Antihypertensives reduce adverse CV outcomes, but not death, in HFpEF patients

Use of antihypertensive medications does not appear to reduce the risk of all-cause mortality in patients with heart failure (HF) with preserved ejection fraction (HFpEF), reports a study presented at AHA 2023. However, treatment with antihypertensives can lower the risk of adverse cardiovascular (CV) outcomes regardless of the patient’s hypertension status.

“Hypertension is a comorbidity that is commonly associated with HFpEF,” according to the investigators, led by Dr Mohammad Alqadi from The University of Toledo, Ohio, US.

Alqadi and his team searched the databases of OVID Medline, Web of Science, and Embase for studies reporting the relationship between antihypertensive medications and CV outcomes in patients with HFpEF. All-cause mortality was the primary endpoint. Secondary endpoints included CV mortality, worsening HF, CV hospitalization, and major adverse CV events (MACE).

Fifteen studies, including a total of 17,507 HFpEF patients, met the eligibility criteria of this meta-analysis. Of the participants, 8,732 received medical therapy and 8,775 received placebo. [AHA 2023, abstract 2187]

Treatment with antihypertensive medications did not result in lower all-cause mortality (odds ratio [OR], 1.01, 95 percent confidence interval [CI], 0.80‒1.27; p=0.95) or CV mortality (OR, 0.97, 95 percent CI, 0.86‒1.08; p=0.53) relative to placebo.

However, antihypertensive use contributed to a significantly reduced risk of MACE (OR, 0.90, 95 percent CI, 0.83‒0.97; p<0.01) or CV hospitalization (OR, 0.89, 95 percent CI, 0.81‒0.97; p<0.04).

“Subgroup analysis demonstrated this to be primarily driven by studies with mixed HFpEF patients with or without hypertension, not HFpEF patients with hypertension,” Alqadi and colleagues said.

A trend toward a reduced risk of worsening HF was observed in patients treated with antihypertensive medications, driven by HFpEF patients with or without hypertension and not HFpEF patients with hypertension (OR, 0.87, 95 percent CI, 0.78‒0.97; p=0.02 vs OR, 0.57, 95 percent CI, 0.18‒1.86; p=0.35). However, this trend did not reach statistical significance.

These findings were consistent with those of a recent Mendelian randomization study, which found a protective effect against HF with the use of beta-blockers and calcium channel blockers (CCBs). It also suggested that pulse pressure (PP) was not independently predictive of HF. [Nutr Metab Cardiovasc Dis 2023;33:1420-1428]

In the said study, multivariable analysis adjusted for systolic blood pressure (SBP) showed no significant association between PP and HF risk (OR, 0.89, 95 percent CI, 0.77‒1.04). [Nutr Metab Cardiovasc Dis 2023;33:1420-1428]

On the other hand, HF risk significantly decreased with genetically proxied beta-blockers (equivalent to a 10-mm Hg SBP reduction; OR, 0.71, 95 percent CI, 0.62‒0.82) and CCBs (OR, 0.71, 95 percent CI, 0.65‒0.78), but not with angiotensin-converting enzyme inhibitors (OR, 0.69, 95 percent CI, 0.40‒1.19) and thiazide diuretics (OR, 0.80, 95 percent CI, 0.47‒1.37). [Nutr Metab Cardiovasc Dis 2023;33:1420-1428]

“Further studies are needed to clarify this association and determine the effect based on specific classes of medications,” the investigators said.