A Yale-coauthored paper in Lancet provides more information about the relative safety and effectiveness of different hypertension drugs in order to inform this critical treatment decision. The study reveals that angiotensin converting enzyme (ACE) inhibitors may not be the best choice for initial treatment.

For those with extremely high blood pressure, or hypertension, there are many initial medication options—so many that it can be hard to know which one to use. Unprecedented in scale, the Lancet study pulled together the data of 4.9 million patients from nine institutional databases across four countries. The researchers used that data to compare the safety and effectiveness of the five classes of first-line hypertension medications, including the popular ACE inhibitors. They were looking at how well each drug prevented the three main health consequences of hypertension—heart attack, heart failure, and stroke—and to what extent each drug caused 46 unwanted side-effects.

"This is a remarkable, massive, multinational study that has provided insights that can inform patient choices about hypertension treatment," says Dr. Harlan Krumholz, Yale cardiologist and author on the Lancet study. "What is distinctive is not only the size, but the advanced methods that optimize the trustworthiness of the results."

The big data revealed patterns that would otherwise have taken 22,000 typical observational studies to spot, say the researchers. One key finding was that thiazide or thiazide-like diuretics are better at preventing heart attack, heart failure, and stroke than ACE inhibitors, while also being safer than ACE inhibitors. Taken individually, the differences in safety and effectiveness of the treatments might seem small, say the scientists, but at scale, they become significant. The researchers report that if the 2.4 million people in the study currently using ACE inhibitors had instead been using thiazide or thiazide-like diuretics, more than 3,100 major cardiovascular events could potentially have been avoided.

"Given that these drugs are inexpensive and have a long track-record, the findings should clearly turn us away from the prevalent practice of starting with ACE inhibitors. These findings support people opting for a thiazide diuretic over an ACE inhibitor for the initial treatment of hypertension," Krumholz concludes.