Associations between initiating antihypertensive regimens on stage I-III colorectal cancer outcomes: A Medicare SEER cohort analysis

Cancer Med. 2021 Aug;10(15):5347-5357. doi: 10.1002/cam4.4088. Epub 2021 Jun 29.

Abstract

Purpose: Colorectal cancer (CRC) diagnosis is associated with high mortality in the United States and thus warrants the study of novel treatment approaches. Vascular changes are well observed in cancers and evidence indicates that antihypertensive (AH) medications may interfere with both tumor vasculature and in recruiting immune cells to the tumor microenvironment based on preclinical models. Extant literature also shows that AH medications are correlated with improved survival in some forms of cancer. Thus, this study sought to explore the impact of AH therapies on CRC outcomes.

Patients and methods: This study was a non-interventional, retrospective analysis of patients aged 65 years and older with CRC diagnosed from January 1, 2007 to December 31st, 2012 in the Surveillance, Epidemiology, and End-Results (SEER)-Medicare database. The association between AH drug utilization on AJCC stage I-III CRC mortality rates in patients who underwent treatment for cancer was examined using Cox proportional hazards models.

Results: The study cohort consisted of 13,982 patients diagnosed with CRC. Adjusted Cox proportional hazards regression showed that among these patients, the use of AH drug was associated with decreased cancer-specific mortality (HR: 0.79, 95% CI: 0.75-0.83). Specifically, ACE inhibitors (hazard ratio [HR]: 0.84, 95% CI: 0.80-0.87), beta-blockers (HR: 0.87, 95% CI: 0.84-0.91), and thiazide diuretics (HR: 0.83, 95% CI: 0.80-0.87) were found to be associated with decreased mortality. An association was also found between adherence to AH therapy and decreased cancer-specific mortality (HR: 0.94, 95% CI: 0.90-0.98).

Conclusion: Further research needs to be performed, but AH medications may present a promising, low-cost pathway to supporting CRC treatment for stage I-III cancers.

Keywords: SEER program; antihypertensive agent; colorectal neoplasms.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / therapeutic use
  • Aged
  • Aged, 80 and over
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / therapeutic use*
  • Colonic Neoplasms / blood supply
  • Colonic Neoplasms / mortality*
  • Colonic Neoplasms / pathology*
  • Confidence Intervals
  • Female
  • Humans
  • Immunity, Cellular / drug effects
  • Male
  • Medicare
  • Medication Adherence
  • Neoplasm Staging
  • Proportional Hazards Models
  • Protective Agents / therapeutic use
  • Rectal Neoplasms / blood supply
  • Rectal Neoplasms / mortality*
  • Rectal Neoplasms / pathology*
  • Retrospective Studies
  • SEER Program
  • Sodium Chloride Symporter Inhibitors
  • Tumor Microenvironment / immunology
  • United States

Substances

  • Adrenergic beta-Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Protective Agents
  • Sodium Chloride Symporter Inhibitors