Table 1.
CV medication harm causing presentation or admission to hospital.
| Author(s) | Type of study | Population/(n) | Country | Type of medication harm | Incidence | % CV medication harm | CV medications rank against other drug classes | Outcomes |
|---|---|---|---|---|---|---|---|---|
| Systematic reviews and meta-analysis | ||||||||
| Runciman et al. 38 | Review of multiple sources: SR, national data bases | Multiple data sources: refer to study | AU | ADR/ADE a | 2–4% of admissions; 30% in ⩾75 years | CV medications leading cause (% NR) | NR | Cost: >AUD$400 million per year Mortality: 27% of AE deaths in 1997–1998 |
| Howard et al. 39 | SR of 17 POS | ⩾16 years/(n = 17 studies) | – | Preventable DRAsa,b | 1.4–15.4% of admissions (3.7% median) | 33% (CV) 16% (diuretics) of preventable DRAs |
2nd (diuretics) 6th (BB) 7th (ACE-I) 9th (positive inotropes) 12th (CCB) 14th (nitrates) |
NR |
| Kongkaew et al. 36 | SR of 25 POS | All patients/(n = 25 studies, 106,586 patients) | – | ADR | 0.16–15.7% of admissions (5.3% median) | 45.7%
c
(median in all adults) 42.5% c (median in older adults) |
1st | Severity (reported by two studies): 3.3% and 38.1% of events were severe |
| Al Hamid et al. 40 | SR of ROS/POS | ⩾18 years/(n = 21 ADR studies, 6 ADE studies) | – | ADR and ADE a | ADR: 1.47% median (ROS), 12% median (POS) ADE: 12.4% median (POS) |
33.9% (median) of ADRs, 42.3% (median) of ADEs | 1st | Refer to study |
| Alhawassi et al. 41 | SR of ROS/POS | ⩾18 years/(n = 14 studies) | – | ADR | 10.0% of admissions (median) | CV medications leading cause (% NR) | NR | NR |
| Oscanoa et al. 42 | SR and MA | ⩾60 years/(n = 42 studies) | – | ADR a | 8.7% | BB, digoxin, ACE-I and CCB were frequently identified (% NR) | NR | NR |
| Literature reviews | ||||||||
| Roughead et al. 43 | Review of 14 studies | All patients/(n = 14 studies, 12,676 patients combined) | AU | DRA a | 2.4–3.6% of admissions | CV medications leading cause (% NR) | NR | NR |
| Wiffen et al. 44 | LR of 69 studies (54 POS, 15 ROS) | All patients/(n = 412,000) | – | ADR | 3.1% of admitted patients | Digoxin (22/69), Diuretics (15/69) identified as leading cause | NR | Cost: £380 million per year |
| Angamo et al. 45 | LR of studies in developed and developing countries | ⩾15 years (n = 43 studies) | – | ADR | Developed: 6.3% (median) Developing: 5.5% (median) | CV medications identified as leading cause (% NR) | NR | Severity: Developed: 20.0% severe (median) Developing: 10.0% (median) |
| Observational, cohort, and cross-sectional studies | ||||||||
| Larmour et al. 46 | PCS | All patients/(n = 5623 admissions) | AU | ADR | 1.6% of admissions | 11.1% of ADRs | 1st | Mortality: 5.6% |
| Stanton et al. 47 | PCS | Adult patients/(n = 691) | AU | ADR | 3.04% of admissions | 9.5% of ADRs | 4th | NR |
| Nelson et al. 48 | PCS | Patients admitted to ICU or internal medicine/(n = 452) | USA | DRA a (includes ADR and DTF) | DRA: 16.2% ADR: 5.3% of patients |
13.2% (diuretics) 10.5% (CV) of patients with DRA |
2nd 5th |
NR |
| Jha et al. 49 | PCS | All patients/(n = 3238 admissions) | USA | ADE a | 2.3% of admissions | 12% of ADEs | 2nd | Cost: $6.3 million per year for all ADEs Severity: 78% severe |
| Burgess et al. 50 | Retrospective secondary data analysis of case series | >60 years/(n = 43,380) | AU | ADR | 0.8% of all admissions for all age-groups | 17.5% of patients >60 years with ADRs | 1st | NR |
| Passarelli et al. 51 | PCS | ⩾60 years admitted to internal medicine/(n = 186) | Brazil | ADR | 11.3% of patients | 22.7% (digoxin) of ADRs causing admission | 1st | LOS: increased (p < 0.001) |
| Budnitz et al. 52 | PCS | All patients/(n = estimated 701,547 cases) | USA | ADE a | NR | 7.6% of ADE hospitalisations | 5th | NR |
| Ducharme et al. 53 | Retrospective analysis of preventability data | ADR data collected over three years at a teaching hospital/(n = 475 ADRs) | USA | pADR | 126 pADRs (% NR) | 11.9% | 4th | NR |
| Edwards et al. 54 | PCS | Patients ⩾17 years/(n = 62,064 admissions) | USA | ADE a | 2.4% of admissions | 28% of ADEs | 2nd | Mortality: 3.2% |
| Ocampo et al. 55 | CSS | Patients ⩾60 years/(n = 400) | Columbia | ADE and ADR | 6.8% | % NR | 3rd | NR |
| Ventura et al. 56 | PCS | All patients/(n = 56,031) | Italy | ADR | 21.2% | % NR | 3rd | NR |
| Budnitz et al. 6 | RCS | ⩾65 years/(n = estimated 99,628 cases) | USA | ADE | NR | 9.8% of ADE hospitalisations | 3rd | NR |
| Conforti et al. 57 | PCS | Patients ⩾65 years/(n = 1023) | Italy | ADR | 11.1% of patients | 46.2% of ADRs | 1st | LOS: increased (no p value reported) |
| Marcum et al. 58 | RCS | ⩾65 years veterans/(n = 6778) | USA | ADR a | 10% of patients | CV medications identified as leading cause (% NR) | NR | NR |
| McLachlan et al. 59 | PCS | All general medical patients/(n = 336) | New Zealand | ADE | 28.6% of admissions | 23% (vasodilators), 16% (diuretics), 11% (chronotropes) | 1st (vasodilators), 3rd (diuretics), 4th (chronotropes) | NR |
| Phillips et al. 60 | PCS | All patients/(n = 370) | AU | ADEa,d | 16% of patients (34.7% were ADRs) | 31.5% of ADEs | 3rd (ACE-I) 5th (BB) 6th (diuretics) 8th (CCB) |
Severity: 34.7% of ADEs were severe |
| Gustafsson et al. 37 | RCS | ⩾65 years with cognitive impairment/(n = 458) | Sweden | DRPa,e | DRP: 41.3% ADR: 18.8% of admissions |
29.5% of DRPs (% of ADRs NR) | 1st | NR |
| de Almeida et al. 61 | RCS | Adult patients/(n = 866) | Brazil | ADR | 2.3% | 14.3% of ADRs | 2nd | Cost: $5698.84 per ADR hospitalisation |
| Paradissis et al. 22 | PCS | ⩾65 years admitted to internal medicine/ (n = 164) | AU | ADE a | 15.2% of patients | 50% of ADEs | 1st | LOS: increased (p = 0.043) |
| Parameswaran et al. 62 | Prospective, CSS | ⩾65 years admitted to hospital/(n = 1008) | AU | ADR | 18.9% of admissions | 23.9% of ADRs (diuretics) 16.4% (ACE-I/ARB) 7.1% (BB) |
1st 2nd 3rd |
Preventable: 87.2% of ADRs Mortality: 2.1% Severity: 2.1% |
| Poudel et al. 63 | Descriptive RCS | All patients/(n = weighted estimate 150 259 899 hospitalisations) | USA | ADE a | 5.97–6.28% of hospitalisations | 13.24% of ADEs (combined) | 8th (diuretics) 11th (anti-HTN) 15th (cardiac glycosides) 17th (anti-arrhythmics) 18th (BB) 21st (antihyperlipidaemic) |
LOS: increased for ADE hospitalisations (p < 0.001) Cost: increased (p < 0.001) Mortality: increased (p < 0.001) |
| Ognibene et al. 64 | RCS | ⩾65 years admitted to internal medicine/(n = 1750) | Italy | ADR f | 6.1% of admissions | 17.6% (Diuretics) | 1st | Mortality: 10.4% of ADRs Severity: 27.4% with residual disability |
| Schurig et al. 65 | PCS | All patients presenting to emergency/(n = 10,174) | Germany | ADR a | 6.5% of admissions | ~19% (BB) ~17% (ACE-I) |
2nd 3rd |
NR |
| Mullan et al. 66 | RCS | ⩾65 years with and without dementia/(n = 228,165 admissions) | AU | MMa,g | 4.6% of admissions | With dementia: 3.9% of MM (anti-HTN) 3.4% (BB) 2.5% (ACE-I) Without dementia: 4.7% (anti-HTN) 4.1% (BB) 2.6% (cardiac glycosides) 2.1% (diuretics) 2.0% (ACE-I) |
With dementia: 4th 5th 8th Without dementia: 5th 6th 7th 8th 10th |
NR |
| Zhang et al. 67 | Population based RCS | All patients/(n = 315,274 ADR admissions) | AU | ADR | 432.3 per 100,000 residents | 4.8% of ADRs (anti-HTN) 3.9% (BB) 2.9% (cardiac stimulant) |
4th 7th 9th |
NR |
| Smeaton et al. 68 | PCS | Patients aged between 45–64 years/(n = 100) | Ireland | ADR | 21% | 52.2% of ADRs | 1st | Preventable: 52.2% of ADRs |
a
Includes medication errors.
b
Includes ADRs, overtreatment, under-treatment and adherence problems.
c
Definition for CV medications incorporated antithrombotics and anticoagulants.
d
Includes non-compliance, untreated indications, improper drug selection, sub/supratherapeutic dose, ADRs, drug interactions and drug use without indication.
e
Includes ADR, dosage too high, dosage too low, ineffective drug, needs additional drug therapy, unnecessary drug therapy and noncompliance.
f
Includes drug–drug interactions.
g
Includes ADR, ADEs and medication errors.
ACE-I, angiotensin-converting enzyme inhibitor; ADE, adverse drug event; ADR, adverse drug reaction; AE, adverse events; anti-HTN, antihypertensives; ARB, angiotensin receptor blocker; AU, Australia; AUD, Australian dollars; BB, beta-blockers; CCB, calcium channel blocker; CCS, case-control study; CSS, cross-sectional study/survey; CV, cardiovascular; DRA, drug-related admission; DRP, drug-related problem; DTF, drug therapeutic failure; ICU, intensive care unit; LOS, length of stay; LR, literature review; MA, meta-analysis; MM, medication misadventure; NR, not reported; OS, observational study; pADE, preventable adverse drug event; PCS, prospective cohort study; POS, prospective observational study (includes CCS/PCS); RCS, retrospective cohort study; ROS, retrospective observational study (includes CCS/RCS); SR, systematic review; USA, United States of America.