For a treatment‑naïve adult with newly diagnosed hypertension and no renal impairment, hyperkalaemia, or history of angio‑edema, does the new Canadian guideline recommend starting a low‑dose perindopril 2 mg/indapamide 0.625 mg fixed‑dose combination as first‑line therapy?

Low-Dose Dual Therapy as First-Line Treatment in Canada

The 2010 Canadian Hypertension Education Program guidelines do support initiating combination therapy with two first-line agents when systolic BP is ≥20 mmHg above target or diastolic BP is ≥10 mmHg above target, but they do not specifically endorse perindopril 2 mg/indapamide 0.625 mg as the preferred first-line regimen for all treatment-naïve patients. 1

Canadian Guideline Framework for Initial Therapy

The Canadian guidelines recommend the following approach for adults without compelling indications:

• First-line monotherapy options include thiazide diuretics, ACE inhibitors (in non-Black patients), long-acting calcium channel blockers, ARBs, or beta-blockers (in patients <60 years), with blood pressure targets of <140/90 mmHg for most patients. 1

• Dual therapy as initial treatment is appropriate when systolic BP is 20 mmHg above target or diastolic BP is 10 mmHg above target—this would mean starting dual therapy for BP ≥160/100 mmHg in most patients. 1

• The guidelines do not mandate a specific two-drug combination as universal first-line therapy; rather, they allow clinicians to select from the first-line agent classes based on patient characteristics. 1

Evidence for Perindopril/Indapamide Low-Dose Combination

The perindopril 2 mg/indapamide 0.625 mg fixed-dose combination has demonstrated efficacy in clinical trials:

• This low-dose combination normalized BP in 83.6% of elderly patients with essential hypertension (achieving diastolic BP ≤90 mmHg) and 81.7% of those with isolated systolic hypertension (achieving systolic BP <160 mmHg) after approximately 1 year of treatment. 2

• The combination was significantly more effective than placebo and achieved similar BP reductions to losartan 50 mg/day or atenolol 50 mg/day, but with significantly higher response and normalization rates than losartan or irbesartan monotherapy. 3

• In patients with chronic renal failure, the combination reduced supine BP from 170.4/101.5 mmHg to 146.5/86.5 mmHg (P<0.0001) with good tolerability. 4

Current Guideline-Recommended Approach vs. Low-Dose Dual Therapy

The dominant contemporary guideline framework (ACC/AHA, ESC/ESH) emphasizes starting with monotherapy in stage 1 hypertension and reserving dual therapy for stage 2 hypertension (≥140/90 mmHg or ≥160/100 mmHg depending on the guideline). 5, 6

• For stage 1 hypertension (130-139/80-89 mmHg), current guidelines recommend initiating with a single thiazide-type diuretic rather than combination therapy. 5

• For stage 2 hypertension (≥160/100 mmHg or >20/10 mmHg above target), dual therapy is appropriate from the outset, with the preferred combination being an ACE inhibitor or ARB + calcium channel blocker + thiazide diuretic as the eventual triple therapy. 5, 6

Practical Considerations

• Single-pill combinations are strongly preferred over separate pills because they significantly improve medication adherence and persistence with treatment. 6

• The perindopril/indapamide combination had a tolerability profile similar to placebo, with most adverse events of mild-to-moderate severity, and coadministration reduced the incidence of hypokalemia seen with indapamide alone. 2

• The most common adverse events with perindopril 2 mg/indapamide 0.625 mg were headache and cough, with hypokalemia occurring at higher incidence than with atenolol or placebo. 3

Clinical Algorithm

For a treatment-naïve adult with newly diagnosed hypertension and no compelling indications:

• If BP is 130-139/80-89 mmHg (stage 1): Start with monotherapy—thiazide diuretic, ACE inhibitor, ARB, or long-acting calcium channel blocker. 5, 1

• If BP is 140-159/90-99 mmHg: Consider either monotherapy with planned escalation or initial dual therapy depending on cardiovascular risk and distance from target. 1

• If BP is ≥160/100 mmHg (stage 2): Initiate dual therapy with two first-line agents, preferably as a single-pill combination. 5, 1

• Perindopril 2 mg/indapamide 0.625 mg is a reasonable option for initial dual therapy in stage 2 hypertension, particularly in elderly patients or those with renal impairment, but it is not mandated as the universal first-line choice. 3, 2, 4