CORD: COmparsion of Recommended Doses of ACE inhibitors and angiotensin II receptor blockers.

OBJECTIVES: The CORD trials tested ramipril and losartan in patients with hypertension.

PATIENTS AND METHODS: CORD IA involving switching from an angiotensin-converting enzyme inhibitor (ACEI) to the angiotensin II receptor blocker (ARB) losartan. 4,016 patients with blood pressure (BP) < 160/100 mm Hg who had been treated with an ACEI for > 3 months were enrolled. The mean age was 62.6 +/- 11.6 years and 53.1% were women. The patients discontinued ACEI and switched to losartan 50 mg once daily. BP, heart rate, biochemistry, blood counts and ECGs were measured at day 1 and months 1, 3, 6 and 12. If the BP was > or = 140/90 mm Hg after 1 month or more, the dose of losartan was increased to 100 mg. After 1 month the BP decreased from 147.4 +/- 14.8/87.7 +/- 9.3 mm Hg to 139.7 +/- 11.8/83.0 +/- 9.3 mm Hg (p < 0.001) and after 1 year to 133.7 +/- 11.3/79.1 +/- 7.06 mm Hg (p < 0.001). The rate of adverse events did not significantly increase and no changes in plasma sodium, potassium, urea or creatinine were observed. CORD IB compared ramipril and losartan. 3,813 patients with BP > or = 140/90 mm Hg who were not being treated with an ACEI or ARB were enrolled. The mean age was 60.5 +/- 12.2 years and 50.5% were women. The patients were randomised to ramipril 5 mg (n = 1,926) or losartan 50 mg (n = 1,887). The dose was doubled if BP after 1 month was > or = 140/90 mm Hg. If the BP after 3 months still was > or = 140/90 mm Hg, another antihypertensive drug was added, typically athiazide diuretic.

RESULTS: After 1 yearthe BP decreased in the ramipril group from 155.9 +/- 13.1/93.0 +/- 8.9 mm Hg to 134.1 +/- 11.2/81.5 +/- 6.8 mm Hg (p < 0.001) and in the losartan group from 156.5 +/- 13.1/93.4 +/- 8.8 to 134.55 +/- 11.3/80.16 +/- 6.6 mm Hg (p < 0.001). No significant differences were found between the groups. A slight increase in plasma potassium (0.2 mmol in both groups) and urea (0.3 mmol in both groups) was observed, but no change in plasma creatinine. There was a small, insignificant decrease in plasma uric acid (in the ramipril group from 325.5 to 320.7 micromol/l and in the losartan group from 321.6 to 318.3 micromol/l) and a slight decrease in plasma glucose and triglycerides (0.2 mmol/l in both measures in both groups). No severe adverse events were observed, but dry cough was 8 times more frequently reported in the ramipril group.

CONCLUSION: CORD IA confirmed that switching from an ACEI to losartan is safe and effective. Titrating the dose upwards or adding diuretics leads to good BP control in the majority of patients (2/3). CORD IB showed no differences between ramipril and losartan in lowering BP and both drugs showed a trend to improve metabolic parameters such as glycaemia, triglyceridaemia and uric acid equally. Dry cough was more frequent after ACEI.