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Several classes of drugs are used to treat hypertension but how they affect cardiovascular morbidity and mortality in high-risk patients is still under investigation. Recent outcome trials have examined the benefits associated with different levels of blood pressure control or have compared several of the 'newer' classes of antihypertensive drugs, such as angiotensin-converting enzyme (ACE) inhibitors and calcium channel blockers, with 'older' drug classes, such as diuretics and β-blockers. Other trials have compared antihypertensive drugs with placebo. We performed a meta-regression analysis of 30 clinical trials that included a total of 149,407 patients. We based our analysis on summary statistics reported in the literature, and showed that blood pressure gradients accounted for most, if not all, of the differences in outcome in patients with hypertension or at high cardiovascular risk. We also conducted a study in older patients with isolated systolic hypertension and showed that antihypertensive drug treatment starting with the dihydropyridine calcium channel blocker, nitrendipine, reduced the risk of stroke and all cardiovascular complications. In addition, nitrendipine-based blood pressure-lowering therapy decreased the incidence of dementia. In diabetic patients, nitrendipine reduced the risk of proteinuria, decreased total mortality, and markedly improved cardiovascular prognosis. Taken together, these findings emphasize the desirability of tight blood pressure control.