follow who were the patients who get the most protection from a CCB (age, sex, smoker, etc.?).
I am still starting with an ACE if no history of allergic disease or ARB if there is, and add diuretic either at the start if I need systolic 40+ lower, or later if not getting the control I need.
Yes, I agree with the author that selecting antihypertensive agent or combination must be done mainly on the basis of underlying diseases or conditions. I also think that for economic reason, thiazide diuretic may be used as first line drug but I do not prefer long term thiazide diuretic for the fear of developing hyperglycemia.
Obviously according to ACCOMPLISH trial, CCB+ACEIs is the next line antihypertensive therapy, I am successfully using CCB+ARB e.g. amlodipine+valsartan and amlodipine+olmesartan.
I think we should rethink about beta blockers. Why not to go for vasodilatory and cardio selective beta blocker like nebivolol?
Great questions.
1. The CHEP guidelines have long endorsed 2 agents for BP control, and the recent updates have amplified the choices of combos, with optimal combos including ACE-i+CCB, ACEi+diuretic. The major difference is cost, and, per the ACCOMPLISH trial, a suggestion of better clinical efficacy. I think the crux of this is to discuss with patients that, although there is an increased cost of medication to them, there is evidence of better clinical outcomes with an ACEi+CCB. We cannot tell the difference based on BP measures alone (as in the study the ACEi-diuretic combo had the SAME BP).
2. Benazepril is not available in Canada. I think its reasonable to extend this data to other long-acting ACEi. Theoretically, ARBs+CCB should show a similar benefit, but we have no trials to back this up.
3. ACEi in combination with CCB therapy seems to reduce the incidence of edema (diuretics don’t help CCB induced edema). You may also be able to use lower CCB doses, thus less CCB-related edema.
4. Bblockers are falling off of favor in most hypertension guidelines around the world, as they are less robust in reducing clinical endpoints. Some data suggest that, although they reduce peripheral BP, central BP’s aren’t reduced as much or at all, and this may explain some of the lack of efficacy.
Yes, I agree with the author that selecting antihypertensive agent or combination must be done mainly on the basis of underlying diseases or conditions. I also think that for economic reason, thiazide diuretic may be used as first line drug but I do not prefer long term thiazide diuretic for the fear of developing hyperglycemia.Obviously according to ACCOMPLISH trial, CCB+ACEIs is the next line antihypertensive therapy, I am successfully using CCB+ARB e.g. amlodipine+valsartan and amlodipine+olmesartan.I think we should rethink about beta blockers. Why not to go for vasodilatory and cardio selective beta blocker like nebivolol?
+1
I am concerned by the under reported incidence of hyponatremis with diuretics particularly in the elderly. Unless the clinican is aware and watchful patients can suffer from protracted hyponatremia with some devastating consequences. As a geriatrician I avoid diuretics.