Calcium Antagonists and Hypertension: Role of co-existent coronary disease, impaired renal function and diabetes

It is generally accepted that blood pressure lowering drugs improve the prognosis of patients with elevated blood pressure. The dihydropyridine calcium antagonist nifedipine is a widely used blood pressure lowering drug. In the mid-1990ties questions were raised on the safety of the short-acting immediate release formulation of this drug, in particular in patients with coronary disease. To answer these questions in the absence of any prospective safety data from randomised trials, two major studies using a more optimal long-acting GITS (gastro-intestinal therapeutic system) formulation of nifedipine were mounted in the late 1990ties. The Intervention as a Goal in Hypertension Treatment (INSIGHT) randomised double-blind trial compared 30 mg nifedipine GITS (n=3157) to co-amilozide (hydrochlorothiazide 25 μg plus amiloride 2•5 mg; n=3164) in patients aged 55-80 years with hypertension (blood pressure at least150/95 mmHg, or at least 160 mmHg systolic) who had at least one additional cardiovascular risk factor. There was no placebo-treated control group. The main results have been published elsewhere (Brown MJ et al. Lancet 2000; 356: 366–72). Up-titration followed by add-on medication was allowed and resulted in blood pressure control to a similar degree. INSIGHT showed that overall nifedipine GITS based treatment was as e_ ective as co-amilozide based treatment in preventing cardiovascular or cerebrovascular complications. The A Coronary disease Trial Investigating Outcome with Nifedipine GITS (ACTION) study compared randomly assigned 60 mg nifedipine GITS (n=3825) to double-blind placebo (n=3840) in patients aged at least 35 years with stable angina pectoris and proven coronary artery disease. ACTION demonstrated that the addition of nifedipine GITS to the conventional treatment of angina pectoris is safe, has no e_ ect on major cardiovascular event-free survival and reduces the need for coronary angiography and interventions. The main results of ACTION have been published (Poole-Wilson PA et al. Lancet 2004;364:849-57). The report is reproduced in this thesis as chapter 2.

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