Update on the management of hypertension: do recent clinical trial results indicate a change in national recommendations for therapy?

Abstract

Numerous hypertension treatment trials have been reported during the past several years. In comparative studies it has been shown that the use of diuretics or diuretics/beta blockers has resulted in a reduction in morbidity/mortality equivalent to the use of other antihypertensive medications. This is true in both young and elderly patients. In one large 8-year study in diabetics, the use of a beta blocker/diuretic combination was shown to be as effective in reducing overall cardiovascular events as an angiotensin-converting enzyme (ACE) inhibitor/diuretic treatment program. Although most data indicate that the degree of blood pressure lowering accounts for most of the benefit, there are some differences in outcome that may be explained by different mechanisms of drug action. For example: 1) diuretics are more effective in preventing heart failure and overall cardiovascular events than alpha blockers; 2) an ACE inhibitor-based program is more effective in the elderly in reducing myocardial infarctions and heart failure than a calcium channel blocker-based program; and 3) a nondihydropyridine is more effective in reducing strokes, but less effective in preventing myocardial infarctions or heart failure, than a program based on diuretic therapy. There is also abundant evidence that the use of ACE inhibitors may prevent the occurrence of diabetes in hypertensive individuals and will reduce cardiovascular events in diabetics. Finally, the angiotensin receptor blockers have been shown to slow the progression of renal disease and prevent the occurrence of end-stage renal disease when compared to treatment regimens that do not include an angiotensin receptor blocker or ACE inhibitor. Updated treatment recommendations should include an ACE inhibitor and possibly an angiotensin receptor blocker along with diuretics and beta blockers as initial therapy. In addition, recommendations for the use of multiple-drug therapy have been reinforced by recent trials. Goal pressures are not readily achieved with monotherapy, especially in high-risk patients.

Figure 1

Relative risk for cardiovascular disease of elevated systolic and diastolic blood pressures (BP). ² Risk of increases in SBP are greater than those of relatively similar increases in DBP, i.e., 140–149 mm Hg greater risk than 90–94 mm Hg; 150–159 mm Hg greater risk than 95–100 mm Hg.

Figure 2

Suggested approach to the treatment of hypertension ¹ BP=Blood pressure; *unless contraindicated; **based on randomized clinical trial data

Figure 3

Results of therapy. Incidence of major and minor cardiovascular events, as well as lifestyle interventions alone and with medication ⁴

Figure 4

Effect of diuretic or diuretic/β blocker‐based treatment programs on cardiovascular events. Combined results are shown from 17 randomized, placebo‐controlled treatment trials. Percentage decrease in events is shown for treated patients vs. controls. 8, 9 CHF=congestive heart failure; LVH=left ventricular hypertrophy; CVD=cardiovascular disease; CHD=coronary heart disease

Figure 5

Reversal of cardiac hypertrophy in hypertensive patients with initial left ventricular hypertrophy treated by antihypertensive drug therapy ¹¹ Nonregressors (solid line and bar) (N=52) Regressors (hatched line and bar) (N=50)

Figure 6

Stroke risk reduction angiotensin‐converting enzyme inhibitor (ACE)/diuretic‐treated patients compared to patients on other medications (placebo). Perindopril Protection Against Recurrent Stroke Study [PROGRESS]. Benefit appears within the first year and continues. ¹⁶ BP=blood pressure

Figure 7

Effect of antihypertensive drug treatment on left ventricular (LV) mass. Pretreatment baseline LV mass is >350 g. ¹² ACE=angiotensin‐converting enzyme (captopril, p = <0.01*); D=diuretic (hydrochlorothiazide, p=<0.001*); BB=β blocker (atenolol, p=<0.05*); CCB=calcium channel blocker (diltiazem); *vs baseline

Figure 8

Comparative effects of tight glucose control vs. tight blood pressure (BP) control (the United Kingdom Prospective Diabetes Study Group [UKPDS]) ²⁰ DM=diabetes mellitus; *p<0.5

Figure 9

Proportion of patients in each group who reached primary end point in the Swedish Trial in Old Patients With Hypertension (STOP‐2) ⁶ ACE=angiotensin‐converting enzyme

Figure 10

Relative risk of cardiovascular mortality and morbidity for ACE inhibitors vs. calcium antagonists in the Swedish Trial in Old Patients With Hypertension (STOP‐2) ⁶ ACE=angiotensin‐converting enzyme; MI=myocardial infarction; CHF=congestive heart failure; *significant difference

Figure 11

Comparisons of angiotensin‐converting enzyme inhibitor‐based with diuretic‐ or β blocker‐based therapy in hypertensive patients. There were no significant differences among the total number of patients (16,161) in the included trials (STOP‐2, UKPDS, and CAPPP, acronyms noted in text). CHD=coronary heart disease; CV=cardiovascular ¹⁰

Figure 12

Comparison of calcium antagonists with other antihypertensives on cardiovascular (CV) end points ²³ N=27,743 in nine trials. MI=myocardial infarction; CHF=congestive heart failure; *p<0.01; **p<0.05 calcium antagonists vs. other antihypertensive agents

Figure 13

Pharmacologic treatment of hypertension* *Modified and updated from JNC VI (see text); **unless contraindicated; ***other fixed‐dose combinations of two different classes of drugs may also be appropriate initial therapy in some cases (diuretics/angiotensin receptor blocker (ARB) or ACE inhibitor/calcium channel blocker; ^based on outcome data; ⁺ACE inhibitor, ARB (usually with a diuretic) also acceptable therapy