Evidence for drug therapy of hypertension

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Evidence for drug therapy of hypertension
Diabetes Care

There are a number of trials demonstrating the superiority of drug therapy versus placebo in reducing outcomes including cardiovascular events and microvascular complications of retinopathy and progression of nephropathy. These studies used different drug classes, including angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers (ARBs), diuretics, and ß-blockers, as the initial step in therapy. All of these agents were superior to placebo; however, it must be noted that many patients required three or more drugs to achieve the specified target levels of blood pressure control. Overall there is strong evidence that pharmacologic therapy of hypertension in patients with diabetes is effective in producing substantial decreases in cardiovascular and microvascular diseases.

There are limited data from trials comparing different classes of drugs in patients with diabetes and hypertension. The UKPDS-Hypertension in Diabetes Study showed no significant difference in outcomes for treatment based on an ACE inhibitor compared with a ß-blocker. There were slightly more withdrawals due to side effects and there was more weight gain in the ß-blocker group. In postmyocardial infarction patients, ß-blockers have been shown to reduce mortality.

There are numerous studies documenting the effectiveness of ACE inhibitors and ARBs in retarding the development and progression of diabetic nephropathy. ACE inhibitors have a favorable effect on cardiovascular outcomes, as demonstrated in the MICRO-HOPE study. This cardiovascular effect may be mediated by mechanisms other than blood pressure reduction. It is possible that other drug classes may behave similarly.

Some studies have shown an excess of selected cardiac events in patients treated with dihydropyridine calcium channel blockers (DCCBs) compared with ACE inhibitors. Ongoing trials including the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT) study should help to resolve this issue. DCCBs in combination with ACE inhibitors, ß-blockers, and diuretics, as in the HOT study and the Systolic Hypertension in Europe (Syst-Eur) Trial, did not appear to be associated with increased cardiovascular morbidity. However, ACE inhibitors and ß-blockers appear to be superior to DCCBs in reducing myocardial infarction and heart failure. Therefore, DCCBs appear to be appropriate agents in addition to, but not instead of, ACE inhibitors and ß-blockers. Non-DCCBs (i.e., verapamil and diltiazem) may reduce coronary events. In short-term studies, non-DCCBs have reduced albumin excretion.

There are no long-term studies of the effect of {alpha}-blockers, loop diuretics, or centrally acting adrenergic blockers on long-term complications of diabetes. The {alpha}-blocker arm of the ALLHAT study was stopped by the data and safety monitoring committee because of an increase in cases of new-onset heart failure in patients assigned to the {alpha}-blocker. While this could merely represent unmasking of heart failure in patients previously treated with an ACE inhibitor or a diuretic, it seems reasonable to use these as second-line agents when preferred classes have been ineffective or when other specific indications, such as benign prostatic hypertrophy (BPH), are present.

© 2003 by the American Diabetes Association, Inc.