Antihypertensive Drugs and COVID-19 Risk: A Cohort Study of 2 Million Hypertensive Patients

Hypertension. 2021 Mar 3;77(3):833-842. doi: 10.1161/HYPERTENSIONAHA.120.16314. Epub 2021 Jan 11.


After initially hypothesizing a positive relationship between use of renin-angiotensin-aldosterone system inhibitors and risk of coronavirus disease 2019 (COVID-19), more recent evidence suggests negative associations. We examined whether COVID-19 risk differs according to antihypertensive drug class in patients treated by ACE (angiotensin-converting enzyme) inhibitors and angiotensin receptor blockers (ARBs) compared with calcium channel blockers (CCBs). Three exclusive cohorts of prevalent ACE inhibitors, ARB and CCB users, aged 18 to 80 years, from the French National Health Insurance databases were followed from February 15, 2020 to June 7, 2020. We excluded patients with a history of diabetes, known cardiovascular disease, chronic renal failure, or chronic respiratory disease during the previous 5 years, to only consider patients treated for uncomplicated hypertension and to limit indication bias. The primary end point was time to hospitalization for COVID-19. The secondary end point was time to intubation/death during a hospital stay for COVID-19. In a population of almost 2 million hypertensive patients (ACE inhibitors: 566 023; ARB: 958 227; CCB: 358 306) followed for 16 weeks, 2338 were hospitalized and 526 died or were intubated for COVID-19. ACE inhibitors and ARBs were associated with a lower risk of COVID-19 hospitalization compared with CCBs (hazard ratio, 0.74 [95% CI, 0.65-0.83] and 0.84 [0.76-0.93], respectively) and a lower risk of intubation/death. Risks were slightly lower for ACE inhibitor users than for ARB users. This large observational study may suggest a lower COVID-19 risk in hypertensive patients treated over a long period with ACE inhibitors or ARBs compared with CCBs. These results, if confirmed, tend to contradict previous hypotheses and raise new hypotheses.

Keywords: COVID-19; angiotensin receptor blockers; angiotensin-converting enzyme inhibitors; calcium channel blockers; hospitalization; mortality; pharmacoepidemiology.

Publication types

  • Observational Study

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Aged, 80 and over
  • Angiotensin Receptor Antagonists / adverse effects*
  • Angiotensin Receptor Antagonists / therapeutic use
  • Angiotensin-Converting Enzyme 2 / drug effects*
  • Angiotensin-Converting Enzyme Inhibitors / adverse effects*
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use
  • Antihypertensive Agents / adverse effects*
  • Antihypertensive Agents / therapeutic use
  • COVID-19 / epidemiology*
  • COVID-19 / etiology
  • Calcium Channel Blockers / adverse effects
  • Calcium Channel Blockers / therapeutic use
  • Comorbidity
  • Disease Susceptibility
  • Drug Utilization
  • Female
  • Follow-Up Studies
  • France / epidemiology
  • Hospital Mortality
  • Hospitalization / statistics & numerical data
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / epidemiology
  • Intubation, Intratracheal / statistics & numerical data
  • Male
  • Middle Aged
  • Pandemics*
  • Receptors, Virus / drug effects*
  • Retrospective Studies
  • SARS-CoV-2 / physiology*
  • Young Adult


  • Angiotensin Receptor Antagonists
  • Angiotensin-Converting Enzyme Inhibitors
  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Receptors, Virus
  • ACE2 protein, human
  • Angiotensin-Converting Enzyme 2