Choice of hypertension medication for the elderly linked to mortality risk — Large-scale medical data analysis by the Institute of Statistical Mathematics and partners

A research group including Professor Hisashi Noma of the Institute of Statistical Mathematics, Associate Professor Haruhisa Fukuda of the Graduate School of Medical Sciences at Kyushu University, and Lecturer Hiroshi Sunada of Tottori University Hospital has revealed through a large-scale medical data analysis that when elderly patients aged 75 and older choose an angiotensin receptor blocker (ARB) rather than a calcium channel blocker (CCB) as a treatment for hypertension, their risk of mortality decreases to 0.89 times and their risk of hospitalization for heart failure decreases to 0.84 times. This finding provides crucial insights for determining treatment strategies in clinical settings. The study was published online in the Journal of the American Geriatrics Society.

Hypertension is a highly prevalent condition among the elderly aged 75 and older, serving as a primary factor for heart disease and mortality. The efficacy of antihypertensive medications has been consistently demonstrated in lowering the risks of heart disease and stroke through numerous randomized clinical trials covering a wide range of age groups. However, high-quality evidence from direct comparisons regarding the best first-line drug specifically for patients aged 75 and older has been limited. This limitation exists because conducting comparative clinical trials has been difficult due to the fact that many elderly patients suffer from multiple co-existing chronic conditions, such as diabetes and reduced kidney function.

ARBs and CCBs are both medications that effectively lower blood pressure, and they are the most frequently prescribed antihypertensive drugs for the elderly in Japan. Although each lowers blood pressure through a different mechanism of action, these differing mechanisms may lead to variations in clinically critical outcomes, such as mortality and heart disease among elderly patients.

The research group conducted a comparative analysis of hypertension medications for elderly patients aged 75 and older using a massive nationwide database aggregating medical records of over 5 million individuals in Japan (the LIFE Study). In particular, they performed a sophisticated analysis utilizing "target trial emulation," a method developed in recent years within the framework of statistical causal inference.

Target trial emulation is an analytical method used to replicate an ideal randomized clinical trial as closely as possible using real-world data recorded in databases, thereby minimizing and controlling biases that could distort conclusions.

From the vast pool of information stored in the database, the researchers focused on patients who had newly initiated treatment with either an ARB or a CCB. They successfully constructed a cohort that mimicked an ideal randomized clinical trial consisting of 29,822 individuals (10,037 in the ARB group and 19,785 in the CCB group).

The analysis, which utilized bias-adjustment methods based on statistical causal inference such as propensity scores, revealed that the ARB group had a significantly lower mortality risk of 0.88 compared to the CCB group.

After five years, the mortality rate was 12.7% for the ARB group compared to 14.8% for the CCB group, resulting in a 2.1% difference. Furthermore, the ARB group exhibited lower hazard ratios across other outcomes: 0.84 for heart failure hospitalization, 0.86 for myocardial infarction, 0.93 for stroke, and 0.61 for end-stage renal disease or dialysis.

Meanwhile, blood pressure during treatment remained almost identical between the two comparative groups. This suggests that these favorable outcomes are not merely due to the effect of lowering blood pressure, but may stem from the unique organ-protective properties that ARBs possess.

By replicating an "ideal clinical trial" as closely as possible using nationwide large-scale clinical data and the latest data science methodologies, this study demonstrated that hypertension treatment centered on ARBs significantly reduces the risks of mortality and heart failure hospitalization compared to treatment centered on CCBs.

This serves as highly valuable reference information for practicing physicians when prescribing antihypertensive drugs to patients aged 75 and older. The research group plans to expand their detailed analyses in the future, looking beyond the suppression of mortality and heart disease to examine the long-term impacts on patient frailty, levels of independence in daily living, and renal function.

Journal Information
Publication: Journal of the American Geriatrics Society
Title: Angiotensin Receptor Blockers Versus Calcium Channel Blockers for First-Line Antihypertensive Therapy and Survival in Adults Aged 75 Years or Older
DOI: 10.1111/jgs.70463