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FM36 Family Medicine
Calcium Channel Blockers
Dihydropyridine CCBs • amlodipine
• nifedipine
• felodipine
Non-Dihydropyridine CCBs • diltiazem
• verapamil
How to Combine Antihypertensive Medications (in general)
ACEI β-blocker CCB Diuretic
Thiazides as First-Line Antihypertensive Therapy – ALLHAT
JAMA 2002;288:2981-2997
Purpose: To evaluate whether calcium channel blocker or angiotensin-converting enzyme inhibitors lower incidence of coronary heart disease (CHD)
or other cardiovascular disease (CVD) relative to treatment with a diuretic.
Methods: Randomized, double-blind, active- controlled clinical trial with mean follow-up of 4.9 yrs. Participants with stage 1 or 2 hypertension (HTN) and at least 1 other CHD risk factor were included, and randomized to receive chlorthalidone (12.5-25 mg/d), amlodipine (2.5-10mg/d), or lisinopril (10-40 mg/d). Target BP was <140/90 mmHg, achieved by titrating the assigned
study drug, and adding open-label agents when necessary. The primary outcome was combined fatal CHD or non-fatal MI. Secondary outcomes were all-cause mortality, stroke, combined CHD, and combined CVD.
Results: 33,357 participants (mean age 67 yr, 53% male, 47% white) were included. There were no significant differences in either the primary outcome or all-cause mortality between treatment groups. For amlodipine vs. chlorthalidone, secondary outcomes were similar except for a higher 6 yr rate of heart failure with amlodipine (10.2% vs. 7.7%; p<0.001). For lisinopril vs. chlorthalidone, lisinopril had higher 6 yr rates of combined CVD (33.3% vs. 30.9%; p<0.001), stroke (6.3% vs. 5.6%; p=0.02) and heart failure (8.7% vs. 7.7%; p<0.001). Conclusion: Thiazide-type diuretics are superior
to CCB and ACEI for preventing one or more major forms of CVD, with similar risks of death and non-fatal MI.
Common Presenting Problems Toronto Notes 2019 Table 21. Pharmacologic Treatment of Hypertension in Patients with Unique Conditions
Condition or Risk Factor
Isolated Diastolic HTN
Isolated Systolic HTN CAD
Prior MI
Left Ventricular Hypertrophy
Cerebrovascular Disease
(stroke/TIA)
Heart Failure
Dyslipidemias
DM with Albuminuria
(ACR >2.0 mg/mmol in men and >2.8 mg/mmol in women)
DM without Albuminuria
(criteria listed above)
Non-Diabetic Chronic Kidney Disease with Proteinuria (urinary protein >500 mg/24 h or ACR >30 mg/mmol)
Renovascular Disease
Asthma Gout
Smoking Pregnancy Elderly (>60 yr)
Emergency
If >3 Cardiovascular Risk Factors or Established Atherosclerotic Disease
Recommended Drugs
Thiazide diuretic, β-blocker, ACEI, ARB, or long-acting CCB (consider ASA and statin in select patients)
Thiazide diuretic, ARB, or long acting dihydropyridine CCB
ACEI or ARB; β-blocker for patients with stable angina
β-blocker and ACEI (ARB if cannot tolerate ACEI)
ACEI, ARB, thiazide, or long-acting CCB
ACEI and diuretic combination ACEI (ARB if ACEI intolerant)
and β-blocker
Spironolactone in patients with NYHA class II-IV
Does not affect initial treatment recommendations
ACEI or ARB
(DHP CCB > hydrochlorothiazide (HCTZ) for combination therapy with ACEI)
ACEI, ARB, DHP CCB, or thiazide diuretic
ACEI (ARB if ACEI intolerant), diuretic as additive therapy
Same as HTN without other indications
K+-sparing and thiazide diuretic for patients on salbutamol
Low dose thiazide ACEI
Methyldopa Hydralazine
Thiazide diuretic, ACEI, ARB, or long-acting CCB (consider ASA and statin in select patients)
BP >169/90 = labetolol, nifedipine
Statin (age >40), low-dose ASA (age >50)
Alternative Drugs
Combinations of first-line drugs
Combinations of first-line drugs
Long acting CCB, when combination therapy for high risk patients, ACEI/DHP CCB is preferred
Long-acting CCB
Combination of additional agents
Combination of additional agents
ARB in addition to ACEI Hydralazine/isosorbide dinitrate combination if ARB or ACEI not tolerated/ contraindicated
Thiazide or loop diuretic is recommended as additive therapy
DHP CCB can also be used
Combination of additional agents
Add thiazide diuretic, cardioselective β-blocker, long acting CCB
Combination of first-line drugs or, first-line agents not tolerated, cardioselective β-blocker or non-DHP CCB
Thiazide for additive antihypertensive therapy, loop diuretic for volume overload
Not Recommended/Notes
β-blocker monotherapy (age >60) or combination of ACEI with an ARB
Same as above
Short-acting CCB (nifedipine)
or ACEI and ARB is not recommended
dBP 60 mmHg may exacerbate MI
ACEI and ARB combination is not recommended
Hydralazine and minoxidil can increase LVH, thus not recommended
ACEI and ARB combination after a stroke is not recommended
Non-DHP CCB not recommended Carefully monitor for side effects if using ACEI and ARB
If serum Cr >150 μmol/L, a loop diuretic should be considered instead of low-dose thiazide diuretic
ACEI and ARB combination not recommended
ACEI and ARB combination is not recommended
Caution in using ACEI or ARB – monitor for AKI
Renal angioplasty and stenting offer no benefits over optimal medical therapy alone
β-blocker, unless specific indications like angina or post-MI
Thiazide, but asymptomatic hyperuricemia is not a contraindication
β-blocker ACEI
β-blocker not recommended as first line treatment
Caution with use of ASA in patients with uncontrolled BP
Labetolol Nifedipine
Adapted from: McAlister FA, Zarnke KB, Campbell NRC, et al. The 2001 Canadian recommendations for the management of hypertension: Part two – Therapy. Can J Cardiol 2002;18:625-641 and The 2012 Canadian Hypertension Education Program Recommendations