Hypertension - Developing an Antihypertensive Regimen

Historically, data from a number of large trials support the overall conclusion that antihypertensive therapy with diuretics and β-blockers has a major beneficial effect on a broad spectrum of cardiovascular outcomes. Similar placebo-controlled data pertaining to the newer agents are generally lacking, except for stroke reduction with the calcium channel blocker nitrendipine in the Systolic Hypertension in Europe trial. However, there is substantial evidence that ACE inhibitors, and to a lesser extent ARBs, reduce adverse cardiovascular outcomes in other related populations (eg, patients with diabetic nephropathy, heart failure, or postmyocardial infarction and individuals at high risk for cardiovascular events). Most large clinical trials that have compared outcomes in relatively unselected patients have failed to show a difference between newer agents - such as ACE inhibitors, calcium channel blockers, and ARBs - and the older diuretics and β-blockers with regard to survival, myocardial infarction, and stroke. Therefore, experts recommend diuretics as the first-line treatment of most older patients with hypertension because these agents are less expensive than the newer agents. Exceptions are appropriate for individuals who have specific indications for another class of agent, such as postmyocardial infarction patients (β-blockers, ACE inhibitors), patients with diabetic nephropathy (ACE inhibitors, ARBs), or other comorbid conditions. Table 11-4 provides suggestions for individualizing first-line treatment based on compelling indications.

More recently, the perception that all antihypertensive drugs are equally effective at controlling cardiovascular risk has been challenged by the results of the ASCOT trial, which suggest that more modern agents (amlodipine/perindopril) are superior to the older combination (atenolol/bendroflumethiazide). For the reasons discussed above, many experts would suggest that β-blockers no longer be considered ideal first-line drugs in the treatment of hypertension without compelling indications for their use and would tend to restrict the use of thiazide diuretics to older patients in whom they are particularly effective, The predominant use of thiazides in older patients would also limit exposure to the cumulative metabolic consequences of these drugs, a particular concern in young persons with hypertension who are subject to lifelong therapy.

For the purpose of devising an optimal treatment regimen, drugs can be divided into two complementary groups easily remembered as AB and CD. A and B refer to drugs that interrupt the renin-angiotensin system (ACE /ARB and β-blockers) and C and D refer to those that do not (calcium channel blockers and thiazide diuretics). Combinations of drugs between these groups are likely to be more potent in lowering blood pressure than combinations within a group. Drugs A/B are more effective in young, white persons, in whom renins tend to be higher, and drugs C/D are more effective in old or black persons, in whom renin levels are generally lower. It is also important to note that antihypertensive treatment is effective at reducing cardiovascular risk at all ages, including the very elderly.