Ramipril (Altace)

Ramipril is an ACE inhibitor. It blocks angiotensin-converting enzyme, which turns angiotensin I into angiotensin II. Angiotensin II is the body's strongest vasoconstrictor and additionally drives aldosterone release, meaning salt and water retention. Both fall away when the enzyme is blocked.

Ramipril itself is a prodrug and is converted in the liver into ramiprilat, which does the actual work. Beyond lowering blood pressure, this class has a well documented protective effect on kidney and heart that goes beyond the pressure effect.

This information is for research and educational purposes only. No medical advice.

ACE has a second job, and that is where the best known side effect comes from: it breaks down bradykinin. Block the enzyme and bradykinin accumulates. In the vessels that is welcome, because it widens them further. In the bronchi it causes a dry irritating cough in roughly one in ten, and that cough does not go away.

The kidney effect works through widening of the efferent vessel in the glomerulus. Filtration pressure falls, the kidney is unloaded and protein excretion drops. That is exactly why the class is standard in proteinuric kidney disease, even though creatinine often rises slightly right after starting. A rise of up to about 30 percent is expected with ACE inhibitors and is not a reason to stop.

HOPE (NEJM 2000) is the trial that built the reputation of this substance. Over 9,000 patients at high cardiovascular risk but without heart failure received 10mg ramipril or placebo. The combined endpoint of heart attack, stroke and cardiovascular death fell by 22 percent. The blood pressure drop alone was too small to explain that, which suggests part of the benefit does not hang on pressure.

MICRO-HOPE (Lancet 2000) saw the same direction in the diabetes subgroup with less nephropathy on top. AIRE (Lancet 1993) showed 27 percent lower mortality after heart attack with heart failure. REIN (Lancet 1997) demonstrated the kidney protection directly: the decline in filtration slowed, and fewer patients reached end-stage renal failure.

• Dry irritating cough: around 10 percent. Harmless, but it does not go away and it does not improve. If it appears, switching to a sartan such as losartan is the answer, since they work similarly without that effect.
• Angioedema: rare but serious. Swelling of lips, tongue or throat needs immediate attention and means the definitive end of this substance class.
• Raised potassium: especially combined with spironolactone or potassium supplements.
• Dizziness on the first dose: hence starting low and taking it in the evening.
• Creatinine rise: a rise of up to about 30 percent is expected. Clearly more than that needs checking.

Store dry, at room temperature and protected from light. Keep out of reach of children.