What are the common side effects of angiotensin converting enzyme (ACE) inhibitor pills?

According to the Council of International Organizations of Medical Sciences (CIOMS), the frequency of adverse drug reactions are as follows:¹

Angiotensin converting enzyme (ACE) inhibitors are generally well tolerated. For the most part, side effects are mild and transient in nature.

Table 1: Common and very common side effects and the percentage of their incidence in manufacturers’ drug trials for ACE inhibitors being used to treat hypertension^2-14

*Brand names with asterisks beside them have been discontinued in the US. The generic versions of these drugs continue to be FDA approved and are available in the US.

Table 2: Common and very common side effects and the percentage of their incidence in manufacturers’ drug trials for ACE inhibitors being used to treat heart failure (HF)^2-14

*Brand names with asterisks beside them have been discontinued in the US. The generic versions of these drugs continue to be FDA approved and are available in the US.

For lisinopril being used to treat acute myocardial infarction (MI), manufacturers report the following common and very common side effects: hypotension (5.3%) and renal dysfunction (1.3%).^7-9

A meta-analysis of 38 published randomized, double blind, placebo-controlled trials examining the effects of ACE inhibitors found the following prevalence of uncommon or common side effects:¹⁵

• Cough (4.8% vs 1.2% placebo, absolute risk 3.6%)
• Dizziness (2.8% vs 2.2% placebo, absolute risk 0.6%)
• Fatigue (2.3% vs 1.7% placebo, absolute risk 0.6%)
• Nausea (0.9% vs 0.6% placebo, absolute risk 0.3%)
• Abdominal cramps (0.4% vs 0.2% placebo, absolute risk 0.2%)
• Rash (0.9% vs 0.8% placebo, absolute risk 0.1%)

Discontinuation

In clinical trials conducted by manufacturers, the following percentages of patients discontinued therapy for clinical adverse experiences. Please note that several manufacturers did not provide the incidence of discontinuation in the placebo arm. Placebo results are noted where the information was available.

• Benazepril: 5% (3% placebo)²
• Captopril: Information not provided³
• Enalapril: 3.3% for hypertension and 5.7% for heart failure^4-5
• Fosinopril: 4.1% (1.1% placebo) for hypertension and 8% (7.5% placebo) for heart failure⁶
• Lisinopril: 5.7% for hypertension and 8.1% (7.7% placebo) for heart failure^7-9
• Moexipril: 3.4% (1.8% placebo)¹⁰
• Perindopril: 6.5% (6.7% placebo)¹¹
• Quinapril: 4.7% for hypertension and 6.8% for heart failure¹²
• Ramipril: 3%¹³
• Trandolapril: 1.4% (2.1% placebo)¹⁴

References

1. Definitions. World Health Organization. https://www.who.int/medicines/areas/quality_safety/safety_efficacy/trainingcourses/definitions.pdf. Accessed January 20, 2022.
2. Lotensin [package insert]. Parsippany, NJ: Validus Pharmaceuticals LLC; 2019.
3. Capoten [package insert]. Chestnut Ridge, NY: Par Pharmaceutical; 2017.
4. Epaned [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
5. Vasotec [package insert]. Bridgewater, NJ: Bausch Health US LLC; 2018.
6. Monopril [package insert]. Princeton, NJ: Bristol-Myers Squibb Company; 2003.
7. Qbrelis [package insert]. Wilmington, MA: Azurity Pharmaceuticals, Inc.; 2020.
8. Prinivil [package insert]. Whitehouse Station, NJ: Merck Sharp & Dohme Corp.; 2021.
9. Zestril [package insert]. Morristown, NJ: Almatica Pharma LLC; 2020.
10. Univasc [package insert]. Smyrna, GA: USB, Inc; 2012.
11. Aceon [package insert]. Cincinnati, OH: Patheon Pharmaceuticals, Inc.; 2017.
12. Accupril [package insert]. New York, NY: Parke Davis, Pfizer; 2021.
13. Altace [package insert]. New York, NY: Pfizer Laboratories; 2022.
14. Mavik [package insert]. Whippany, NJ: Halo Pharmaceutical Inc.; 2017.
15. Law M, Wald N, Morris J. Lowering blood pressure to prevent myocardial infarction and stroke: a new preventive strategy. Health Technol Assess 2003; 7 (31): 1-94.