V. Goals of Therapy for Adults With Hypertension Without Compelling Indications for Specific Agents

Prevention and Treatment

Subgroup Members: George K. Dresser, MD, PhD; Robert J. Herman, MD; Pavel Hamet, MD, PhD; Ellen Burgess, MD; Richard Lewanczuk, MD, PhD; Jean C. Gregoire, MD; Luc Poirier, BPharm, MSc
Central Review Committee: Doreen M. Rabi, MD, MSc; Stella S. Daskalopoulou, MD, PhD; Kaberi Dasgupta, MD, MSc; Kelly B. Zarnke, MD, MSc; Kara Nerenberg, MD, MSc; Kerry McBrien, MD, MPH; Kevin C. Harris, MD, MHSc; Alexander A. Leung, MD, MPH
Chair: Raj Padwal, MD, MSc

This information is based on the Hypertension Canada guidelines published in Leung, Alexander A. et al. Hypertension Canada’s 2016 Canadian Hypertension Education Program Guidelines for Blood Pressure Measurement, Diagnosis, Assessment of Risk, Prevention, and Treatment of Hypertension. Can J Cardiol 2016; 32(5): 569-588.

Recommendations

  1. The systolic blood pressure (SBP) treatment goal is a pressure level of < 140 mm Hg (Grade C). The diastolic blood pressure (DBP) treatment goal is a pressure level of < 90 mm Hg (Grade A).
  2. In the very elderly (≥ age 80 years), the BP target is < 150 mm Hg (Grade C).

Background

1. The systolic blood pressure (SBP) treatment goal is a pressure level of < 140 mm Hg (Grade C). The diastolic blood pressure (DBP) treatment goal is a pressure level of < 90 mm Hg (Grade A).

Specified targets are deduced from clinical trial literature demonstrating the benefits of antihypertensive therapy (1-4).

A goal of <140/90 mmHg is to some extent a compromise – high risk patients may benefit from lower thresholds (see Section on Global Vascular Protection) and very low risk patients may not derive substantial benefits from achieving BP levels <140/90 mmHg.  Nevertheless, most trials in the field of hypertension achieved BP levels less than these thresholds and, therefore, <140/90 mmHg represents a reasonable compromise for the BP goal in most individuals.

Patients with hypertension who have concomitant diabetes mellitus derive benefits from even lower treatment thresholds and treatment targets (see Diabetes section).

2. In the very elderly (age ≥ 80 years), the BP target is < 150 mm Hg (Grade C).

The Hypertension in the Very Elderly Trial (HYVET) trial enrolled 3845 subjects aged 80 years or older with SBP ≥ 160 mm Hg (baseline BP 173/91 mm Hg) (14). Initial treatment was sustained-release indapamide 1.5 mg per day or placebo. The ACE inhibitor perindopril (2 mg or 4 mg), or matching placebo, was added as necessary to achieve target BP of 150/80 mm Hg. Patients were followed for the primary outcome of fatal or non-fatal stroke and a number of secondary outcomes including all-cause mortality and cardiovascular mortality.

BP was reduced to 144/77 mm Hg in the active treatment group and was 15.0/6.1 mm Hg lower than the placebo group. The HYVET data safety and monitoring board stopped the trial at the second interim analysis (median follow-up of 1.8 years) because significantly lower rates of the primary outcome and all-cause mortality were found in the group receiving active treatment. In the final analysis, fatal or non-fatal stroke occurred in 1.2% of subjects receiving active treatment, and in 1.8% in those patients receiving placebo (HR, 0.70; 95%CI, 0.49–1.01). Statistically significant reductions in stroke mortality (0.7% vs. 1.1%; HR, 0.61; 95%CI, 0.38–0.99) and all-cause mortality (4.7% vs. 6.0%; HR, 0.79; 95%CI, 0.65–0.95) were observed. Of note, fewer serious adverse events were reported in the active treatment group.

Some methodological limitations of HYVET were noted. The a priori stopping rule significance level for the primary end point was not followed and between the interim and final analyses, statistical significance for the primary endpoint crossed the 0.05 threshold. Furthermore, most of the secondary outcome results (e.g., reductions in fatal stroke and all cardiovascular deaths) are no longer significant if the issue of multiple statistical testing is taken into account. Finally, the trial enrolled a relatively healthy sample of very elderly patients; thus, caution and close follow-up are warranted when generalizing to frailer patients.

Higher risk very elderly patients may benefit from more intensive BP lowering.  This is covered in more detail in the Global Vascular Protection section.

References

  1. Blood Pressure Lowering Treatment Trialists Collaboration. Blood pressure-lowering treatment based on cardiovascular risk: a meta-analysis of individual patient data. Lancet 2014;384:591-598.
  2. Ettehad D, Emdin CA, Kiran A, Anderson SG, Callender T, Emberson J, Chalmers J, Rodgers A, Rahimi K. Blood pressure lowering for prevention of cardiovascular disease and death: a systematic review and meta-analysis. Lancet 2015;387:957-967.
  3. Xie X, Atkins E, Lv J, Bennett A, Neal B, Ninomiya T, Woodward M, MacMahon S, Turnbull F, Hillis GS, Chalmers J, Mant J, Salam A, Rahimi K, Perkovic V, Rodgers A. Effects of intensive blood pressure lowering on cardiovascular and renal outcomes: updated systematic review and meta-analysis. Lancet 2015;387:435-443.
  4. Sundström J, Sheikhi R, Östgren CJ, Svennblad B, Bodegård J, Nilsson PM, Johansson G. Blood pressure levels and risk of cardiovascular events and mortality in type-2 diabetes. J Hypertens 2013;31:1603-1610.
  5. McAlister FA, Levine M, Zarnke K, Campbell NRC, et al., for the Canadian Hypertension Recommendations Working Group. The 2000 Canadian recommendations for the management of hypertension: Part one–Therapy. Can J Cardiol 2001;17:543-59.
  6. Ogilvie RI, Burgess ED, Cusson JR, Feldman RD, Leiter LA, Myers MG. Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of essential hypertension. CMAJ 1993;149(5):575-84.
  7. Collins R, Peto R, MacMahon S, et al. Blood pressure, stroke, and coronary heart disease. Part 2: Short-term reductions in blood pressure: overview of randomised drug trials in their epidemiological context. Lancet 1990;335:827-38.
  8. SHEP Co-operative Research Group. Prevention of stroke by antihypertensive drug treatment in older persons with isolated systolic hypertension: final results of the Systolic Hypertension in the Elderly Program (SHEP). JAMA 1991;265:3255-64.
  9. Blood Pressure Lowering Trialists’ Collaboration. Effects of ACE inhibitors, calcium antagonists, and other blood-pressure-lowering drugs: results of prospectively designed overviews of randomised trials. Lancet 2000;356:1955-64.
  10. Hansson L, Zanchetti A, Carruthers SO, et al. Effects of intensive blood-pressure lowering and low-dose aspirin in patients with hypertension: principal results of the Hypertension Optimal Treatment (HOT) randomised trial. Lancet 1998;351:1755-62.
  11. UK Prospective Diabetes Study Group. Tight blood pressure control and risk of macrovascular and microvascular complications in type 2 diabetes: UKPDS 38. BMAJ 1998;317:703-13 .
  12. Estacio R, Jeffers B, Hiatt W, et al. The effect of nisoldipine as compared with enalapril on cardiovascular outcomes in patients with non-insulin dependant diabetes and hypertension. N Engl J Med 1998;338:645-52.
  13. Gueyffier F, Bulpitt C, Boissel JP, et al. Antihypertensive drugs in very old people: a subgroup meta-analysis of randomised controlled trials. Lancet 1999;353:793-6.
  14. Beckett NS, Peters R, Fletcher AE, et al. Treatment of hypertension in patients 80 years of age or older. N Engl J Med 2008;358:1887-98.