Are ACE inhibitors no longer useful in CVD ?

Most guidelines for the management of patients with cardiovascular disease recommend angiotensin-converting enzyme (ACE) inhibitors as first-choice therapy, whereas angiotensin receptor blockers (ARBs) are merely considered an alternative for ACE inhibitor-intolerant patients.Dr. Messerli and colleagues conducted a Study to compare outcomes and adverse events between ACE inhibitors and ARBs in patients with hypertension.The researchers found that there is " very little clinical reason" to use angiotensin-converting enzyme (ACE) inhibitors for the treatment of hypertension or other cardiovascular indications because angiotensin receptor blockers (ARBs) are just as effective with fewer side effects. The study has been published in Journal of the American College of Cardiology.

The researchers reviewed data from 119 randomized clinical trials of ACE inhibitors and ARBs in more than half a million patients and found no difference in efficacy between the two drug classes with regard to the surrogate endpoint of blood pressure and the outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease.

The authors have reviewed the mechanisms of action for the two agents, as well as their effects on blood pressure, left ventricular hypertrophy, and proteinuria. Key outcomes studies and meta-analyses in patients without heart failure, including HOPE, CAMELOT, ALLHAT, and REACH, among others, do not support the superiority of ACE inhibitors over ARBs according to them.

The researchers concluded the in patients with hypertension and hypertension with compelling indications there were no difference in efficacy between ARBs and ACE inhibitors with regard to the surrogate endpoint of blood pressure and outcomes of all-cause mortality, cardiovascular mortality, myocardial infarction, heart failure, stroke, and end-stage renal disease. However, ACE inhibitors remain associated with a cough and a very low risk of angioedema and fatalities. Overall withdrawal rates because of adverse events are lower with ARBs than with ACE inhibitors. The equal outcome efficacy but fewer adverse events with ARBs indicates that at present there is little if any, a reason to use ACE inhibitors for the treatment of hypertension or its compelling indications.

The first ACE inhibitor, captopril, came on the market in 1981, while the first ARB, losartan, debuted in 1995. Both agents are commonly used in patients with hypertension, heart failure, CAD, diabetes, and chronic kidney disease, but guidelines have tended to recommend ACE inhibitors as first-line therapy.According to author ever since the HOPE study, published in 2000, ACE inhibitors have become a sacred cow and nobody dared to say anything against them.

The latest AHA/ACC guidelines and the upcoming European guidelines have placed both ARBs and ACE with regard to efficacy in the same class, and they consistently state, ‘an ACE inhibitor or an ARB’ can be used—there is no longer any priority given to the ACE inhibitor.But the side-effect profile must be considered by the guidelines to go one step further,according to author.

ACE inhibitors have remained a preferred choice as compared to ARBs in heart failure but lately, it has been found that adding a neprilysin inhibitor to an ARB is better than an ACE inhibitor alone.According to available data, about 80% of patients with hypertension in the world do not have their blood pressure controlled, control of which is a public health need at present.Experts, therefore, feel that more time and effort should be directed at improving blood pressure control rather than deciding which pharmacological agent is better for ACE inhibitor and ARB.