Table 3.
Statin adherence exposure definitions, outcomes, results and confounders considered in multivariable models of studies included in the systematic review
| Study ID | Author | Patient population | Exposure definition | Type of variable | Variable categories and reference group | Outcomes | Main results | Confounders according to WHO dimensions | ||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Statin adherence studies | ||||||||||||
| A1 | Wei et al. (2002) [32] | AMI | PDC statin initiation to outcome/end of study | Fixed in time | ≥0.80 0.40–070 <0.39 0* (NA) |
(i) AMI | (i) RR 0.19 (0.08–0.47) | P | C | T | S | H |
| (ii) Mortality | (ii) RR 0.47 (0.22–0.99) | |||||||||||
| A2 | Howell et al. (2004) [40] | Primary care | PDC statin from first to last statin prescription | Fixed in time | ≥0.80* <0.80 |
(i) AMI | (i) Not reported | P | C | – | – | – |
| (ii) Mortality | (ii) HR 2.54 (1.31–4.93) | |||||||||||
| A3 | Blackburn et al. (2005) [34] | CAD | Statin fill frequency | Fixed in time | ≥80% ≤60%* (NA) |
(i) AMI | HR 0.45 (0.20–0.99) | P | C | T | – | H |
| (ii) Mortality | HR 0.68 (0.14–3.26) | |||||||||||
| A4 | Ho et al. (2006) [42] | Diabetes | 1 year PDC from statin initiation | Fixed in time | ≥0.80* (A) <0.80 |
Mortality | OR 1.39 (1.18–1.63) | P | C | – | – | – |
| A5 | Ho et al. (2006) [36] | Diabetes with IHD | 1 year PDC from statin initiation | Fixed in time | ≥0.80 <0.80* (NA) |
Mortality | OR 0.59 (0.41–0.87) | P | C | – | – | – |
| A6 | Bouchard et al. (2007) [24] | General population | PDC statin initiation to outcome/end of study | Fixed in time | ≥0.90 <0.90* (NA) |
(i) CAD <1 year | (i) OR 1.02 (0.87–1.18) | P | C | T | S | – |
| (ii) CAD >1 year | (ii) OR 0.81 (0.67–0.97) | |||||||||||
| A7 | Rasmussen et al. (2007) [35] | AMI | 1 year PDC from statin initiation | Fixed in time | ≥0.80* (A) 0.40–0.80 <0.40 |
Mortality | RR 1.25 (1.09–1.42) | P | C | – | S | H |
| A8 | Ho et al. (2008) [37] | CAD | PDC over 180 day time intervals | Time dependent | ≥0.80* (A) <0.80 |
(i) Mortality | (i) HR 1.85 (1.63–2.09) | P | C | – | – | – |
| (ii) CVD mortality | (ii) HR 1.62 (1.24–2.13) | |||||||||||
| (iii) CVD | (iii) HR 1.35 (1.21–1.50) | |||||||||||
| A9 | Perreault et al. (2008) [25] | General population | MPR statin initiation to outcome/end of study | Fixed in time | ≥80% 60–79% 40–59% 20–39% 1–19%* (NA) |
(i) CHF <1 year | (i) OR 0.72 (0.53–0.98) | P | C | T | S | – |
| (ii) CHF >1 year | (ii) OR 0.81 (0.71–0.91) | |||||||||||
| A10 | Wei et al. (2008) [33] | CVD | PDC statin initiation to outcome/end of study | Fixed in time | ≥0.80 <0.80* (NA) |
CVD | HR 0.66 (0.47–0.91) | P | C | – | S | – |
| A11 | McGinnis et al. (2009) [38] | AMI | PDC statin initiation to outcome/end of study | Fixed in time | ≥0.80 <0.80* (NA) |
– | (i) HR 0.44 (0.30–0.64) | P | C | – | – | – |
| (ii) HR 0.99 (0.76–1.30) | ||||||||||||
| A12 | Perreault et al. (2009) [26] | General population | MPR statin initiation to outcome/end of study | Fixed in time | ≥80% 60–79% 40–59% 20–39% 1–19%* (NA) |
(i) CAD <1 year | (i) OR 0.88 (0.77–1.01) | P | C | T | S | – |
| (ii) CAD >1 year | (ii) OR 0.82 (0.77–0.87) | |||||||||||
| A13 | Perreault et al. (2009) [27] | General population | MPR statin initiation to outcome/end of study | Fixed in time | ≥80% 60–79% 40–59% 20–39% 1–19%* (NA) |
(i) CVA <1 year | (i) OR 1.03 (0.76–1.38) | P | C | T | S | – |
| (ii) CVA >1 year | (ii) OR 0.74 (0.65–0.84) | |||||||||||
| A14 | Shalev et al. (2009) [41] | (i) General population (ii) CHD |
PDC statin initiation to outcome/end of study | Fixed in time | PDC ≥ 0.90 PDC < 0.90* (NA) |
Mortality | (i) HR 0.55 (0.49–0.61) | P | C | T | S | H |
| (ii) HR 0.49 (0.46–0.53) | ||||||||||||
| A15 | Corrao et al. (2010) [29] | General population | PDC statin initiation to outcome/end of study | Time dependent | >75% 51–75% 26–50% ≤25%* (NA) |
IHD | HR 0.81 (0.71–0.94) | P | C | T | – | – |
| A16 | Tuppin et al. (2010) [39] | AMI | PDC statin initiation to outcome/end of study | Fixed in time | >0.80* (A) ≤0.80 |
Mortality or ACS | HR 1.58 (1.37–1.81) | P | C | – | S | H |
| A17 | Dragomir et al. (2010) [28] | General population | MPR statin initiation to outcome/end of study | Fixed in time | ≥0.80* (A) <0.80 |
(i) CAD | (i) HR 1.07 (1.01–1.13) | P | C | – | S | H |
| (ii) CVA | (ii) HR 1.13 (1.01–1.25) | |||||||||||
| (iii) CHF | (iii) HR 1.13 (1.01–1.15) | |||||||||||
| A18 | Degli Esposti et al. (2012) [30] | General population | PDC statin initiation to outcome/end of study | Fixed in time | >80% 61–80% 41–60% 21–40%* (NA) |
(i) Mortality | (i) HR 0.46 (0.38–0.55) | P | C | – | – | – |
| (ii) AMI | (ii) HR 0.79 (0.56–1.10) | |||||||||||
| (iii) CVA | (iii) HR 0.73 (0.58–0.90) | |||||||||||
| A19 | Rabinowich et al. (2012) [31] | General population | PDC statin initiation to outcome/end of study | Fixed in time | ≥66% 33–66% <33%* (NA) |
VTE | HR 0.78 (0.69–0.89) | P | C | – | – | – |
| Statin discontinuation studies | ||||||||||||
| D20 | Ho et al. (2006) [43] | AMI | Statin discontinuation at 1 month postdischarge | Fixed in time | Nondiscontinuer* (A) Discontinuer |
Mortality | HR 2.86 (1.47–5.55) | P | C | – | S | H |
| D21 | Colivicchi et al. (2007) [44] | CVA | Statin discontinuation at 1, 6 and 12 months after discharge | Time dependent | Nondiscontinuer* (A) Discontinuer |
Mortality | HR 2.78 (1.96–3.72) | P | C | – | – | – |
| D22 | Penning-van Beest et al. (2007) [46] | (i) General population (ii) CVD |
Continuous statin use in the first 2 years of treatment | Fixed in time | 2 years continous use 18 months–2 years continuous use <18 months continous use* (NA) |
AMI | (i) RR 0.70 (0.60–0.81) | P | C | S | – | – |
| (ii) RR 0.70 (0.54–0.91) | ||||||||||||
| D23 | Daskalopoulou et al. (2008) [45] | AMI | Statin discontinuation in the first 90 days post-AMI | Fixed in time | Non-user* (NU) Users Starters Stoppers |
Mortality | RR 1.88 (1.13–3.07) | P | C | – | – | H |
| D24 | De Vera et al. (2011) [47] | Rheumatoid arthritis | Statin discontinuation status in month before outcome | Time dependent | Nondiscontinuer* (A) Discontinuer |
AMI | HR 1.67 (1.24–2.25) | P | C | T | – | H |
| D25 | De Vera et al. (2012) [48] | Rheumatoid arthritis | Statin discontinuation status in month before outcome | Time dependent | Nondiscontinuer* (A) Discontinuer |
(i) CVD mortality | (i) HR 1.60 (1.15–2.23) | P | C | T | – | H |
| (ii) Mortality | (ii) HR 1.79 (1.46–2.20) | |||||||||||
| Statin persistence studies | ||||||||||||
| P26 | Hippisley-Cox & Coupland (2006) [49] | IHD | Persistence of statin use (months) | Time dependent | >60 months No statin use* (NU) |
Mortality | HR 0.20 (0.08–0.47) | P | C | – | S | – |
| P27 | Haukka et al. (2012) [50] | General population | Statin use as function of time | Time dependent | Persistent Nonpersistent* (NA) |
Mortality | HR 0.39 (0.37–0.40) | P | C | – | — | – |
| P28 | Rublee et al. (2012) [51] | (i) General population (ii) CHD |
Persistence of statin use using anniversary method | Time dependent | Persistent Nonpersistent* (NA) |
(i) CVD (ii) CVD |
(i) HR 0.82 (0.74–0.91) | P | C | – | S | H |
| (ii) HR 0.74 (0.66–0.82) | ||||||||||||
Abbreviations are as follows: ACS, acute coronary syndrome; AMI, acute myocardial infarction; CAD, coronary artery disease; CHF, chronic heart failure; CVA, cerebrovascular accident; CVD, cardiovascular disease; HR, hazard ratio; MPR, medication possession ratio; OR, odds ratio; PDC, proportion of days covered; RR, relative risk; VTE, venous thromboembolism. Abbreviations for confounders considered according to the World Health Organization's five dimensions (factors) of medication non-adherence are as follows: C, condition factors; H, healthcare system factors; P, patient factors; S, social/economic factors; T, therapy factors.
*
Abbreviations for referent categories are as follows: A, adherent group is referent category; NA, non-adherent group is referent category; NU, non-user group is referent category.