Report of the Canadian Hypertension Society Consensus Conference: 3. Pharmacologic treatment of essential hypertention

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Table 1: Levels of evidence for rating studies of treatment, prevention and quality assurance

I. A randomized controlled trial (RCT) that demonstrates a statistically significant difference in at least one important outcome -- e.g., survival or major illness.

OR

If the difference is not statistically significant, an RCT of adequate sample size to exclude a 25% difference in relative risk with 80% power, given the observed results.

II. An RCT that does not meet the level I criteria.

III. A nonrandomized trial with contemporaneous controls selected by some systematic method (i.e., not selected by perceived suitability for one of the treatment options for individual patients).

OR

Subgroup analysis of a randomized trial.

IV. A before-after study or case series (of a least 10 patients) with historical controls or controls drawn from other studies.

V. Case series (at least 10 patients) without controls.

VI. Case report (fewer than 10 patients).

Table 2: Grading system for recommendations

B. The best evidence available was at level II.

C. The best evidence available was at level III.

D. The best evidence available was lower than level III and inclued expert opinion.

Table 3: Recommendations for the initial drug treatment of essential hypertension

Problem                                              Drug(s)
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Essential hypertension without          Low-dose thiazide diuretic or
 coexisting medical conditions           ß-blocker
 or target-organ damage
  Partial response to monotherapy       Combined diuretic and ß-blocker or
   with diruetics and ß-blockers         monotherapy with an a-blocker,
                                         angiotensin-converting enzyme (ACE)
                                         inhibitor, calcium entry blocker or
                                         centrally acting drug
  Adverse effects of or contra-         Other monotherapy as above
   indication to diuretics or
   ß-blockers

Essential hypertension with             Monotherapy as appropriate
 coexisting medical conditions or
 target-organ damage
  Inadequate response. Coexisting       Diuretic with an ACE inhibitor,
   medical conditions or target-organ    calcium entry blocker, a-blocker,
   damage may determine the choice.      other vasodilator or a centrally
                                         acting drug
                                        ß-blocker with a dihydropyridine
                                         calcium entry blocker, a-blocker,
                                         other vasodilator or centrally
                                         acting drug
  Adverse effects of or contra-         ACE inhibitor and calcium entry
   indication to diuretics or            blocker or other combination
   ß-blockers

Table 4: Commonly used antihypertensive drugs

                                                   Daily dose, mg
Drug*                                            Starting     Full
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Thiazide diuretics
 Chlorthalidone (Hygroton)                          12.5        25
 Hydrochlorothiazide (HydroDiuril, Esidrix)         25          50
 Indapamide (Lozide)                                 2.5         2.5
 Metolazone (Zaroxolyn)                              2.5         5
Beta-blockers
 Acubutolol (Monitan, Sectral) (S)                 200         800
 Atenolol (Tenormin)                                50         100
 Labetalol (Trandate)                              200        1200
 Metoprolol (Lopresor, Betaloc)                     50         200
 Nadolol (Corgard)                                  40         160
 Oxprenolol (Trasicor) (S)                          80         320
 Pindolol (Visken) (S)                              10          30
 Propranolol (Inderal)                              80         320
 Timolol (Blocadren)                                10          40
ACE inhibitors
 Captopril (Capoten)                                25         100
 Enalapril (Vasotec)                                10          40
 Lisinopril (Prinivil, Zestril)                     10          40
 Quinapril (Accupril)                               10          40
Calcium entry blockers
 Diltiazem (Cardizem)                              180         360
 Felodipine (Plendil, Renedil) (V)                   5          20
 Nicardipine (Cardene) (V)                          60         120
 Nifedipine (Adalat) (V)                            20          80
 Verapamil (Isoptin)                               240         480
Centrally acting drugs
 Clonidine (Catapres)                                0.2         1.2
 Methyldopa (Aldomet)                              500        2000
 Reserpine (Serpasil)                                0.1         0.25
Alpha-blockers
 Doxazosin (Cardura)                                 1          16
 Prazosin (Minipress)                                1          20
 Terazosin (Hytrin)                                  1          20
Direct-acting vasodilators
 Hydralazine (Apresoline) (V)                       50         200
 Minoxidil (Loniten) (V)                             5          20
Combinations
 Hydrochlorothiazide/amiloride (Moduret)
 Hydrochlorothiazide/atenolol (Tenoretic)
 Hydrochlorothiazide/enalapril (Vaseretic)
 Hydrochlorothiazide/spironolactone (Aldactazide)
 Hydrochlorothiazide/timolol (Timolide)
 Hydrochlorothiazide/triamterene (Dyazide)
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*(S)= sympathonimetic activity, (V) = vasodilator.