How do you prescribe ACEIs and ARBs for hypertension?

28 Jan 2022 How do you prescribe ACEIs and ARBs for hypertension?

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Posted at 15:33h in Portrait by

An individual Portrait on prescribing of thiazides, ACEIs and ARBs was sent to approximately 3850 eligible family doctors in BC, randomized to receive this Portrait in two groups: an early group in March 2021 and a delayed group in January 2022. This Portrait was accompanied by Therapeutics Letter #133: Primary hypertension therapy: after thiazide, an ACEI or an ARB?

Below is a sample Portrait containing fictional individual physician data. View this sample Portrait in PDF format, or click on the DOWNLOAD button above. If you are a BC family physician and wish to sign up for (or opt out of) receiving Portrait, click on the REGISTER button above.

Abbreviations used

ACEI: angiotensin-converting enzyme inhibitor
ALLHAT: Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack
ARB: angiotensin II receptor blocker
CCI: Canadian Classification of Health Interventions
ICD-9: International Classification of Diseases, Ninth Revision
ICD-10: International Classification of Diseases, Tenth Revision
MSP: Medical Services Plan
RCMP: Royal Canadian Mounted Police
T2DM: type 2 diabetes mellitus

Sample Portrait

References

  1. Therapeutics Initiative. Primary hypertension therapy: after thiazide, an ACEI or an ARB? Therapeutics Letter. 2021 (Sep-Oct);133:1-2.

Data definitions

Who received this Portrait?

All BC physicians meeting all of the following criteria received an individual ACEI, ARB, and thiazide prescribing Portrait:

  • General practice physicians, including family practitioners, who were registered by the BC Medical Services Plan (MSP) as a private practice, and
  • had a valid mailing address in BC according to the College of Physicians and Surgeons of British Columbia’s public physician information, and
  • had ≥100 prescriptions filled at a community  pharmacy in 2020 according to PharmaNet claims data, and
  • prescribed an oral thiazide (hydrochlorothiazide, chlorthalidone, or indapamide), ACEI, or ARB (a.k.a. Portrait drugs) as first-line hypertensive treatment to at least three patients; or prescribed an oral ACEI or ARB to at least three new users in 2019-2020 according to PharmaNet claims data.
    • First-line users were identified as those without Portrait drugs or other antihypertensive drugs in the previous three years, including: acebutalol, aliskiren, amiloride, amlodipine, atenolol, bisoprolol, diltiazem, eplerenone, felodipine, furosemide, hydralazine, labetalol, metoprolol, nadolol, nebivolol, nifedipine, pindolol, propranolol, spironolactone, timolol, triamterene, and verapamil.
    • New users were defined as patients without ACEI or ARB filled in the previous 365 days. These patients could have used antihypertensives from another therapeutic class.

Physicians may have received a Portrait with masked data (i.e. patient count listed as *1-5) if they met the above requirements but prescribed to between 1 and 5 patients for that section of the Portrait. Data elements that contained <6 patients were masked to comply with privacy requirements.

How were patients assigned to this Portrait?

Patients were included in a physician’s Portrait if they met all of the following criteria:

  • were continuously registered with the MSP for a year before dispensing, and
  • filled a prescription for a thiazide, ACEI, or ARB with that physician’s prescribing number in a community pharmacy (based on PharmaNet data), and
  • were age ≥ 18 years at time of the refilling.

Patients were excluded from a physician’s Portrait if they met any of the following criteria:

  • had heart failure (ICD-9 428.x; ICD-10 I50.x) or dialysis (MSP fee items 33758, 33723, 33759, 33761) in the 365 days before prescription, or
  • were hospitalized for stroke/myocardial infraction/angina pectoris (primary or secondary diagnosis; ICD-9 codes 433.x, 434.x, 430.x, 431.x, 432.x, 436, 438.x, 411.x, 412.x, 413.x, 414.x; ICD-10 codes I60.x, I61.x, I62.x, I63.x, I64.x, I65.x, I66.x, I67.x, I69.x, I25.x) in the previous 28 days, or
  • had percutaneous coronary intervention (CCI codes 1IJ50.x, 1.IJ.57.GQ.x) or coronary artery bypass surgery (CCI codes1IJ76.x, 1IJ.80.x, 1IJ57LA.x) in the previous 28 days, or
  • were on MSP plan P (palliative), or
  • were pregnant, defined as female, age 10-60 with any of the following:
    • a record of MSP fee item 14090 or 14091 in the last 280 days without a code of delivery/pregnancy outcome (ICD-9 codes 630.x, 631.x, 632.x, 633.x, 634.x, 635.x, 636.x, 637.x, V27.x, 656.4 ; ICD-10 codes O00.x, O01.x, O02.x, O03.x, O04.x, O05.x, Z37.x, O36.4x) after these codes and before drug dispensation, or
    • a diagnosis of gestational hypertension (ICD-9 codes 642.x; ICD-10 codes O13.x-O16.x) in the 270 days drug dispensation.

The Portrait data included patients with and without type 2 diabetes mellitus(T2DM). There is insufficient evidence to treat hypertensive patients with T2DM differently than non-diabetics. In the ALLHAT review, results favoured thiazides over ACEIs as first-line treatment, including in people with diabetes or impaired fasting glucose levels1.

What prescriptions were included in this Portrait?

Thiazide, ACEI, and ARB prescription records were extracted from PharmaNet claims data and included all prescriptions filled at a community pharmacy in BC with that physician’s prescribing number.

Portrait drugs were all oral formulation prescription thiazides, ACEIs, and ARBs, available in BC:

hydrochlorothiazide, chlorthalidone, indapamide, benazepril, captopril, cilazapril, enalapril, fosinopril, lisinopril, perindopril, quinapril, ramipril, trandolapril, azilsartan, candesartan, eprosartan, irbesartan, losartan, olmesartan, telmisartan, and valsartan.

The following prescription data were not included:

  • Prescription data for patients who are federally insured (e.g. Veterans, RCMP, Armed Forces and beneficiaries of Non-Insured Health Benefits),
  • Prescription paid by PharmaCare Plan W (First Nations Health Benefits),
  • Reversed prescription claims,
  • Out-of-province prescriptions, and
  • Drugs dispensed in hospitals.

Research component

The research objective is to determine the impact of the Portrait on physician prescribing of thiazides, ACEIs and ARBs. This impact is evaluated at an aggregated level by comparing pooled prescribing data from physicians in the early mailing group to pooled prescribing data from physicians in the delayed group. All prescribing data analyzed for this evaluation do not contain names, only encrypted patient and physician numbers. No physician or patient will be identified in any reports or publications. As a reminder, Portrait’s data access agreement requires the masking of data elements when <6 individuals (patients or physicians) are included. Ethics approval for this evaluation will be obtained from the University of British Columbia Ethics Review Board. This evaluation is being led by Drs. Colin Dormuth and Greg Carney, University of British Columbia, Faculty of Medicine, Department of Anesthesiology, Pharmacology, & Therapeutics.

If you have any questions or would like further information with respect to this evaluation, you may contact the Portrait team at (604) 822-4887 or email Portrait@ti.ubc.ca

FAQ

Can I request the names of my patients included in this Portrait?

No. Portrait’s data access agreement only permits access to encrypted patient identifiers. There is no way for us to identify individual patients in the data or to provide you with a list.

However, other resources may be available for you. Contact your Practice Support Program (PSP) regional team to discuss how they might help you use your EMR to identify these patients.

Some observational studies have suggested an association between thiazides and skin cancer, as well as thiazides and electrolyte imbalances. Why do you recommend the first-line prescribing of thiazides, with this evidence in circulation?

Observational studies have suggested an association between treatment with thiazides and the diagnosis of skin cancer1,2,3, however, other observational studies have not shown this association.  At the present time it is not known whether thiazides cause skin cancer.

Thiazide-type diuretics can occasionally cause clinically significant hypokalemia or hyponatremia (or both). This is probably more common in elderly people, but the true frequency is unknown. Narrative reviews focusing on metabolic effects of diuretics do not provide an estimate of the incidence nor how they compare to other drug classes.

Our current interpretation of available evidence:

  • Thiazides can reduce plasma potassium and sodium and raise plasma uric acid and (slightly) total cholesterol and triglycerides. It is not possible to reliably estimate the incidence of these effects, yet they seldom lead to a need to stop the drug.
  • Cochrane systematic reviews of head-to-head randomized trials find that low-dose thiazides are equal to other drug classes for mortality and better than other drug classes for morbidity.4 First-line thiazides reduce stroke and heart failure better than renin angiotensin system inhibitors, and reduce heart failure compared with calcium channel blockers.5 First-line low dose thiazides result in fewer treatment withdrawals due to adverse effects, compared with all other antihypertensive drug classes, both individually and in combination with other drugs.6
  • In people age 60 or over, a review mainly including trials with first-line thiazides found modest reduction in all-cause mortality, and significant reductions in cardiovascular morbidity/mortality, compared to placebo or no treatment. Withdrawals due to adverse events were higher in treatment groups than in control groups. Total withdrawals from treatment did not differ in the thiazide-diuretic groups, compared with other drug classes. Withdrawals included patients withdrawing because of electrolyte abnormalities, need for laboratory monitoring, or any other reason.7
  • In Cochrane reviews of thiazide-like drugs, the underlying RCTs did not specifically report on skin cancers as adverse events or serious adverse events. Participants who withdrew from therapy because of a skin cancer, or who died in relation to a skin cancer would have been included in overall numbers reported for withdrawals due to adverse events and mortality.
  • The Therapeutics Initiative is currently studying the association between antihypertensive drugs and skin cancer. Once complete we will share on the TI website.
  • Based on all of the above information, we conclude that low dose thiazides are still first choice in terms of outcomes that patients find important, including stroke, heart failure and withdrawals due to adverse effects.8 As in all patient care, choice should be adjusted according to patient goals and factors.

References:

  1. Drucker AM, Hollestein L, Na Y, et al. Association between antihypertensive medications and risk of skin cancer in people older than 65 years: a population-based study. CMAJ 2021;193:E508-16. https://www.cmaj.ca/content/193/15/E508
  2. Pedersen SA, Gaist D, Schmidt SAJ, et al. Hydrochlorothiazide use and risk of nonmelanoma skin cancer: A nationwide case-control study from Denmark. J Am Acad Dermatol 2018;78:673-681. https://pubmed.ncbi.nlm.nih.gov/29217346/
  3. Pottegård A, Pedersen SA, Schmidt SAJ, et al. Use of hydrochlorothiazide and risk of skin cancer: a nationwide Taiwanese case-control study. Br J Cancer 2019;121:973-8. https://www.nature.com/articles/s41416-019-0613-4
  4. Wright JM, Musini VM, Gill R. First‐line drugs for hypertension. Cochrane Database of Systematic Reviews 2018, Issue 4. Art. No.: CD001841. DOI: 10.1002/14651858.CD001841.pub3. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD001841.pub3/full
  5. Chen Y, Li L, Tang W, Song J, Qiu R, Li Q, Xue H, Wright JM. First-line drugs inhibiting the renin angiotensin system versus other first-line antihypertensive drug classes for hypertension. Cochrane Database of Systematic Reviews 2018, Issue 11. Art. No.: CD008170. DOI: 10.1002/14651858.CD008170.pub3. https://www.cochrane.org/CD008170/HTN_renin-angiotensin-system-inhibitors-versus-other-types-medicine-hypertension/
  6. Zhu J, Chen N, Zhou M, Guo J, Zhu C, Zhou J, Ma M, He L. Calcium channel blockers versus other classes of drugs for hypertension. Cochrane Database Syst Rev. 2021 Oct 17;10(10):CD003654. doi: 10.1002/14651858.CD003654.pub5. PMID: 34657281; PMCID: PMC8520697. https://pubmed.ncbi.nlm.nih.gov/34657281/
  7. Wright JM, Lee, CH, Chambers, GK, Systematic review of antihypertensive therapies CMAJ July 13, 1999 161 (1) 25-32. https://www.cmaj.ca/content/161/1/25
  8. Musini VM, Tejani AM, Bassett K, Puil L, Wright JM. Pharmacotherapy for hypertension in adults 60 years or older. Cochrane Database of Systematic Reviews 2019, Issue 6. Art. No.: CD000028. DOI: 10.1002/14651858.CD000028.pub3. https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD004349.pub3/full

I don’t see my question here. Where can I find more information?

We welcome your feedback.  Questions can be directed to our Portrait team by phone (604) 822-4887 or email Portrait@ti.ubc.ca. You can also check out our program FAQ page.

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