Losartan (Cozaar)

Losartan is an angiotensin II receptor blocker, a sartan for short. It blocks the same pathway as an ACE inhibitor but one step later: not the formation of angiotensin II, but its docking at the AT1 receptor. The result is similar, the route there is different.

That is exactly where the main practical difference comes from. Because ACE is left untouched, bradykinin is broken down normally, and the dry cough of ACE inhibitors does not appear. That is the most common reason someone switches from ramipril to a sartan.

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

Losartan itself has only a short half-life of around two hours. The effect is carried by the active metabolite EXP3174, which binds about ten times more strongly and stays in circulation for six to nine hours. That is why one dose per day is enough despite the short half-life of the parent compound.

The uric acid effect is a genuine peculiarity and not a class effect: losartan inhibits the URAT1 transporter in the kidney, through which uric acid is reabsorbed. More is therefore excreted. Anyone dealing with gout or elevated uric acid alongside gets an added benefit that valsartan or telmisartan do not offer.

LIFE (Lancet 2002) is the most informative trial, because it ran not against placebo but against an active comparator. Over 9,000 hypertensives with cardiac hypertrophy received losartan or atenolol. At practically identical blood pressure reduction, losartan produced 13 percent fewer cardiovascular events and around 25 percent fewer strokes. Same pressure, different outcome, and that is a strong argument.

The diabetes subgroup (Lancet 2002) came out even more clearly, with an additional advantage in all-cause mortality. RENAAL (NEJM 2001) demonstrated kidney protection in diabetic nephropathy: the combined endpoint of doubling creatinine, end-stage renal failure and death fell by 16 percent.

ELITE II (Lancet 2000) belongs here for honesty: in heart failure, losartan was not superior to the ACE inhibitor captopril on mortality. It was better tolerated, it was not more effective. Sartans are therefore second choice in heart failure, for when an ACE inhibitor is not an option.

• Clearly fewer than with ACE inhibitors: in the trials the discontinuation rate sat at placebo level. That is the main advantage of the class.
• Raised potassium: especially combined with potassium-sparing agents.
• Dizziness: mostly at the start or when increasing too fast.
• Angioedema: very rare, but described with sartans too. Anyone who had it on an ACE inhibitor is not automatically safe here.
• Kidney values: check after starting, as with ACE inhibitors.

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