Risk of acute myocardial infarction after discontinuation of antihypertensive agents: a case-control study.
We performed a nested case-control study in a cohort of antihypertensive drug users to assess the association between discontinuation of different antihypertensive agents and the risk of acute myocardial infarction (AMI). Cases and controls were drawn from the Utrecht Cardiovascular Pharmacogenetics database. Patients who were hospitalised for their first AMI were considered cases and controls were not hospitalised for AMI. Antihypertensive users were defined as current users if the index date (date of AMI) fell within the prescribed duration or as discontinuers if this date fell outside the prescribed duration. According to the recency of discontinuation, discontinuers were divided into the following: recent discontinuers (⩽90 days), intermediate-term discontinuers (91-180 days) and long-term discontinuers (>180 days). We found that the risk of AMI was significantly increased in discontinuers, regardless of time since discontinuation, of beta-blockers (adjusted odds ratio (OR) 1.54; 95% confidence interval (CI; 1.25-1.91), P-value<0.0005), calcium channel blockers (CCBs; adjusted OR 2.25; 95% CI (1.53-3.30), P-value<0.0005) and diuretics (adjusted OR 1.76; 95% CI (1.24-2.48), P-value=0.002) compared to current users of these drugs. Moreover, the risk of AMI was significantly increased in long-term discontinuers (beta-blockers, CCBs, angiotensin-converting enzyme inhibitors and diuretics) and intermediate-term discontinuers (beta-blockers and CCBs) versus current users of these drugs. There was no difference in AMI risk between recent discontinuers of antihypertensive drugs versus current users of these drugs. In conclusion, discontinuation of antihypertensive drugs increases the risk of AMI after >90 days of discontinuation. This further underlines the importance of persistence to antihypertensive drug therapy to reduce the risk of AMI in patients with hypertension.
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
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Alharbi
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
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Souverein
Department of Clinical Chemistry and Haematology, Division of Laboratory and Pharmacy, University Medical Center Utrecht, Utrecht, The Netherlands.
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de Groot
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Department of Respiratory Disease, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
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Maitland-van der Zee
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.
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de Boer
Division of Pharmacoepidemiology and Clinical Pharmacology, Utrecht Institute for Pharmaceutical Sciences, Utrecht University, Utrecht, The Netherlands.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands.
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Klungel
D000368:Aged; D000959:Antihypertensive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D001794:Blood Pressure / Q000187:drug effects*; D016022:Case-Control Studies; D016009:Chi-Square Distribution; D016208:Databases, Factual; D004334:Drug Administration Schedule; D005260:Female; D006760:Hospitalization; D006801:Humans; D006973:Hypertension / Q000150:complications / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D016015:Logistic Models; D008297:Male; D055118:Medication Adherence; D008875:Middle Aged; D009203:Myocardial Infarction / Q000175:diagnosis / Q000209:etiology* / Q000517:prevention & control; D009426:Netherlands; D016017:Odds Ratio; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors; D016896:Treatment Outcome
D000959:Antihypertensive Agents