Choice of therapy for adults with hypertension without compelling indications for specific agents

• Recommended monotherapy choices are:
  1. a thiazide/thiazide-like diuretic (Grade A), with longer-acting diuretics preferred (Grade B);
  2. a b-blocker (in patients younger than 60 years; Grade B);
  3. an ACE inhibitor (in nonblack patients; Grade B);
  4. an ARB (Grade B); or
  5. a long-acting CCB (Grade B).
  6. Recommended SPC choices are those in which an ACE inhibitor is used with a CCB (Grade A), an ARB is used with a CCB (Grade B), or an ACE inhibitor or ARB is used with a diuretic (Grade B).
  7. Hypokalemia should be avoided in patients treated with thiazide/thiazide-like diuretic monotherapy (Grade C).
• Additional antihypertensive drugs should be used if target BP levels are not achieved with standard-dose monotherapy (Grade B). Add-on drugs should be chosen from first-line choices. Useful choices include a thiazide/thiazide-like diuretic or CCB with either: ACE inhibitor, ARB, or b-blocker (Grade B for the combination of thiazide/thiazide-like diuretic and a dihydropyridine CCB; Grade A for the combination of dihydropyridine CCB and ACE inhibitor; and Grade D for all other combinations). Caution should be exercised in combining a nondihydropyridine CCB and a b-blocker (Grade D). The combination of an ACE inhibitor and an ARB is not recommended (Grade A).
• If BP is still not controlled with a combination of 2 or more first-line agents, or there are adverse effects, other antihypertensive drugs may be added (Grade D).
• Possible reasons for poor response to therapy (Supplemental Table S6) should be considered (Grade D).
• a-Blockers are not recommended as first-line agents for un-complicated hypertension (Grade A); b-blockers are not recommended as first-line therapy for uncomplicated hy-pertension in patients 60 years of age or older (Grade A); and ACE inhibitors are not recommended as first-line therapy for uncomplicated hypertension in black patients (Grade A). However, these agents may be used in patients with certain comorbid conditions or in combination therapy.

• Initial therapy should be single-agent therapy with a thiazide/thiazide-like diuretic (Grade A), a long-acting dihydropyridine CCB (Grade A), or an ARB (Grade B). If there are adverse effects, another drug from this group should be substituted. Hypokalemia should be avoided in patients treated with thiazide/thiazide-like diuretic mon-otherapy (Grade C).
• Additional antihypertensive drugs should be used if target BP levels are not achieved with standard-dose mono-therapy (Grade B). Add-on drugs should be chosen from first-line options (Grade D).
• If BP is still not controlled with a combination of 2 or more first-line agents, or there are adverse effects, other classes of drugs (such as a-blockers, ACE inhibitors, cen-trally acting agents, or nondihydropyridine CCBs) may be combined or substituted (Grade D).
• Possible reasons for poor response to therapy (Supplemental Table S6) should be considered (Grade D).
• a-Blockers are not recommended as first-line agents for uncomplicated isolated systolic hypertension (Grade A); and b-blockers are not recommended as first-line therapy for isolated systolic hypertension in patients aged 60 years or older (Grade A). However, both agents may be used in patients with certain comorbid conditions or in combination therapy.

• The SBP treatment goal is a pressure level of < 140 mm Hg (Grade C). The DBP treatment goal is a pressure level of < 90 mm Hg (Grade A). These targets were established using OBPM.

• It is recommended that hypertensive patients and normotensive individuals at increased risk of devel-oping hypertension consume a diet that emphasizes fruits, vegetables, low-fat dairy products, whole grain foods rich in dietary fibre, and protein from plant sources that is reduced in saturated fat and cholesterol (Dietary Approaches to Stop Hypertension [DASH] diet63-66; Supplemental Table S5; Grade B).

• Hypertension frequently coexists with other con-ditions that influence therapeutic decision-making. Polypharmacy and competing risks need to be considered carefully.
• Adults with diabetes and certain forms of chronic kidney disease (Table 9) might benefit from more intensive BP targets (ie, SPB 130 mm Hg or 120 mm Hg).

There has been significant interest in the potential role of newer diabetes therapies in the management of cardiovascular risk in adults with diabetes and hypertension. This topic has been reviewed and discussed by the HCGC at our 2017 and 2019 consensus conferences and a formal recommendation has not been developed for the use of sodium-glucose co-transporter-2 (SGLT2) inhibitors in the management of persons with comorbid diabetes and hypertension. However, the rationale for reviewing this topic is summarized herein. SGLT2s have been shown to improve survival and improve clinical outcomes in persons with type 2 diabetes, diabetes and heart failure, and diabetes-related kidney disease (GFR 30-60 mL/min/m2).Benefits on heart outcomes (namely reduced hospitalizations for heart failure) have been recently reported in the Dapagliflozin in Patients with Heart Failure and Reduced Ejection Fraction (DAPA-HF) trial, which enrolled 4744 patients with HFrEF, 58% of which did NOT have type 2 diabetes.

Although SGLT2s appear to have clinically significant benefits in persons with diabetes, diabetes-related kidney disease, and HFrEF, SGLT2s are not an approved antihy-pertensive therapy, and have not been included in the Hypertension Canada guidelines as a recommended therapy for patients with these conditions. However, Hypertension Canada does acknowledge that there is a potential role for SGLT2s in patients to reduce weight, improve hemoglobin A1C, modestly reduce SBP, and improve cardiovascular outcomes in patients with complex comorbidities.